| Title of Invention | "INHIBITORS OF THE 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 ENZYME" |
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| Abstract | The present invention relates to compounds which are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome and other diseases and conditions that are mediated by excessive glucocorticoid action. |
| Full Text | Inhibitors of the 11-beta-h)droxysteroid deh)drogenase Field of in)ention The present in)ention relates to compounds mat are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present in)ention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome and other diseases and conditions that are mediated by excessi)e glucocorticoid action. Background of the Invention Insulin is a hormone that modulates glucose and lipid metabolism. Impaired action of insulin (i.e., insulin resistance) results in reduced insulin-induced glucose uptake, oxidation and storage, reduced insulin-dependent suppression of fatty acid release from adipose tissue (i.e., lipolysis) and reduced insulin-mediated suppression of hepatic glucose production and secretion. Insulin resistance frequently occurs in diseases that lead to increased and premature morbidity and mortality. Diabetes mellitus is characterized by an ele)ation of plasma glucose le)els (hyperglycemia) in the fasting state or after administration of glucose during a glucose tolerance test "While this disease may be caused by se)eral underlying factors, it is generally grouped into two categories, Type 1 and Type 2 diabetes. Type 1 diabetes, also referred to as Insulin Dependent Diabetes Mellitus ("IDDM"), is caused by a reduction of production and secretion of insulin. In type 2 diabetes, also referred to as non-insulin dependent diabetes mellitus, or NIDDM, insulin resistance is a significant pathogenic factor in the de)elopment of hyperglycemia. Typically, the insulin le)els in type 2 diabetes patients are ele)ated (i.e., hyperinsulinemia), but mis compensatory increase is not sufficient to o)ercome the insulin resistance. Persistent or uncontrolled hyperglycemia in both type 1 and type 2 diabetes mellitus is associated with increased incidence of macro)ascular and/or micro)ascular effects. Glitazones (i.e., 5-benzylthiazolidine-2,4-diones) are a newer class of compounds used in the treatment of type 2 diabetes. These agents may reduce insulin resistance in multiple tissues, thus lowering blood glucose. The risk of hypoglycemia may also be a)oided. Glitazones modify the acti)ity of the Peroxisome Proliferator Acti)ated Receptor ("PPAR") gamma subtype. PPAR is currently belie)ed to be the primary therapeutic target for the main mechanism of action for the beneficial effects of these compounds. Other modulators of the PPAR family of proteins are currently in de)elopment for the treatment of type 2 diabetes and/or dyslipidemia. Marketed glitazones suffer from side effects including bodyweight gain and peripheral edema. Additional treatments to normalize blood glucose le)els in patients with diabetes mellitus are needed. Other therapeutic strategies are being explored. For example, research is being conducted concerning Glucagon-Like Peptide 1 ("GLP-1") analogues and inhibitors of Dipeptidyl Peptidase I) ("DPP-I)") that increase insulin secretion. Other examples include: Inhibitors of key enzymes in)ol)ed in the hepatic glucose production and secretion (e.g., Eructose-l,6-bisphosphatase inhibitors) and direct modulation of enzymes in)ol)ed in insulin signaling (e.g., Protein Tyrosine Phosphatase-lB, or "FTP-IB"). Another method of treating or prophylactically treating diabetes mellitus includes using inhibitors of 11-p-hydroxysteroid dehydrogenase Type 1 (1 Ip-HSDl). Such methods are discussed in J.R. Seckl et al., Endocrinology, 142: 1371-1376,2001 and references cited therein. Glucocorticoids are steroid hormones that are potent regulators of glucose and lipid metabolism. Excessi)e glucocorticoid action may lead to insulin resistance, type 2 diabetes, dyslipidemia, increased abdominal obesity and hypertension. Glucocorticoids circulate in the blood in an acti)e form (i.e., cortisol in humans) and an inacti)e form (i.e., cortisone in humans). 11P-HSD1, which is highly expressed in li)er and adipose tissue, con)erts cortisone to cortisol leading to higher local concentration of cortisol. Inhibition of 1 Ip-HSDl pre)ents or decreases the tissue specific amplification of glucocorticoid action thus imparting beneficial effects on blood pressure and glucose- and lipid-metabolism. Thus, inhibiting 1 Ip-HSDl benefits patients suffering from non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome and other diseases and conditions mediated by excessi)e glucocorticoid action. complications including atherosclerosis, coronary heart disease, peripheral )ascular disease, stroke, nephropathy, neuropathy and retinopathy. TnsuHn resistance, e)en in the absence of profound hyperglycemia, is a component of the metabolic syndrome. Recently, diagnostic criteria for metabolic syndrome ha)e been established. To qualify a patient as ha)ing metabolic syndrome, three out of the fi)e following criteria must be met: ele)ated blood pressure abo)e 130/85 mmHg, fasting blood glucose abo)e 110 mg/dl, abdominal obesity abo)e 40" (men) or 35" (women) waist circumference and blood lipid changes as defined by an increase in triglycerides abo)e 150 mg/dl or decreased HDL cholesterol below 40 mg/dl (men) or 50 mg/dl (women). It is currently estimated that 50 million adults, in the US alone, fulfill these criteria. That population, whether or not they de)elop o)ert diabetes mellitus, are at increased risk of de)eloping the macro)ascular and micro)ascular complications of type 2 diabetes listed abo)e. A)ailable treatments for type 2 diabetes ha)e recognized limitations. Diet and physical exercise can ha)e profound beneficial effects hi type 2 diabetes patients, but compliance is poor. E)en in patients ha)ing good compliance, other forms of therapy may be required to further impro)e glucose and h'pid metabolism. One therapeutic strategy is to increase insuun le)els to o)ercome insulin resistance. This may be achie)ed through direct injection of insulin or through stimulation of the endogenous insulin secretion hi pancreatic beta cells. Sulfonylureas (e.g., tolbutamide and glipizide) or meglitinide are examples of drugs that stimulate insulin secretion (i.e., insuun secretagogues) thereby increasing circulating insulin concentrations high enough to stimulate insulin-resistant tissue. Howe)er, insulin and insulin secretagogues may lead to dangerously low glucose concentrations (i.e., hypoglycemia). In addition, insulin secretagogues frequently lose therapeutic potency o)er time. Two biguanides, metformin and phenformin, may impro)e insulin sensiti)ity and glucose metabolism hi diabetic patients. Howe)er, the mechanism of action is not well understood. Both compounds may lead to lactic acidosis and gastrointestinal side effects (e.g., nausea or diarrhea). Alpha-glucosidase inhibitors (e.g., acarbose) may delay carbohydrate absorption from the gut after meals, which may hi turn lower blood glucose le)els, particularly in the postprandial period. Like biguanides, these compounds may also cause gastrointestinal side Signmajy of the Invention All patents, patent applications and literature references cited in the specification are herein incorporated by reference in their entirety. One aspect of the present in)ention is directed toward a compound of formula (I) (Formula Remo)ed) wherein A1, A2, A3 and A4 are each indi)idually selected from the group consisting of hydrogen, alkenyi, alkyl, alkyl-NH-alkyl, alkylcafbonyl, alkylsulfonyl, carboxyalkyl, carboxycycloalkyl, cyano, cycloalkyl, cycloalkylcarbonyl, cycloalkylsulfonyl, aryl, arylalkyl, aryloxyalkyl, arylcarbonyl, arylsulfonyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocycleoxyalkyl, heterocyclesulfonyl, halogen, haloalkyl, -NR5-[C(R6 R7)]n-C(0)-R8, -O-[CCR9R10)3,rC(OR1If -OR12, -S-alkyl, -S(0alkyl, -N(R13R14), -CO2R15, -C(O)-N(RI6R17), -C(R18R19)-OR20,-C(R2IB -C(=NOH)-N(H)2, •C(RlltR.l9*KXO)N(RaRMX -S-NCRR26), and-C(R18aR19a)- R18* and R19* are each independently selected from the group consisting of hydrogen and alkyl; nisOorl; pisOorl; D is a member selected from the group consisting of a -O-, -S-, -S(O)- and -S(O)z-; E is a member selected from the group consisting of alkyl, alkoxyalkyl, carboxyalkyl, carboxycycloalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, or R4 and E taken together with the atoms to which they are attached form a heterocycle; R1 is a member selected from the group consisting of hydrogen and alkyl; R2 is a member selected from the group consisting of hydrogen, alkyl and cycloalkyl; R3 and R4 are each independently selected from the group consisting of hydrogen, alkyl, carboxyalkyl, carboxycycloalkyl, cycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle and heterocyclealkyl, or R3 and R4 taken together with the atoms to which they are attached form a ring selected from the group consisting of cycloalkyl and heterocycle; R5 is a member selected from the group consisting of hydrogen, alkyl, carboxyalkyl, cycloalkyl, carboxycycloalkyl, aryl, arylalkyl, aryloxyalkyl, hydroxy, alkoxy, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heterocycle, heterocyclealkyl and heterocycleoxyalkyl; R6 and R7 are each independently selected from the group consisting of hydrogen and. alkyl, or R6 and R7 taken together with the atom to which they are attached form a ring selected from the group consisting of cycloalkyl and heterocycle; R8 is selected from the group consisting of hydrogen, alkyl, carboxy, carboxyalkyl, cycloalkyl, carboxycycloalkyl, aryl, arylalkyl, aryloxy, aryloxyalkyl, hydroxy, alkoxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroaryloxyalkyl, heterocycle, heterocyclealkyl, heterocycleoxy, heterocycleoxyalkyl and -NCRR28); R9 and R10 are each independently selected from the group consisting of hydrogen and alkyl, or R9 and R10 taken together with the atom to which they are attached form a ring selected from the group consisting of cycloalkyl and heterocycle; R11 is selected from the group consisting of hydroxy and -N(R29R30); R12 is selected from the group consisting of hydrogen, alkyl, carboxyalkyl, cycloalkyl, carboxycycloalkyl, aryl, arylalkyl, aryloxyalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heterocycle, heterocyclealkyl and heterocycleoxyalkyl; R13 and RM are each independently selected from the group consisting of hydrogen, alkyl, alkylsufonyl, aryl, arylalkyl, aryloxyalkyl, arylsulfonyl, carboxyalkyl, cycloalkyl, carboxycycloalkyl, cycloalkylsulfonyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocycleoxyalkyl and heterocyclesulfbnyl; R15 is selected from the group consisting of hydrogen, alkyl, carboxyalkyl, cycloalkyl, carboxycycloalkyl, aryl, arylalkyl, aryloxyalkyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heterocycle, heterocyclealkyl and heterocycleoxyalkyl; R16 and R17 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkylsufonyl, aryl, arylalkyl, aryloxy, aryloxyalkyl, arylsulfonyl, carboxy, carboxyalkyl, carboxycycloalkyl, cycloalkyl, cycloalkyloxy, cycloalkylsulfonyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heteroaryloxy, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocycleoxyalkyl, heterocycleoxy, heterocyclesulfbnyl, hydroxy, and - R202), or, R16 and R17 taken together with the atom to which Ihey are attached form a heterocycle; R201 and R202 are independently selected from the group consisting of hydrogen and alkyl; R18, R19 and R20 are each independently selected from the group consisting of hydrogen, alkyl, aryl, arylalkyl, carboxyalkyl, carboxycycloalkyl, cycloalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle and heterocyclealkyl; R21 and R22 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylcarbonyl, arylsulfonyl, cycloalkyl, carboxyalkyl, carboxycycloalkyl, cycloalkylcarbonyl, cycloalkylsulfonyl, heteroaryl, heteroarylcarbonyl, heteroarylsulfonyl, heterocycle, heterocyclecarbonyl and heterocyclesulfonyl; R23 and R24 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkoxy, alkylsulfonyl, aryl, arylcarbonyl, aryloxy, arylsulfonyl, carboxyalkyl, carboxycycloalkyl, cycloalkyl, cycloalkylcarbonyl, cycloalkyloxy, cycloalkylsulfonyl, heteroaryl, heteroarylcarbonyl, heteroaryloxy, heteroarylsulfonyl, heterocycle, heterocyclecarbonyl, heterocycleoxy, heterocyclesulfonyl and hydroxy, or, R23 and R24 taken together with the atom to which they are attached form a ring selected from the group consisting of heteroaryl and heterocycle; R25 and R26 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkylsufonyi, aryl, arylalkyl, aryloxy, aryloxyalkyl, arylsulfonyl, carboxy, carboxyalkyl, carboxycycloalkyl, cycloalkyl, cycloalkyloxy, cycloalkylsulfonyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heteroaryloxy, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocycleoxyalkyl, heterocycleoxy, heterocyclesulfonyl, and hydroxy, or, R25 and R26 taken together with the atom to which they are attached form a heterocycle; R27 and R28 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkylsufonyi, aryl, arylalkyl, aryloxy, aryloxyalkyl, arylsulfonyl, carboxy, carboxyalkyl, cycloalkyl, cycloalkyloxy, carboxycycloalkyl, cycloalkylsulfonyl, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroaryloxyalkyl, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocycleoxy, heterocycleoxyalkyl, heterocyclesulfonyl and hydroxy, or, R27 and R28 taken together with the atom to which they are attached form a heterocycle; and R29 and R30 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkylsufonyi, aryl, arylalkyl, aryloxy, aryloxyalkyl, arylsulfonyl, carboxy, carboxyalkyl, cycloalkyl, cycloaBcyloxy, carboxycycloalkyl, cycloalkylsulfonyl, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroaryloxyalkyl, heteroarylsulfbnyl, heterocycle, heterocyclealkyl, heterocycleoxy, heterocycleoxyalkyl, heterocyclesulfonyl, and hydroxy, or, R29 and R30 taken together with the atom to which they are attached form a heterocycle; pro)ided that, if R1 is hydrogen; then at least one of A1, A2, A3 and A4 is not hydrogen. A further aspect of the present in)ention encompasses the use of the compounds of formula (I) for the treatment of disorders mat are mediated by 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme, such as non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome and other diseases and conditions that are mediated by excessi)e glucocorticoid action, comprising administering a therapeutically effecti)e amount of a compound of formula (I). According to still another aspect, the present in)ention is directed to a pharmaceutical composition comprising a therapeutically effecti)e amount of a compound of formula (1) in combination with a pharmaceutically suitable carrier. Detailed description of the In)ention All patents, patent applications and literature references cited in the specification are herein incorporated by reference in their entirety. One aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; and A1, R3, R4, D and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (T), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are hydrogen; and A1, D and E are as described in Ihe summary of the in)ention. Another aspect qfjhe present jnyention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are hydrogen; D is -O-; and A1 and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 andR2 are hydrogen; R3 and R4 are hydrogen; Dis-O-; E is as described in the summary of the in)ention; and A1 is selected from the group consisting of A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O)-N(R16R17), -CCR-CCOJNCR224), -C(=NOH)-N(H)2, -SCO)NCR226), -CO2R15, -CCRSCOCR226), and * CCRNO24) wherein R12, R15, R16, R17, R18, R19, R18*, R19a, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are hydrogen; Dis-O-; A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O)-N(R16R17), -CCR'CNCR224), -C(=NOH)-N(H)2, -S(0)2-N(R25R26), -CO2R15, -C(R188R19aS(0)rN(R25R26), and -CRNR24) wherein R12, R15, R16, R17, R18, R19, RI8a, R19a, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention; and E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyl. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 is hydrogen; R4 is alkyl; and A1, D and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I); wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 is hydrogen; R4isa]kyl; D is -Q-; and A1 and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 is hydrogen; R4 is alkyl; Dis-O-; E is as described in the summary of the in)ention; and A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -COR119)-20, -C(O N(R16R17), -C(R18tR19C(0)N23R24), -CX=NOH)-N(H)2, -SCOrNCR226), -COjR15, -CR18iR19S(0)rN(R25R26), and -CCRRNCR224) wherein R12, R15, R16, R17, R18, R19, R18*, R19*, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 is hydrogen; R4 is alky]; Dis-O-; A1 is selected from the group consisting of alkenyl, alkylsulfonyi, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR2l, -C(O)-N(R16R17), -CCR-RJ-CNCRR24), -C(=NOH)-N(H)2, -SCQk-NCR226), -COaR15, -CCR'RSCOk-NCR226), and -CCRR-NfR224) wherein R12, R15, R16, R17, R18, R19, R18t, R19*, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention; and B is selected from the group consisting of aryl, cycloaflcyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyL Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are alkyl; and A1, D and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are alkyl; D is -O-; and A1 and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are alkyl; Dis-O-; E is as described in the summary of the in)ention; and A1 is selected from the group consisting of alkenyl, alkylsulfonyi, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(Oalkyl, -C(R18R19OR20, -C(O N(R16R17), -C(R18aR19a)-C(0)N(R23R24), -C(=NOHN(H)2, -S(O)2-N(R25R26), -CO15, -CCR-SCO)NOR226), and -CCRR-NCRR24) wherein R12, R15, R16, R17, R18, R19, R18a, R19t, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (1), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3andR4arealkyl; Dis-O-; A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(0)-alkyl, -C(R-18R-19OR20, -0(O !*17 18*19t2324 226 " -C(=NOHN(H)2, -SCO-NCR226), -CO2R", NCR224) wherein R12, R1S, R16, R17, R18, R19, R18*, R19§, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention; and E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyl. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 andR2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a ring selected from the group consisting of cycloalkyl and heterocycle; and A1, D and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a cycloalkyl ring; and A1, D and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; RJ andR2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a cycloalkyl ring; D is -O-; and A1 and E are as described in the summary of the in)ention. Another, aspect of he present in)ention is directed toward a compound of formula (1), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with die atoms to which they are attached form a cycloalkyl ring; Dis-O-; E is as described in the summary of the in)ention; and A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -ORU, carboxyalkyl, -S-alkyl, -S(Oalkyi, -C(R18R19)-OR20, -C(0)-N(R16R17), 119)XOJN(R°Ra4X -C(==NOH)-NCH)2, -SCONCR226), -C0#}5, .C(Ri8.Ri9,).S(0)2.N(R25R26)) md -CCR-NR24) wherein R12, R15, R16, R17, R18, R19, R18a, R19*, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a cycloalkyl ring; Dis-O-; A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O N(R16R17), -C(R18*R19i)-C(0)N(R23R24), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -CCRR-SCO-NCRR26), and -CR-NCR214) wherein Ru, R15, R16, Rn, R", R19, R18*, R19a, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention; and E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyl. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a cyclopropyl ring; Dis-O-; A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalky], -OR12, carboxyalkyl, -S-alkyi, -S(O)-alkyl, -C(R1SR19)-OR20, -C(O N(R15R"), -C(R1BBR19-C(0)N(R23R24), -C(=NOH)-N(H)2, -SCOJrNCR226), -COzR15, -CCR'O)NCR226), and -QRRNCR224) wherein R12, R15, R16, R17, R18, R19, R18t, R19*, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention; and E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyL Another aspect of the present in)ention is directed toward a compound of formula (T), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a cyclobutyl ring; Dis-O-; A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-aftyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O)-N(R16R"), -C(R1819s)-C(O)N(R23R24), -C(=NOH)-N(H)2, -SCONCRR26), -COjR15, inR12, R15, R16, R17, R18, R19, R18a, R19*, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention; and E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyL Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 jmd A4 arejiydrogen; R1 andR2 are hydrogen; and R3 and R4 taken together with the atoms to which they are attached form a heterocycle, and A1, D and B are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a heterocycle; D is -O-; and A1 and B are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a heterocycle; B is as described in the summary of the in)ention; D is -O-; and A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyi, -OR12, carboxyalkyl, -S-alkyl, -S(Oalkyl, -C(R18R19OR20, -C(O)-N(RI6R17), -C(R1BtR198)-C(O)N(R23R24), -C(=NOH)-N(H)2,-S(O)2-N(R25R\CO2R15, -C(R18aR19ll)-S(0)2-N(R25R26), and -CRNOR24) wherein R12, R15, R1*, R17, R18, R19, R18*, R198, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a heterocycle; Dis-O; A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyi, -OR12, carboxyalkyl, -S-alkyl, -S(0)-alkyl, -CpWOR20, -C(0)-N(R16R17), -CCR'))CCOCR224), -C(=NOH)-N(H)2, -S-NCR226), -C02R15, -C(R18aR198)-S(0)r-N(R25R26), and -QRR-NCR224) wherein R12, R15, R16, R17, R18, R19, R18a, R19a, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention; and E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyl. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R4 and B taken together with the atoms to which they are attached form a heterocycle; and A1 and D are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R4 and B taken together with the atoms to which they are attached form a heterocycle; D is -O- and A1 is as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R4 and E taken together with the atoms to which they are attached form a heterocycle; D is -O-; and A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-aIlcyl, -C(R18R19OR2°, -C(O)-N(R16R"), -CXR-CCOJNCR224), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -CCR'R-SCOz-NCR226), and -CCRR22)-]*224) wherein R12, R15, R16, R17, R18, R19, R18*, R19*, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (T), wherein A1 is selected from the group consisting of alkylsulfbnyl, aryisulfonyl, cyclpalkylsulfonyl, heteroarylsulfpnyl and heterocyclesulfqnyl; A2, A3 and A4 are hydrogen; D is -O-; and R1, R2, R3, R4, and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (I), wherein A1 is (Ofe-NCRR26) wherein R25 and R26 are as described in the summary of the in)ention; A2, A3 and A4 are hydrogen; D is -O-; and R1, R2, R3, R4, and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (T), wherein A1 is -C(0)-N(RlfiR17) wherein R16 is selected from the group consisting of hydrogen and aOcyl and R17 is selected from the group consisting of arylalkyl and heteroarylalkyl; Dis-O-; A2, A3 and A4 are hydrogen; and R1, R2, R3, R4, and E are as described in the summary of the in)ention. Another aspect of the present in)ention is directed toward a compound of formula (T), wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; D is selected from the group consisting of -S-, -S(O)- and -8(0)2; and A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O)-N(R16R17), -CCRR')WR24), -C(=NOH)-N(H)2, -SNCRR26), -CCbR15, -CCRRSCOk-NCRR2*), and -C'RNCR224) wherein R12, R15, R16, R17, R18, R19, R18*, R19a, R21, R22, R23, R24, R25, and R26 are as described in the summary of the in)ention; E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyl; and R3- and R4 are each independently selected from the group consisting of hydrogen, alkyl and arylalkyl, or R3 and R4 together with the atom to which they are attached form a cycloalkyl ring. Another aspect of the present in)ention is directed to a compound selected from the following group E-4-[(2-memyl-2-phenoxypropanoyl)amino]adamantane-l-carboxamide; -[(2-metiiyl-2-{[4-(trifluoromemyl)benzyl]oxy}propanoyl)amino]adamantane-l-carboxamide; 5-4-({2-mefliyl-2-[(2-methylcyclohex5)oxy]pr{q)anoyl} amino)adamantane-l-carboxylic acid; j&-4-({2-metliyl-2-[(3-methylcyclohexyi)oxy]propaiioyl}amino)adamantaiie-l-carboxylic acid; E-4- {[2-(cyclolie|)tyloxy)-2-methylpropanoyl]aamno} adamantane-1-carboxylic acid; E-4- {[2-(cyclohexylmet:hoxy)-2-methyIpropanoyl]amino} adamantane-1-carboxylic acid; #-4-{[2-(4-orophenoxy)-2-meihyfcropanoyl]anm E-4-{[24hlorophenoxy)-2-methyIpropanoyl]arnino}adamantane-l-caiboxaniide; JF-4{2-methyI-2-[(4-methylcyclohexyI)oxy]pitanoyl}amino)adamantane-l-carboxamide; E[(2-pheiK)xypropanoyl)amino]adamantane-l-carboxarnide; E-4- {[2-methyI-2-(2-methy]pheiioxy)propanoyl] amino) adamantane-1 -carboxylic acid; E-4- {[2-methyl-2-(4-methylphenoxy)piopanoyl]amino} adamantane-1 -carboxylic acid; J5-4-{[2-(2-cUorophenoxy)-2-memylpropanoyl]amino}adamaiitane-l-carboxylicacid; E-4- {[2-(2-meflioxyphenoxy)-2-methy]propanoyl]amino} adamantane-1-carboxamide; E{[2-(4-methoxyphenoxy)-2-methylpropanoyl]atnmo}adamantane-l-carboxamide; E-4-({2-methyl-2-[3-(trifluoromemyl)phenoxy]propanoyl}amino)adarnaiitane-l-carboxamide; -4-{[2-(3-methoxyphenoxy)-2-methylpropanoyl]ammo}adamantane-l-carboxamide; E-2-(4-Coro-phenoxy)-N-(5-hydroxy-adamantan-2-yl)-2-memyl-propionamide; E-{[2-Metoyl-2-(4-me1hylphenoxy)propmoyl]ainino}adamantane-l-carboxamide; E-4-{[2-(3-CHonhenoxy)-2-metbylprbpanoyl]aniino}adamantane-l-carboxamide; N-4-({2-Memyl-2-[4-(trifluoromethoxy)phenoxy]propanoyl}amino)adamantane-l-carboxamide; N-4-{[2-(3-Bromophenoxy)-2-me&ylpropanoyl]amino}adamantane-l-carboxylic acid; 4-({[((E)-4-{[2-(4-Chlorophenoxy)-2-methylpropanoyl]amino}-l-adamantyl)carbonyl]amino}methyl)benzoic acid; -4-{[2-(2,3-Dimetbylphenoxy)-2-memylpropanoyl]arnino}adaman1ane-l-carbo acid; tert-Buty!42-{[(E)-5-(aminocaibonyl)-2-adamantyl]amino}-lJl-dimethyl-2-oxoethoxy)phenylcarbamate; E-N-[4-(Aminocarbonyl)benzyl]-4-{[2-(4-chlorophenoxy)-2-methylpropanoyl]amino}adamantane-l-caiboxamide; -N-[4-(Aminocarbonyl)methyl]-4-{[2-(4-chlorophenoxy)-2-methylpropanoyljamino} adamantane-1 -carboxamide; 3-({[((E4-{[2-(4-C!hloropIienoxy)-2-inethylpropanoyl]amino}-l-adamantyl)carbonyl]arDino}methyl)benzoic acid; {2-[(5-Bromopyridm-2-yl)oxy]-2-me1hylpropanoyl}aniino)adamantane-l-carboxamide; E-4- {[2-(2Jyanophenoxy)-2-methylpiDpaiioyl]ainino}adainantane-1 -caiboxaniide; N-4-{[24-Hydroxyphenoxy)-2-methylpropanoyl]amino}adaiaantane-larboxamide; ((E)-4- {[2-(4-Chlorophenoxy)-2-methylpropanoyl]amino} -1 -adamantyl)acetic acid; N-[(-52-Amino-2-oxoethyl)-2-adamantyl]-2-(4-chlorophenoxy)-2-methylpropanamide; 24-CMorophetioxy)-2-methyl-N-[(jB)-5-{2H-tetraazol-5-y]meihyl)-2-adamantyljpropanamide; N- {(E)-5-[(Aminosulfonyl)methyl]-2-adamantyl} -2-(4-chlorophenoxy)-2-methylpropanamide; N- {(-5-[(20-Ammo(ydroxyiinino)methyl]-2-adamantyl} -2-(4-chlorophenoxy)-2-methylpropanamide; 5-N-[4-(Aminosulfonyl)benzyl]-4-{[2-(4-chloroplienoxy)-2-me1hylpropanoyl]amino}adamantane-l-carboxamide; _ E-4-{[2-(4-Chlorophenoxy)-2-methylpropanoyl]ainino}-N-(4-{[(methylsulfonyl)amino]carbonyl}benzyl)adamantane-1 -carboxamide; JJ-4-( {2-[(4-Chlorophenyl)tbio]-2-methylpropanoyl} amino)adamantane-1 -carboxylic acid; E-4-( {2-[(4-MeQioxyphenyl)thio]-2-methylpropanoyl} amino)adamantane-l -carboxamide amide; E-({2-[(4-Memoxyphenyl)sulfinyl]-2-methyipropanoyl}amino)adamantane-l-carboxamide; {2-[(4-Meflioxyphenyl)sulfonyl]-2-meatylpropanoyl}aniino)adamantaTie-l-carboxamide; E4{2-[4-CMaro-2-(pyrrolidin-l-ylsulfonyl)phenoxy]-2-methylpropanoyl}amiao)adamaiitane-l-caiboxamide; J({2TMefhyl-2-[4metibylsi)lfony carboxamide; 5({2-Me1hyl-2-[2methyls\jifonyl)pheaioxy]propaiioyl}ainino)adamantari6-l-carboxamide; E-4-({2-Methyl-2-[4-iyrroKdin-l-ylsulfonyl)phenoxy]propanoyl} amino)adamantane-l-carboxamide; 2-(2-McmfluoropheiKxy)-N-[(-5-hydroxy-2-adamantyl]-2-methylpropanamide; 2-(2-(orofluorophemoxy)-2-me%l-N-[(E5-(2H-tetraazol-5-yl)-2-adamantyl]propanainide; 2-(2-GMoro-fluorophenoxy)-2-metiiyl-N-[(JS)-5-(methyltbio)-2-adamantyl]propanamide; adamantyljpropanamide; 22-CUoioflu adamantyl]propanamide; {[14_(orophenoxy)cyclobutyl]carbonyl}amino)adamantane-l-carboxaniide; 4-[{[2-(4-Chlonhenoxy)-2-mefliylpropanoyl]amino} -1-adamantyl)methyl]sulfonyl}amino)inethyl]benzoic acid; 2-(4-CUorophenoxy)-N-[(E5-(lH-imidazol-2-yQ-2-adamantyl]-2-methylpropanamide; (23-(®-{[2-(4-Chlorophe!noxy)-2-mettiylpropaiioyl]ainino}-l-adamantyl)acrylic acid; (E)-4-[(2-Methyl-2-{[5-(lH-pyrazol-l-yl)pyridin-2-yl]oxy}propanoyl)amino]adamantaiie-l-carboxamide; 2-(4-ChlorophenoxyN-[(E)-5-isoxazol-5-yl-2-adamantyl]-2-methylpropanamide; 2-(4-Chlorophenoxy)-2-methyl-N- {(JS)-5-[(2-morpholin-4-ylefhoxy)methyl]-2-adamantyl}propanamide; N-[(5-(Aminosulfonyl)-2-adamantyl]-2-(2!Moiophenoxy)-2-methylpropanamide; N-[(E)-5-(Ajiunosulfonyl)-2-adamantyl]-2-me N-[(-5Aminosulfonyl)-2-adamantyl]-2-m6lhyl-2-(4-me1hyhaioxy)propaiiamide; N-[(E)-5-(Aminosiilfonyl)-2-adamantyl]-2-me1hyl-2-[2-(trifluoromethyl)phenoxy]propanamide; N-[(E)-5AnunosuIfonyl)-2-adainantyi]-2-meihyl-2-[2-(trifluoromethoxy)phenoxy]propananiide; N-[(JS)-5-(Ammosulfonyl)-2-adamantyl]-2-(2-chloro-4-fluorophenoxy)-2-methylpropanamide; E-4- {[2-(2-chlorophenoxy)-2-methyl-3-phenylpropanoyl]amino} adamantane-1 -carboxamide; 2-(4Uorophenoxy)-N-[(5-hydroxy-2-adamantyl]-2-metibyIpropanamide; -({2-methyl-2-[(5-morpholinylpyridin-2-yl)oxy]propanoyl}amino)adamantane-l -carboxamide; E-4-{[2-mefliyl-2-(pyridin-2-yloxy)propanoyl]amino} adamantane-1-carboxamide; 2-(4-chloropheQoxy)-2-methyl-N- { E)-5-[(methylamino)sulfonyl]-2-adamantyl}propanamide; 3-((E){[2-(4Uorophenoxy)-2-methylpropanoyl]amino}-l-adamantyl)propanoic acid; 2-(4-chlorophenoxy)-N- {(E)-5-[(dimethyiamino)sulfonyl]-2-adamantyl} -2-methylpropanamide; JE-4-[(2-{[5-(lH-imidazol-l-yl)pyridin-2-yl]oxy}-2-methylpropanoyl)amino]adamantane-l-carboxanude; 2-(4-chlorophenoxy)-2-methyl-N-[(E)-5-(lH-pyrazol-3-yl)-2-adamantyljpropanamide; N-[(-5anunosulfonyl)-2-adamantyl]-2-(3-cUorophenoxy)-2-methy)ropananude; N-[(E)-5-(aininosulfonyl)-2-adamantyl]-2-methyl-2-(3-methylphenoxy)propananude; N-[(E)-5-(aniinosulfonyl2-adainantyl]-2-(2-metlioxyphenoxy)-2-methylpropanamide; N-[(E)-5-(aminosulfon54)-2-adamantjd]-2-(3-met;hoxyphKioxy)-2-methylpropanamide; N-[(5ammosulfonyl)-2-adamantyl]-2-(4-metlioxyphaioxy)-2-methylpropanamide; N-[(20-Ma*°onyl)-2-adamantyl]-2-(4H5y {[2-metfayl-22-metfayhenoxy)propanoyl]amino}adamantane-l-carioxamide; N-4-{[2-methyl-2-(3-methylphenoxy)piopanoyl]amino}adamantane-lK;arboxamide; N-[(2-methyl-2-{[(lSS2-me&ylcyclohexyl]oxy}pn)panoyl)aniino]adamantane-1-carboxylic acid; 5-4-({2-methyl-2-[(2-methylcyclohexyl)oxy]propanoyl}amino)adamantane-l-carboxamide -4-{[2-(cycloheptyloxy)-2-methylpropanoyl]amino}adamanfane-l-carboxamide; E-4- { [2-(cyclohexylmethoxy)-2-methylpropanoyl]amino} adamantane- 1 -carboxarnide; carboxamide; E"-4- {[2-(2-chlorophenoxy)-2-methylpropanoyl]amino} adamantane-1-carboxamide; 4-{[({(fi)-4-[(2-me(hyl-2-phenoxypropanoyl)amino]-l-adamantyl}carbonyl)amino]methyl}benzoic acid; ({2-[(4,4-dimethylcyclohexyl)oxy]-2-methyropanoyl}amino)adamaiitane-l-carboxylic acid; -4-{[2-me%l-2-(lA3,4-tetrahydronaphthalcai-2-yloxy)propanoyl]aniino}adamantane-l-carboxylic acid; E-4-{[24-bromchenoxy)-2-methylpK)panoyl]amino}adamantane-l-carboxylic acid; E-4- {[2-methyl-2-(l-naphthyloxy)propanoyl]amino} adamantane-1-carboxylic acid; -4-{[223-dicUorophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4- {[2-(2,4-dichlorophenoxy)-2-methylpropanoyl]amino} adamantane-1-carboxylic acid; E-4-{[2-(2,5cUorophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; 5{[22,4-dimethylphenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; -{[2-(2,5-dimetJiylphenoxy)-2-methylpropanoyl]aniino}adamantane-l-carboxylic acid; {[2-meihyl-22-naphfliyloxy)piopanoyl]amino}adamantane-l-carboxylicacid; J5-4- {[2-(4-bromo-2-fluorophenoxy)-2-methylpropanoyl]amino} adamantane-1 -carboxylic acid; E-4-({2-methyl-2-[(7-methyl-2,3-dihydro-lH-inden-4-yl)oxy]propanoyl}aniino)adamantane- 1-carboxylic acid; N{[2-(4-bromcH2Uoropheooxy)-2-me1hylpropanoyl]amino}adamantane-l-carboxylic acid; {[21,r-biphenyl-3-yloxy)-2-methyropanoyI]amino}adamantane-l-carboxyKc acid; E~4- {[2-(2-bromophenoxy)-2-methylpropanoyl]amino}adamantane-l-caiboxylic acid; N-N-[4-(aminocarbonyl)benzyl]-4-[(2-methyl-2-phenoxypropanoyl)amino]adamantane-l-carboxamide; 5-4-{[2-(4-chlorophenoxy)-2-methylpropanoyl]amino}-N-(l,3-tbiazol-5-ylmethyl)adamantane-l-carboxamide; -4-{[2-(4-chlorophenoxy)-2-mefliylpropanoyl]amino}-N-jyridin-4-ylmetbyl)adamantane-l-carboxamide; E-A- {[2-(4-aminophenoxy)-2-mettiylpropanoyl]aiDino} adamantane-1-caiboxamide; E{2-methyl-2-[2-(trifluorometiioxy)phaioxy]propanoyl}ainino)adamaiitane-l-carboxamide; N-4-({2-methyI-2-[2-(trifluoroinethyl)phenoxy]propanoyl}amino)adamantan&-l-carboxamide; B-4-({2-methyl-2-[4-(pyrrolidin-l-ylsdfonyl)phraaoxy]propanoyl}amino)adamantane-l-carboxamide; 2-(2hlorofluorophenoxy)-N-[(-5-hydroxy-2-adamantyl]-2Tmelhylpropaiiairdde 2-(2UorofluorophenoxyN-[(5yano-2-adamantyl]-2-me%lpropanamide; E-4-[(2-methyl-2- {4-[(trifluoroacetyl)amino]phenoxy}propanoyl)amino] adamantane-1-carboxamide; E-4- {[2-(3-bromo-4-methoxyphaioxy)-2-me1iiylpropaiioyl]ainino} adamantane-1-carboxamide; {[22,5bromo-4-methoxyphenoxy)-2-methylpropanoyl]ainino}adamaiitane-l-carboxamide; jF{[22-bromomethoxyphenoxy)-2-mefliylpropanoyl]amino}adamantan&-l-carboxamide; N-4-{[2-(2-chloro-4-fluorophenoxy)-2-methylpropanoyl]amino}-N-dimethyladamantane-1 -carboxamide; 2-(4-cUorophenoxy)-N(J5)-5-{[(4Haie 2-adamantyl)-2-metiiylpropanamide; E-4- {[2-(4- {[(tert-butylamino)crbonyl]amino}phenoxy)-2-methyipropanoyl]amino}adamantane-l-cartoxamide; ethyl 4-(2- {[(5-(aminocarbonyl)-2-adamflntyl]amino} -1,1 -dimethyl-2-oxoethoxy)phenylcarbamate; Er-4-[(2-methyl-2- {4-[(propylsulfonyl)ammo]phenoxy}propanoyl)ainmo] adamantane-1-carboxamide; E-4-[(2- {4-[(3,3-dinietiiylbutanDyl)amino]pheaoxy} -2-methylpropanoyl)amino] adamantane-1 -carboxamide; E-4- {[2-methyl-2-(phenylsulfinyl)propanoyl]amino} adamantane-1-carboxylic acid; E{[2-methyl-2-(phenylsulfonyl)propanoyl]amino}adamaatane-l-carboxylicacid; N-[(-5-cyano-2-adamantyl]-2-[(4-me1hoxyphenyl)sulfonyl]-2-methylprDpanamide; 2-[(4-me&oxypheayl)sulfonyl]-2-methyl-N-[(-5-(2H-tetraazol-5-yl)-2-adamanty]]propanamide; and E-4-({2-[4-(benzyloxy)pheiioxy]-2-me1hylpropanoyl}amino)adamantane-l-carboxamide. Another embodiment of the present in)ention discloses a method of inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme, comprising administering to a mammal, a therapeutically effecti)e amount of the compound of formula (I). Another embodiment of the present in)ention discloses a method of treating disorders in a mammal by inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme, comprising administering to a mammal, a therapeutically effecti)e amount of the compound of formula (T). Another embodiment of the present in)ention discloses a method of treating non-insulin dependent type 2 diabetes in a mammal by inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effecti)e amount of the compound of formula Q. Another embodiment of the present in)ention discloses a method of treating insulin resistance in a mammal by inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effecti)e amount of the compound of formula Q. Another embodiment of the present in)ention discloses a method of treating obesity in a mammal by inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effecti)e amount of the compound of formula 0). Another embodiment of the present in)ention discloses a method of treating lipid disorders in a mammal by inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effecti)e amount of the compound of formula (I). Another embodiment of the present in)ention discloses a method of treating metabolic syndrome in a mammal by inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effecti)e amount of the compound of formula (I). Another embodiment of the present in)ention discloses a method of treating diseases and conditions that are mediated by excessi)e glucocorticoid action in a mammal by inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effecti)e amount of the compound of formula (I). Another embodiment of the present in)ention discloses a pharmaceutical composition comprising a therapeutically effecti)e amount of the compound of formula (I) in combination with a phannaceutically suitable carrier. Definition of Terms The term "aDcenyl" as used herein, refers to a straight or branched chain hydrocarbon containing from 2 to 10 carbons and containing at least one carbon-carbon double bond formed by the remo)al of two hydrogens. Representati)e examples of alkenyl include, but are not limited to, ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl, 2-heptenyl, 2-methyl-l-heptenyl, and 3-decenyl. Alkenyls of the present in)ention can be unsubstituted or substituted with one substituent selected from the group consisting of carboxy, alkoxycarbonyl and aryloxycarbonyl. The term "alkoxy" as used herein, refers to an alkyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. Representati)e examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentyloxy and hexyloxy. The term "alkoxyalkyl" as used herein, refers to an alkoxy group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representati)e examples of alkoxyalkyl include, but are not limited to, tert-butoxymethyl, 2-ethoxyethyl, 2-methoxyethyl and methoxymethyl. The term "alkoxycarbonyl" as used herein, refers to an alkoxy group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representati)e examples of alkoxycarbonyl include, but are not limited to, methoxycarbonyl, ethoxycarbonyl andtert-butoxycarbonyl. The term "alky!" as used herein, refers to a straight or branched chain hydrocarbon containing from 1 to 10 carbon atoms. Representati)e examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tort-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methyIhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl and n-decyL The term "alkylcarbonyr as used herein, refers to an alkyl group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representati)e examples of alkylcarbonyi include, but are not limited to, acetyl, 1-oxopropyl, 2,2-dimethyl-l-oxopropyl, 1-oxobutyl and 1-oxopentyl. The term "alkylsulfonyT1 as used herein, refers to an alkyl group, as defined herein, appended to the parent molecular moiety through a sulfonyl group, as defined herein. Representati)e examples of alkylsulfonyl include, but are not limited to, methylsulfonyl and ethylsulfonyl. The term "alkyl-NH" as used herein, refers to an alkyl group, as defined herein, appended to the parent molecular moiety through a nitrogen atom. The term "alkyl-NH-alkyl" as used herein, refers to an alkyl-NH group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. The term "aryl" as used herein, means a phenyl group, or a bicyclic or a tricyclic fused ring system. Bicyclic fused ring systems are exemplified by a phenyl group appended to the parent molecular moiety and fused to a cycloalkyl group, as defined herein, a phenyl group, a heteroaryl group, as defined herein, or a heterocycle, as defined herein. Tricyclic fused ring systems are exemplified by an aryl bicyclic fused ring system, as defined herein and fused to a cycloalkyl group, as defined herein, a phenyl group, a heteroaryl group, as defined herein, or a heterocycle, as defined herein. Representati)e examples of aryl include, but are not limited to, anthracenyl, azulenyl, fluorenyl, indanyl, indenyl, naphthyl, phenyl and tetrahydronaphthyl. The aryl groups of this in)ention may be optionally substituted with 1,2,3,4 or 5 substituents independently selected from alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylsulfonyl, aDcynyl, aryl, arylalkoxy, arylcarbonyl, aryloxy, arylsulfonyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, ethylenedioxy, formyl, haloalkoxy, haloalkyl, halogen, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocycle, heterocyclecarbonyl, heterocycleoxy, heterocyclesulfonyl, hydroxy, hydroxyalkyl, nitro, RfRgN-, RfRgNalkyl, RjRgNcarbonyl, -N(H)C(O)N(H)(alkyl), and RfRgNsulfonyl, wherein Rf and Rg are independently selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, cycloalkyl, haloalkyl, haloalkylcarbonyl and cycloalkylalkyl wherein the cycloalkyl, the cycloalkyl of cycloalkylalkyl as represented by Rf and Rg are each independently unsubstituted or substituted with 1,2 or 3 substituents independently selected from the group consisting of halogen, alkyl and haloalkyl. The substituent aryl, the aryl of arylalkoxy, the aryl of arylcarbonyl, the aryl of aryloxy, the aryl of arylsulfonyl, the substituent heteroaryl, the heteroaryl of heteroarylalkyl, the heteroaryl of heteroarylcarbonyl, the substituent heterocycle, the heterocycle of heterocyclecarbonyl, the heterocycle of heterocycleoxy, the heterocycle of heterocyclesulfonyl may be optionally substituted with 1,2 or 3 substituents independently selected from the group consisting of alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkynyl, carboxy, carboxyalkyl, cyano, haloalkyl, halogen, hydroxy, hydroxyalkyl, nitro, RfRgN-, RfRgNalkyl, RfRgNcarbonyl and RfRgNsulfonyl wherein Rf and Rg are as described herein. The term "arylalkyl" as used herein, refers to an aryl group, as defined herein, appended to the parent molecular moiety through an alky] group, as defined herein. • Representati)e examples of arylalkyl include, but are not limited to, benzyl, 2-phenylethyl, 3-phenylpropyl and 2-naphth-2-ylefhyL The term "arylcarbonyl" as used herein, refers to an aryl group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representati)e examples of arylcarbonyl include, but are not limited to, benzoyl and naphthoyl. The term "aryl-NH-" as used herein, refers to an aryl group, as defined herein, appended to the parent molecular moiety through a nitrogen atom. The term "aryl-NH-alkyl" as used herein, refers to an aryl-NH- group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. The term "arylalkoxy" as used herein, refers to an aryl group, as defined herein, appended to the parent molecular moiety through an alkoxy moiety, as defined herein. The term "aryloxy" as used herein, refers to an aryl group, as defined herein, appended to the parent molecular moiety through an oxy moiety, as defined herein. Representati)e examples of aryloxy include, but are not limited to phenoxy, naphthyloxy, 3-bromophenoxy, 4-chlorophenoxy, 4-methylphenoxy and 3,5-dimettioxyphenoxy. The term "aryloxyalkyl" as used herein, refers to an aryloxy group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. The term "aryloxycarbonyl" as used herein, refers to an aryloxy group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. The term "arylsulfbnyl" as used herein, refers to an aryl group, as defined herein, appended to the parent molecular moiety through a sulfonyl group, as defined herein. Representati)e examples of arylsulfonyl include, but are not limited to, phenylsulfonyl, 4-bromophenylsulfonyl and naphthylsulfbnyl. The term "carbonyl" as used herein refers to a -C(O)- group. The term "carboxy" as used herein refers to a -C(O)-OH group. The term "carboxyalkyl" as used herein refers to a carboxy group as defined herein, appended to the parent molecular moiety through an alkyl group as defined herein. The term "carboxycycloalkyl" as used herein refers to a carboxy group as defined herein, appended to the parent molecular moiety through an cycloalkyl group as defined herein. The term "cycloaDcyl" as used herein, refers to a monocyclic, bicyclic, or tricyclic ring system. Monocyclic ring systems are exemplified by a saturated cyclic hydrocarbon group containing from 3 to 8 carbon atoms. Examples of monocyclic ring systems include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Bicyclic fused ring systems are exemplified by a cycloalkyl group appended to the parent molecular moiety and fused to a cycloalkyl group, as defined herein, a phenyl group, a heteroaryl group, as defined herein, or a heterocycle, as defined herein. Tricyclic fused ring systems are exemplified by a cycloalkyl bicyclic fused ring system, as defined herein and fused to a cycloalkyl group, as defined herein, a phenyl group, a heteroaryl group, as denned herein, or a heterocycle, as defined herein. Bicyclic ring systems are also exemplified by a bridged monocyclic ring system in which two non-adjacent carbon atoms of the monocyclic ring are linked by an atkylene bridge of between one and three additional carbon atoms. Representati)e examples of bicyclic ring systems include, but are not limited to, bicyclo[3.1.1]heptane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane and bicyclo[4.2.1]nonane. Tricyclic ring systems are also exemplified by a bicyclic ring system in which two non-adjacent carbon atoms of the bicyclic ring are linked by a bond or an alkylene bridge of between one and three carbon atoms. Representati)e examples of tricyclic-ring systems include, but are not limited to, tricyclo[3.3.1.03'7]nonane andtricyclo[3.3.1.137]decane (adamautane). The cycloalkyl groups of this in)ention maybe substituted with 1,2,3,4 or 5 substituents independently selected from alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkynyl, aryl, arylalkyl, arylcarbonyl, aryloxy, arylsulfonyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, cycloalkyl, ethylenedioxy, fonnyl, haloalkoxy, haloalkyl, halogen, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocycle, heterocyclealkyl, heterocyclecarbonyl, heterocycleoxy, hydroxy, hydroxyalkyl, nitro, RfRgN-, RfRgNalkyl, RfRgNcarbonyl and RfRgNsulfonyl, wherein Rf and Rg are independently selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, cycloalkyl, haloalkyl, haloalkylcarbonyl and cycloalkylalkyl wherein the cycloalkyl, the cycloalkyl of cycloalkylalkyl as represented by Rf and Rg are each independently unsubstituted or substituted with 1,2 or 3 substituents independently selected from the group consisting of halogen, alkyl and haloalkyl. The substituent aryl, the aryl of arylalkyl, the aryl of arylcarbonyl, the aryl of aryloxy, the aryl of arylsulfonyl, the substituent heteroaryl, the heteroaryl of heteroarylalkyl, the heteroaryl of heteroarylcaibonyl, the substituent heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclecarbonyl, the heterocycle of heterocycleoxy, the heterocycle of heterocyclesulfonyl may be optionally substituted with 0,1,2 or 3 substituents independently selected from the group consisting of alkoxy, alkoxyalkyl, aDcoxycarbonyl, alkyl, alkylcaibonyl, alkynyl, carboxy, carboxyalkyl, cyano, haloalkyl, halogen, hydroxy, hydroxyalkyl, nitro, RRgN-, RfRgNalkyl, RRgNcarbonyl and RfRgNsulfonyl wherein Rf and Rg are as described herein. The term "cycloalkylalkyl" as used herein, refers to a cycloalkyl group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representati)e examples of cycloalkylalkyl include, but are not limited to, cyclopropyhnethyl, 2-cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl and 4-cycloheptylbutyl. The term "cycloalkylcarbonyl" as used herein, refers to cycloalkyl group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representati)e examples of cycloalkylcarbonyl include, but are not limited to, cyclopropylcarbonyl, 2-cyclobutylcarbonyl and cyclohexylcarbonyl. The term "cycloalkyloxy" as used herein, refers to cycloalkyl group, as defined herein, appended to the parent molecular moiety through an oxy group, as defined herein. The term "cycloalkylsulfonyr as used herein, refers to cycloalkyl group, as defined herein, appended to the parent molecular moiety through a sulfonyl group, as defined herein. Representati)e examples of cycloalkylsulfonyl include, but are not limited to, cyclohexylsulfonyl and cyclobutylsulfonyl. The term "halo" or "halogen" as used herein, refers to -C3, -Br, -I or -F. The term "haloalkyl" as used herein, refers to at least one halogen, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representati)e examples of haloalkyl include, but are not limited to, chloromethyl, 2-fluoroethyl, trifluoromethyl, pentafluoroethyl and 2-chloro-3-fluoropentyl. The term "haloalkylcarbonyl" as used herein, refers to a haloalkyl group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. The term "heteroaryl" as used herein refers to an aromatic monocyclic ring or an aromatic bicyclic ring system. The aromatic monocyclic rings are fi)e or six membered rings containing at least one heteroatom independently selected from the group consisting of N, O and 8. The fi)e membered aromatic monocyclic rings ha)e two double bonds and the six membered aromatic monocyclic rings ha)e three double bonds. The bicyclic heteroaryl groups are exemplified by a monocyclic heteroaryl ring appended to the parent molecular moiety and fused to a monocyclic cycloalkyl group, as defined herein, a monocyclic aryl group, as defined herein, a monocyclic heteroaryl group, as defined herein, or a monocyclic heterocycle, as defined herein. Representati)e examples of heteroaryl include, but are not limited to, benzimidazolyl,.benzofuranyl, benzothiazolyl, benzothienyl, benzoxazolyl, furyl, imidazolyl, indazolyl, indolyl, indolizinyl, isobenzofuranyl, isoindolyl, isoxazolyl, isoquinolinyl, isothiazolyl, naphthyridinyl, oxadiazolyl, oxazolyl, phthalazdnyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, quinolinyl, quinolizinyl, quinoxalinyl, quinazolinyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, triazolyl and triazinyl. The term "heteroarylalkyr as used herein, refers to a heteroaryl, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. The heteroaryls of this in)ention may be optionally substituted with 1,2 or 3 substituents independently selected from alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkynyl, aryl, arylalkyl, arylcarbonyl, aryloxy, arylsulfonyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, cycloalkyl, ethylenedioxy, formyl, haloalkoxy, haloalkyl, halogen, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, heterocyclecarbonyl, heterocycleoxy, hydroxy, hydroxyalkyl, nitro, RfRgN-, RfRgNaDcyl, RfRgNcarbonyl and RfRgNsulfonyl, wherein Rf and Rg are independently selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, cycloalkyl, haloalkyl, haloalkylcarbonyl and cycloalkylalkyl wherein the cycloalkyl, the cycloalkyl of cycloalkylalkyl as represented by Rf and Rg are each independently unsubstituted or substituted with 1,2 or 3 substituents independently selected from the group consisting of halogen, alkyl and haloalkyl. The substituent aryl, the aryl of arylalkyl, the aryl of arylcarbonyl, the aryl of aryloxy, the aryl of arylsulfonyl, the substituent heteroaryl, the heteroaryl of heteroarylalkyl, the substituent heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclecarbonyl, the heterocycle of heterocycleoxy maybe optionally substituted with 1,2 or 3 substituents independently selected from the group consisting of alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkynyl, carboxy, carboxyalkyl, cyano, haloalkyl, halogen, hydroxy, hydroxyalkyl, ratio, RfRgN-, RNalkyl, RRgNcarbonyl and RRgNsulfonyl wherein Rf and Rg are as described abo)e. The term "heterocycle" as used herein, refers to a non-aromatic monocyclic ring or a non-aromatic bicyclic ring. The non-aromatic monocyclic ring is a three, four, fi)e, six, se)en, or eight membered ring containing at least one heteroatom, independently selected from the group consisting of N, O and S. Representati)e examples of monocyclic ring systems include, but are not limited to, azetidinyl, azuidinyl, diazepinyl, dithianyl, imidazolinyl, imidazolidinyl, isothiazolinyl, isoxazofinyl, isoxazolidinyl, morpholinyl, oxazolinyl, oxazolidinyl, piperazinyl, piperidinyl, pyranyl, pyrazolinyl, pyrazolidinyl, pyrrolinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydro-2H-pyranyl, tetrahydro-2H-pyran-2-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothienyl, thiazolinyl, thiazolidinyl, thiomorpholinyl, 1,1-dioxidothiomorpholinyl (thiomorphotine sulfone) and thiopyranyl. The bicyclic heterocycles are exempUfied by a monocyclic heterocycle appended to the parent molecular moiety and fused to a monocyclic cycloalkyl group, as defined herein, a monocyclic aryl group, a monocyclic heteroaryl group, as denned herein, or a monocyclic heterocycle, as defined herein. Bicyclic ring systems are also exempUfied by a bridged monocyclic ring system in which two non-adjacent atoms of the monocyclic ring are linked by abridge of between one and three additional atoms selected from the group consisting o f carbon, nitrogen and oxygen. Representati)e examples of bicyclic ring systems include but are not limited to, for example, benzopyranyl, benzothiopyranyl, benzodioxinyl, 1,3-benzodioxolyl, cinnolinyl, 1,5-diazocanyl, 3,9-diaza-bicyclo[4.2.1]non-9-yl» 3,7-diazabicyclo[3.3.1]nonane, octahydro-pyrrolo[3,4-c]pyrrole, indolinyl, isoindolinyl, 2,3,4,5-tetrahydro-lH-benzo[c]azepine, 23A5-le1iahydro-lH-benzo[fe]azepme,2,3,4,5-tetrahydKKlH-ben2X)[fl tetrahydroisoquinoUnyl and tetrahydroquinolinyl. The heterocycles of this in)ention may be optionally substituted with 1,2 or 3 substituents independently selected from alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkynyl, aryl, arylalkyl, arylcarbonyl, aryloxy, arylsulfonyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, ethylenedioxy, fonnyl, haloalkoxy, haloalkyl, halogen, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, heterocyclecarbonyl, heterocycleoxy, hydroxy, hydroxyalkyl, nitro, RRgNaDcyl, RNcarbonyl and RNsulfonyl, wherein Rf and Rg are independently selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, cycloalkyi, haloalkyl, haloalkylcarbonyl and cycloalkylalkyl wherein the cycloalkyi, the cycloalkyi of cycloalkylalkyl as represented by Rf and Rg are each independently unsubstituted or substituted with 1,2 or 3 substituents independently selected from the group consisting of halogen, alkyl and haloalkyl. The substituent aryl, the aryl of arylalkyl, the aryl of arylcarbonyl, the aryi of aryloxy, the aryl of arylsulfonyl, the heteroaryl, the heteroaryl of heteroarylaBcyl, the substituent heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclecarbonyl, the heterocycle of heterocycleoxy, may he optionally substituted with 1,2 or 3 substituents independently selected from the group consisting of alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, atkynyl, carboxy, carboxyalkyl, cyano, haloalkyl, halogen, hydroxy, hydroxyalkyl, nitro, RfRgN-, RfRgNalkyl, RfRgNcarbonyl and RfRgNsulfonyl wherein Rf and Rg are as described herein. The term "heterocyclealkyl" as used herein, refers to a heterocycle, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representati)e examples of heterocyclealkyl include, but are not limited to, pyridin-3-yhnethyl and 2-pyrirmdin-2-ylpropyL The term "heterocyclealkoxy" as used herein, refers to a heterocycle, as defined herein, appended to the parent molecular moiety through an alkoxy group, as defined herein. The term "heterocycleoxy" as used herein, refers to a heterocycle, as defined herein, appended to the parent molecular moiety through an oxy group, as defined herein. The term "heterocycleoxyalkyl" as used herein, refers to a heterocycleoxy, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. The term "heterocycle-NH-" as used herein, refers to a heterocycle, as defined herein, appended to the parent molecular moiety through a nitrogen atom. . The term "heterocycle-NH-alkyl" as used herein, refers to a heterocycle-NH-, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. The term "heterocyclecarbonyl" as used herein, refers to a heterocycle, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representati)e examples of heterocyclecarbonyl include, but are not limited to, 1-piperidinylcarbonyl, 4-morphoUnylcarbonyl, pyridin-3-ylcarbonyl and quinolin-3-ylcarbonyl. The term "heterocyclesulfonyl" as used herein, refers to a heterocycle, as defined herein, appended to the parent molecular moiety through a sulfonyl group, as defined herein. Representati)e examples of heterocyclesulfbnyi include, but are not limited to, 1-piperidinylsulfonyl, 4-morpholinylsulfonyl, pyridin-3-ylsulfonyl and quinoKn-3-ylsulfonyl. The term "hydroxy" as used herein, refers to an -OH group. The term "hydroxyalkyl" as used herein, refers to a hydroxy group, as denned herein, appended to the parent molecular moiety through an alley! group, as defined herein. Representati)e examples of hydroxyalkyl include, but are not limited to, hydroxymethyl, 2-hydroxyemyl, 3-hydroxypropyl and 2-ethyl-4-hydroxyheptyL The term "oxo" as used herein, refers to a =O group. The term "oxy" as used herein, refers to a -O- group. The term "sulfonyl" as used herein, refers to a -S(O)r group. Salts The present compounds may exist as therapeutically suitable salts. The term "therapeutically suitable salt," refers to salts or zwitterions of the compounds which are water or oil-soluble or dispersible, suitable for treatment of disorders without undue toxicity, irritation and allergic response, commensurate with a reasonable benefit/risk ratio and effecti)e for their intended use. The salts may be prepared during the final isolation and purification of the compounds or separately by reacting an ammo group of the compounds with a suitable acid. For example, a compound may be dissol)ed in a suitable sol)ent, such as but not limited to mefhanol and water and treated with at least one equi)alent of an acid, like hydrochloric acid. The resulting salt may precipitate out and be isolated by filtration and dried under reduced pressure. Alternati)ely, the sol)ent and excess acid may be remo)ed under reduced pressure to pro)ide the salt Representati)e salts include acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, form ate, isethionate, fumarate, lactate, maleate, methanesulfonate, naphthylenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, oxalate, maleate, pi)alate, propionate, succinate, tartrate, trichloroacetate, trifluoroacetate, glutamate, para-toluenesulfonate, undecanoate, hydrochloric, hydrobromic, sulfuric, phosphoric and the like. The amino groups of the compounds may also be quatemized with alkyl chlorides, bromides and iodides such as methyl, ethyl, propyl, isopropyl, butyl, lauryl, myristyl, stearyl and the like. Basic addition salts may be prepared during the final isolation and purification of the present compounds by reaction of a carboxyl group with a suitable base such as the hydroxide, carbonate, or bicarbonate of a metal cation such as lithium, sodium, potassium, calcium, magnesium, or aluminum, or an organic primary, secondary, or tertiary amine. Quaternary amine salts deri)ed from methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine. tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorphoUne, dicyclohexylamine, procaine, dibenzylamine, N,N-dibenzylphenethylamine, 1-ephenamine andNJ-dibenzylethylenediamine, ethylenediamine, ethanolamine, diethanolamine, piperidine, piperazine and the like, are contemplated as being within the scope of the present in)ention. The present compounds may also exist as therapeutically suitable prodrugs. The term "therapeutically suitable prodrug," refers to those prodrugs or zwitterions which are suitable for use in contact with the tissues of patients without undue toxicity, irritation and allergic response, are commensurate with a reasonable benefit/risk ratio and are effecti)e for their intended use. The term "prodrug," refers to compounds that are rapidly transformed in )i)o to the parent compounds of formula (I-DCc) for example, by hydrolysis in blood. The term "prodrug," refers to compounds that contain, but are not limited to, substituents known as "therapeutically suitable esters." The term "therapeutically suitable ester," refers to alkoxycarbonyl groups appended to the parent molecule on an a)ailable carbon atom. More specifically, a "therapeutically suitable ester," refers to alkoxycarbonyl groups appended to the parent molecule on one or more a)ailable aryl, cycloaDcyl and/or heterocycle groups as defined herein. Compounds containing therapeutically suitable esters are an example, but are not intended to limit the scope of compounds considered to be prodrugs. Examples of prodrug ester groups include pi)aloyloxymethyl, acetoxymethyl, phthalidyl, indanyl and methoxymethyl, as well as other such groups known in the art Other examples of prodrug ester groups are found in T. Higuchi and ). Stella, Pro-drugs as No)el Deli)ery Systems, )ol. 14 of the A.C.S. Symposium Series and in Edward B. Roche, ed., Biore)ersible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference. Optical Isomers-Diastereomers-Geometric Isomers Asymmetric centers may exist hi the present compounds. Indi)idual stereoisomers of the compounds are prepared by synthesis from chiral starting materials or by preparation of racemic mixtures and separation by con)ersion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, or direct separation of the enantiomers on chiral chromatographic columns. Starting materials of particular stereochemistry are either commercially a)ailable or are made by the methods described hereinbelow and resol)ed by techniques well known in the art Geometric isomers may exist in the present compounds. The in)ention contemplates the )arious geometric isomers and mixtures thereof resulting from the disposal of substituents around a carbon-carbon double bond, a cycloalkyl group, or aheterocycloalkyl group. Substituents around a carbon-carbon double bond are designated as being of Z or E configuration and substituents around a cycloalkyl or heterocycloalkyl are designated as being of cis or trans configuration. Furthermore, the in)ention contemplates the )arious isomers and mixtures thereof resulting from the disposal of substituents around an adamantane ring system. Two substituents around a single ring within an adamantane ring system are designated as being of Z or E relati)e configuation. For examples, see C. D. Jones, M. Kaselj, R. N. Sal)atore, W. J. leNoble J. Org. Chem. 63:2758-2760,1998. The compounds and processes of the present in)ention will be better understood in connection with the following synthetic schemes and Experimentals that illustrate a means by which the compounds of the in)ention may be prepared. The compounds of this in)ention may be prepared by a )ariety of procedures and synthetic routes. Representati)e procedures and synthetic routes are shown in, but are not limited to, Schemes 1-18. Abbre)iations which ha)e been used in the descriptions of the Schemes and the Examples that follow are: Cbz for benzyloxycarbonyl; CbzCl for benzyloxycarbonyl chloride; DCE for 1,2-dichloroethane; DCM for dichloromethane; DMAP for dimethylaminopyridine; DME for 1,2-dimethoxy ethane; DMF for N,N-dimethylfonn amide; DMSO for dimethylsulfoxide; DAST for (diethylamino)sulfur trifluoride; DIPEA for Hunig's base for diisopropylethylamine; DMPU for l,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone; EDQ for (3-dimemylaminopropyl)-3-emylcarbodiimideHCl; EtOAc for ethyl acetate; Et2O for diethyl ether, EtOH for ethanol; HATU for O-(7-azabenzotriazol-l-yl)-N, N, N', N'-tetramethyluronium hexafluoro-phosphate; HOBt for hydroxybenzotriazole hydrate; iPrOH for isopropyl alcohol; KOTMS for potassium trimethylsilanolate; LAH for lithium aluminum hydride; MeOH for mernanol; NMO for H-methyhnorpholine H-oxide; NaOAC for sodium acetate; OXONE for potassium peroxymonosulfate; tBuOK for potassium tert-butoxide; TBTU for O-benzotriazol-1 -yl-N,N,N', J'-tetramethyluronium tetrafluoroborate; THF for tetrahydrofuran; TosMIC for p-toluenesulfonyhnemyl isocyanide; TPAP for tetrapropylammomum perruthenate; TFAA for trifhloroacetic anhydride; tosyl for para-toluene sulfonyl, mesyl for methane sulfonyl, and triflate for trifluoromethane sulfonyl. Schemel (Scheme Remo)ed) Acids of general formula (2) wherein X = OH can be coupled to substituted adamantamines of general formula (1) with reagents such as EDCI and HOBt to pro)ide amides of general formula (3). Substituted adamantanes of general formula (3), wherein A1, A2, A3, A4, R1, R2, R3, R4, D and E are as defined in formula I, may be prepared as in Scheme 1. Substituted adamantamines of general formula (1), purchased or prepared using methodology known to those in the art, may be treated with acylatmg agents of general formula (4), wherein X is chloro, bromo, or fluoro, Y is a lea)ing group such as Br (or a protected or masked lea)ing group) to pro)ide amides of general formula (5). The substituted amides of general formula (5) may be treated with nucleophiles of general formula (6), wherein J is oxygen or sulfur and a base such as sodium hydride. When J is sulfur that reaction may be followed by oxidation with reagents like Oxone to pro)ide amides of general formula (3) wherein D can become S(O) or 8(0)7. hi some examples, A1, A2, A3 and/or A4 hi amines of formula (1) may exist as a group further substituted with a protecting group such as a carboxylic acid protected as the methyl ester. Examples containing a protected functional group may be required due to the synthetic schemes and the reacti)ity of said groups and could be later remo)ed to pro)ide the desired compound. Such protecting groups can be remo)ed using methodology known to those skilled hi the art or as described in T. W. Greene, P. G. M. Wuts "Protecti)e Groups hi Organic Synthesis" 3rd ed. 1999, Wiley & Sons, Inc. Scheme 2 reducti)e amination (Scheme Remo)ed) Substituted adamantane amines of general formula (8), wherein A1, A2, A3, A4, R1 and R2 are as defined in formula I, may be prepared as hi Scheme 2. Substituted adamantane ketones of general formula (7) can be purchased or prepared using methodology known to those hi the art Ketones of general formula (7) can be treated with ammonia or primary amines (R2NH2) followed by reduction with reagents such as sodium borohydride or Efc o)er Pd/C hi a sol)ent like methanol to pro)ide amines of general formula (8). La some examples, A1, A2, A3 and/or A4 in ketones of formula (7) may be a functional group substituted with a protecting group such as a carboxylic acid protected as the methyl ester. These protecting groups can be remo)ed using methodology known to those hi the art hi amines of general formula (8) or in compounds subsequently prepared from ketones of general formula (7) or amines of general formula (8). Scheme 3 (Scheme Remo)ed) Substituted adamantanes of general formula (10), wherein A2, A3 and A4 are as defined in formula I, may be prepared as in Scheme 3. Substituted adamantanes of general formula (9) can be purchased or prepared using methodology known to those skilled in the art Adamantanes of general formula (9) can be treated with oleum and formic acid followed by an alcohol GOH, where G is an alkyl, cycloalkyl, hydrogen, aryl, or acid protecting group, to pro)ide adamantanes of general formula (10). In some examples, G in formula (10) may be a protecting group such as methyl. These protecting groups can be remo)ed using methodology known to those skilled in the art from adamantanes of general formula (10) or in compounds subsequently prepared from (10). Scheme 4 Amide coupling (Scheme Remo)ed) Substituted adamantanes of general formula (14), wherein A2, A3, A4, R1, R2, R3, R4, D, E, R16 and R17 are as denned in formula I, may be prepared as in Scheme 4. Adamantyl acids of general formula (11) may be prepared as described herein or using methodology known to those skilled in the art The acids of general formula (11) may be coupled with amines of general formula (12), wherein R16 and R17 are defined as in formula I, with reagents such as O-(benzotrialzol-l-yl)-l,l,3,3-tetramethyluronium tetrafluoroborate (TBTU) to pro)ide amides of general formula (13). In some examples, A2, A3, A4, R1, R2, R3, R16 and R17 in amines of formula (13) may contain a functional group substituted with a protecting group, for example, a carboxy protected as an ester. These protecting groups may be remo)ed using methodology known to those in the art to pro)ide amides of general formula (14). Scheme 5 (Scheme Remo)ed) Acids of general formulas (17) wherein R3, R4, D and E are as defined in fonnula (T) can be prepared as shown in Scheme 5. Phenols and thiols of general formula (15) wherein D is -O- or -S-, purchased or prepared using methodology known to those skilled in the art, may be treated with a reagent like l,l,l-trichloro-2-methyl-propan-2-ol (16) in the presence of a base like sodium hydroxide in a sol)ent like acetone to pro)ide acids of general fonnula (17). Esters of general fonnula (18) wherein P is an acid protecting group such as, but not limited to, Q-Cs alkyl, aryl (substituted or unsubstituted) or arylalkyl (substituted or unsubstituted), may undergo an aromatic substitution or related reaction with halides of fonnula E-Xi wherein Xi is Cl, Br or I and E is as defined in fonnula (I), in the presence of a base like sodium hydride in a sol)ent like DMPU to afford compounds of fonnula (19). Remo)al of the acid protecting group, P, pro)ides acids of formula (17). Clea)age of the acid protecting group can be conducted by either acidic or basic hydrolysis when P is Q-C6 alkyl, or hydrogenolyis when P is benzyt Alternati)ely, esters of general formula (18) may be coupled with halides of fonnula wherein Xi is Cl, Br or I and E is aryl or heteroaryl, under with a metal catalyst like palladium along with ligands, to pro)ide compounds of formula (19). Compounds of formula (19) can also be obtained from the reaction of bromcesters of general formula (20), with compounds of formula (15) wherein D is -O- or-S-and B is defined as in formula CD, in the presence of a base such as, but not limited to, potassium carbonate, to pro)ide esters of general formula (19). Scheme 6 Substituted adamantane amides of general formula (21), wherein Rf and Rg are independently selected from the group consisting of hydrogen, alkyl, alkoxyaDcyl, alkylsulfonyl, cycloalkyl, and cycloalkylalkyl wherein the cycloalkyl, the cycloalkyl of cycloalkylalkyl as represented by Rf and Rg are each independently unsubstituted or substituted with 1,2 or 3 substituents independently selected from the group consisting of alkyl, halogen, and haloalkyl, Z is alkyl, aryl, heteroaryl, cycloalkyl, heterocycle, arylalkyl, heteroarylalkyl or heterocyclealkyl, and A2, A3, A4, R1, R2, R3, R4, R18, R2, D and E are as denned in formula (I), can be prepared as shown in Scheme 6. . Adamantane acids of general formula (20) can be coupled with amines of formula RjRgNH, in the presence of a coupling agent such as, but not limited to, TBTU, and a base such as, but not limited, to diisopropylethylamine. The reaction is generally performed in a sol)ent such as, but not limited to, DMF, at a temperature of about room temperature to about 50 °C to pro)ide amides of general formula (21). Scheme 7 (Scheme Remo)ed) Substituted adamantanes of general formula (25), (26), and (27), wherein A2, A3, A4, R1, R2, R3, R4, D and E are as defined in formula I, can be prepared as shown in Scheme 7. Adamantanes of general formula (22) wherein P is hydrogen or an acid protecting group such as, but not limited to, Ci-Ce alkyl, aryl (substituted or unsubstituted) or arylalkyl (substituted or unsubstituted), can be con)erted to aldehydes of formula (23) by (a) treatment with a reducing agent such as, but not limited to, lithium aluminum hydride, in a sol)ent nice THF; and (b) treating the product from step (a) with an oxiding agent such as, but not limited to, TPAP, in the presence of NMO, and in a sol)ent like dichloroethane. Adamantane aldehydes of general formula (23) can be treated with TosMIC and a base like t-BuOK in a sol)ent mixture like DME and ethanol to pro)ide nitriles of general formula (24). Nitriles of general formula (24) can be hydrolyzed with potassium hydroxide in a sol)ent like ethylene glycol to pro)ide acids of general formula (25). When treated with hydrogen peroxide and sodium hydroxide in a sol)ent mixture like methanol and DMSO, nitriles of general formula (24) can be transformed to amides of formula (26). Tetrazoles of formula (27) can be prepared from adamantanes of general formula (24) when treated with reagents like sodium azide and zinc bromide in a sol)ent like water and isopropanoL (Scheme Remo)ed) Substituted adamantanes of general formula (30), wherein A2, A3, A4, R1, R2, R3, R4, D and E are as defined in formula CO, can be prepared as shown in Scheme 8. Substituted adamantanes of general formula (28) can be dehydrated with a reagent like TBTU in the presence of a base like isopropylethylamine in a sol)ent like N,N-dimethylacetamide to pro)ide nitrites of general fonnula (29). Nitriles of general formula (29) can be treated with reagents like trimethyl tin chloride and sodium azide in a sol)ent like toluene to pro)ide tetrazoles of general fonnula (30). Alternati)ely, adamantane amines of general formula (31) wherein P is hydrogen or Ci-Cg alkyl, can be (a) treated with a reagent like CbzCl in a sol)ent tike dichloromethane in the presence of a base like diisopropylethylamine; (b) treating the resulting product with a reagent like KOTMS in a sol)ent like THF; and (c) treating the acid &om step (b) with ammonia or ammonium hydroxide in the presence of a reagent like EDCI and HOBt, and a base like diisopropylethylamine, in a sol)ent like DMF, to yield adamantane amides of general formula (32) wherein P is a protecting group like -QCtyOCHCeHs. The amides of general fonnula (32) can be (a) treated with a reagent like trifluoroacetic anhydride hi a sol)ent like dichloromethane in the presence of a base like trietbylamme; and (b) treating the intermediate from step (a) with a catalyst like Pd(OH)2 on carbon under an atmosphere of hydrogen, to pro)ide amines of formula (33). Amines of general formula (33) can be coupled to acids of general formula (17), in the presence of a reagent like HATU and a base like diisopropylethylamine, in a sol)ent like DMF, to pro)ide compounds of general formula (29). Scheme 9 Substituted adamantanes of general formula (34), wherein A2, A3, A4, R1, R2, R3, R4, D and B are as defined in formula I, can be prepared from treatment of compounds of formula (29) with hydroxylamine hydrochloride in a sol)ent like DMSO, in the presence of a base like diisopropylethylamine. Scheme 10 (Scheme Remo)ed) Substituted adamantanes of general fonnula (37) and (38), wherein A2, A3, A4, R1, R2, R3, R4, D and E are as defined in formula I, and R101 is aHcyl, cycloalkyl, aryl, heteroaryl, or heterocycle, can be prepared as shown hi Scheme 10. Substituted adamantanes of general fonnula (35) can be (a) treated with trifluoroacetic anhydride in a sol)ent like trifluoroacetic acid; and (b) treating the product of step (a) with a thiol of formula R101SH at ele)ated temperature, typically at about 120 °C for a period of about 20 hours, hi a sol)ent like trifluoroacetic acid to pro)ide thioethers of general formula (36). Thioethers of general formula (36) can be oxidized with an oxidizing agent such as, but not limited to, 3-chloroperbenzoic acid, hi a sol)ent such as, but not limited to, dichloromethane, to pro)ide sulfoxides of general formula (37) and/or sulfones of general formula (38). Substituted adamantines of general formula (42), wherein A2, A3, A4, R!, R2, R3, R4, R25, R26, D and B are as defined in formula (I), can be prepared as shown in Scheme 11. Substituted adamantanes of general formula (22) wherein P is hydrogen or an acid protecting group such as, but not limited to, Ci-Q alkyl, aryl (substituted or unsubstituted) or arylalkyl (substituted or unsubstituted), can be con)erted alcohols of formula (39) by treatment with a reducing agent such as, but not limited to, lithium aluminum hydride or diisobutylaluminum hydride in a sol)ent like THF. Reaction of the alcohols of general formula (39) with trifluoromethanesulfonic anhydride in the presence of a base like pyridine and in a sol)ent like dichloromethane pro)ides the intermediate triflate that can be isolated. Treatment of the triflate with potassium thioacetate in a sol)ent like dimethylformamide yields adamantanes of general formula (40). Adamantane tbioacetates of general formula (40), when treated with an oxidizing agent such as, but not limited to, hydrogen peroxide and abase like sodium acetate in a sol)ent like acetic acid pro)ides sulfonic acids of general formula (41). Sulfonic acids of general formula (41) can be coupled with an amine of formula R25R2SNH wherein R25 and R26 are defined as hi formula I to pro)ide compounds of formula (42). Numerous reaction conditions for such a con)ersion are known to one skilled hi the art One such coupling utilizes triphosgene in the presence of a base like triethylamine with a catalytic amount of dimethylfonnamide in a sol)ent like dichloromethane, followed by the addition an amine of formula RNH. Compounds of formula (42) wherein R25 is as defined hi formula (T) other than hydrogen and R26 is hydrogen, or R25 and R26 are as defined in formula (I) other than hydrogen, can also be obtained from the mono or dialkylation of compounds of formula (42) wherein R25 and R26 are hydrogen. - The mono alkylation can be facilitated with an alkylating reagent of formula RXi wherein R23 is methyl, benzyl, and allyl, and Xi is a lea)ing group such as, but not limited to, Cl, Br, I, triflate or tosylate. The reaction is generally conducted in the presence of a base such as, but not limited to, alkali metal carbonates (for example, cesium carbonate and the like), in a sol)ent such as, but not limited to, DMF, pro)iding compounds of fonnula (42) wherein R25 is methyl, benzyl, and allyl, and R2* is hydrogen. Further alkylation with R2! wherein R26 is methyl, benzyl, and allyl and Xi as defined abo)e, using the aforementioned reaction condition, affords compounds of fonnula (42) wherein R25 and R26 are independently selected from the group consisting of methyl, benzyl, and allyl. The reaction can be conducted stepwise or in situ without isolating the product of the monoalkylation. Alternati)ely, compounds of fonnula (42) wherein R25 and R26 are identical and are as defined in formula 0) other than hydrogen, can be prepared from the reaction of compounds of formula (42) wherein R25 and R26 are hydrogen and about two equi)alents of the alkylating agent. Scheme 12 (Scheme Remo)ed) Substituted adamantines of general formula (46), wherein A2, A3, A4, R1, R2, R3, R4, R16, R17, D and E are as defined hi formula (I) can be prepared as shown in Scheme 12. Substituted adamantanes of general formula (43) can be carbonylated with formic acid and oleum and poured into a solution of formula R15OH to pro)ide an adamantane of general formula (44) wherein R15 is as defined in formula (I). Adamantanes of general fonnula (44) wherein R15 is not hydrogen can be con)erted to admantanes of formula (44) wherein R15 is hydrogen using methodologies listed in T. W. Greene, P. G. M. Wuts "Protecti)e Groups in Organic Synthesis" 3rd ed. 1999, Wiley & Sons, Inc. The resulting acids can be coupled to amines of general formula R16R17NH to pro)ide amides of formula (45) in the presence of coupling reagents such as, but not limited to, EDCI and HOBt in a sol)ent like dichloromethane. Adamantanes of general formula (45) may be treated with alcohols or thiols of general formula (15) wherein D is -O- or -S- and E is defined as in formula (1), in the presence of a base like potassium carbonate in a sol)ent like toluene to pro)ide adamantanes of general formula (46). Adamantanes of general formula (46) wherein D is -S- can be con)erted to compounds of formula (46) wherein D is -S(O)- or -S(O)z- by reacting with an oxidizing agent such as, but not limited to, oxone in a sol)ent like methanol. Scheme 13 (Scheme Remo)ed) Substituted adamantanes of general formula (54), wherein A2, A3, A4, R25 and R26 are as denned in formula I, may be prepared as shown in Scheme 13. Substituted adamantanes of general formula (47) can be brominated with a reagent like hydrobromic acid in a sol)ent like water to pro)ide bromides of general formula (48). Adamantanes of general formula (48) when treated with ethylene glycol and a catalytic amount of an acid like p-toluenesitlfonic acid in a sol)ent like benzene pro)ide adamantanes of general formula (49). Bromides of general formula (49) can be (a) treated with Rieke zinc in a sol)ent like tetrahydrofuran; and (b) followed by treatment with reagent (50) (prepared as described in Han, Z.; Krishnamurthy, D.; Gro)er, P.; Fang, Q. K.; Senanayake, C. H. /. Am. Chem. Soc. 2002,124,7880-7881) in a sol)ent like tetrahydrofuran to pro)ide adamantanes of general formula (51). Adamantanes of general formula (51) maybe treated with lithium amide of formula LiNHR226 (prepared in situ by reacting ammonia with lithium or amines of formula R226 wherein R25 and R26 are other man hydrogen, with t-butyl lithium) in a sol)ent mixture like ammonia and tetrahydrofuran. The resulting sulfinamides can be oxidized with a reagent like osmium tetroxide with a catalyst oxidant like NMO in a sol)ent like tetrahydrofuran to pro)ide sulfonamides of general formula (52). Adamantanes of general formula (52) can be deketalized with reagents like hydrochloric acid in a sol)ent like water and tetrahydrofuran to pro)ide ketones of formula (53). Ketones of formula (53) can be treated with amines of formula R25R26NH followed by reduction with reducing reagents such as, but not limited to, sodium borohydride or hydrogen o)er Pd/C in a sol)ent like ' methanol to pro)ide amines of general formula (54). Scheme 14(Scheme Remo)ed) Substituted adamantanes of general formula (55), (56) and (57) wherein R102 is hydrogen, alkyl or aryl, and A2, A3, A4, R1, R2, R3, R4, R23, R24, D and E are as defined in formula (I), can be prepared as shown in Scheme 14. Substituted adamantanes of general formula (23) can be treated with reagents like ammonia and glyoxal in a sol)ent like water to pro)ide imidazoles of general formula (55). Reaction of compounds of formula (23) with Wittig reagent such as, but not limited to, triethyl phosphonoacetate and a base like sodium hydride in a sol)ent like dimethoxyethane pro)ides esters of general formula (56) wherein R102 is alkyl or aryl. Esters of general formula (56) can be clea)ed with h'thium hydroxide in a sol)ent mixture like tetrahydroruran and water to pro)ide acids of general formula (56) wherein R102 is hydrogen. Adamantanes of general formula (23) can be reducti)ely aminated with amines of general formula R23R24NH with a reagent like sodium triacetoxyborohydride in the presence of an acid like acetic acid in a sol)ent like dichloroethane to yield amines of general formula (57). Scheme 15 (Scheme Remo)ed) Substituted adamantanes of general formula (60), wherein A2, A3, A4, R1, R2, R3, R4, D and E are as defined hi formula I and Q is hydrogen, alkyl, or cycloalkyl, can be prepared as shown in Scheme 15. Substituted adamantanes of general formula (23) can be treated with a reagent like acetylenemagnesium chloride in a sol)ent like THE to yield alcohols of general formula (58). Adamantane alcohols of general formula (58) can be oxidized with a reagent like Dess-Martin periodinane in a sol)ent like dichloromethane to pro)ide alkynones of general formula (59). Alkynones of general formula (59) can be reacted with a reagent like hydroxylamine hydrochloride in the presence of a base like potassium carbonate in a sol)ent like isopropanol to pro)ide heterocycles of general formula (60). Scheme 16 (Scheme Remo)ed) Substituted adamantanes of general formula (61), wherein A2, A3, A4, R1, R2, R3, R4, R20, D and E are as defined in formula (I), can be prepared as shown in Scheme 16. Adamantanes of general formula (39) can be alkylated with a reagent of formula R20Xi, wherein X] is a halide or other lea)ing group like bromide, iodide, tosylate or triflate, in the presence of a base like sodium hydride in a sol)ent like dimethylformamide to yield ethers of general formula (61). Scheme 17 (Scheme Remo)ed) Substituted adamantanes of general formula (63), wherein B is aryl or heteroaryl and A1, A2, A3, A4, R1, R2, R3, R4, and D are as defined in formula (I) and R103 and R104 are alkyl, alkoxyalkyl, cycloalkyl, aryl, heteroaryl, heterocycle, heteroaryl, heteroarylalkyl, cycloalkylalkyl, arylalkyl, heteroarylalkyl, or heterocyclealkyl, or R103 and R104 combined to the atom to which they are attached form a heterocycle or heteroaryl can be prepared as shown in Scheme 17. Substituted adamantanes of general formula (62) wherein Xj is a halide or triflate can be coupled with amines of formula NHR103R104 with a reagent combination like copper iodide and N,N-dimethylglycine in a sol)ent like DMSO under microwa)e heating to pro)ide adamantanes of general formula (63). Scheme 18 Substituted adamantanes of general formula (65), wherein m is 1 or 2, A1, A2, A3, A4, R1, R2, R3, R4 and D are as defined in formula (T), E is aryl or heteroaryl, and X2 is halogen, can be prepared as shown in Scheme 18. Adamantanes of general formula (64) can be halogenated with a reagent like N-bromosuccinimde in the presence of an acid like HBr in a sol)ent like dichloromethane to yield aryl halides of general formula (65). It is understoond that the schemes described herein are for illustrati)e purposes and that routine experimentation, including appropriate manipulation of the sequence of the synthetic route, protection of any chemical functionality that are not compatible with the reaction conditions and deprotection are included in the scope of the in)ention. Protection and Deprotection of carboxytic acids and amines are known to one skilled in the art and references can be found in "Protecti)e Groups in Organic Synthesis", T.W. Greene, P.G.M. Wuts, 3rd edition, 1999, Wiley & Sons, Inc. The compounds and processes of the present in)ention will be better understood by reference to the following Examples, which are intended as an illustration of and not a limitation upon the scope of the in)ention. Further, all citations herein are incorporated by reference. Compounds of the in)ention were named by ACD/ChemSketch )ersion 5.01 (de)eloped by Ad)anced Chemistry De)elopment, Inc., Toronto, ON, Canada) or were gi)en names consistent with ACD nomenclature. Adamantane ring system isomers were named according to common con)entions. Two substituents around a single ring within an adamantane ring system are designated as being of Z or E relati)e configuation (for examples see C. D. Jones, M. Kaselj, R. N. Sal)atore, W. J. le Noble J. Org. Chem. 63:2758-2760, 1998). Example 1 -42-methyl-2-phenoy-propionylamino)adamantane-l-carboylic acid amide Example 1A E- and Z- S-h)droy-2-adamantamine A solution of 5-hydroxy-2-adamantanone (10 g, 60.161mmoles) and 4A molecular sie)es (5 g) in methanolic ammonia (7N, 100 mL) was stirred o)ernight at room temperature. The mixture was cooled in an ice bath, treated by the portionwise addition of sodium borohydride (9.1 g, 240.64 mmoles) and stirred at room temperature for 2 hours. The mixture was filtered and MeOH was remo)ed under reduced pressure. The mixture was taken into DCM (100 mL), acidified with IN HC1 to pH = 3 and the layers separated. The aqueous layer was treated with 2N NaOH solution to pH = 12 and extracted three times with 4:1 THFrDCM. The combined organic extracts were dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to pro)ide the title compound as a white solid (9.84 g, 97.9%). Example IB B-2-bromo-N5-h)droy-adamantan-2-yl)2-methyl-propionamide A solution of E- and Z-5-hydroxy-2-adamantamine (0.868g, 5.2 mmoles) in DCM (15.0 mL) and DIPEA (2.5 mL) was cooled in an ice bath and treated with 2-bromoisobutyryl bromide (0.72 mL, 5.8 mmoles) in DCM (2.5 mL). The mixture was stirred for 2 hours at room temperature and DCM was remo)ed under reduced pressure. The residue was partitioned between water and ethyl acetate. The organic layer was washed with saturated sodium bicarbonate, water, dried (MgSC) and filtered. The filtrate was concentrated under reduced pressure to pro)ide the title compound as dark beige solid (1.17 g, 71%). The isomers were separated by column chromatography (silica gel, 5-35% acetone in hexane) to furnish 0.78 g of E-2-bromo-NK5-hydroxy-adamantan-2-yI)-2-methyl-propionamide and 0.39 g of Z-2-bromo-N-(5-hydroxy-adamantan-2-yl)-2-memyl-propionamide. Example 1C -42-bromo-2-memyl-propioymino)aHT|nrttane-l-carboxylic acid methyl ester A solution of E- 2-bromo-N-(5-hydroxy-adamantan-2-yl)-2-methyl-propionamide (0.78 g, 2.48mmol) in 99% formic acid (2.5 mL) was added dropwise with )igorous gas e)olution o)er 10 minutes to a rapidly stirred 30% oleum solution (7.5 mL) heated to 60 °C (W. J. le Noble, S. Sri)asta)a, C. K. Cheung, J. Qrg. Chem. 48:1099-1101,1983). Upon completion of addition, more 99% formic acid (2.5 mL) was slowly added o)er the next 10 minutes. The mixture was stirred another 60 minutes at 60 °C and then slowly poured into )igorously stirred iced water (30.0 mL) cooled to 0 °C. The mixture was allowed to slowly warm to 23 °C, filtered and washed with water to neutral pH (100 mL). The precipitate was dried in a )acuum o)en, taken into MeOH and treated with thionyl chloride at 0°C (0.2 mL, 2.8 mmoles). The reaction mixture was stirred at room temperature for 3 hours and then MeOH was e)aporated under reduced pressure to pro)ide the title compound as an off-white solid. Example ID E-4-(2-me&yl-2-phenoy-T)ropionylaTTiinr)-aH amantane-1 -carboylic acid Step A A solution of phenol (20.7 mg, 0.22 mmoles) and sodium hydride (60%, 10.8 mg, 0.27 mmoles) in toluene (2 mL) was stirred at room temperature for 1 hour. Then E-4-(2-bromo-2-methyl-propionylamino)-adamantane-l-carboxylic acid methyl ester (71.6 mg, 0.2 mmoles) was added and the resulting mixture was shaken at 100°C for 48 hours. After that the reaction mixture was cooled and filtered. The filtrate was concentrated under reduced pressure to pro)ide crude methyl ester of the title compound that was purified on re)erse phase HPLC. StepB The methyl ester of the title compound obtained from step A was hydrolyzed with 2N aqueous NaOH, THF and ethanol (2:1:1,2 mL) at room temperature o)ernight The reaction mixture was acidified with IN HC1 and extracted with ethyl acetate. The organic layer was separated, washed with water and brine respecti)ely, dried (MgSOt) and filtered. The filtrate was concentrated under reduced pressure to pro)ide the title compound. Example IB A solution of N2-methyl-2-phenoxyropionylamino)-adam.antane-l-carboxylic acid (23 mg, 0.064 mmoles) hi DCM (2 mL) was treated with HOBt (9.5 mg, 0.07 mmoles) and EDCI (14.7 mg, 0.077 mmoles) and stirred at room temperature for 1 hour. Excess of aqueous (30%) ammonia (2 mL) was added and the reaction was stirred for additional 20 hours. The layers were separated and the aqueous layer extracted twice more with methylene chloride (2x2 mL). The combined organic extracts were washed with water (3x2 mL), brine (2 mL), dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to pro)ide the crude title compound that was purified on re)erse phase HPLC to pro)ide the title compound. *H NMR (500 MHz, DMSO-D6) 8 ppm 7.26 - 7.31 (m, 2 H) 7.25 (d, .E=7.49 Hz, 1 H) 7.02 (t, 7.33 Hz, 1 H) 6.95 (s, 1 H) 6.91 (d, j=7.80 Hz, 2 H) 6.68 (s, 1 H) 3.79 - 3.88 (m, 1H) 1.91 (s, 2 H) 1.76 -1.87 (m, 5 H) 1.71 (s, 2 H) 1.65 (d, JM2.79 Hz, 2 H) 1.45 (s, 6 H) 1.38 (d, =12.79 Hz, 2 H). MS (ESI+) m/z 357 (M+H)*. Example 2 jg-f2-methyl-2-f4-ftrifluorome&yl-benzyloy)propfo The title compound was prepared according to the procedure outlined in Example ID and IE substituting 4-(trifluoromethyl)benzyl alcohol for phenol. *H NMR (500 MHz, DMSO-D6) 8 ppm 7.73 (d, 8.11 Hz, 2 H) 7.62 (d, =8.11 Hz, 2 H) 7.07 (d, J=1A9 Hz, 1 H) 6.95 (s, 1 H) 6.68 (s, 1 H) 4.60 (s, 2 H) 3.78 (d, =7.49 Hz, 1 H) 1.88 (s, 2 H) 1.76 - 1.85 (m, 5 H) 1.72 (s, 2 H) 1.59 (d, 13.10 Hz, 2 H) 1.39 - 1.44 (m, 8 H). MS (ESI+) m/z 439 Example 3 A two phase suspension of 2-bromo-2-memyl-propionylamino)-adamantane-l-carboxylic acid methyl ester (71.6 ing, 0.2 mmoles), 2-methylcyclohexanol (0.033 mT., 0.24 mmoles) and tetrabutylammonium bromide (6 mg, 0.02 mmoles) in DCM (1.0 mL) and 50% aqueous NaOH (1 .0 mL) was stirred at room temperature for 20 hours. After that the reaction mixture was diluted with DCM, neutralized with 3N HC1 and layers separated. Organic layer was washed with water (3x2 mL), dried (MgSC4) and filtered. The filtrate was concentrated under reduced pressure to pro)ide crude methyl ester of the title compound that was purified on re)erse phase HPLC and hydrolyzed with 2N aqueous NaOH, THF and ethanol (2: 1 : 1, 2 mL) at room temperature for 20 hours. The reaction mixture was acidified with IN HC1 and extracted with ethyl acetate. The organic layer was separated, washed with water and brine respecti)ely, dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to pro)ide the title compound. 'H NMR (400 MHz, DMSO-D6) 8 ppm 1 1.77 - 12.49 (m, 1 H) 7.27 (d, .E=7.98 Hz, 1 H) 3.76 (d, J=6.15 Hz, 1 H) 3.19 - 3.28 (m, 1 H) 0.98 - 1.96 (m, 28 H) 0.85 - 0.96 (m, 3 H) MS (ESI+) m/z 378 (M+H)+ Example 4 [2-methyl-23-methyl-c)cloheyloy)propionylamino1-adamaTitaiie-l-caiboylic acid The title compound was prepared according to the procedure outlined in Example 3 substituting 3-methylcyclohexanol for 2-methylcyclohexanoL !H NMR (400 MHz, DMSO-D6) 5 ppm 1 1.70 - 12.38 (m, 1 H) 7.16 (d, Ml 36 Hz, 1 H) 3.76 (s, 1 H) 3.41 - 3.53 (m, 1 H) 1.33 - 1.96 (m, 18 H) 1.05 - 1.31 (m, 8 H) 0.66 - 0.99 (m, 5 H). MS (ESI+) m/z 378 CM-fH)* Example 5 g(2)cloheptyloxy-2-methyl-propionylamino)a"7arttane-l-carboylic acid The title compound was prepared according to the procedure outlined in Example 3 substituting cycloheptanol for 2-methylcyclohexanoL 'H NMR (400 MHz, DMSO-D6) 5 ppm 11.85 - 12.35 (m, 1 H) 7.21 (d, .E=7.67 Hz, 1 H) 3.70 - 3.88 (m, 2 H) 1.37 - 1.96 (m, 25 H) 1 .27 (s, 6 H). MS (ESI+) m/z 378 (M+H)+ Example 6 E-4-(2-( cycloheylrn ethoyy-2-methyl-propionylaniino)adaniantane- 1 -carboylic acid The title compound was prepared according to the procedure outlined in Example 3 substituting cyclohexylmethanol for 2-methylcyclohexanoL *H NMR (400 MHz, DMSO-D6) 6 ppm 1 1 .70 - 12.50 (m, 1 H) 7.06 (d, J*7.36 Hz, 1 H) 3.76 (d, 7.98 Hz, 1 H) 3. 19 (d, .E=6.14 Hz, 2 H) 1.41 - 1.95 (m, 19 H) 1.26 (s, 6 H) 0.90 - 1.25 (m, 5 H). MS (ESI+) m/z 378 Example 7A N-Amino-floamantane-l-carboylic acid To 1.0 g (10 wt%) of 5% Pd/C is added 4-oxo-adamantane-l-carboxylic acid (10.0 g, 5 1 .5 mmol) followed by 7M NHs in MeOH (200 mL). The reaction mixture is stirred under an atmosphere of Ha at 23 °C for 16-24 hours; water (200 mL) is added; and the catalyst is remo)ed by filtration. The catalyst is washed with methanol and the filtrate solution is concentrated under reduced pressure at a bath temperature of 35 °C until sol)ent stops coming o)er. Approximately 150 mL of a slurry remains. Acetonitrile (300 mL) is added to the slurry which is thai stirred for 3 hours at 23 °C. The slurry is filtered and washed once with acetonitrile (100 mL). The wet cake is dried at 50 °C and 20 mmHg under N2 to yield E-4-anu'no-adamantane-l-carboxylic acid (8.65 g, 86%, 13.1:1.0 E:Z ratio by !H-NMR in D20). Methanol (85 mL) was cooled to 0 °C; acetyl chloride (15.5 mL) was added dropwise; and then the solution was warmed to 23 °C for 15-20 minutes. N-4-Amino-adamantane-l-carboxylic acid (8.53 g, 43.7 mmol) was added and the reaction solution was heated to 45 °C for 16 hours. The reaction solution was cooled to 23 °C and acetonitrile (85 mL) was added. The reaction solution was concentrated under reduced pressure to ~l/4 )olume. .The reaction solution was further chase distilled with acetonitrile (2x85 mL). The resulting suspension was cooled to 23 °C and filtered. The filtrate was recirculated twice to wash me wet cake. The product was dried at 50 °C, 20 mmHg for 16 hours to afford 2-4-amino-adamantane-l-carboxylic acid methyl ester as a white crystalline solid (10.02 g, 93%). Example 7C E-4( 2-r4-chloro-phenoy)2-memyl-propioriy1flTnino')-adarnantane-l -carboylic acid To the solution of 2-4-Adamantamine -1-carboxylic acid methyl ester (49 mg, 0.2 mmoles) and triethylamine (0.097 mL, 0.7 mmoles) in DCM (1.0 mL) was added a solution of 2-(4-chlorophenoxy)-2-methylpropionyl chloride (55 mg, 0.24 mmoles) in DCM (1.0 mL). The resulting reaction mixture was stirred at room temperature for 20 hours and concentrated under reduced pressure. The residue was partitioned between ethylacetate and water. The organic layer was separated and washed with IN HC1, water and brine, dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to pro)ide the crude methyl ester of the title compound that was purified on re)erse phase HPLC and hydrolyzed with 2N aqueous NaOH, THF and ethanol (2:1:1, 2 mL) at room temperature for 20 hours. The reaction mixture was acidified with IN HC1 and extracted with ethyl acetate. The organic. layer was separated, washed with water and brine respecti)ely, dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to pro)ide the title compound. *H NMR (500 MHz, DMSO-D6) 8 ppm 1 1.94 - 12.25 (m, 1 H) 7.30 - 7.36 (m, 3 H) 6.87 - 6.94 (m, 2 H) 3.80 - 3.87 (m, 1 H) 1.93 (s, 2 H) 1.85 (d, .7=2.44 Hz, 3 H) 1 .80 (d, J=2.75 Hz, 2 H) 1.75 (s, 2 H) 1.68 (d, J=12.82 Hz, 2 H) 1.46 (s, 6 H) 1.38 (d, .7=12.82 Hz, 2 H). MS (ESI+) m/z 392(M+H)+ Example 8 carboxlic acid amide The title compound was prepared according to the procedure outlined in Example IB from E[24H;Uoro-phenoxy2-memyl-propionylammo]-adamantane-larboxylic acid (Example 7C). XH NMR (400 MHz, DMSO-D6) 8 ppm 7.25 - 7.36 (m, 3 H) 6.94 - 6.99 (m, 1 H) 6.89 - 6.94 (m, 2 H) 6.69 (s, 1 H) 3.83 (d, .E=7.67 Hz, 1 H) 1.91 (s, 2 H) 1.75 - 1.87 (m, 5 H) 1.63 - 1.73 (m, 4 H) 1.46 (s, 6 H) 1.32 - 1.42 (m, 2 H). MS (ESI+) m/z 391 Examle 9 amide The title compound was prepared according to the procedures outlined in Example 3 and IE, substituting 4-methylcyclohexanol for 2-methylcyclohexanol. !H NMR (400 MHz, DMSO-D6) 8 ppm 7.14 (d, 1 H) 6.98 (s, 1 H) 6.70 (s, 1 H) 3.72 - 3.82 (m, 1 H) 3.39 - 3.50 (m, 1 H) 1.19 - 1.96 (m, 26 H) 0.91 - 1.05 (m, 2 H) 0.81 - 0.89 (m, 3 H). MS (ESI4-) m/z 377 Example 10 -4-[(2-phenoypropanoylamino'|adamantane-l-carboxaTnide The title compound was prepared according to the procedure outlined in Example 7C and IE substituting 2-phenoxy-propionyl chloride for 2-(4-chlorophenoxy)-2-methylpropionyl chloride. 'H NMR (400 MHz, DMSO-D6) 8 ppm 7.74 (d, J*=7.36 Hz, 1 H) 7.26 (t, .E=7.98 Hz, 2 H) 6.83 - 6.99 (m, 4 H) 6.68 (s, 1 H) 4.86 (q, .7=6.55 Hz, 1 H) 3.78 (d, .7=7.06 Hz, 1 H) 1.69 - 1.92 (m, 11 H) 1.43 (d, .7=6.44 Hz, 3 H) 1.37 (d, .7=12.89 Hz, 2 H). MS (BSI+) m/z 343 (M+H)+ Example 1 1 2-methylphenoxy\propanoyl1aiPmo}adamantane-larboyu'c acid The title compound was prepared according to the procedure outlined in Example ID substituting 2-methylphenol for phenol. *H NMR (500 MHz, DMSO-D6) 6 ppm 11.58-12.61 (br. s, 1 H) 7.28 (d, J=H32 Hz, 1 H) 7.19 (d, 7.32 Hz, 1 H) 7.05 - 7.13 (m, 1 H) 6.91 (t, =6.87 Hz, 1 H) 6.82 (d, 7.93 Hz, 1 H) 3.79 - 3.88 (m, 1 H) 2.22 (s, 3 H) 1.95 (s, 2 H) 1.86 (d, 2.75 Hz, 3 H) 1.82 (s, 2 H) 1.76 (s, 2 H) 1.68 (d, .M3.12 Hz, 2 H) 1.46 (s, 6 H) 1 .43 (d, .M3.73 Hz, 2 H). MS (BSI+) m/z 372 (M+H)+ N-4-l[2-methyl-24-me&ylphenoxyforopanoyl]gt™ acid The title compound was prepared according to the procedure outlined in Example ID substituting 4-methylphenol for phenol. 'H NMR (500 MHz, DMSO-D6) 6 ppm 1 1 .75 -12.46 (br.s, 1 H) 7.30 (d, JJ32 Hz, 1 H) 7.08 (d, J=8.24 Hz, 2 H) 6.81 (d, =8.54 Hz, 2 H) 3.80 - 3.86 (m, 1 H) 2.23 (s, 3 H) 1.94 (s, 2 H) 1.86 (d, 2.44 Hz, 3 H) 1.82 (s, 2 H) 1.76 (s, 2 H) 1.69 (d, JH2.82 Hz, 2 H) 1.38 - 1.45 (m, 8 H). MS (ESI+) m/z 372 (M+H)+ Example 13 The title compound was prepared according to the procedure outlined in Example ID substituting 2-chlorophenol for phenol 'H NMR (500 MHz, DMSO-D6) 5 ppm 1 1 .50 - 12.76 (br. s, 1 H) 7.63 (d, =7.63 Hz, 1 H) 7.57 (dd, 7.93, 1.53 Hz, 1 H) 7.36 (t, 1 H) 7.24 (dd, .7=8.24, 1.22 Hz, 1 H) 7.16 (t, 1 H) 3.88 - 3.98 (m, 1 H) 2.04 (s, 2 H) 1.94 (d, J=Q.M Hz, 5 H) 1.82 - 1.88 (m, 4 H) 1.52 - 1.59 (m, 8 H). MS (ESI+) m/z 392 (M+H)+ Example 14 jg-4- lf22-me1hoxhenoy)2-methylprop»pnY)'[aTTiino} adamantane- 1 -carboxamide The title compound was prepared according to the procedure outlined in Example ID and IE substituting 2-methoxyphenol for phenol 'H NMR (400 MHz, DMSO-D6) 5 ppm 7.91 (d, j=7.67 Hz, 1 H) 7.05 -- 7.1 1 (m, J H) 7.00 (s, 1 H) 6.86 - 6.93 (m, 1 H) 6.71 (s, 1 H) 3.81 - 3.88 (m, 1 H) 3.79 (s, 3 H) 1.96 (s, 2 H) 1.76 - 1.92 (m, 9 H) 1.54 (d, =13.20 Hz, 2 H) 1.36 (s, 6 H). MS (ESI+) m/z 387 (M+H)+ Example IS E-4- f [24-metfaoyphoy)2-metfa)Ipropanoyl1aininoTadama"tane-l-cafboxamide The title compound was prepared according to the procedure outlined in Example ID and IB substituting 4-methoxyphenol for phenol. JH NMR (400 MHz, DMSO-D6) 5 ppm 7.30 (d, =7.36 Hz, 1 H) 6.93 - 7.01 (m, 1 H) 6.82 - 6.92 (m, 4 H) 6.70 (s, 1 H) 3.85 (d, =7.06 Hz, 1 H) 3.71 (s, 3 H) 1.92 -1.97 (m, 2 H) 1.77 - 1.89 (m, 5 H) 1.74 (s, 3 H) 1.71 (s, 1 H) 1.44 (d, JH2.58 Hz, 2 H) 1.37 (s, 6 H). MS (ESI+) m/z 387 (M+H)* Example 16 JE-4-( (2-methyl-2-[3-(tnflMfrfTnethylphenoxyjpropano'3d) airirooadamaTitane-1 -carboy anide The title compound was prepared according to the procedure outlined in Example ID and IE substituting 3-trifluoromethylphenol for phenol. !H NMR (400 MHz, DMSO-D6) 6 ppm 7.53 (t, .E=7.98 Hz, 1 H) 7.37 (dd, 12.12,7.21 Hz, 2 H) 7.19 (dd, 1 H) 7.14 (s, 1 H) 6.95 (s, 1 H) 6.68 (s, 1 H) 3.81 (s, 1 H) 1.90 (s, 2 H) 1.80 (d, 7.67 Hz, 4 H) 1.76 (s, 1 H) 1.70 (s, 2 H) 1.61 (d, 2 H) 1.52 (s, 6 H) 1.32 (d, 7=13.50 Hz, 2 H). MS (ESI+) m/z 425 Example 17 E-4-(r2-(3-methoyphenoy)2-memylprc The title compound was prepared according to the procedure outlined in Example ID and IE substituting 3-methoxyphenol for phenol. JH NMR (500 MHz, DMSO-D6) 8 ppm 7.26 (d, J=7.32 Hz, 1 H) 7.17 (t, 8.24 Hz, 1 H) 6.98 (s, 1 H) 6.71 (s, 1 H) 6.60 (dd, 8.39, 1.98 Hz, 1 H) 6.43 - 6.48 (m, 2 H) 3.82 (d, J=7.02 Hz, 1 H) 3.70 (s, 3 H) 1.91 (s, 2 H) 1.76 -1.86 (m, 5 H) 1.71 (s, 2 H) 1.66 (d, J=12.82 Hz, 2 H) 1.46 (s, 6 H) 1.36 (d, =12.51 Hz, 2 H). MS (ESI+) m/z 387 (M+H)* Example 18 The title compound was prepared according to the procedure outlined in Example 7C substituting 4-adamantamine hydrochoride for E-4-adamantarnine -I-carboxylic acid methyl ester. JH NMR (400 MHz, DMSO-D6) 8 ppm 7.30 - 7.35 (m, 2 H) 7.25 (d, =7.36 Hz, 1 H) 6.89 - 6.94 (m, 2 H) 3.83 - 3.91 (m, 1 H) 1.82 (d, .M0.74 Hz, 2 H) 1.77 (s, 5 H) 1.64 - 1.73 (m, 5 H) 1 .42 - 1.49 (m, 8 H). MS (ESI+) m/z 348 (M+H)*. Example 19 The title compound was prepared according to the procedure outlined in Example 1C substituting E-4-aminoadamantan-l-ol for E"-4-adamantamine -l-carboxylic acid methyl ester. JH NMR (400 MHz, DMSO-D6) 8 ppm 7.30 - 7.35 (m, 2 H) 7.22 (d, =7.06 Hz, 1 H) 6.88 - 6.94 (m, 2 H) 4.21 - 4.52 (br s, 1 H) 3.75 - 3.80 (m, 1 H) 1.96 (s, 2 H) 1.91 (s, 1 H) 1.64 - 1 .71 (m, 2 H) 1 .53 - 1.62 (m, 6 H) 1 .45 (s, 6 H) 1 .27 (d, .M2.58 Hz, 2 H). MS (ESI+) rn/z364(M+H)+. Examle 20 A solution of the product of Example 12 (24 mg, 0.064 mmol) in DCM (2 mL) was treated with HOBt (9.5 mg, 0.07 mmol) and EDCI (14.7 mg, 0.077 mmol) and stirred at room temperature for 1 hour. Excess of aqueous (30%) ammonia (2 mL) was added and the reaction was stirred for additional 20 hours. The layers were separated and the aqueous layer extracted with DCM (2x2 mL). The combined organic extracts were washed with water (3x2 mL), brine (2 mL), dried (MgSO-O and filtered. The filtrate was concentrated under reduced pressure to pro)ide the crude compound that was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (25mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.l% aqueous TFA o)er 8min (lOmin run time) at a flow rate of 40mL/min. to pro)ide the title compound. :H NMR (500 MHz, DMSO-dg) 8 ppm 7.28 (d, J = 7.36 Hz, 1H), 7.08 (d, j= 8.12 Hz, 2H), 6.98-6.99 (bs, 1H), 6.80-6.82 (m, 2H), 6.71-6.73 (bs, 1H), 3.81-3.86 (m, 1H), 2.23 (s, 3H), 1.91-1.93 (m, 2H), 1.77-1.87 (m, 5H), 1.71-1.73 (m, 2H), 1.65-1.70 (m, 2H), 1.41 (s, 6H), 1.37-1.42 (m, 2H). MS (ESI+)m/z 371 (M+H)+. Example 214- (f 2-3-Chlorophenoyl-2-roetfo Example 21 A Example 21 A was prepared according to the procedure outlined in Example ID, substituting 3-chlorophenol for phenol. Examle 21B The title compound was prepared using the procedure as described in Example IE, substituting the product of Example 21 A for the product of Example ID. *H NMR (500 MHz, DMSO-ds) 8 ppm 7.35 (d, J= 6.93 Hz, IH), 7.31 (t, J= 8.10 Hz, IH), 7.07 (dd, j= 7.83, 1.91 Hz, IH), 6.97-6.98 (bs, IH), 6.92 (t, J= 2.15 Hz, IH), 6.87 (dd, j= 8.22, 2.29 Hz, IH), 6.70-6.72 (bs, IH), 1.90-1.93 (m, 2H), 1.70-1.71 (m, 2H), 1.49 (s, 6H), 3.80-3.84 (m, IH), 1.76-1.85 (m, 5H), 1.60-1.68 (m, 2H), 1.33-1.37 (m, 2H). MS (ESIH-) m/z 391 (M+H)+. Example 22 -Methyl-2-[4-(trifluoromethoxyphenoxy]propano'yl) aminQ)aamantane-l- carboxamide Example 22A Example 22A was prepared according to the procedure outlined in Example ID, substituting 4-trifluoromethoxyphenol for phenol. Example 22B -4-f(2-Methyl-2-[4-(trifliu)romethoxyphenoy]pix)panoyl}ammoadaniantane-l- carboxamide The title compound was prepared using the procedure as described in Example IE, substituting the product of Example 22A for the product of Example ID. *H NMR (400 MHz, DMSO-de) 5 ppm 7.41 (t, j= 8.25 Hz, IH), 7.33 (d, j= 6.94 Hz, IH), 7.00 (d, j= 8.15 Hz, IH), 6.90-6.96 (m, 2H), 6.82-6.84 (bs, IH), 6.67-6.69 (bs, IH), 3.79-3.84 (m, IH), 1.87-1.90 (m, 2H), 1.75-1.86 (m, 5H), 1.69-1.71 (m, 2H), 1.63-1.69 (m, 2H), 1.51 (s, 6H), 1.29-1.37 (m, 2H). MS (ESI+) m/z 441 (M-f-H)"1". Example 23 )-2-methylpropano yll amino) adarn a The title compound was prepared according to the procedure' outlined in Example ID, substituting 3-bromo-phenol for phenol. JH NMR (500 MHz, DMSO-ds) 8 ppm 12.05-12.10 (s, 1H), 7.38 (d, J= 6.82 Hz, 1H), 7.19-7.27 (m, 2H), 7.06 (t, j= 2.06 Hz, 1H), 6.91 (ddd, j= 8.09, 2.36, 1.18 Hz, 1H), 3.80-3.84 (m, 1H), 1.93-1.96 (m, 2H), 1.84-1.85 (m, 4H), 1.77-1.80 (m, 1H), 1.74-1.76 (m, 2H), 1.65-1.70 (m, 2H), 1.48 (s, 6H), 1.36-1.40 (m, 2H). MS (BSI+) m/z437(M+H)+. nrar[riniit)ncarbon)naminom.eth)rrt)eDzoic acid To a solution of the product of Example 7C (200 mg, 0.51 mmol) and TBTU (246 mg, 0.77 mmol) in DMF (5 mL) was added WAT-dusopropylemylamine (0.27 mL, 1.53 mmol) followed by 4-aminomethyl-benzoic acid methyl ester hydrochloride (123 mg, 0.61 mmol) and stirred at room temperature for 20 hours. The reaction mixture was concentrated in )acua. The residue was taken in ethyl acetate and washed with water and brine respecti)ely, dried (MgSCU) and concentrated in )acua to get crude methyl ester of the title compound that was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (40mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous TFA o)er 12min (15min run time) at a flow rate of 70mL/min. and concentrated. The methyl ester of the title compound was hydrolyzed as described in step B of Example ID. The crude acid product was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (40mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrUe:0.1% aqueous TFA o)er 12min (15min run time) at a flow rate of 70mL/min.to pro)ide the title compound. ]H NMR (400 MHz, DMSO-ds) 5 ppm 12.77-12.82 (bs, 1H), 8.08 (t, J= 5.96 Hz, 1H), 7.88 (d, j= 7.99 Hz, 2H), 7.29-7.36 (m, 5H), 6.91-6.93 (m, 2H), 4.31 (d, j= 5.86 Hz, 2H), 3.84-3.89 (m, 1H), 1.93-1.96 (m, 2H), 1.82-1.91 (m, 5H), 1.77-1.79 (m, 2H), 1.67-1.72 (m, 2H), 1.47 (s, 6H), 1.32-1.45 (m, 2H). MS (ESH-) m/z 525(M+H)+. Example 25 A 2-C23-Dimethylphenoy)-2-mettiyl-propioDic arid To an ice cold solution of 2,3-dimethylphenol (136 mg, 1.0 mmol) and 1,1,1-tricMoro-2-methyl-2-propanol hydrate (492 mg, 2.75 mmol) in acetone (2 mL) was added powdered sodium hydroxide (393 mg, 9.83 mmol) in three equal portions at 1 hour inter)al. After each addition reaction mixture was allowed to come to room temperature. Before last addition of sodium hydroxide, acetone (2 mL) was added to the reaction mixture. The reaction mixture was stirred at room temperature for 48 hours and concentrated in )acua. The residue was diluted with water and acidified to pH 1 with aqueous HC1 and extracted with diethyl ether (3x5 mL). The organic layers were pooled, dried (Na2SC4) and filtered. The filtrate was concentrated under reduced pressure to pro)ide the crude that was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (40mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous TFA o)er 12min (15min run time) at a flow rate of 70mL/min. to pro)ide the title compound as a pale yellow solid (158 mg, 76%). Example 25B E-4- (f 2-(2.3-Dimethylphenoxy)2-methylpropanoyl] amino} adamantane-1 -c arboylic acid To a solution of the product of Example 25A (20.8 mg, 0.1 mmol) and TBTU (48 mg, 0.15 mmol) in DMF (1 mL) was added H-diisopropylethylamine (0.052 mL, 0.3 mmol) followed by the product of Example 7B (30 mg, 0.12 mmol) and stirred at room temperature for 20 hours. The reaction mixture was concentrated in )acua. The residue was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (25mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous TFA o)er 8min (lOmin run time) at a flow rate of 40mL/min. and hydrolyzed as described in step B of Example ID to pro)ide the title compound. *H NMR (500 MHz, DMSO-de) 8 ppm 12.03-12.14 (bs, 1H), 7.30 (d, J = 7.30 Hz, 1H), 6.98 (t, J= 7.79 Hz, 1H), 6.84 (d, J= 7.44 Hz, 1H), 6.68 (d, J= 8.14 Hz, 1H), 3.84-3.88 (m, 1H), 2.22 (s, 3H), 2.14 (s, 3H), 1.95-1.97 (m, 2H), 1.83-1.88 (m, 5H), 1.76-1.78 (m, 2H), 1.69-1.73 (m, 2H), 1.41-1.48 (m, 2H), 1.43 (s, 6H). MS (ESI-f) m/z 386 (M+H)+. Examle 26 oxoethoy)phenylcarbamatB Example 26A Example 26A was prepared according to the procedure outlined in Example 25 A, substituting (4-hydroxy-phenyl)-carbamic acid tert-butyl ester for 2,3-dimethylphenol. Example 26B was prepared using the procedure as described in Example 25B, substituting the product of Example 26A for the product of Example 25 A Example 26C tert-Butyl 4-(2-ir()-5-('iTiiTiocarbon'yl)2-adai»ntYl]ainn}-1 J-fHmefhyl-2- oxoetfaoyfohenylcarbamate The title compound was prepared using the procedure as described in Example IE, substituting the product of Example 26B for the product of Example ID. 1H NMR (400 MHz, DMSO-ds) 5 ppm 9.18-9.20 (bs, IH), 7.34 (d, J= 8.50 Hz, 2H), 7.28 (d, J= 7.37 Hz, IH), 6.96-6.98 (bs, IH), 6.84 (d, J= 8.77 Hz, 2H), 6.68-6.70 (bs, IH), 3.81-3.87 (m, IH), 1.92-1.95 (m, 2H), 1.80-1.89 (m, 5H), 1.68-1.75 (m, 4H), 1.46 (s, 9H), 1.39-1.46 (m, 2H), 1 .39 (s, 6H). MS (ESI+) m/z 472 (M+H)+. Examle 27 The title compound was prepared according to the procedure outlined in Example IE substituting the product of Example 24 for the product of Example ID. !H NMR (400 MHz, DMSO-dfi) 8 ppm 8.03-8.08 (m, IH), 7.86-7.88 (bs, IH), 7.80 (d, J= 8.09 Hz, 2H), 7.32-7.35 (m, 2H), 7.26-7.32 (m, 2H), 724-7.27 (m, 2H), 6.91-6.93 (m, 2H), 4.29 (d, J= 5.87 Hz, 2H), 3.83-3.89 (m, IH), 1.82-1.96 (m, 7H), 1.77-1.79 (m, 2H), 1.66-1.72 (m, 2H), 1.46 (s, 6H), 1.37-1.42 (m, 2H). MS (ESI+) m/z 524 (M+H)+. Example 28A Example 28A was prepared according to the procedure outlined in Example 24, substituting glycine methyl ester hydrochloride for 4-arnmomethyl-benzoic acid methyl ester hydrochloride. Ryamle 28B memylpropanoyllaminol adamantane-1 -cafboxamide Hie title compound was prepared using the procedure as described in Example IE, substituting the product of Example 28A for the product of Example ID. JH NMR (400 MHz, DMSO-de) 5 ppm 7.49-7.54 (m, 1H), 7.32-7.35 (m, 2H), 7.31 (d, J= 7.21 Hz, 1H), 7.08-7.11 (bs, 1H), 6.93-6.97 (m, 1H), 6.91-6.93 (m, 2H), 3.82-3.87 (m, 1H), 3.58 (d, J= 5.68 Hz, 2H), 1.92-1.98 (m, 2H), 1.80-1.90 (m, 5H), 1.74-1.76 (m, 2H), 1.65-1.71 (m, 2H), 1.46 (s, 6H), 1.36-1.41 (m, 2H). MS (ESI+) m/z 448 (M+Hf. Examle 29 adamant)ncarbotiyaminnmeth)nbenzoic acid The title compound was prepared according to the procedure outlined in Example 24, substituting 3-aminomethyl-benzoic acid methyl ester hydrochloride for 4-aminomethyl-benzoic acid methyl ester hydrochloride. !H NMR (400 MHz, DMSO-d6) 6 ppm 12.81-12.91 (m, 1H), 8.06-8.12 (m, 1H), 7.77-7.82 (m, 2H), 7.40-7.44 (m, 2H), 7.31-7.35 (m, 2H), 7.30-7.32 (m, 1H), 6.91-6.93 (m, 2H), 4.30 (d, j= 5.89 Hz, 2H), 3.83-3.88 (m, 1H), 1.93-1 .96 (m, 2H), 1.82-1.90 (m, 5H), 1.77-1.79 (m, 2H), 1.67-1.72 (m, 2H), 1.46 (s, 6H), 1.37-1.42 (m, 2H). MS (ESI+) m/z 525 (M+H)+. Examle 30 Example 30A 2-(5-Bromo-p)ridin-2-yloy)2-methyl-propionicacid Step A To a stirred and cooled (0°C) solution of 2-hydroxy-2-me&yl-propionic acid methyl ester (2.6 mL, 22.70 mmol) and 5-bromo-2-fluoro-pyridine (3.32 g, 18.92 mmol) in THF (26 mL) and DMPU (13 mL) was added portionwise NaH (Ig, 60% in oil, 24.59 mmol). After the addition, the resulting mixture was wanned to room temperature and stirred o)ernight Saturated NHtCl was then added to quench the reaction and EtaO was used to partition the mixture. The organic phase was washed with water, brine, dried o)er MgSO4, and filtered. After concentration, the residue was purified o)er silica gel using 20% EtOAc / hexane and concentrated to gi)e a clear oil. StepB The product of Step A (1.56 g, 5.71 mmol) was dissol)ed in THF (30 mL) and KOTMS (1.1 g, 8.57 mmol) was added in one portion. The resulting solution was stirred at room temperature o)ernight Et2O (30 mL) and water (40 mL) were added to the reaction to partition the mixture. The phases were separated, and the aqueous phase was acidified using 10% NaHSCU solution and extracted with EtOAc. The combined organic phases were dried o)er MgSC4, filtered and concentrated to gi)e the title compound as a white solid. Examle 30B Step A HATU (2.46 g, 6.48 mmol) was added in one portion to a solution of the product of Step B of Example 30A (1.40 g, 5.40 mmol), the product of Example 7B (1.45 g, 5.95 mmol), and DIPEA (2.82 mL, 16.2 mmol) in dry CH2Cl2 (20 mL). The resulting solution was allowed to stir at room temperature o)ernight before it was diluted with CEfeCk and washed with aqueous NaHSO4 solution, 1 M NaOH, dried (Na2SC4) and e)aporated. The residue was purified o)er silica gel using 30% EtOAc / hexanes and concentrated to gi)e an oil. StepB To the product of Step A (2.27 g, 5.04 mmol) in THF (15 mL) was added KOTMS (1 .42 g, 1 1 .08 mmol) and the resulting solution was stirred at room temperature o)ernight before it was diluted with Et2O and water. The phases were separated and the aqueous phase was acidified with NaHSCU solution and extracted with EtOAc. The combined organic phases were dried (MgSCU) and e)aporated to gi)e a white solid. StepC EDCI (1.40 g, 7.25 mmol) was added to a solution of the product of Step B (2.17 g, 4.84 mmol), HOBt (1. 1 7 g, 8.71 mmol), DIPEA (2.5 mL, 14.4 mmol) in dry CH2C12 (20 mL). The resulting solution was allowed to stir at room temperature for 1 hr before NHs solution was added (12 mL, 2M in iPrOH). The mixture was stirred for 2 hours at 25°C, diluted with CH2Ck and washed with NaHSC4 solution, 1M NaOH, brine, dried (Na2SO4) and e)aporated. The residue was purified o)er silica gel using 5% MeOH / CH2Cl2 to gi)e the title compound as a white solid. 1R NMR (300 MHz, CD3OD) 8 ppm 8.1 1 (d, J= 2.52 Hz, 1H), 7.82 (dd, J= 8.74, 2.60 Hz, 1H), 6.84 (d, J= 8.74 Hz, 1H), 3.89-3.92 (m, 1H), 1.91-1.99 (m, 6H), 1.83 (s, 3H), 1.66 (s, 6H), 1.41-1.62 (m, 4H). MS (ESI+) M/z 436 (M+H)+. Example 31 A Example 31 A was prepared according to the procedure outlined in Example 25 A, substituting 2-hydroxy-benzonitrile for 2,3-dimethylphenol. Example 3 IB Example 3 IB was prepared using the procedure as described in Example 25B, substituting the product of Example 31 A for the product of Example 25A Examle 3 1C The title compound was prepared using the procedure as described in Example IE, substituting the product of Example 31B for the product of Example ID. 1H NMR (500 MHz, DMSO-de) 8 ppm 7.78 (dd, J= 7.68,1.75 Hz, 1H), 7.62 (ddd, j= 8.54,7.48,1.68 Hz, 1H), 7.49 (d, j= 6.94 Hz, 1H), 7.17 (td, J= 7.58,0.87 Hz, 1H), 7.08 (d, j= 8.53 Hz, 1H), 6.98-6.99 (bs, 1H), 6.71-6.72 (bs, 1H), 3.83-3.87 (m, 1H), 1.94-1.96 (m, 2H), 1.75-1.88 (m, 7H), 1.71-1.73 (m, 2H), 1.60 (s, 6H), 1.35-1.39 (m, 2H). MS (ESI+) m/z 382 (M+H)+. Example 32 Example 32A was prepared according to the procedure outlined in Example 25A, substituting 4-benzyloxy-phenol for 2,3-dimethylphenoL Example 32B Example 32B was prepared according to the procedure outlined in Example 25B, substituting the product of Example 32A for the product of Example 25 A. Example 32C Example 32C was prepared according to the procedure outlined in Example IE, substituting the product of Example 32B for the product of Example ID. Example 32D E-4-(r2-f4-H)droyphenoy)2-memylpropano)nanimoadamantane-l-carhn-gaipiHe The product of Example 32C (62 mg, 0.13 mmol) was debenzylated using 20% Pd(OH)2/C (63 mg) and methanol (2mL) at 60 psi at room temperature for 20 hours. The reaction mixture was filtered and concentrated under reduced pressure to pro)ide the crude product that was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (25mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous TFA o)er 8min (lOmin run time) at a flow rate of 40ml/min. to pro)ide title compound as a white solid. 1H NMR (400 MHz, DMSO-de) 5 ppm 9.12 (s, 1H), 7.28 (d, J= 7.49 Hz, 1H), 6.96-6.99 (bs, 1H), 6.77-6.79 (m, 2H), 6.69-6.71 (bs, 1H), 6.63-6.69 (m, 2H), 3.81-3.87 (m, 1H), 1,93-1,95 (m, 2H), 1.78-1.89 (m, 5H), 1.69-1.76 (m, 4H), 1.42-1.47 (m, 2H), 1.35 (s, 6H). MS (ESI+) m/z 373 (M+H)"1". Example 33A 2-(4-cMorophenoy)N-[fjft-5-fli)droymem To a cold (-30°C) solution of the methyl ester of Example 7C (870 mg, 2.15 mmol) in THF (3.0 mL) was added IN LAH in THF solution (3.22 ml, 3.22 mmol) slowly under N2 flow. The reaction mixture was stirred from -30°C to 0°C for 3 hours. It was quenched with water carefully, acidified with IN HC1 and extracted with DCM 3 times. The combined organic layer was dried o)er NajSO filtered, concentrated under reduced pressure and the residue purified by flash chromatography with 30% ethyl acetate / 70% hexane to pro)ide the title compound (690 mg, 85%). 'H NMR (300 MHz, CDCU) 8 ppm 9.32 - 9.39 (m, 1 H), 7.17 - 7.29 (m, 2H), 7.00 (d, 1 H), 6.81 - 6.91 (m, 2 H), 3.99 - 4.12 (m, 1 H), 1.44 - 2.15 (m, 21 H). MS (ESR) m/z 378 (M+H)+. Example 33B g-4-[244-CMorophenoy)2-memyl-propionylaimo)adamantane-l-carbaldeh)de To a solution of the product of Example 33A (990 mg, 2.63 mmol) in DCE (8.0 mL) were added NMO (461 mg, 3.94 mmol), TPAP (46 mg, 0.13 mmol) and molecular sie)es at room temperature under Nj flow. The reaction mixture was stirred o)ernight at room temperature. It was filtered through Celite and washed with DCM 3 times. The combined filtrate was concentrated under reduced pressure and purified by flash chromatography with 30% ethyl acetate / 70% hexane to pro)ide the title compound (740 mg, 75%). *H NMR (300 MHz, CDC13) 8 ppm 9.36 (m, 1 H), 7.20 - 7.26 (m, 2 H), 6.95 - 7.05 (m, 1 H), 6.82 - 6.91 (m, 2 H), 4.00 - 4.10 (m, 1 H), 1.48 - 2.13 (m, 19 H). MS (ESI+) m/z 376 (M+H)+. Example 33C To a cold (0°C) solution of the product of Example 33B (375 mg, 1 mmol) in DME (5.0 mL) / EtOH (0.15 ml) was added TosMIC (254 mg, 1.3 mmol) and f-BuOK (281 mg, 2.5 mmol) under Na flow. The reaction mixture was stirred at room temperature for 2 hrs, then heated to 35-40°C for 30 minutes. It was filtered through AfeOa plug after it was cool down to room temperature and washed with DMB (3 X). The combined filtrate was concentrated under reduced pressure and purified by flash chromatography with 30% ethyl acetate/ 70% hexane to pro)ide the title compound (200 mg, 52%). *H NMR (400 MHz, CDC13) 5 ppm 7.19 - 7.29 (m, 2 H), 6.91 - 7.01 (m, 1 H), 6.81 - 6.90 (m, 2 H), 3.96 - 4.05 (m, 1 H), 2.14 (s, 2 H), 1.94 - 2.08 (m, 3 H), 1.47 - 1.75 (m, 15 H). MS (ESI+) m/z 387 (M+H)+. Example 33D To a solution of the product of Example 33C (40 mg, 0.1 mmol) in ethylene glycol (0.5 ml) was added 25% KOH solution (0.2 ml). The reaction mixture was heated to 150°C o)ernight and concentrated. The residue was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (25mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous TEA o)er 8min (lOmin run time) at a flow rate of 40mL/min. to pro)ide the title compound (19 mg, 45%). JH NMR (400 MHz, CDC13) 5 ppm 7.19 - 7.25 (m, 2 H), 6.96 - 7.02 (m, 1 H), 6.82 - 6.90 (m, 2 H), 3.98 - 4.07 (m, 1 H), 2.1 1 -2.1 8 (m, 2 H), 1.88 - 2.03 (m, 3 H), 1.47 - 1.85 (m, 16 H). MS (ESI+) m/z 406 (MfH)+. Examle 34 To a solution of the product of Example 33C (22 mg, 0.057 mmol) in MeOH (0.15 ml) / DMSO (0.005 ml) were added 30% H202 (0.01 1 ml) and 0.2 M NaOH (0.006 ml). The reaction mixture was heated to 50°C o)ernight and concentrated. The residue was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (25mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous TFA o)er 8min (lOmin run time) at a flow rate of 40mL/min. to pro)ide the title compound (13 mg, 56%). 'H NMR (500 MHz, CDC13) 5 ppm 7.21 - 7.26 (m, 2 H), 6.94 - 7.04 (m, 1 H), 6.84 - 6.91 (m, 2 H), 5.62 - 5.72 (m, 1 H), 5.35 - 5.43 (m, 1 H), 3.97 - 4.06 (m, 1 H), 1.89 - 2.05 (m, 5 H), 1.48 - 1.80 (m, 18 H). MS (ESI+) m/z 405 (M+H)+. To a solution of Ihe product of Example 33C (65 mg, 0.168 mmol) in water (0.2 ml) / isopropanol (0.1 ml) were added NaNs (22 mg, 0.337 mmol) and ZnBra (19 mg, 0.084 mmol). The reaction mixture was heated to 1 50°C in a sealed tube for two days and concentrated. The residue was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (25mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous TFA o)er 8min (lOmin run time) at a flow rate of 40mL/min. to pro)ide the title compound (43 mg, 45%). ]H NMR (400 MHz, CD3OD) 8 ppm 7.34 - 7.43 (m, 1 H), 7.23 - 7.31 (m, 2 H), 6.89 - 6.96 (m, 2 H), 3.84 - 3.92 (m, 1 H), 2.75 (s, 2 H), 1.86 -2.02 (m, 3 H), 1.43 - 1.74 (m, 16 H). MS (ESI+) m/z 430 (M+H)*. Examle 36 C solution of the product of Example 33A (0.71 g, 1.88 mmol) in GFfcCfc (5.0 mL) and pyridine (0.46 mL, 5.64 mmol) was added trifluoromethanesulfonic anhydride (0.35 mL, 2.07 mmol). The reaction mixture was stirred under an atmosphere of NZ for 30 min at 0°C. The crude products were diluted with EtOAc, washed with water and brine, dried o)er Na2SC4, filtered, and concentrated in )acua. The resulting crude material was dissol)ed hi DMF (5.0 mL), treated with potassium thioacetate (0.43 g, 3.76 mmol), and heated to 70°C o)ernight The crude reaction mixture was diluted with EtOAc, washed with water (3x) and brine, dried o)er Na2SO4, filtered, and concentrated in )acua. The crude product was purified by silica gel chromatography employing a sol)ent gradient (hexane-60:40 hexane:EtOAc) to yield the title compound(0.74 g, 90%) as a white solid. *H NMR (300 MHz, CDC13) 5 ppm 7.23 (d, J± 8.82 Hz, 2 H), 6.95 (m, 1 H), 6.86 (d, 8.82 Hz, 2 H), 3.98 (m, 1 H), 2.76 (s, 2 H), 2.35 (s, 3 H), 1.89 - 1.97 (m, 3 H) 1.45-1.68 (m, 10 H), 1.50 (s, 6H). MS (ESI+) m/z 436 (M+H)+. To a solution of the product of Example 36A (0.74 g, 1.70 mmol) and NaOAc (0.1392 g, 1 .70 mmol) in acetic acid (10 mL) was added 30% hydrogen peroxide in water (1.6 mL, 15.3 mmol). The reaction solution was stirred at room temperature o)ernight and excess peroxide quenched by adding dimethylsulfide (1.9 mL, 25.5 mmol) and stirring for 2 h. The reaction solution was concentrated under reduced pressure to pro)ide the crude product as a white solid. JH NMR (300 MHz, CDC13) 5 ppm 7.22 (d, J= 8.85 Hz, 2 H), 7.07 (d, J= 7.94 Hz, 1 H), 6.86 (d, =8.85 Hz, 2 H), 3.95 (m, 1 H), 2.80 (s, 2 H), 1.51 - 2.17 (m, 13 H) 1.46 (s, 6H). MS (ESI+) m/z 442 (M+H)+. To a solution of the product of Example 36B (55.8 mg, 0.126 mmol) in DCM (1.2 mL) and DMF (1 drop) was added triphosgene (27.4 mg, 0.0922 mmol) and triethylamine (0.018 mL, 0.126 mmol). The resulting reaction mixture was stirred at room temperature for 2 hours and ammonia (0.5 M in dioxane, 2.5 mL, 1 .26 mmol) was added. After stirring for 2 h at room temperature the reaction was quenched with water and extracted with EtOAc. The organic layer was then rinsed with brine, dried o)er Na2SO4, filtered, and concentrated in )acua. The crude product was purified by re)erse phase preparati)e HPLC using acetonitrile:10mM NHtOAc on YMC Guardpak column to pro)ide the title compound (20 mg, 36%) as a white solid. 'H NMR (400 MHz, CDCU) 5 ppm 7.24 (d, J = 8.9 Hz, 2 H), 6.98 (d, j= 8.28 Hz, 1 H), 6.86 (d, =8.9 Hz, 2 H), 4.79 (s, 2H), 4.04 (m, 1 H), 3.04 (s, 2H), 1.87-2.04 (m, 8 H), 1.54-1.66 (m, 5 H), 1.50 (s, 6H). MS (ESI+) m/z 441 (M+H)+. Examle 37 Carhamoyl-adamantan-2-yl)-carbamic acid benzyl ester Step A CbzCl (3.48 mL, 24.72 mmol) was added dropwise to a stirred and cooled (0°C) solution of the product of Example 7B (5.05 g, 20.60 mmol) and DIPEA (7.9 mL, 4532 mmol) in dry CHaQa (100 mL). After the addition, the solution was allowed to warm to room temperature and stirred for another 2 hrs. Saturated NaHCOs solution was added to quench the reaction and the phases were separated. The organic phase was washed with NaHSO* solution, NaHCOs solution, dried (Na2SO4), filtered, and concentrated. The residue was purified o)er silica gel using 20% EtOAc in hexanes and concentrated. StepB The product of step A (6.49 g, 18.91 mmol) was dissol)ed in dry THF (90 mL) and KOTMS (4.85 g, 37.82 mmol) was added at room temperature. The resulting solution was stirred o)ernight before water (100 mL) and EtjO (100 mL) were added and the phases were separated. The aqueous phase was acidified using solid NaHSQ* until pH 1 was reached The aqueous phase was then extracted using EtOAc. The combined organic extract was dried (MgSO4), filtered, and concentrated. Step C The product of Step B (18.91 mmol) was dissol)ed in dry CHzGb (60 mL) and DEPEA (10 mL, 56.7 mmol), HOBt (5.1 g, 37.82 mmol), and EDCI (5.4 g, 28.36 mmol) were added to the solution. The resulting mixture was stirred for 1 h before NHs (30 mL, 2 M in iPrOH, 56.7 mmol) was added. After 1 h of stirring at 25 °C, the solution was diluted with CH2C12 (200 mL) and washed withNaHSO* solution, 1M NaOH, water, dried (NfeSO*) and filtered. The residue was purified o)er silica gel using 5% MeOH in CHaCfe to pro)ide the title compound as a solid. Example 37B E~4- Amino-adamantane-1 -carbonitrile Step A . The product of Step C of Example 37 A, 18.91 mmol) was dissol)ed in dry CHjClz (60 mL) and Et3N (10.5 mL, 75.64 mmol). TFAA (7.9 mL, 56.73 mmol) was added dropwise to the solution at 0°C. After the addition, the solution was allowed to warm to room temperature and stirred for 3 hours before MeOH was added to quench the reaction. The solution was washed with NaHSO* solution, NaHCOs solution, dried (NajSCU), filtered and concentrated. The residue was purified o)er silica gel using 30% EtOAc in hexanes and concentrated to yield an oil. StepB Pd(OHb / C (0.9 g) was added to a solution of the product of Step A (3.22 g, 10.38 mmol). The solution was stirred at room temperature under HI (balloon) until starting material was consumed. The mixture was filtered through a pad of Celite and concentrated in )acua to pro)ide the title compound as a solid. Example 37C Step A HATU (0.64 g, 1 .67 mmol) was added in one portion to a stirred solution of 2-(4-chloro-phenoxy)-2-methyl-propionic acid (0.3 g, 1.50 mmol) and die product of Step B of Example 37B (0.27 g, 1.53 mmol), and DIPEA (0.73 mL, 4!2 mmol) in dry DMF (7 mL). The reaction was allowed to stir for 5 hours before it was diluted with CHCli and washed with NaHSO4 solution, 1M NaOH, brine, and dried (Na2SO4), and e)aporated. The residue was purified o)er silica gel using 20% EtOAc / hexanes and concentrated to yield a white solid. StepB To the product of Step A (87 mg, 0.209 mmol) was added NHaOHCl (87 mg, 1.25 mmol), DIPEA (0.29 mL, 1 .67 mmol) and dry DMSO (1 mL). The resulting solution was heated at 80°C for 8 hrs. The sol)ent was e)aporated and the residue was purified on HPLC using CHsCN / water 1% TFA as eluent to pro)ide the title compound as an oil. !H NMR (300 MHz, CD3OD) 8 ppm 7.49-7.54 (m, 1H), 7.26-7.30 (m, 2H), 6.92-6.96 (m, 2H), 3.97-4.03 (m, 1H), 2.10-2.15 (m, 2H), 1.98-2.08 (m, 5H), 1.92-1.94 (m, 2H), 1.76-1.83 (m, 2H), 1.57-1.64 (m, 2H), 1.53 (s, 6H). MS (ESI+) m/z406.1(MfH)+. Examle 8 methylpropanoyl]ar"i™"}artatnantane-l-carboxamide The title compound was prepared according to the procedure outlined in Example 24, substituting 4-aminomethyl-benzenesulfonamide hydrochloride for 4-aminomethyl-benzoic cid methyl ester hydrochloride. 'H NMR (500 MHz, DMSO-de) 8 ppm 8.10-8.15 (m, 1H), 7.75 (d, J= 8.08 Hz, 2H), 7.37 (d, J= 8.03 Hz, 2H), 7.31-7.35 (m.-SH), 729-7.29 (bs, 2H), 6.91-6.93 (m, 2H), 4.30 (d, j= 5.87 Hz, 2H), 3.84-3.88 (m, 1H), 1.93-1.95 (m, 2H), 1.82-1.92 (m, 5H), 1.76-1.78 (m, 2H), 1.67-1.71 (m, 2H), 1.46 (s, 6H), 1.37-1.41 (m, 2H). MS OBSH-)m/z560(M+H)+. Examle 39 To a solution of the product of Example 24 (26 rag, 0.05 mmol) in DMF (1 mL) were added DMA (7 mg, 0.055 mmol), EDCI (12 mg, 0.06 mmol) and methylsulfonamide (7 mg, 0.075 mmol). The reaction mixture was stirred at room temperature for 72 hours, concentrated in acua, and the residue was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (25mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous TFA o)er 8min (lOmin run time) at a flow rate of 40mL/min. to pro)ide the title compound. 'H NMR (400 MHz, DMSO-dfi) 8 ppm 12.01-12.05 (bs, 1H), 8.11 (W= 6.06 Hz, 1H), 7.87 (d, J= 8.19 Hz, 2H), 7.30-7.37 (m, 5H), 6.91-6.93 (m, 2H), 4.31 (d, /» 5.89 Hz, 2H), 3.83-3.87 (m, 1H), 3.36 (s, 3H), 1.82-1.96 (m, 7H), 1.77-1.79 (m, 2H), 1.67-1.72 (m, 2H), 1.47 (s, 6H), 1.37-1.42 (m, 2H). MS (ESI+) m/z 602 (M+Hf. Example 40 jg-4-f |2-rf4-Chlorophenyltfaio1-2-mcthylpropanoyl) amino')adainantinie-l -carboylic acid Example 40A Example 40A was prepared according to the procedure outlined in Example 25 A, substituting 4-chloro-benzenethiol for 2,3-dimethylphenoL Example 40B The title compound was prepared according to the procedure outlined in Example 25B, substituting the product of Example 40A for the product of Example 25A. !H NMR (400 MHz, DMSO-de) 6 ppm 7.42-7.45 (m, 2H), 7.36-7.39 (m, 2H), 7.11-7.21 (m, IH), 3.72-3.78 (m, IH), 1.91-1.94 (m, 2H), 1.79-1.92 (m, 6H), 1.75-1.80 (m, 3H), 1.44 (s, 8H). MS (ESI+)m/z408(M+H)+. Example 41 E-4-( 12-f (4-Methoyphen)nthio1-2-me1hylpropano)n aminofedaTnantane-l -carboy amide amide Example 41A -4-(2-Bromo-2-mefe\d-propionylamuio)aaTpa'nta'e-i-carboylic acid A solution of the product of Example IB (0.78 g, 2.48 mmol) in 99% formic acid (2.5 mL) was added dropwise with )igorous gas e)olution o)er 10 minutes to a rapidly stirred 30% oleum solution (7.5 mL) heated to 60°C (W. J. le Noble, S. Sri)asta)a, C. K. Cheung, J. Org. Chem. 48:1099-1101,1983). Upon completion of addition, more 99% formic acid (2.5 mL) was slowly added o)er the next 10 minutes. The mixture was stirred for another 60 minutes at 60°C and then slowly poured into )igorously stirred iced water (30.0 mL) cooled to 0°C. The mixture was allowed to slowly warm to 23°C, filtered and washed with water to neutral pH (100 mL). The precipitate was dried in a )acuum o)en o)ernight to pro)ide the title compound. Example 41B -4-(2-Brcmio-2-methyl-propionylarmno)adarnantane-l-carboylic acid amide A solution of the product of Example 41A (250 mg, 0.670 mmol) in DCM (30 mL) was treated with HOBt (109 mg, 0.80 mmol) and EDCI (154 mg, 0.80 mmol) and stirred at room temperature for 3 hour. Excess of aqueous (30%) ammonia (20 mL) was added and the reaction was stirred for additional 20 hours. The layers were separated and the aqueous layer extracted twice more with methylene chloride (2x40 mL). The combined organic extracts were washed with water (3x20 mL) and brine (20mL); dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to pro)ide the crude title compound that was purified by normal phase column chromatography (silica gel, 5% methanol in DCM) to afford the title compound. MS (ESI+) m/z 343 (M+H)"1". Eyample41C B-4-[2-(4-Methoy-phecylsuIfan)I)2-metfayl-propiQn)1aTnmo]-adamantane- 1 -carboyKc acid amide A solution of 4-methoxy-benzenethiol (44 mg, 0.3 1 mmol) and sodium hydride (60%, 15.0 mg, 0.37 mmol) in toluene (4 mL) was stirred at room temperature for 1 hour. The product of Example 41B (106.0 mg, 0.31 mmol) was added to the solution and the resulting mixture was stirred at 100°C for 24 hours. The reaction mixture was cooled and filtered. The filtrate was concentrated under reduced pressure to pro)ide crude product that was purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (25mm X 1 00mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous TFA o)er 8min (lOmin run time) at a flow rate of 40rnL/min. to afford the title compound. *H NMR (500 MHz, DMSO-de) 5 ppm 7.33-7.35 (m, 2H), 7.11 (d, .7=7.18 Hz, 1H), 6.99-7.01 (s, 1H), 6.93-6.95 (m, 2H), 6.72-6.74 (s, 1H), 3.75-3.79 (m, 1H), 3.77 (s, 3H), 1.79-1.95 (m, 9H), 1.75-1.77 (m, 2H), 1.44-1.48 (m, 2H), 1.39 (s, 6H). MS (ESI+) m/z 403 (M+H)+. Example 42 -me&ylroan A solution of the product of Example 41 C (53 mg, 0.087 mmol) in methanol (5 mL) was treated with OXONB (80 mg, 0.130 mmol) and stirred at room temperature for 7 hours. The reaction mixture was filtered. The filtrate was concentrated under reduced pressure to pro)ide crude title compound that was subsequently purified by re)erse phase preparati)e HPLC on YMC Guardpak column using a gradient of 0% to 70% acetonitrile:0.1% aqueous TFA o)er 8mm (lOmin run time) at a flow rate of 40mL/min. to afford the title compound. JH NMR (400 MHz, DMSO-de) S ppm 7.49-7.52 (m, 2H), 7.32 (d, J - 6.93 Hz, 1H), 7.09-7.12 (m, 2H), 6.96-6.99 (s, 1H), 6.68-6.71 (s, 1H), 3.82 (s, 3H), 3.75-3.81 (m, 1H), 1.89-1.92 (m, 3H), 1.73-1.86 (m, 8H), 1.42-1.51 (m, 2H), 1.34 (s, 3H), 1.25 (s, 3H). MS (ESI+) m/z 419 (M+H)+. Example 43 A solution of the product of Example 41 C (53 mg, 0.087 mmol) in methanol (5 mL) was treated witii OXONE (80 mg, 0.130 mmol) and stirred at room temperature for 24 hour. The reaction mixture was filtered. The filtrate was concentrated under reduced pressure to pro)ide crude title compound that was subsequently purified by re)erse phase preparati)e HPLC on a Waters Symmetry C8 column (25mm X 100mm, 7um particle size) using a gradient of 10% to 100% acetonitrile:0.1% aqueous TFA o)er 8min (lOmin run time) at a flow rate of 40rnL/min. to afford the title compound. !H NMR (400 MHz, DMSO-dg) 8 ppm 7.72 (d, J= 8.65 Hz, 2H), 7.17-720 (m, 3H), 6.97-6.99 (s, IH), 6.70-6.72 (s, IH), 3.88 (s, 3H), 3.77-3.83 (m, IH), 1.94-1.97 (m, 3H), 1.82-1.89 (m, 6H), 1.76-1.78 (m, 2H), 1.49-1.54 (m, 2H), 1.45 (s, 6H). MS (ESI+) m/z 435 (M+H)*. Example 44 -4-fl2-|•4-COl2-fpm)din-l-ylsnlfonylphenoy-2- 2-H)droy-5-chlorobenzene sulfonyl chloride 4-Chlorophenol (4 g, 31.25 mmol) was added in portions to chlorosulfonic acid (10.3 mL, 156 mmol) while cooling in an ice bath. The resulting solution was stirred at 25°C for 20hrs. This was then added drop- wise to ice and water resulting in an emulsion. This was extracted with CHClj, dried (Na2SO4) and concentrated in )acuo. Heptane was added and e)aporated and replaced with cyclohexane. The resulting mixture was filtered and concentrated to gi)e the title compound as an oil (2.16 g). Example 44B 2-Hydroy-5-chlorobenzene sulfonyl pyrrolidine To a solution of the product of Example 44A (2.16 g, 9.51 mmol) in CHd3 (8 mL) was added, with ice cooling, pyrrolidine (4.05 g, 57.04 mmol). The mixture was stirred at 25°C for 2 hrs, then concentrated in )acuo. The residue was dissol)ed in toluene, washed with HC1 and water, dried (NaaSQO and concentrated. The resulting oil was crystallized from hexane and chromatographed (CH2Cl2) to yield the title compound (1.92 g), m.p.101-102°C. 2-[4-CMoro-2-fpyrroHdine-l-sulfonyl'-phenoy1-2-methyl-propionicacid The product of Example 44B (1.0 g, 3.82 mmol) and l,l,l-trichloro-2-methyl-2-propanol hydrate (1 .832 g, 10.32 mmol) were dissol)ed in acetone (8.5 mL). Powdered NaOH (0.47 g. 1 1.75 mmol) was added with cooling. The resulting mixture was stirred for 1 .5 hr at 25°C. A second batch of powdered NaOH (0.47 g) was added and stirred for another 1.5 hrs. The last batch of powdered NaOH (0.47 g) was then added along with acetone (2.5 mL). The resulting mixture was stirred for 15 hrs at 25°C. Acetone was added and the solution was filtered. The resulting solution was concentrated. Water (3 mL) was added and concentrated HC1 was added to acidify the mixture, which was extracted with toluene, dried and concentrated. The residue was chromatographed on silica gel. Eluting with CHiCfe ga)e 380 mg reco)ered starting material. Changing to 5% MeOH in ethyl acetate ga)e the title compound (357 mg, 27% yield). Example 44D -4-(-f2-[4-Chloro-2-(p)rrolidin-l-ylsulfonylphsnoy1-2- The product of Example 7B (75 mg, 0.305 mmol), the product of Example 44C (116 mg, 0.335 mmol), and TBTU (108 mg, 0.336 mmol) were suspended in dimethylacetamide ' (0.5 mL). Diisopropylethylamine (135 mg, 1.05 mmol) was added and the resulting solution stirred at 25°C for 15 hrs. Toluene was added, and concentrated. More toluene was added, and washed with dil HaPO HiO, and then KHCX3. The organic phase was dried (Na2SO4), and filtered. The sol)ents were remo)ed in )acuo and the residue crystallized from ether and heptane to yield the title compound (133 mg), m.p. 152-154°C. Example 44B BI2-[4-CMoro-2-(p)n:oUdine-l-sulfonyl)phenoxy]-2-mettyl-propionylamino)- adamantane-1-cafboylic acid A solution of the product of Example 44D (125 mg, 0.231 mmol) in MeOH (0.75 mL) was treated with NaOH (100 mg) in water (0.5 mL). The mixture was heated until all was soluble and stirred at 60°C for 1 hour. The sol)ent was remo)ed in )acuo and the residue acidified with HC1, extracted with CHCls, dried (Na2SO4), filtered, and concentrated. The residue was crystallized from ether to yield the title compound (92 mg, 77% yield), m.p. 226- 228°C. Example 44F -4-fl2-[4-Chloro-2-fpyrrolidin-l-ylsulfonylphenoy]-2- methylpropanoyn amino)adamantane-1 -carboxamide The product of Example 44E (76 mg, 0.145 mmol), TBTU (52 mg, 0.162 mmol), and diisopropylethylamine (40 mg, 0.31 mmol) were dissol)ed in N,N-dimethylacetamide (0.3 mL). After 25 min. at 25°C, a solution of 10% ammonia in THF was added. A solid fonned and the mixture was stirred for3 hrs at 25°C. Toluene was added and the mixture concentrated in )acuo. The residue was dissol)ed in CHCls and washed with dil HsPO H2O, and KHCO3; dried (Na2SCU), filtered and concentrated in )acuo. The residue was crystallized from ether to yield the title compound (64 mg, m.p. 249-252°C). ]H NMR (400MHz, CDC13) 8 ppm 7.85 (d, J= 2 Hz, 1H), 7.37 (dd, .7= 2,9 Hz, 1H), 7.25 (d, j= 8 Hz, 1H), 7.05 (d, j= 9 Hz, 1H), 5.62 (br s 1H), 5.40 (br s, 1H), 3.96 (d, J= 8 Hz, 1H), 3.38-3.46 (m, 4H), 1.81-2.03, (m, 9H), 1.86-1.94 (m, 4H), 1.76 (s, 6H), 1.63 (d, J= 12 Hz, 2H), 1.44 (d, j= 12 Hz, 2H). MS (ESI+) m/z 524,526 (M+H)+. Example 45 -4-ff2-Memyl-2-[4-(memylsulfonylhenoy]propanoyllanodno)aQniantane-l-caiboxamide Example 4SA Example 45 A was prepared according to the procedure outlined in Example 44C, substituting 4-(methanesulfonyI)-phenoI for the product of Example 44B. Example 45B Example 45B was prepared according to the procedure outlined in Example 44D, substituting the product of Example 45A for the product of Example 44C. Example 45C Example 45C was prepared according to the procedure outlined in Example 44E, substituting me product of Example 45B for the product of Example 44D. Example 45D Ef(2-Meihyl-2-[44methylsiilfonylphenoy1propanoyl)aminoadamantane-l-carboxamide The title compound was prepared according to the procedure outlined in Example 44F, substituting the product of Example 45C for the product of Example 44E. The product had m.p. 217-219 °C. 'H NMR (500 MHz, CDC13) 6 ppm 7.85 (d, J= 8 Hz, 2H), 7.05 (d, J= 8 Hz, 2H), 6.66 (d, J= 7 Hz, 1H), 5.65 (br s, 1H), 5.49 (br s 1H), 4.06 (d, J= 7 Hz, 1H), 3.05 (s, 3H), 1.86-2.10 (m, 9H), 1.62 (s, 6H), 1.52 (s, 4H). MS (ESI+) m/z 435 (M+H)+. Example 46 -4-((2-Methyl-2-[2-fmemylsulfonyl)phenoy]propanoynaDMnoadamantane-l-carboxamide Example 46A 2-Mefliyl-2-f2-methylsulfanyl-phenoy)propionic acid, etfayl ester 2-Methylsulfanyl-phenol (2.00 g, 14.29 mmol), 2-bromo-2-methyl-propionic acid, ethyl ester (28 g, 142.8 mmol) and powdered KaCOs (4.93 g, 35.7 mmol) were mixed (no sol)ent) and stirred at 105°C for 8 hrs. After cooling, water and CHCU were added. The CHClj was separated, dried (MgSO,*) and concentrated. Xylene was added and concentrated in )acua (4 times) to remo)e the bromo ester. The resulting oil was chromatographed on silica, eluting with CH2Cl2 to obtain the title compound (2.30 g, 63% yield). Example 46B 2-Metfayl-2-(2-methanesulfonyl-phenoxy)propionic acid, ethyl ester To the product of Example 46A (1.00 g, 3.93 mmol) in CH2Cl2 (15 mL), was added, in portions, 3-chloroperoxybenzoic acid (3.00 g of 70%, 12.16 mmol) while stirring and cooling in a water bath. The mixture was stirred at 25°C for 20 hrs. Chloroform was added and the mixture was washed with KHCOs, Na2S2C3, and again with KHCOs. The solution was dried (Na2SO4), filtered and concentrated. Heptane was added and concentrated to obtain an oil that solidified (1.22 g, theory = 1.142 g). Example 46C 2-Methyl-2-f2-meflianesulfonyl-phenoy)-propionicacid The product of Example 46B (1.22 g) was dissol)ed in MeOH (8 mL) and treated with 50% NaOH (1.75 g, 21.27 mmol) and water (6 mL). The mixture was heated until all was soluble and stirred at 25°C for 1 hr. The sol)ents were remo)ed in )acua, water (6 mL) was added and the solution acidified with HCI. The mixture was extracted with CHClj, dried (Na2SQO, filtered and concentrated in )acua. The residue was crystallized from ether and heptane (1:4) to yield the title compound (0.953 g), m.p. 114-1 16°C. Example 46D Example 46D was prepared according to the procedure outlined in Example 44D substituting the product of Example 46C for the product of Example 44C. Example 46E was prepared according to the procedures outlined in Example 44E substituting the product of Example 46D for the product of Example 44D. The title compound was prepared according to the procedure outlined in Example 44F, substituting the product of Example 46E for the product of Example 44E. *H NMR (500 MHz, CDC13) 8 ppm 7.99 (dd, J= 7, 2 Hz, 1H), 7.53 (m, 1H), 7.10-7.16 (m, 2H), 5.60 (br s 1H), 5.40 (br s, 1H), 3.95 (d, J= 8 Hz, 1H), 3.27 (s, 3H), 1.80-1.96 (m, 9H), 1.55 (d, .7=12 Hz, 2H), 1.37 (d, J= 12 Hz, 2H). MS (ESI+) m/z 435 (M+H)+. -4-rf2-f4-Chloro-2-rfdieth)1aminft)Siilfnnyl]Phenoy)-2- Example 47A Example 47A was prepared according to the procedure outlined in Example 44B, substituting diethylamine for pyrrolidine. Example 47B was prepared according to the procedure outlined in Example 44C, substituting the product of Example 47A for the product of Example 44B. Example 47C Example 47C was prepared according to the procedure outlined in Example 44D, substituting the product of Example 47B for the product of Example 44C. Example 47D Example 47D was prepared according to the procedure outlined in Example 44E, substituting the product of Example 47C for the product of Example 44D. Examle 47B The title compound was prepared according to the procedure outlined in Example 44F, substituting the product of Example 47D for the product of Example 44E. The compound had m.p. 159-161°C. *H NMR (400 MHz, CDC13) 8 ppm 7.83 (d, J= 2 Hz, 1H), 7.34 (dd, J - 2, 9 Hz, 1H), 7.05 (d, J= 8 Hz, 1H), 6.98 (d, j= 9 Hz, 1H), 5.58 (br s 1H), 5.38 (br s, 1H), 3.95 (d, J= 8 Hz, 1H), 3.40 (q, j= 7 Hz, 4H), 1.81-1.98, (m, 9H), 1.75 (s, 6H), 1.56 (d, J= 12 Hz, 2H), 1.42 (d, j= 12 Hz, 2H), 1.17 (t, J= 7 Hz, 6H). MS (ESI+) m/z 526, 528 (M+H)+. Example 48 jg-4-( (2-Methyl-2-f 4-fpyrrolidin- 1 -ylsulfonylphenoxy]propanoyll aminoadamantane- 1 - carboxamide Example 48A I -(4-Me1faoxy-benzenesulfonyl)p)rrolirii'ne 4-Methoxy-benzenesulfonyl chloride (3.00 g, 14.52 mmol) was slowly added to a solution of pyrrolidine (5.15 g, 72.6 mmol) in CHC13 (15 mL) with stirring at 0°C. The reaction mixture was allowed to warm up to room temperature and then stirred for 1 hour. After that the reaction mixture was concentrated in )acua. The residue was dissol)ed in toluene and washed with aqueous HsPCU solution, and then aqueous KHCOa solution. The organic phase was dried with NazSC, and filtered. The sol)ents were remo)ed in )acua and the residue crystallized from ether and heptane to pro)ide the title compound (3.21 g, m.p. 88-89°C). Example 48B 1 -(4-Hydroxy-be|[eqesulfon)D-p)rrolidine The product of Example 48A (3.21 g, 13.3 mmol) was dissol)ed in CH2C12 (30 mL), cooled to -78°C and treated with BBr3 (8.31 g, 3.26 mmol). The resulting dark red solution was stirred at 2S°C for 4 mip, then cooled to -78°C. Methanol (100 mL) was added slowly. The solution was concentrated in )acua. Toluene was added to the crude and concentrated again. After adding more toluene, the solution was washed with water and concentrated in )acua. The residue was dissol)ed in ether and extracted with NaOH (1.0 g) in water (8 mL). The aqueous layer was remo)ed and stirred 15 minutes, then acidified with concentrated HQ. This mixture was extracted with toluene, dried (NazSQ*), filtered, concentrated in )acua and the residue crystallized from ether and heptane (2:1) to pro)ide the title compound (1.063 g, m.p. 122-125°C). Example 48C Example 48C was prepared according to the procedure outlined in Example 44C, substituting the product of Example 48B for the product of Example 44B. Example 48D Example 48D was prepared according to the procedure outlined in Example 44D, substituting the product of Example 480 for the product of Example 44C. Example 48E Example 48E was prepared according to the procedure outlined hi Example 44E, substituting fhe product of Example 48D for the product of Example 44D. The title compound was prepared according to the procedure outlined in Example 44F, substituting the product of Example 48E for the product of Example 44E. The compound had m.p. 206-209°C. !H NMR (500 MHz, CDC13) 8 ppm 7.76 (d, J= 8 Hz, 2H), 7.02 (d, j= 8 Hz, 2H), 6.71 (d, J= 8 Hz, IH), 5.65 (br s, IH), 5.54 (br s, IH), 4.067 (d, J- 8 Hz, IH), 3.20-3.26 (m, 4H), 1.86-2.06 (m, 9H), 1.77-1.82 (m, 4H), 1.61 (s, 6H), 1.51 (s, 4H). MS (ESI+) m/z 490 (M+H)+. Example 49A 2-C4-Fluoro-2-chiorophenoy)2-methyl-propionic acid 4-Fluoro-2-chlorophenol (6.00g, 41.1 mmol) was reacted with l,l,l-trichloro-2-methyl-2-propanol hydrate (120 g, 12.70 mmol) as described in Example 44C to pro)ide the title compound (6.075 g, 64% yield, m.p. 63-65°C). Example 49B 2-f2-CMoro-4-fluQrcphenoxy)N-[rj5-h)droy-2-adamantyl]-2-methylpropanamide The product of Example 1A (175 mg, 1.05 mmol), 2-(4-fluoro-2-chlorophenoxy)-2-methyl-propionic acid (232 mg, 1.00 mmol), and TBTU (353 mg, 1.1 mmol) were dissol)ed in N,N-dimethylacetamide. Di-isopropylethylamine (258 mg, 2.0 mmol) was added and the mixture was stirred for 18 hrs at 25°C. After that the reaction mixture was concentrated in )acua. The residue was dissol)ed in toluene and washed with aqueous HsPC solution, and then aqueous KHCOs solution. The organic phase was dried with Na2SO4, and filtered. The sol)ents were remo)ed in )acua and the residue crystallized from ether and heptane to pro)ide the title compound (262 mg, m.p. 177-179°C). !H NMR (500 MHz, CDC13) 5 ppm 7.47 (d, .j= 8 Hz, IH), 7.18 (dd, J= 2,8 Hz, IH), 7.08 (dd, J= 5 Hz, 8 Hz, IH), 6.94 (m, IH), 4.07 (d, J= 8 Hz, IH), 2.12-2.21 (m, 3H), 1.91 (d, J= 11 Hz, 2H), 1.70-1.84 (m, 6H), 1.43-1.65 (m, 3H), 1.53 (s, 6H). MS (ESI+) m/z 382, 384 (M+H)+. Example 50 2-f2-CMorofiuorophenoy)2-methyl-N-rf-S2H-tetraazol-5-yl)2- ExampleSOA Example 50A was prepared according to the procedure outlined in Example 44D, substituting the product of Example 49A for the product of Example 44C. Example SOB Example 50B was prepared according to the procedure outlined in Example 44E, substituting the product of Example 50A for the product of Example 44D. Example 50C Er2-f2-CMorofluorophenoy)2-meth Step A E[2-(2-Qiloro-4-fluoro-phenoxy)-2-memyl-propionylaniino]-adamantane-l-carboxylic acid amide was prepared according to the procedure outlined in Example 44F, substituting the product of Example 50B for the product of Example 44E. StepB The solution of the product of Step A (207 mg, 0.506 mmol) in dioxane (0.5 mL) and pyridine (100 mg) was treated with trifluoroacetic anhydride (167 mg, 0.795 mmol). The mixture was stirred 5 hr at 25°C and concentrated in )acua after adding toluene. More toluene was added and the solution was washed with dilute HaPO water, and aqueous KHCOa solution respecti)ely. After drying with NajSO the solution was filtered, concentrated in )acua and the residue crystallized from ether and heptane to yield the title compound (115 mg, m.p. 159-160°C). Example 50D 242-CMoro-fluorcyhenoy)2-memyl-N-[f542H-tetraazol-S-yl)2- adpmant)ripropanamide A solution of the product of step B of Example 50C (50 mg, 0.128 mmol), trimethyltin chloride (31 mg, 0.153 mmol) and NaN3 (10 mg, 0.153 mmol) in toluene (0.3 mL) was stirred and heated for 64 hrs in a sealed )ial at 120°C. The mixture was cooled and 4N HC1 in dioxane (1 mL) was added. After stirring 90 min at 25°C the solution was concentrated HI )acua. Water and HC1 were added and the mixture was extracted with CHC13, dried with Na2SO4, filtered, concentrated and treated with ether to pro)ide the title compound (33 mg, m.p. 256-257°C). 'H NMR (400 MHz, DMSO-ds) 5 ppm 7.52 (d, J= 8 Hz, 1H), 7.15-7.23 (m, 2H), 3.98 (d, j= 8 Hz 1H), 1.98-2.12 (m, 9H), 1.90 (d, J= 13 Hz, 2H), 1.60 (d, J= 13 Hz, 2H), 1.46 (s, 6H). MS (ESI+) m/z 434, 435 (M+H)+. A solution of the product of Example 49B (150 mg, 0.392 mmol) in CF3COOH (750 mg) was treated with trifhioroacetic anhydride (375 mg, 1.78 mmol) for 5 min. Then, CF3COOH (1.68 g, 14.9 mmol) andNaSCH3 (549 mg, 7.8 mmols) were added to the 7 mL sealed tube. This mixture was heated at 120°C for 20 hrs. After cooling, toluene was added, and the mixture concentrated in )acuo. More toluene was added and this was shaken with K2CO3 solution. The toluene layer was separated, dried (Na2SO4), concentrated and chromatographed in 4%EtOAc in DCM to gi)e the title compound (132 mg, m.p. 100-101°C). 1HNMR(400MHz,CDClJ)8ppm7.50(d,J=8Hz, lH),7.17(dd,J=2,8Hz, 1H), 7.08 (dd, J= 5, 8Hz, 1H), 6.93 (m, 1H), 4.07 (d, J= 8 Hz, 1H), 1.82-2.15 (m, 9H), 2.03 (s, 3H), 1.82 (d, J= 13 Hz, 2H), 1.59 (d, J= 13 Hz, 2H), 1.54 (s, 6H),.MS (ESI+) m/z 412, 414 (M+Hf Example 52 2-(2-C!hlorQfluorophenoxy)2-memyl-N-[fjE)S-('memylsullbnl-2-- A solution of the product of Example 51 (100 mg, 0.235 mmol) in CH2Cl2 (1 ml) was treated with 3-chloroperbenzoic acid (180 mg, 70%, 1.05 mmol). After stirring for 17 hrs at 25°C, CHC13 was added to the reaction mixture and the solution was extracted with KHC03, Na2S2O3, and KHCOs. After drying (Na2SO4), filtered and concentrating, the residue was crystallized from heptane and ether to pro)ide the title compound (89 mg, m.p. 172-173°C). 'H NMR (400MHz, CDC13) 6 ppm 7.55 (d, j= 8 Hz, 1H), 7.18 (dd, J=* 2, 8 Hz, 1H), 7.09 (dd, j= 5, 8 Hz, 1H), 6.95 (m, 1H), 4.09 (d, J= 8 Hz, 1H), 2.76 (s, 3H), 2.07-2.25 (rn, 9H), 1.90 (d, j= 13 Hz, 2H), 1.65 (d, 7= 13 Hz, 2H), 1.54 (s, 6H). MS (ESI+) m/z 444, 446 (M+H)*.A-solution of tbe product of Example 51 (71 rug, 0.172 mmql) in acetic acid (75 mL) was prepared. Sodium perborate (NaB03.H20, 18 mg, 0.18 mmol) was added and the mixture was stirred 16 hr at 25 °C. Toluene was added. The mixture was concentrated and more toluene added. This was washed with KCOs, dried (Na2SO4), filtered, and concentrated in )acua. The residue was crystallized from ether to get the title compound (44 mg, m.p. 134-135°C). 'H NMR (500MHz, CDClj) 8 ppm 7.58 (d, j= 8 Hz, 1H), 7.19 (dd, J = 2, 8 Hz, 1H), 7.10 (dd, J = 5, 8 Hz, 1H), 6.95 (m, 1H), 4.10 (d, J= 8 Hz, 1H), 2.42 (s, 3H), 2.17-2.30 (m, 3H), 2.01 (d, J= 13 Hz, 2H), 1.82-2.05 (m, 6H), 1.55 (d, J - 13 Hz, 2H), 1.54 (s, 6H). MS (ESI+) m/z 428, 430 (M+H)+. Example 54 5-Hydroxy-2-adamantanone (5.00 g, 30.1 mmol) was mixed with 48% hydrobromic .acid (50 mL) and heated at 100°C for 48 hours (H. W. Geluk, J. L. M. A. Schlatmann, Tetrahedron 24: 5369-5377, 1968). Reaction diluted with water and extracted twice with ether. Combined extracts dried (Na2SO4), decanted, and e)aporated under reduced pressure. The residue was purified on normal phase HPLC (silica gel, 5-10% ethyl acetate in hexane) to pro)ide the title compound (4.19 g, 61%). Example 54B l-Bromoadamantan-4-one etfaylene ketal The product of Example 54A (4.19 g, 18.3 mmol), ethylene glycol (2.05 mL, 36.6 mmol), and a catalytic amount of p-toluenesulfonic acid (20 mg) were dissol)ed in benzene [100 mL) and heated at reflux with a Dean-Stark apparatus attached for 16 hours (M. Xie, W. J. le Noble, J. Org. Chem. 54:3836-3839,1989). The reaction was cooled, washed with 2N sodium carbonate, water, and brine. The organic solution was dried (Na2SO4), filtered, and e)aporated under reduced pressure to pro)ide the title compound. Example 54C flN. 2iS-l-Amino-2-indanol--4-toluene sulfonamide (11, 2iSAminoindanol (5.00 g, 33.5 mmol) and ethyl acetate (75 mL) were added to a solution of sodium carbonate (6.89 g, 65.0 mmol) in water (30 mL) mat had been stirring at room temperature for 20 minutes. After stirring this mixture for 20 minutes, a solution of p-toluenesulfonyl chloride (6.20 g, 32.5 mmol) in 1:1 THF/ethyl acetate (12 mL) was added drop-wise using an addition funnel o)er a period of 20 minutes (Z. Han, D. Krishnamurthy, P. Gro)er, Q. K. Fang, C. H. Senanayake, J. Am. Chem. Soc. 124:7880-7881,2002). Reaction stirred 16 hours at room temperature. Stirring was stopped, and the layers separated. The organic phase was washed with water, IN hydrochloric acid, and brine. The organic solution was dried (Na2SC4), filtered, and e)aporated under reduced pressure to pro)ide the title compound. A solution of the product of Example 54C (10.2 g, 33.5 mmol) at-45°C in anhydrous THF (50 mL) was treated slowly, in one portion, with thionyl chloride (3.67 mL, 50.3 mmol). A solution of imidazole (6.84 g, lOlmmol) in anhydrous THF (50 mL) was then added drop-wise to this solution o)er 40 minutes using an addition funnel (Z. Han, D. Krishnamurthy, P. Gro)er, Q. K. Fang, C. H. Senanayake, J. Am. Chem. Soc. 124: 7880-7881,2002).. Reaction stirred two hours at -45°C and was then quenched at -45°C with saturated sodium bicarbonate. The mixture was then diluted with ethyl acetate and warmed to room temperature with stirring. The layers were allowed to separate and the organic phase was washed with water and brine. The organic solution was dried (Na2SC4), filtered, and e)aporated under reduced pressure to pro)ide the title compounds. Example S4B indan-2-yl ester and (RW4-Adamantanone ethylene ketalYl-sulfinic acid-HR, 2S)-l-(4- toluenesulfbnylinT|i'no)J'nfy'n-2-yl ester A 0.76M solution of Rieke Zinc (57 mL, 43.0 mmol) in THF was added at room temperature to a degassed solution under nitrogen containing the product of Example 54B (7.82 g, 28.6 mmol) in anhydrous THF (10 mL). Reaction stirred 16 hours at room temperature. More 0.76M Rieke Zinc (50 mL, 38.0 mmol) in THF was added, and reaction mixture stirred an additional 20 hours. This reaction mixture containing the zinc bromide was added drop-wise using a cannule to a -45°C solution under nitrogen of the product of Example 54D (6.66 g, 19.1 mmol) in anhydrous THF (10 mL). Reaction stirred 16 hours at room temperature. Reaction mixture diluted with ethyl acetate, washed with brine, dried (Na2SC4), filtered, and e)aporated under reduced pressure. The residue was purified on normal phase HPLC (silica gel, 30-40% ethyl acetate in hexane) to pro)ide the title compound. Ryample 54P l-frS)Aminosti1fif|y'|)adTnantfln-4-one ethylene ketal and l-f(TO-Ainmosulfin)nadamantn- 4-one ethylene ketal A three-necked flask under argon equipped with a glass stir bar, a thermometer, a gas inlet, and an ammonia condenser (-78°C) in a -50°C bath was charged with anhydrous liquid ammonia (40 mL). A few crystals of iron nitrate nonahydrate (5 mg) were added to the ammonia, followed by portion-wise addition of lithium wire (650 mg, 93.7 mmol) in a controlled manner keeping the internal temperature at about -45°C. When all the lithium was added and the blue solution became a grey suspension, the mixture was stirred for an additional two hours at -45°C. The mixture was then cooled to -78°C, and a solution of the product of Example 54E (7.00 g, 12.9 mmol) in anhydrous THF (30 mL) was added drop-wise o)er a period of 30 minutes. Reaction mixture stirred 2 hours at —78°C and then quenched with saturated ammonium chloride. Reaction mixture allowed to warm to room temperature, and product extracted with ethyl acetate. Extracts washed with brine, dried (NaaS04), filtered, and e)aporated under reduced pressure. The residue was purified on normal phase HPLC (silica gel, 5% methanol in ethyl acetate) to pro)ide the title compound (1.19 g, 36%). Example S4G l-Aminosulfonyladamantan-4-one ethylene ketal A solution of the product of Example 54F (1.19 g, 4.63 mmol) in anhydrous THF (10 mL) at room temperature was treated with a 2.5 wt % solution of osmium tetroxide (0.35 mL) in 2-propanol and 4-methylmorpholine H-oxide (0.55 g, 4.67 mmol). Reaction stirred at room temperature for 16 hours. Reaction diluted with ethyl acetate, washed with water and brine, dried (NajSO, filtered, and e)aporated under reduced pressure to pro)ide the title compound. Example 54H 1 -Aminosulfbnylaffotn antfln-4-one A solution of the product of Example 54G (1.26 g, 4.63 mmol) in THF (15 mL) at room temperature was treated with IN hydrochloric acid (14 mL). Reaction heated at 60°C for 16 hours. Reaction quenched with saturated sodium bicarbonate, and product extracted with 20% methanol in chloroform (2X) and 40% THF in DCM (2X). Extracts dried (Na2SO4), filtered, and e)aporated under reduced pressure to pro)ide the title compound (0.880 g, 82%). Example 541 N-4.Aminn-aHftinantane-l-sulfonic Q- amide The title compound was prepared according to the procedure outlined in Example 7A substituting the product of Example 54H for 4-oxo-adamantane-l-carboxylic acid. Example54 The product of Example 541 (100 mg, 0.44 mmol), 2-(4-chlorophenoxy)-2-methylpropionic acid (93 mg, 0.44 mmol), and TBTU (209 mg, 0.65 mmol) were mixed in DMF (2 mL) at room temperature for 10 minutes, H-diisopropylethylamine (0.15 mL, 0.87 mmol) was added to this solution, and the reaction stirred 16 hours at room temperature. Reaction was diluted with ethyl acetate, washed with water, saturated sodium bicarbonate, IN phosphoric acid, and brine. Organic phase dried (Na2SO4), filtered, and e)aporated under reduced pressure. The residue was purified by flash chromatography on silica gel (20-30% ethyl acetate in hexane) to pro)ide the title compound. *H NMR (500 MHz, DMSO-de) 5 ppm 7.43 (d, J=6 hz, 1 H) 7.33 (d, J*=8 Hz, 2 H) 6.91 (d, =8 Hz, 2 H) 6.58 (s, 2 H) 3.79 (m, 1 H) 2.04 (bs, 2 H) 2.00-1.80 (m, 7 H) 1.71 (m, 2 H) 1.46 (s, 6 H) 1.35 (m, 2 H). MS (ESI+) m/z427(M+H)+. Example S5A Ethyl l-C4-chlorophenoyk)clobutanecarboxylic acid A mixture of p-chlorophenol (621 mg, 4.83 mmol), ethyl 1- bromocyclobutanecarboxylate (1.0 g, 4.83 mmol) and potassium carbonate (1.33 g, 9.66 mmol) in DMF (14.5 ml) was stirred and heated to about 55-60 °C under a nitrogen atmosphere for about 1 8 hours. The sol)ent was remo)ed under high )acuum, the residue was taken up in diethyl ether (50 ml) and was washed with water and brine (1 5 ml each). The organic layer was dried (MgSO, and filtered. The sol)ent was remo)ed under )acuum and the residue was purified by flash column chromatography on silica gel using hexanes/ethyl acetate (2 : 1) as the mobile phase to pro)ide 320 mg (26 %) of the title compound. MS (DO): m/z 272 Example 55B l-(4-Qilorophenoy)c)clobutanecarboylic acid To the product of Example 55A (320 mg, 1.26 mmol) was added glacial acetic acid (1 0 ml) followed by 5% aqueous hydrochloric acid (2.5 ml) and the mixture was heated to reflux for about 18 hours. The mixture was cooled and was e)aporated to dryness. The residue was taken up in toluene and was e)aporated to dryness two times to pro)ide 250 mg (87%) of the title compound. MS (DO): m/z 244 (M+Nftt)*. ....... A mixture of the product of Example 55B (207 mg, 0.81 mmol), the product of Example 7B (200 mg, 0.81 mmol), O-benzotriazol-l-yl-AT,J);H',Htetramethyluroiuum tetrafluoroborate (523 mg, 1.63 mmol) and J))7)-diisopropylethylamine (0.57 ml, 3.26 mmol) in DMF (1 1 ml) was stirred at ambient temperature under a nitrogen atmosphere for about 18 hours. The sol)ent was e)aporated in high )acuum and the residue was purified by flash column chromatography on silica gel using hexanes/ethyl acetate (2 : 1) as the mobile phase to pro)ide 240 mg (70 %) of the title compound. MS (DCT) m/z 418 (M+H)+. jg-4-f f [l-f4-C3ilorophenoxycyclobutyl]carboY}Tni'flf)aa'nr|antane-l- carboxyh'c acid To a solution of the product of Example 55C (240 mg, 0.57 mmol) in dioxane (8 ml) was added 2N aqueous hydrochloric acid (8 ml) and the mixture was heated to about 60 °C for about 18 hours. The mixture was cooled and concentrated in )acua down to the water phase. The precipitate was filtered off and was dried under high )acuum to pro)ide 200 mg (86 %) of the title compound. MS (DCI) m/z 404 (M+H)+. Example 55E A solution of the product of Example 55D (200 mg, 0.5 mmol), N~(3-oemylanunopropyl)-emylcarbodiimide hydrochloride (380 mg, 2.0 mmol) and 1-hydroxybenzotriazole hydrate (217 mg, 1.61 mmol) in dichloromethane (17 ml) was stirred at ambient temperature under a nitrogen atmosphere for about 1 hour. A 0.5 M solution of ammonia in dioxane (9.9 ml, 4.95 mmol) was added and stirring was continued for about 2 hours. Ammonium hydroxide (8.5 ml) was added to the reaction mixture and stirring was continued for about 2 hours. The mixture was diluted with dichloromethane (55 ml), the layers were separated, the organic layer was dried (MgSCU), filtered, and was e)aporated in )acua. The residue was purified by flash column chromatography on silica gel using dichloromethane/methanol (15 : 1) as the mobile phase to pro)ide 113 mg (57 %) of the title compound. *H NMR (400 MHz, DMSO-d6) 5 ppm 7.33-7.29 (m, 2H), 7.08-7.07 (m, 1H), 6.92 (bs, 1H), 6.74-6.70 (m, 2H), 6.66 (bs, 1H), 3.76-3.74 (m, 1H), 2.68-2.62 (m, 2H), 2.33-2.25 (m, 2H), 1.89-1.64 (m, 11H), 1.37-1.34 (m, 2H), 1.22-1.19 (m, 2H). MS (ESI+) m/z 403 Examle 56 adamantyltoemyl]sulfonyl)ammo\memyl1hsm'c acid Step A To a solution of the product of Example 36B (395 mg, 0.895 mmol) in DCM (8.9 mL) and DMF (1 drop) was added triphosgene (194 mg, 0.653 mmol) and triethylamine (0.125 mT,, 0.895 mmol). The resulting reaction mixture was stirred at room temperature for 1 .5 hours and then one half of the solution was added dropwise to a solution of methyl 4-(aminomethyl)-benzoate hydtochloride (67.6 mg, 0.447 mmol) and triethylamine (0.16 mL, •1.12 mmol) in DCM (1 .0 mL). After stirring at room temperature o)ernight, the reaction was quenched with water and extracted with EtOAc. The organic layer was then rinsed with brine, dried o)er Na2SC4, filtered, and concentrated in )acua. StepB The product of Step A was dissol)ed in a mixture of TED, water, and ethanol and treated with excess NaOH. After stirring at room temperature o)ernight the reaction was concentrated in )acuo. The crude product was purified by re)erse phase preparati)e HPLC using acetonitrile:10mM NEUOAc on YMC Guardpak column to pro)ide the title compound (25 mg, 10%). JH NMR (500 MHz, CDC13) 5 ppm 8.06 (d, J= 8.6 Hz, 2 H), 7.44 (d, j= 8.6 Hz, 2 H), 7.24 (d, j== 8.6 Hz, 2 H), 6.98 (d, j= 8.2 Hz, 1 H), 6.86 (d, J±8.6 Hz, 2 H), 4.92 (m, 1H), 4.37 (d, j= 5.5 Hz, 2 H), 4.03 (m, 1 H), 2.83 (s, 2H), 1.50-2.17 (m, 11 H), 1.50 (s, 6H). MS (ESI+) m/z 575 (M+H)+. Example 57 2-(4-CMorophenoy)N-rf-S-nH-imazol-2-yl)2-adamantyl]-2-memylpropanamide The product of Example 33B (0.1 g, 0.266 mmol) and glyoxal (0.1 1 g, 40 wt% in water, 0.8 mmol) was dissol)ed in ammonia solution (6 mL, 7 N). The reaction )essel was sealed and stirred at room temperature for 1 day. The yplatiles were e)aporated and the residue was purified by re)erse phase HPLC using CHaCN / 0. 1 % TFA in water to pro)ide the title compound as an oil. !H NMR (300 MHz, CDsOD) 5 ppm 1.48 - 1.59 (s, 6 H) 1.60 -1.73 (m, 2 H) 1.77 - 1.94 (m, 2 H) 2.02 - 2.12 (m, 3 H) 2.12 - 2.27 (m, 6 H) 4.01 - 4.12 (m, 1 H) 6.88 - 7.02 (m, 2 H) 7.21 - 7.35 (m, 2 H) 7.44 - 7.49 (m, 2 H) 7.49 - 7.60 (m, 1 H). MS (ESI-f) m/z 414.1 (M+H)+. Example 58 lic acid Example 5SA, ( 2iiW3-ff ffi-4- f f 2-f4-!3ilorophenoxy)-2-nietfaylpropanpYl]aTiol-l-adaniantyl)acrylic arid ethyl ester To a cold (0°C) solution of triethyl phosphonoacetate (022 ml, 1.1 nunol) in DME (1 .0 mL) was added NaH (60% in oil, 42 mg, 1 . 1 mmol) under Nz flow. The reaction mixture was stirred for 10 minutes and a solution of the product of Example 33B (375 mg, Immol) in DME (0.2 ml) was added slowly at 0°C. It was allowed to warm up to room temperature and stirred for 5 hours. It was quenched with water and extracted with DCM 3 times. The combined organic layer was dried o)er Na2S04, filtered, concentrated under reduced pressure and purified by flash chromatography with 30% ethyl acetate / 70% hexane to pro)ide the title compound, 350 mg (79%). *H NMR (300 MHz, CDC13) 8 ppm 7.20 -7.26 (m, 2 H), 6.94 - 7.03 (m, 1 H), 6.84 - 6.91 (m, 2 H), 6.80 (d, 1 H), 5.69 (d, 1 H), 4.19 (q, 2 H), 3.98 - 4.08 (m, 1 H), 1.91 - 2.08 (m, 3 H), 1.46 - 1.83 (m, 16 H), 1.29 (t, 3 H). %). MS (ESI+)m/z446(M+H)f. Example 58B f23-ffJ5fr2-f4-CMoiophenoy)2-met To a solution of the product of Example 58A (45 mg, 0.1 mmol) in THF / water (0.1 ml / 0.05 ml) was added LiOHJHfeO (26 mg, 0.6 mmol). It was stirred at room temperature o)ernight It was acidified with IN HC1 and extracted with DCM 3 times. The combined organic layer was dried o)er NajSO filtered, concentrated under reduced pressure and purified by flash chromatography with 30% ethyl acetate / 70% hexane to pro)ide the title compound 35 mg (83%). !H NMR (400 MHz, CDC13) 6 ppm 7.20 - 7.28 (m, 2 H), 6.96 -7.04 (m, 1 H), 6.82 - 6.95 (m, 3 H), 5.70 (d, 1 H), 4.00 - 4.09 (m, 1 H), 1.93 - 2.08 (m, 3 H), 1.47 - 1.85 (m, 16 H). MS (ESI+) m/z 418 (M+H)+. Example 59 f_4-|'(2-Methyl-2-l[5-flH-p)razol-l-yl\p)ridin-2-yl]oy)propgao'yl')ai carboxamide Cul (10.5 mg, 0.055 mmol), N,N,-dimethylglycine (11.3 mg, 0.109 mmol), K2CCb (76 mg, 0.549 mmol), pyrazole (22 mg, 0.329 mmol), and the product of step C of Example 30B (80 mg, 0.183 mmol) was dissol)ed in DMSO (1 mL) and the resulting mixture was heated in Personal Chemistry's Emry Optimizer microwa)e instrument at 160°C for 20 minutes. The mixture was diluted with EtO Ac and filtered through a pad of silica and after e)aporation the residue was purified by re)erse phase HPLC using CH3CN / 0.1% TFA in water to gi)e me title compound. 1HNMR(300MHz,CD3OD)8ppml.40- 1.64(m,4H) 1.66 - 1.76 (m, 7 H) 1.77 - 1.87 (m, 3 H) 1.90 - 2.04 (m, 7 H) 3.93 (s, 1 H) 6.53 (dd, J= 2.54, 1.86 Hz, 1 H) 7.01 (d, J« 8.82 Hz, 1 H) 7.72 (d, j= 2.03 Hz, 1 H) 8'.07 (dd, J = 8.99, 2.88 Hz, 1 H) 8.15 (d, J= 3.05 Hz, 1 H) 8.45 (d, J= 2.71 Hz, 1 H) 8.45 (d, j= 2.71 Hz, 1 H). MS (ESI+) m/z 424.2 (M+H)+. Example 60 24-CMorophenoxy)N-[(jES-isoxazol-5-yl-2-adamantyl]-2-methylpropanamide Ryamle 60A Step A Acetylenemagnesium chloride (8.22 mL, 0.5 M in THF, 4.1 1 mmol) was added dropwise to a stirred and cooled (-78°C) solution of the product of Example 33B (0.514 g, 1.37 mmol) in dry THF. The resulting solution was warmed gradually to room temperature before it was quenched with saturated NHLjCl solution. The mixture was partitioned with EtjO and water. The organic phase was washed with brine, dried (MgSCU), filtered, and e)aporated to gi)e crude alcohol as an oil. StepB Dess-Matinperiodinane(l & 2.43 mmol) was added in one portion to asolutionof the product of Step A (0.65 g, 1 .62 mmol) in dry CH2Cl2. The resulting solution was stirred for 3 hours at room temperature before it was quenched with saturated NaHCOs solution and NajSaOs solution. The mixture was stirred for 1 hour before the phases were separated. The organic phase was dried (NaaSOA), filtered, and the sol)ent was e)aporated. The residue was purified o)er silica gel using 30% EtOAc in haxanes to pro)ide the title compound as a yellow solid. Example 60S 2-(4-C!bJorophenoxy)N-[()5-isoxazol-5-yl-2-adarnantyl]-2-methylpropapamide NH2OHJHC1 (0.23 g, 2.75 mmol) and KjCCb (0.38 g, 2.75 mmol) was added to a solution of the product of Step B of Example 60A (0.1 1 g, 0.275 mmol) in isopropanol. The. reaction was heated (80°C) for 3 hours. The reaction mixture was diluted with EtOAc and filtered through a pad of Celite and after e)aporation the residue was purified by re)erse phase HPLC using CH3CN / 0.1% TFA in water to pro)ide the title compound. *H NMR (300 MHz, CDsOD) 6 ppm 1.53 (s, 6 H) 1.65 (d, 2 H) 1.91 - 2.04 (m, 4 H) 2.11 (s, 6 H) 4.06 (d, j= 7.46 Hz, 1 H) 6.12 (d, J= 2.03 Hz, 1 H) 6.96 (d, j= 8.82 Hz, 2 H) 7.29 (d, J= 9.16 Hz, 2 H) 7.48 (d, J= 6.78 Hz, 1 H) 8.25 (d, J= 2.03 Hz, 1 H). MS (ESI+) m/z 415.1 (M+H)+. Example 61 24-Chlorohenoy)2-me1fal-N-(fE)S-(2-morholin-4-ylethoxtaiethl-2~ A solution of the product of Example 33 A (61 mg, 0.16 mmol) and 4-(2-Chloro-ethyl)-morpholine hydrochloride (36 mg, 0.19 mmol) in DMF (4 mL) was treated with sodium hydride (60%, 20.0 mg, 0.5 mmol) and was stirred at 100°C for 24 hours. Then the reaction mixture was cooled and filtered. The filtrate was concentrated under reduced pressure to pro)ide crude title compound that was purified by re)erse phase preparati)e HPLC using acetonitrile:10mM NKUOAc on YMC Guardpak column to afford the title compound. JH NMR (500 MHz, CD3OD) 5 ppm 7.41 (s, 1 H) 7.26 - 7.30 (m, 2 H) 6.93 -6.96 (m, 2 H) 3.92 (s, 1 H) 3.66 - 3.72 (m, 4 H) 3.56 (t, j= 5.49 Hz, 2 H) 3.03 (s, 2 H) 2.59 (t, j= 5.49 Hz, 2 H) 2.52 - 2.57 (m, 4 H) 1.96 (d, J = 2.14 Hz, 2 H) 1.86 (s, 1 H) 1.72 (s, 1 H) 1.69 (s, 1 H) 1.67 (s, 4 H) 1.57 (d, J= 3.36 Hz, 2 H) 1.53 (s, 2 H) 1.51 (s, 6 H). MS (BSI+) m/z491(M+H)+. Example 62 N-[f-5Aininosiilfonyl)2-adaniaatyl1-2-f2-cMon)phenoy)2-metfadpropanarnide Example 62A 2-(2-ChloropheDoy)2-methylpropionic acid The title compound was prepared according to the procedure outlined in Example 44C substituting 2-chlorophenol for the product of Example 44B. Examle 62B The title compound was prepared according to the procedure outlined in Example 54J substituting tile product of Example 62A for 2-(4-chlorophenoxy)-2-methylpropionic acid. JH NMR (400 MHz, CDC13) 5 ppm 7.61 (d, =8 Hz, 1 H), 7.42 (dd, .E=8 & 2 Hz, 1 H), 7.21 (m, 1 H), 7.13 (dd, .E=8 & 2 Hz, 1 H), 7.05 (m, 1 H), 4.32 (s, 2 H), 4.09 (m, 1 H), 2.30-2.10 (m, 8 H), 1.90 (m, 2 H), 1.60 (m, 3 H), 1.46 (s, 6 H). MS (ESI+) m/z 427 (M+H)+. Example 63 Example 63 A 2-Methyl-2-f 2-methylphenoxy)propionic acid The title compound was prepared according to the procedure outlined in Example 44C, substituting 2-methylphenol for the product of Example 44B. Example 63B The title compound was prepared according to the procedure outlined in Example 54J substituting the product of Example 63A for 2-(4-chlorophenoxy)-2-memylpropionic acid. 'H NMR (400 MHz, CDC13) 8 ppm 7.19 (dd, j=8 & 2 Hz, 1 H), 7.14 (d, 8 Hz, 1 H), 7.09 (m, 1 H), 6.96 (m, 1 H), 6.86 (dd, J=B & 2 Hz, 1 H), 4.33 (s, 2 H), 4.09 (m, 1 H), 2.28 (s, 3 H), 2.30-2.05 (m, 8 H), 1.71 (m, 2 H), 1.59 (m, 3 H), 1.52 (s, 6 H). MS (ESI+) m/z 407 Example 64 Example 64A 2-Metfayl-2-f 4-merthylphenoypropionic acid The title compound was prepared according to the procedure outlined in Example 44C, substituting 4-methylphenol for the product of Example 44B. Examle 64B The title compound was prepared according to the procedure outlined in Example 54 J substituting the product of Example 64A for 2-(4-chlorophenoxy)-2-methylpropionic acid. 'H NMR (400 MHz, CDC13) 8 ppm 7.14 (d, =8 Hz, 2 H), 7.08 (d, J=Z Hz, 2 H), 6.82 (d, 8 Hz, 1 H), 4.46 (s, 2 H), 4.06 (m, 1 H), 2.31 (s, 3 H), 2.30-2.00 (m, 8 H), 1.72 (m, 2 H), 1.59 (m, 3 H), 1.49 (s, 6 H). MS (ESI+) m/z 407 (M+H)+. Example 65 N-[f-5-fAminosulfonyl)2-adamantyl]-2-methyl2-[2-rtrifluorometh)nphenoy)propanamide Example 65A 2-Methyl-2-(2-trifluorometfaylphenoy')propionicacid The title compound was prepared according to the procedure outimed irriJxample 44C, substituting 2-trifluoromethylphenol for the product of Example 44B. Example 6SB N-fj-5-(Aminosulfonyl)2-adamantl-2-methl-2-2 The title compound was prepared according to the procedure outlined in Example 54 J substituting the product of Example 65 A for 2-(4-chlorophenoxy)-2-methylpropionic acid. 1H NMR (400 MHz, CDC13) 5 ppm 7.61 (dd, J"=8 & 2 Hz, 1 H), 7.45 (m, 1 H), 7.1 1 (m, 2 H), 7,01 (d, 8 Hz, 1 H), 4.42 (s, 2 H), 4.06 (m, 1 H), 2.30-2.05 (m, 8 H), 1.70 (m, 3 H), 1.64 (s, 6 H), 1 .55 (m, 2 H). MS (ESI+) m/z 461 (M+H)*. Example 66 N-r)-5-fAniinosulfonyl)2-adamaptyl-2-meflil-2-r2- Example 66A 2-Methyl-2-(2-trifluoromethoypheDoytpropioDic acid The title compound was prepared according to the procedure outlined in Example 44C, substituting 2-trifluoromethoxylphenol for the product of Example 44B. Examle The title compound was prepared according to the procedure outlined in Example 541 substituting the product of Example 66 A for 2-(4-chlorophenoxy)-2-methylpropionic acid. 'H NMR (400 MHz, CDC13) 6 ppm 7.31 (dd, 8 & 2 Hz, 1 H), 7.22 (m, 1 H), 7.18 (d, 8 Hz, 1 H), 7.08 (m, 2 H), 4.39 (s, 2 H), 4.05 (m, 1 H), 2.30-2.05 (m, 8 H), 1.75 (m, 2 H), 1.59 (m, 3 H), 1 .55 (s, 6 H). MS (ESI-f) m/z 427 (M+H)+. Example 67 N-fr/rwS-fATninosulfon)n-2-adamantyl1-2-f2-chloro-4-fluorophenoy)2- methylpropanamide The title compound was prepared according to the procedure outlined in Example 54J substituting the product of Example 49 A for 2-(4-cMorophenoxy)-2-memylpropionic acid. *H NMR (400 MHz, CDC13) S ppm 7.54 (d, =8 Hz, 1 H), 7.17 (m, 1 H), 7.08 (m, 1 H), 6.93 (m, 1 H), 4.26 (s, 2 H), 4.08 (m, 1 H), 2.35-2.05 (m, 8 H), 1.87 (m, 2 H), 1 .60 (m, 3 H), 1.54 (s, 6 H). MS (ESI-f) m/z 445 (M+H)+. Biological Data: Measurement of Inhibition Constants; The ability of test compounds to inhibit human llp-HSD-1 enzymatic acti)ity in )itro was e)aluated in a Scintillation Proximity Assay (SPA). Tritiated-cortisone substrate, NADPH cofactor and titrated compound were incubated with truncated human 1 lp-HSD-1 enzyme (24-287AA) at room temperature to allow the con)ersion to cortisol to occur. The reaction was stopped by adding a non-specific 11 p)HSD inhibitor, l'8p-glycyrrhetinic acid. The tritiated cortisol was captured by a mixture of an anti-cortisol monoclonal antibody and SPA beads'coated with anti-mouse antibodies. The reaction plate was shaken at room temperature and the radioacti)ity bound to SPA beads was then measured on a p-scintillation counter. The 11-PHSD-1 assay was carried out in 96-well microtiter plates in a total )olume of 220 pi To start the assay, 188 pi of master mix which contained 17.5 nM 3H-cortisone, 157.5 nM cortisone and 181 mM NADPH was added to the wells. In order to dri)e the reaction in the forward direction, 1 mM G-6-P was also added. Solid compound was dissol)ed in DMSO to make a 10 mM stock followed by a subsequent 10-fold dilution with 3% DMSO in Tris/EDTA buffer (pH 7.4). 22 p.1 of titrated compounds was then added in triplicate to the substrate. Reactions were initiated by the addition of 10 pi of O.lmg/ml E.coli lysates o)erexpressing llp-HSD-1 enzyme. After shaking and incubating plates for 30 minutes at room temperature, reactions were stopped by adding 10 pi of 1 mM glycyrrhetinic acid. The product, tritiated cortisol, was captured by adding 10 pi of 1 pM monoclonal anti-cortisol antibodies and 100 ul SPA beads coated with anti-mouse antibodies. After shaking for 30 minutes, plates were read on a liquid scintillation counter Topcount. Percent inhibition was calculated based on the background and the maximal signal. Wells that contained substrate without compound or enzyme were used as the background, while the wells that contained substrate and enzyme without any compound were considered as maximal signal. Percent of inhibition of each compound was calculated relati)e to the maximal signal and IC50 cur)es were generated. This assay was applied to 1 lp-HSD-2 as well, whereby tritiated cortisol and NAD* were used as substrate and cofactor, respecti)ely. Compounds of the present in)ention are acti)e hi the 11-pHSD-l assay described abo)e and show selecti)ity for human 11-p-HSD-l o)er human 1 l-p-HSD-2, as indicated in Table 1. Table 1.11-p-HSD-l and ll-p-HSD-2 acti)ity for representati)e compounds. (Table Removed)The data in Table 1 demonstrates that compounds A, B, C, D and E are acti)e in the human HP-HSD-I enzymatic SPA assay described abo)e and that the tested compound showed selecti)ity for 11P-HSD-1 o)er 11 p-HSD-2. The 11 {5-HSD-l inhibitors of this in)ention generallyha)e an inhibition constant lUso of less than 600 nM and preferably less than 50 nM. The compounds preferably are selecti)e, ha)ing an inhibition constant ICso against 11 p-HSD-2 greater than 1000 nM and preferably greater than 10,000 nM. Generally, the ICso ratio for 1 lp-HSD-2 to llp-HSD-1 of a compound is at least 10 or greater and preferably 100 or greater. Metabolic Stability Incubation conditions: Metabolic stability screen: each substrate (10 uM) was incubated with microsomal protein (0.1 - 0.5 mg/ml) in 50mM potassium phosphate buffer (pH 7.4) in 48-Well plate. The enzyme reaction was initiated by the addition of ImM NADPH, then incubated at 37°C in a Forma Scientific incubator (Marietta, OH, USA) with gentle shaking. The reactions were quenched by the addition of 800 ul of ACN/MeOH (1:1, )/)), containing 0.5 pM of internal standard (IS), after 30 min incubation. Samples were then filtered by using Capti)a 96-Well Filtration ()arian, Lake Forest, CA, USA) and analyzed by LC/MS (mass spectrometry). Li)er microsomal incubations were conducted in duplicate. LC/MS analysis: The parent remaining in the incubation mixture was determined by LC/MS. The LC/MS system consisted of an Agilent 1100 series (Agilent Technologies, Waldbronn, Germany) and API 2000 (MDS SCffiX, Ontario, Canada). A Luna C8(2) (50 x 2.0 mm, particle size 3 jam, Phenomenex, Torrance, CA, USA) was used to quantify each compound at ambient temperature. The mobile phase consisted of (A): 10 mM NELAC (pH 3.3) and (B): 100% ACN and was deli)ered at a flow rate of 0.2 ml/min. Elution was achie)ed using a linear gradient of 0-100% B o)er 3 min, then held 100% B for 4 min and returned to 100% A in 1 min. The column was equilibrated for 7 min before the next injection. The peak area ratios (each substrate o)er IS) at each incubation time were expressed as the percentage of the ratios (each substrate o)er IS) of the control samples (0 min incubation). The parent remaining in the incubation mixture was expressed as the percentage of the )alues at 0 min incubation. The percentage turno)er is calculated using the following equation (%tumo)er = 100%turno)er - %parent remaining) and is recorded as the percentage turno)er in the Table 2. Mouse Li)er Microsomal Turno)er (%) Table 2. Microsomal metabolic stability. Compound Human Li)er Microsomal Turno)er (%) (Table Removed) Compounds A, B and E contain a substituted adamantane, whereas the adamantane ring of compound EE is unsubstituted. The microsomal, metabolic, stability data in Table 2 demonstrates that substituted adamantane compounds of the present in)ention may exhibit an increase in metabolic stability compared to unsubstituted adamantane compounds which may lead to longer in )i)o half li)es and pharmacokmetic ad)antages o)er unsubstituted Glucocorticoids are steroid hormones that play an important role hi regulating multiple physiological processes in a wide range of tissues and organs. For example, glucocorticoids are potent regulators of glucose and lipid metabolism. Excess glucocorticoid action may lead to insulin resistance, type 2 diabetes, dyslipidemia, )isceral obesity and hypertension. Cortisol is the major acti)e and cortisone is the major inacti)e form of glucocorticoids in humans, while corticosterone and dehydrocorticosterone are the major acti)e and inacti)e forms in rodents. Pre)iously, the main determinants of glucocorticoid action were thought to be the circulating hormone concentration and the density of glucocorticoid receptors hi the target tissues. In the last decade, it was disco)ered that tissue glucocorticoid le)els may also be controlled by 1 1 p-hydroxysteroid dehydrogenases enzymes (1 1 B-HSDs). There are two 1 1 P-HSD isozymes which ha)e different substrate affinities and cofactors. The 1 lp-hydroxysteroid dehydrogenases type 1 enzyme (1 lp-HSD-1) is a low affinity enzyme with Km for cortisone hi the micromolar range that prefers NADPH/NADP* (nicotinamide adenine dinucleotide) as cofactors. 1 1 P-HSD- 1 is widely expressed and particularly high expression le)els are found hi li)er, brain, lung, adipose tissue and )ascular smooth muscle cells. In )itro studies indicate mat 1 1 P-HSD- 1 is capable of acting both as a reductase and a dehydrogenase. Howe)er, many studies ha)e shown that it is predominantly a reductase in )i)o and hi intact cells. It con)erts inacti)e 1 1-ketoglucocorticoids (i.e., cortisone or dehydrocorticosterone) to acti)e 11-hydroxyglucocorticoids (i.e., cortisol or corticosterone) and therefore amplifies the glucocorticoid action in a tissue-specific manner. With only 20% homology to llp-HSD-l,the llp-hydroxysteroiddehydrogenases type 2 enzyme (11P-HSD-2) is a NAD+-dependent, high affinity dehydrogenase with a Km for cortisol in the nanomolar range. 11 P-HSD-2 is found primarily in mineralocorticoid target tissues, such as kidney, colon and placenta. Glucocorticoid action is mediated by the binding of glucocorticoids to receptors, such as mineralocorticoid receptors and glucocorticoid receptors. Through binding to its receptor, the main mineralocorticoid aldosterone controls the water and salts balance in the body. Howe)er, the mineralocorticoid receptors ha)e a high affinity for both cortisol and aldosterone. 11 P-HSD-2 con)erts cortisol to inacti)e cortisone, therefore pre)enting the non-selecti)e mineralocorticoid receptors from being exposed to high le)els of cortisol. Mutations in the gene encoding 11 P-HSD-2 cause Apparent Mineralocorticoid Excess Syndrome (AME), which is a congenital syndrome resulting hi h)pokaleamia and se)ere hypertension. AME Patients ha)e ele)ated cortisol le)els in mineralocorticoid target tissues due to reduced 11 P-HSD-2 acti)ity. The AME symptoms may also be induced by administration of 11 P-HSD-2 inhibitor, glycyrrhetinic acid. The acti)ity of 11 P-HSD-2 in placenta is probably important for protecting the fetus from excess exposure to maternal glucocorticoids, which may result in hypertension, glucose intolerance and growth retardation. Due to the potential side effects resulting from 11 P-HSD-2 inhibition, the present in)ention describes selecti)e llp-HSD-1 inhibitors. Glucocorticoid le)els and/or acti)ity may contribute to numerous disorders, including Type K diabetes, obesity, dyslipidemia, insulin resistance and hypertension. Administration of the compounds of the present in)ention decreases the le)el of cortisol and other 1 lp-hydroxysteroids in target tissues, thereby reducing the effects of glucucocrticoid acti)ity in key target tissues. The present in)ention could be used for the treatment, control, amelioration, pre)ention, delaying the onset of or reducing the risk of de)eloping the diseases and conditions that are described herein. Since glucocorticoids are potent regulators of glucose and lipid metabolism, glucocorticoid action may contribute or lead to insulin resistance, type 2 diabetes, dyslipidemia, )isceral obesity and hypertension. For example, cortisol antagonizes the insulin effect in li)er resulting in reduced insulin sensiti)ity and increased gluconeogenesis. Therefore, patients who already ha)e impaired glucose tolerance ha)e a greater probability of de)eloping type 2 diabetes in the presence of abnormally high le)els of cortisol. Pre)ious studies (B. R. Walker et al., J. of Clin. Endocrinology and Met, 80:3155-3159,1995) ha)e demonstrated that administration of non-selecti)e 1 lp-HSD-1 inhibitor, carbenoxolone, impro)es insulin sensiti)ity in humans. Therefore, administration of a therapeutically effecti)e amount of an 1 lp-HSD-1 inhibitor may treat, control, ameliorate, delay, or pre)ent the onset of type 2 diabetes. Administration of glucocorticoids in )i)o has been shown to reduce insulin secretion in rats (B. Billaudel et al., Horm. Metab. Res. 11: 555-560,1979). It has also been reported that con)ersion of dehydrocorticosterone to corticosterone by 1 lp-HSD-1 inhibits insulin secretion from isolated murine pancreatic P cells. (B. Da)ani et al., J. Biol. Chem., 275: 34841-34844,2000), and that incubation of isolated islets with an 1 lp-HSD-1 inhibitor impro)es glucose-stimulated insulin secretion (H Orstater et al., Diabetes Metab. Res. Re).. 21:359-366,2005). Therefore, administration of a therapeutically effecti)e amount of an 11P-HSD-1 inhibitor may treat, control, ameliorate, delay, or pre)ent the onset of type 2 diabetes by impro)ing glucose-stimulated insulin secretion in the pancreas. Abdominal obesity is closely associated with glucose intolerance (C. T. Montaque et al., Diabetes, 49: 883-888,2000), hyperinsulinemia, hypertriglyceridemia and other factors of metabolic syndrome (also known as syndrome X), such as high blood pressure, ele)ated YLDL and reduced HDL. Animal data supporting the role of 11 p-HSD-1 in the pathogenesis of the metabolic syndrome is extensi)e (Masuzaki, et al.. Science. 294:2166-2170,2001; Paterson, J.M., et al.; Proc Natl. Acad. ScL USA. 101:7088-93,2004; Montague and O'Rahilly. Diabetes. 49:883-888,2000). Therefore, administration of a therapeutically effecti)e amount of an 11 P-HSD-1 inhibitor may treat, control, ameliorate, delay, or pre)ent the onset of obesity. Long-term treatment with an 11 p-HSD-1 inhibitor may also be useful in delaying the onset of obesity, or perhaps pre)enting it entirely if the patients use an 1 ip-HSD-1 inhibitor in combination with controlled diet, exercise, or in combination or sequence with other pharmacological approaches. By reducing insulin resistance and/or maintaining serum glucose at normal concentrations and/or reducing obestity compounds of the present in)ention also ha)e utility in the treatment and pre)ention of conditions that accompany Type 2 diabetes and insulin resistance, including the metabolic syndrome or syndrome X, obesity, reacti)e hypoglycemia, and diabetic dyslipidemia. 11P-HSD-1 is present in multiple tissues, including )ascular smooth muscle, where local glttcocorticoid le)els that are thought to increase insulin resistance, leading to reductions in nitric oxide production, and potentiation of the )asoconstricti)e effects of both catecholamines and angiotensin E (M. Pirpiris et al., Hypertension, 19:567-574,1992, C. Kernel et al., Steroids, 58:580-587,1993, B, R. Walker and B. C. Williams, dan. Sci. 82:597-605,1992; Hodge, G. et al Exp. Physiol 87:1-8,2002. High le)els of cortisol in tissues where the mineralocorticoid receptor is present may lead to hypertension, as obser)ed in Cushing's patients (See, D. N. Orth, N. Engl. J. Med. 332:791-803,1995, M. Boscaro, et al, Lancet, 357:783-791,2001, X. Bertagna, et al, Cushing's Disease. In: Melmed S., Ed. The Pituitary. 2nd ed. Maiden, MA: Blackwell; 592-612,2002). Transgenic mice o)erexpressing 11 p-HSD-1 in li)er and fat are also hypertensi)e, a phenotype belie)ed to result from glucocorticoid acti)ation of the renin angiotensin system (Paterson, J.M. et al, PNAS. 101: 7088-93,2004; Masuzaki, H. et al, J. Clin. In)est 112: 83-90,2003). Therefore, administration of a therapeutically effecti)e dose of an 1 lp-HSD-1 inhibitor may treat, control, ameliorate, delay, or pre)ent the onset of hypertension. Cushing's syndrome is a life-threatening metabolic disorder characterized by sustained and ele)ated glucocorticoid le)els caused by the endogenous and excessi)e production of cortisol from the adrenal glands. Typical Cushingoid characteristics include central obesity, diabetes and/or insulin resistance, moon face, buffalo hump, skin thinning, dyslipidemia, osteoporosis, reduced cogniti)e capacity, dementia, hypertension, sleep depri)ation, and atherosclerosis among others (Principles and Practice of Endocrinology and Metabolism. Edited by Kenneth Becker, Lippincott Williams and Wilkins Pulishers, Philadelphia, 2001; pg 723-8). The same characteristics can also arise from the exogenous administration of high doses of exogenous glucocorticoids, such as prednisone or dexamethasone, as part of an anti-inflammatory treatment regimen. Endogenous Cushings typically e)ol)es ftom pituitary hyperplasia, some other ectopic source of ACTH, or from an adrenal carcinoma or nodular hyperplasia. Administration of a therapeutically effecti)e dose of an 11 P-HSD-1 inhibitor may reduce local glucocorticoid concentrations and therefore treat, control, ameliorate, delay, or pre)ent the onset of Cushing's disease and/or similar symptoms arising from glucocorticoid treatment. 11 P-HSD-1 is expressed in mammalian brain, and published data indicates that ghicocorticoids may cause neuronal degeneration and dysfunction, particularly in the aged (deQuer)sin etal.\ Hum Mol Genet. 13: 47-52,2004; Belanoffef al. J. PsychiatrRes. 35: 127-35,2001). E)idence in rodents and humans suggests that prolonged ele)ation of plasma glucocorticoid le)els impairs cogniti)e function that becomes more profound with aging. (Issa, AM. et al. J. Neurosci. 10:3247-54,1990; Lupien, S J et al. Nat Neurosci. 1: 69-73, 1998; Yau,JX.W.etal/¥oc NatlAcadSci USA. 98: 4716-4712,2001). Thekkapatefa/ has recently shown that 11J3-HSD-1 mRNA is expressed in human hippocampus, frontal cortex and cerebellum, and that treatment of elderly diabetic indi)iduals with the non-selecti)e HSD1/2 inhibitor carbenoxolone impro)ed )erbal fluency and memory (Proc Natl AcadSci USA. 101: 6743-9,2004). Additional CNS effects of glucocorticoids include glucocorticoid-induced acute psychosis which is of major concern to physicians when treating patients with these steroidal agents (Wolkowitzef a/.; Ann NY AcadSci. 1032: 191-4,2004). Conditional mutagenesis studies of the glucocorticoid receptor in mice ha)e also pro)ided genetic e)idence mat reduced glucocorticoid signaling in the brain results in decreased anxiety (Tranche, F. et al. (1999) Nature Genetics 23:99-103). Therefore, it is expected that potent, selecti)e llp-HSD-1 inhibitors would treat, control, ameliorate, delay, or pre)ent the onset of cogniti)e decline, dementia, steroid-induced acute psychosis, depression, and/or anxiety. In Cushing's patients, excess cortisol le)els contributes to the de)elopment of hypertension, dyslipidemia, insulin resistance, and obesity, conditions characteristic of metabolic syndrome (Orth, D.N. et al N. Engl. J. Med. 332:791-803,1995; Boscaro, M. et al., Lancet, 357:783-791,2001, Bertagna, X. et al, Cushing's Disease. In: Melmed S., Ed. The Pituitary. 2nd ed. Maiden, MA: Blackwell; 592-612,2002). Hypertension and dyslipidemia are also associated with de)elopment of atherosclerosis. 11J3-HSD-1 knockout mice are resistant to the dyslipidemic effects of a high fat diet and ha)e an impro)ed lipid profile )s wild type controls (Morton N.M. et al, JBC, 276:41293-41300,2001), and mice which o)erexpress llp-HSD-1 in fat exhibit the dyslipidemic phenotype characteristic of metabolic syndrome, including ele)ated circulating free fatty acids, and triclylgerides (Masuzaki, H., et al Science. 294:2166-2170,2001). Adrninistration of a selecti)e 110-HSD-1 inhibitor has also been shown to reduce ele)ated plasma triglycerides and free fatty acids in mice on a high fat diet, and significantly reduce aortic content of cholesterol esters, and reduce progression of atherosclerotic plaques in mice (Hermanowski-)osalka, A et al. J.Exp.Med. 202: 517-27,2005). The administration of a therapeutically effecti)e amount of an 11P-HSD-1 inhibitor would therefore be expected to treat, control, ameliorate, deky, or pre)ent the onset of dyslipidemia and/or atherosclerosis. Glucocorticoids are known to cause a )ariety of skin related side effects including 3km thimg, and impairment of wound healing (Anstead, G. Ad) Wound Care. 11: 277-85,1998; Beer, et al; )itam Horm. 59: 217-39,2000). llp-HSD-1 is expressed in human skin fibroblasts, and it has been shown that the topical treatment with the non-selecti)e HSD1/2 inhibitor glycerrhetinic acid increases the potency of topically applied hydrocortisone in a skin )asoconstrictor assay (Hammami, MM, and Siiteri, PK. J. Clin. Endocrinol Metab. 73:326-34,1991). Ad)antageous effects of selecti)e llp-HSD-1 inhibitors such as B)T.2733 on wound healing ha)e also been reported (WO 2004/11310). High le)els of glucocorticoids inhibit blood flow and formation of new blood )essels to healing tissues. In )itro and in )i)o models of angiogenesis ha)e shown that systemic antagonism with the glucocorticoid receptor RU-486 enchances angiogenesis in subcutaneous sponges as well as in mouse myocardium following coronary artery ligation (Walker, et al, PNAS, 102: 12165-70,2005). 1 lp-HSD-1 knockout mice also showed enhanced angiogenesis in )itro and in )i)o within sponges, wounds, and infarcted myocardium. It is therefore expected that potent, selecti)e 11 p-HSD-1 inhibitors would treat, control, ameliorate, delay, or pre)ent the onset of skin thinning and/or promote wound healing and/or angiogenesis. Although cortisol is an important and well-recognized anti-inflammatory agent (J. Baxer, Pharmac. Ther., 2:605-659,1976), if present in large amount it also has detrimental effects, hi certain disease states, such as tuberculosis, psoriasis and stress hi general, high glucocorticoid acti)ity shifts the immune response to a humoral response, when in fact a cell based response may be more beneficial to patients. Inhibition of 11 P-HSD-1 acti)ity may reduce glucocorticoid le)els, thereby shifting the immuno response to a cell based response. (D. Mason, Immunology Today, 12:57-60,1991, G. A, W. Rook, Baillier's Clin. Endocrinol. Metab. 13:576-581,1999). Therefore, administration of llp-HSD-1 specific inhibitors could treat, control, ameliorate, delay, or pre)ent the onset of tuberculosis, psoriasis, stress, and diseases or conditions where high glucocorticoid acti)ity shifts the immune response to a humoral response. One of the more significant side effects associated with topical and systemic glucocorticoid therapy is glaucoma, resulting in serious increases in intraocular pressure, with the potential to result in blindness (Armaly et al.; Arch OpkthdlmoL 78: 193-7,1967; Stokes etal; In)est Ophthabnol )is Sd. 44: 5163-7,2003;). The cells that produce the majority of aqueous humor in the eye are the nonpigmented epithelial cells (NPE). These cells ha)e been demonstrated to express llp-HSD-1, and consistent with the expression of llp-HSD-1, is the finding of ele)ated ratios of cortisolrcortisone in the aqueous humor (Rauz et al.. In)est Ophthcdmol )is Sd. 42: 2037-2042,2001). Furthermore, it has been shown that patients who ha)e glaucoma, but who are not taking exogenous steroids, ha)e ele)ated le)els of cortisol )s. cortisone in their aqueous humor (Rauz et al. QJM. 96: 481-490,2003.) Treatment of patients with the nonselecti)e HSD1/2 inhibitor carbenoxolone for 4 or 7 days significantly lowered intraocular pressure and local cortisol generation within the eye (Rauz etal.;QJM. 96: 481-490,2003.). It is therefore expected that potent, selecti)e llp-HSD-1 inhibitors would treat, control, ameliorate, delay, or pre)ent the onset of glaucoma. Glucocorticoids (GCs) are known to increase bone resorption and reduce bone fonnationin mammals (Turner et al. Caldf Tissue Int. 54: 311-5,1995; Lane, NBet al. MedPediatrOncol. 41: 212-6,2003). llp-HSD-lmRNA expression and reductase acti)ity ha)e been demonstrated in primary cultures of human osteoblasts in homogenates of human bone (Bland et al; J. Endocrinol. 161:455-464,1999; Cooper et al.; Bone, 23: 119-125, 2000). In surgical explants obtained from orthopedic operations, llp-HSD-1 expression in primary cultures of osteoblasts was found to be increased approximately 3-fold between young and old donors (Cooper et al.; J. Bone AGner Res. 17: 979-986,2002). Glucocorticoids, such as prednisone and dexamethasone, are also commonly used to treat a )ariety of inflammatory conditions including arthritis, inflammatory bowl disease, and asthma. These steroidal agents ha)e been shown to increase expression of 1lp-HSD-1 mRNA and acti)ity in human osteoblasts (Cooper ef al.; J. Bone Miner Res. 17: 979-986, 2002). These studies suggest mat 11 P-HSD-1 plays a potentially important role in the de)elopment of bone-related ad)erse e)ents as a result of excessi)e glucocorticoid le)els or acti)ity. Bone samples taken from healthy human )olunteers orally dosed with the non-selecti)e HSD1/2 inhibitor carbenoxolone showed a significant decrease in markers of bone resorption (Cooper ef al.; Bone. 27: 375-81,2000). It is therefore expected mat potent, selecti)e 11 p-HSD-1 inhibitors would treat, control, ameliorate, delay, or pre)ent the onset of conditions of glucocorticoid-induced or age-dependent osteoporosis' The following diseases, disorders and conditions can be treated, controlled, pre)ented or delayed, by treatment with the compounds of this in)ention: (1) hyperglycemia, (2) low glucose tolerance, (3) insulin resistance, (4) lipid disorders, (5) hyperlipidemia, (6) hypertriglyceridemia, (9) hypercholesterolemia, (10) low HDL le)els, (11) high LDL le)els, (12), atherosclerosis and its sequelae, (13) )ascular restensosis, (14) pancreatitis, (15) obdominal obesity, (16) neurodegenerati)e disease, (17) retinopathy, (18) nephropather, (19), neuropathy, (20) hypertension and other disorders where insulin resistance is a component, and (21) other diseases, disorders, and conditions that can benefit from reduced local glucocorticoid le)els. Therapeutic compositions of the present compounds comprise an effecti)e amount of the same formulated with one or more therapeutically suitable excipients. The term "therapeutically suitable excipient," as used herein, generally refers to pharmaceutically suitable, solid, semi-solid or liquid fillers, diluents, encapsulating material, formulation auxiliary and the like. Examples of therapeutically suitable excipients include, but are not limited to, sugars, cellulose and deri)ati)es thereof, oils, glycols, solutions, buffers, colorants, releasing agents, coating agents, sweetening agents, fla)oring agents, perfuming agents and the like. Such therapeutic compositions may be administered parenterally, intracisternally, orally, rectally, intraperitoneally or by other dosage forms known in the art Liquid dosage forms for oral administration include, but are not limited to, emulsions, microemulsions, solutions, suspensions, syrups and elixirs. Liquid dosage forms may also contain diluents, solubilizing agents, emulsifying agents, inert diluents, wetting agents, emulsifiers, sweeteners, fla)orants, perfuming agents and the like. Injectable preparations include, but are not limited to, sterile, injectable, aqueous, oleaginous solutions, suspensions, emulsions and the like. Such preparations may also be formulated to include, but are not limited to, parenterally suitable diluents, dispersing agents, wetting agents, suspending agents and the like. Such injectable preparations may be sterilized by filtration through a bacterial-retaining filter. Such preparations may also be formulated with sterilizing agents that dissol)e or disperse in the injectable media or other methods known in the art The absorption of the compounds of the present in)ention may be delayed using a liquid suspension of crystalline or amorphous material ha)ing poor water solubility. The rate of absorption of the compounds generally depends upon the rate of dissolution and crystallinity. Delayed absorption of a parenterally administered compoimd may also be accomplished by dissol)ing or suspending the compound in oil. Injectable depot dosage forms may also be prepared by microencapsulating the same in biodegradable polymers. The rate of drug release may also be controlled by adjusting the ratio of compound to polymer and the nature of the polymer employed. Depot injectable formulations may also prepared by encapsulating the compounds in liposomes or microemulsions compatible with body tissues. Solid dosage forms for oral administration include, but are not limited to, capsules, tablets, gels, pills, powders, granules and the like. The drug compound is generally combined with at least one therapeutically suitable excipient, such as carriers, fillers, extenders, disintegrating agents, solution retarding agents, wetting agents, absorbents, lubricants and the like. Capsules, tablets and pills may also contain buffering agents. Suppositories for rectal administration may be prepared by mixing the compounds with a suitable non-irritating excipient that is sofid at ordinary temperature but fluid in the rectum. The present drug compounds may also be microencapsulated with one or more excipients. Tablets, dragees, capsules, pills and granules may also be prepared using coatings and shells, such as enteric and release or rate controlling polymeric and nonpolymeric materials. For example, the compounds may be mixed with one or more inert diluents. Tableting may further include lubricants and other processing aids. Similarly, capsules may contain opacifying agents that delay release of the compounds hi the intestinal tract Transdermal patches ha)e the added ad)antage of pro)iding controlled deli)ery of the present compounds to the body. Such dosage forms are prepared by dissol)ing or dispensing the compounds in suitable medium. Absorption enhancers may also be used to increase the flux of the compounds across the skin. The rate of absorption may be controlled by employing a rate controlling membrane. The compounds may also be incorporated into a polymer matrix or gel. For a gi)en dosage form, disorders of the present in)ention maybe treated, prophylatically treated, or ha)e their onset delayed in a patient by administering to the patient a therapeutically effecti)e amount of compound of the present in)ention in accordance with a suitable dosing regimen, hi other words, a therapeutically effecti)e amount of any one of compounds of formulas I thru DC is administered to a patient to treat and/or prophylatically treat disorders modulated by the n-beta-hydroxysteroiddehydrogenaserype 1 enzyme. The specific therapeutically effecti)e dose le)el for a gi)en patient population may depend upon a )ariety of factors including, but not limited to, the specific disorder being treated, the se)erity of the disorder; the acti)ity of the compound, the specific composition or dosage form, age, body weight, general health, sex, diet of the patient, the time of administration, route of administration, rate of excretion, duration of the treatment, drugs used in combination, coincidental therapy and other factors known in the art The present in)ention also includes therapeutically suitable metabolites formed by in )i)o biotransformation of any of the compounds of formula I thru DC. The term "therapeutically suitable metabolite", as used herein, generally refers to a pharmaceutically acti)e compound formed by the in )i)o biotransform ation of compounds of formula I thru DC. For example, pharmaceutically acti)e metabolites include, but are not limited to, compounds made by adamantane hydroxylation or polyhydroxylation of any of the compounds of formulas I thru DC A discussion of biotransformation is found in Goodman and Oilman's, The Pharmacological Basis of Therapeutics, se)enth edition, MacMillan Publishing Company, New York, NY, (1985). The total daily dose (single or multiple) of the drug compounds of the present in)ention necessary to effecti)ely inhibit the action of 11-beta-hydroxysteroid dehydrogenase type 1 enzyme may range from about 0.01 mg/kg/day to about 50 mg/kg/day of body weight and more preferably about 0.1 mg/kg/day to about 25 mg/kg/day of body weight. Treatment regimens generally include administering from about 10 mg to about 1000 mg of the compounds per day in single or multiple doses. It is understood that the foregoing detailed description and accompanying examples are merely illustrati)e and are not to be taken as limitations upon the scope of the in)ention, which is defined solely by the appended claims and their equi)alents. )arious changes and modifications to the disclosed aspects will be apparent to those skilled in the art Such changes and modifications, including without limitation those relating to the chemical structures, substituents, deri)ati)es, intermediates, syntheses, formulations and/or methods of use of the in)ention, may be made without departing from the spirit and scope thereof What is claimed, 1. A compound of formula (I) (Formula I Removed) wherein A1, A2, A3 and A4 are each individually selected from the group consisting of hydrogen, alkenyl, alkyl, alkyl-NH-alkyl, alkylcarbonyl, alkylsulfonyl, carboxyalkyl, carboxycycloalkyl, cyano, cycloalkyl, cycloalkylcarbonyl, cycloalkylsulfonyl, aryl, arylalkyl, aryloxyalkyl, arylcarbonyl, arylsulfonyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocycleoxyalkyl, heterocyclesulfonyl, halogen, haloalkyl, -NR5-[C(R6R7)]n-C(O)-R8, -O-[C(R9R10)]p-C(O)-R11, -OR12, -S-alkyl, -S(0)alkyl, -N(R13R14), -CO2R15, -C(O)-N(R16R17), -C(R18R19)-OR20,-C(R21R22)-N(R23R24), -C(=NOH)-N(H)2, -C(R18aR19a)C(O)N(R23R24), -S(O)2-N(R25R26), and -C(R18aR19a)- R18a and R19a are each independently selected from the group consisting of hydrogen and alkyl; n is Oor l; p is O or l; D is a member selected from the group consisting of a -O-, -S-, -S(O)- and -S(O)2-; E is a member selected from the group consisting of alkyl, alkoxyalkyl, carboxyalkyl, carboxycycioalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, or R4 and E taken together with the atoms to which they are attached form a heterocycle; R1 is a member selected from the group consisting of hydrogen and alkyl; R2 is a member selected from the group consisting of hydrogen, alkyl and cycloalkyl; R3 and R4 are each independently selected from the group consisting of hydrogen, alkyl, carboxyalkyl, carboxycycloalkyl, cycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle and heterocyclealkyl, or R3 and R4 taken together wilh the atoms to which they are attached form a ring selected from the group consisting of cycloalkyl and heterocycle; R5 is a member selected from the group consisting of hydrogen, alkyl, carboxyalkyl, cycloalkyl, carboxycycloalkyl, aryl, arylalkyl, aryloxyalkyl, hydroxy, alkoxy, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heterocycle, heterocyclealkyl and heterocycleoxyalkyl; R6 and R7 are each independently selected from the group consisting of hydrogen and alkyl, or R6 and R7 taken together with the atom to which they are attached form a ring selected from the group consisting of cycloalkyl and heterocycle; R8 is selected from the group consisting of hydrogen, alkyl, carboxy, carboxyalkyl, cycloalkyl, carboxycycloalkyl, aryl, arylalkyl, aryloxy, aryloxyalkyl, hydroxy, alkoxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroaryloxyalkyl, heterocycle, heterocyclealkyl, heterocycleoxy, heterocycleoxyalkyl and -N(R27R28); R9 and R10 are each independently selected from the group consisting of hydrogen and alkyl, or R9 and R10 taken together with the atom to which they are attached form a ring selected from the group consisting of cycloalkyl and heterocycle; R11 is selected from the group consisting of hydroxy and -N(R29R30); R12 is selected from the group consisting of hydrogen, alkyl, carboxyalkyl, cycloalkyl, carboxycycloalkyl, aryl, arylalkyl, aryloxyalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heterocycle, heterocyclealkyl and heterocycleoxyalkyl; R13 and R14 are each independently selected from the group consisting of hydrogen, alkyl, alkylsufonyl, aryl, arylalkyl, aryloxyalkyl, arylsulfonyl, carboxyalkyl, cycloalkyl, carboxycycloalkyl, cycloalkylsulfonyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocycleoxyalkyl and heterocyclesulfonyl; R15 is selected from the group consisting of hydrogen, alkyl, carboxyalkyl, cycloalkyl, carboxycycloalkyl, aryl, arylalkyl, aryloxyalkyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heterocycle, heterocyclealkyl and heterocycleoxyalkyl; R16 and R17 are each independently selected from the group qonsisting of hydrogen, alkyl, alkoxy, alkylsufonyl, aryl, arylalkyl, aryloxy, aryloxyalkyl, arylsulfonyl, carboxy, carboxyalkyl, carboxycycloalkyl, cycloalkyl, cycloalkyloxy, cycloalkylsulfonyl, heteroaryl, heteroarylalkcyl, heteroaryloxyalkyl, heteroaryloxy, heteroarylsulfonyl, heterocycle, heterocyclealkcyl, heterocycleoxyalkyl, heterocycleoxy, heterocyclesulfonyl, hydroxy, and- alkyl-C(O)N(R201R202), or, R16 and R17 taken together with the atom to which they are attached form a heterocycle; R201 and R202 are independently selected from the group consisting of hydrogen and alkyl; R18, R19 and R20 are each independently selected from the group consisting of hydrogen, alkyl, aryl, arylalkyl, carboxyalkyl, carboxycycloalkyl, cycloalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle and heterocyclealkyl; R21 and R22 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylcarbonyl, arylsulfonyl, cycloalkyl, carboxyalkyl, carboxycycloalkyl, cycloalkylcarbonyl, cycloalkylsulfonyl, heteroaryl, heteroarylcarbonyl, heteroarylsulfonyl, heterocycle, heterocyclecarbonyl and heterocyclesulfonyl; R23 and R24 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkoxy, alkylsulfonyl, aryl, arylcarbonyl, aryloxy, arylsulfonyl, carboxyalkyl, carboxycycloalkyl, cycloalkyl, cycloalkylcarbonyl, cycloalkyloxy, cycloalkylsulfonyl, heteroaryl, heteroarylcarbonyl, heteroaryloxy, heteroarylsulfonyl, heterocycle, heterocyclecarbonyl, heterocycleoxy, heterocyclesulfonyl and hydroxy, or, R23 and R24 taken together with the atom to which they are attached form a ring selected from the group consisting of heteroaryl and heterocycle; R25 and R26 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkylsufonyl, aryl, arylalkyl, aryloxy, aryloxyalkyl, arylsulfonyl, carboxy, carboxyalkyl, carboxycycloalkyl, cycloalkyl, cycloalkyloxy, cycloalkylsulfonyl, heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heteroaryloxy, heteroarylsulfonyl, heterocycle, beterocyclealkyl, heterocycleoxyalkyl, heterocycleoxy, heterocyclesulfonyl, and hydroxy, or, R25 and R26 taken together with the atom to which they are attached form a heterocycle; R27 and R28 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkylsufonyl, aryl, arylalkyl, aryloxy, aryloxyalkyl, arylsulfonyl, carboxy, carboxyalkyl, cycloalkyl, cycloalkyloxy, carboxycycloalkyl, cycloalkylsulfonyl, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroaryloxyalkyl, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocycleoxy, heterocycleoxyalkyl, heterocyclesulfonyl and hydroxy, or, R27 and R28 taken together with the atom to which they are attached form a heterocycle; and R29 and R30 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkylsufonyl, aryl, arylalkyl, aryloxy, aryloxyalkyl, arylsulfonyl, carboxy, carboxyalkyi, cycloalkyl, cycloalkyloxy, carboxycycloalkyl, cycloalkylsulfonyl, heteroaryl, heteroarjialkyl, heteroaryloxy, heteroaryloxyalkyl, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocycleoxy, heterocycleoxyalkyl, heterocyclesulfonyl, andhydroxy, or, R29 and R30 taken together with the atom to which they are attached form a heterocycle; provided that, if R1 is hydrogen; then at least one of A1, A2, A3 and A4 is not hydrogen. 2. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; and R1 and R2 are hydrogen. 3. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; and R3 and R4 are hydrogen. 4. The compound according to claim 1 , wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are hydrogen; and Dis-O-. s --; an A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyi, -S-alkyl, -S(O)-alkyl, -C(RI8R19)-OR20, -C(O)-N(R16R17), -C(R18aR19a)-C(O)N(R23R24), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -C(R18aR19a)-S(O)2-N(R25R26), and -C(R21R22)-N(R23R24). 6. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are hydrogen; Dis-O-; A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)alkyl, -C(R18Rt9)-OR20, -C(O)-N(R16R17), -C(R18aR19a)-C(O)N(R23R24), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -C(R18aR19a)-S(O)2-N(R25R26), and -C(R21R22)-N(R23R24); and E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl, and cycloalkylalkyl. 7. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 is hydrogen; and R4 is alkyl. 8. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 is hydrogen; R4 is alkyl; and Dis-O-. 9. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 is hydrogen; R4 is alkyl; D is -O-; and A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-aIkyl, -C(R18R19)-OR20, -C(O)-N(R16R17), -C(R18aR19a)-C(O)N(R23R24), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -C(R18aR19a)S(O)2-N(R25R26), and -C(R21R22)-N(R23R24). 10. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 is hydrogen; R4 is alkyl; D is-O-; A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20. -C(O)-N(R16R17), -C(R18aR19a)-C(O)N(R23R24), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -C(R18aR19a)-S(O)2-N(R25R26), and -C(R21R22)-N(R23R24); and E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylakyl, and cycloalkylalkyl. 11. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; and R3andR4are alkyl. 12. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are alkyl; and D is-O-. 13. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are alkyl; D is-O-; and A1 is selected from the group consisting of A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O)-N(R16R17), -C(R18aR19a)-C(O)N(R23R24), -C(=NOH)-N(H)2,-S(O)2-N(R25R26),-CO2R15, -C(R18aR19a)-S(O)2-N(R25R26), and - 14. The compound according to claim 1 , wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 are alkyl; D is-O-; A1 is selected from the group consisting of A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O)-N(RI6R17), -C(R18aR19a)-C(O)N(R23R24), -C(=NOH)-N(H)2-S(O)2,N(R25R26), -CO2R15, -C(R18aR19a)-S(O)2-N(R25R26), and - E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyl. 1 5. The compound according to claim 1 , wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; and R3 and R4 taken together with the atoms to which they are attached form a ring selected from the group consisting of cycloalkyl and heterocycle. 1 6. The compound according to claim 1 , wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; and R3 and R4 taken together with the atoms to which they are attached form a cycloalkyl ring. 17. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a cycloalkyl ring; and D is-O-. 18. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a cycloalkyl ring; D is-O-; and A1 is selected from the group consisting of A1 is selected from the group consisting of alkenyl, alkylsulfbnyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O)-N(R16R17), -C(R18aR19a)-C(O)N(R23R24), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -C(R18aR19a)-S(O)2-N(R25R26), and - 19. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a cycloalkyl ring; D is-O-; A1 is selected from the group consisting of A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O)-N(R16R17), -C(R188R19a)-C(O)N(R23R24), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -C(R18aR19a)-S(O)2-N(R25R26), and -C(R21R22)-N(R23R24); and E is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyl. 20. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; and R3 and R4 taken together with the atoms to which they are attached form a heterocycle. 21. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a heterocycle; and D is-O-. 22. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a heterocycle; D is -O-; and A1 is selected from the group consisting of A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carhoxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20. -C(O)-N(R16R17), -C(R18aR19a)C(O)N(R23R24), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -C(R18aR19a)S(O)2--N(R25R26), and - 23. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R3 and R4 taken together with the atoms to which they are attached form a heterocycle; D is-O-; A1 is selected from the group consisting of A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O)-N(R16R17), -C(R18aR19a)-C(O)N(R23R24), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -C(R18aR19a)-S(O)2-N(R25R26), and -C(R21R22)-N(R23R24); and B is selected from the group consisting of aryl, cycloalkyl, heteroaryl, heterocycle, arylalkyl and cycloalkylalkyl. 24. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; and R4 and E taken together with the atoms to which they are attached form a heterocycle. 25. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R4 and B taken together with the atoms to which they are attached form a heterocycle; and D is -O-. 26. The compound according to claim 1, wherein A2, A3 and A4 are hydrogen; R1 and R2 are hydrogen; R4 and E taken together with the atoms to which they are attached form a heterocycle; D is -O-; and A1 is selected from the group consisting of A1 is selected from the group consisting of alkenyl, alkylsulfonyl, cyano, heteroaryl, heteroarylalkyl, -OR12, carboxyalkyl, -S-alkyl, -S(O)-alkyl, -C(R18R19)-OR20, -C(O)-N(R16R17), -C(R18aR19a)-C(O)N(R23R24), -C(=NOH)-N(H)2, -S(O)2-N(R25R26), -CO2R15, -C(R18aR19a)S(O)2-N(R25R26), and - 27. The compound according to claim 1, wherein A1 is selected from the group consisting of alkylsulfonyl, arylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl and heterocyclesulfonyl; A2, A3 and A4 are hydrogen; and D is-O-. 28. The compound according to claim 1, wherein D is -O-; A1 is -S(O)2-N(R25R26); and A2, A3 and A4 are hydrogen. 29. The compound according to claim 1, wherein A1 is -C(O)-N(R.16R.17) wherein R16 is selected from the group consisting of hydrogen and alkyl and R17 is selected from the group consisting of arylalkyl and heteroarylalkyl; D is -O-; and A2, A3 and A4 are hydrogen. 30. The compound according to claim 1, that is a member selected from the group consisting of E-4-[(2-memyl-2-phenoxypropanoyl)amino]adaniantane-l-carboxamide; E-4-[(2-memyl-2-{[4^trifluoromemyl)benzyl]oxy}propanoyl)amino]adamantane-l-carboxamide; E-4-({2-methyl-2-[(2-methylcyclohexyl)oxy]propanoyl}amino)adamantane-l-carboxylic acid; E-4-{2-methyl-2-[(3-methylcyclohexyl)oxy]propanoyl}amino)adamantane-l-carboxylic acid; E-4-{[2-(cycloheptyloxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4-{[2-(cyclohexyhnemoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4-{[2-(4-chlorophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4- {[2-(4-chlorophenoxy)-2-me1hylpropanoyl]amino} adamantane-1 -carboxamide; E-4-({2-memyl-2-[(4-methylcyclohexyl)oxy]propanoyl}amino)adamantane-l-carboxamide; E-4-[(2-phenoxypropanoyl)amino]adamantane-l-carboxamide; E-4-{[2-methyl-2-(2-methylphenoxy)propanoyl]amino}adamantane-l-carboxylic acid; E-4-{[2-methyl-2-(4-methylphenoxy)propanoyl]amino}adamantane-l-carboxylic acid; E-4-{[2-(2-chlorophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4- {[2-(2-methoxyphenoxy)-2-methylpropanoyl]amino} adamantane-1-carboxamide; E-4-{[2-(4-methoxyphenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxamide; E-4-{2-methyl-2-[3-(trifluoromethyl)phenoxy]propanoyl}amino)adamanatane-l-carboxamide; E-4-{[2-(3-methoxyphenoxy)-2-methypropanoyl]amino}adamantane-l-carboxamide; E-2-(4-chloro-phenoxy)-N-(5-hydroxy-adamantan-2-yl)-2-methyl-propionamide; E- {[2-Methyl-2-(4-methylphenoxy)propanoyl]amino} adamantane-1-carboxamide; E-4-{[2-(3-chlorophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxamide; E-4-({2-Methyl-2-[4-(trifluoromethoxy)phenoxy]propanoyl} amino)adamantane- 1-carboxamide; E-4-{[2-(3-Bromophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; adamantyl)carbonyl]amino}methyl)benzoic acid; E-4- { [2-(2,3-Dimethylphenoxy)-2-methylpropanoyl]amino} adamantane- 1-carboxylic acid; tert-Butyl 4-(2- {[(E)-5-(aminocarbonyl)-2-adamantyl]amino}-l,l-dimethyl-2-oxoethoxy)phenylcarbamate; E-N-[4-(Aminocarbonyl)benzyl]-4-{[2-(4-chlorophenoxy)-2-methylpropanoyl]amino} adamantane- 1 -carboxamide; E-N-[4-(Aminocarbonyl)methyl]-4-{[2-(4-chlorophenoxy)-2-methylpropanoyl]amino} adamantane-1-carboxamide; 3-({[((E)-4-{[2-{4-Chlorophenoxy)-2-methylpropanoyl]amino}-l-adamantyl)carbonyl]amino}methyl)benzoic acid; E-4-({2-[(5-Bromopyridin-2-yl)oxy]-2-methylpropanoyl}ammo)adamantane-l-carboxamide; E-4- {[2-(2-Cyanophenoxy)-2-methylpropanoyl]amino} adamantane-1-carboxamide; E-4-{[2-(4-Hydroxyphenoxy)-2-memylpropanoyl]amino}adamantane-l-carboxamide; ((E)-{[2-(4-(Chlorophenoxy)-2-methylpropanoyl]amino}-l-adamantyl)acetic acid; N-[(E)-5-(2-Amino-2-oxoethyl)-2-adamantyl]-2-(4-chlorophenoxy)-2- methylpropanamide; 2-(4-Chlorophenoxy)-2-methyl-N-[(E)-5-(2H-tetraazol-5-ylmethyl)-2-adamantyl]propanamide; N-{(E)-5-[(Aminosulfonyl)methyl]-2-adamantyl}-2-(4-chlorophenoxy)-2-methylpropanamide; N-{(E)-5-[(Z)-Amino(hydroxyimino)methyl]-2-adamantyl}-2(4-chlorophenoxy)-2-methylpropanamide; E-N-[4-(Aminosulfonyl)benzyl]-4-{[2-(4-chlorophenoxy)-2-methylpropanoyl]amino} adamantane-1 -carboxamide; E-4-{[2-(4-Chlorophenoxy)-2-methylpropanoyl]amino}-N-(4-{[(methylsulfonyl)amino]carbonyl}benzyl)adamantane-l-carboxamide; acid; E-4-({2-[(4-Methoxyphenyl)thio]-2-methylpropanoyl}amino)adamantane-l-carboxamide amide; ^-4-({2-[(4-Methoxyphenyl)sulfinyl]-2-mefliylpropanoyl}amino)adamantane-l-carboxamide; E-4-({2-[(4-Methoxyphenyl)sulfonyI]-2-me1hylpropanoyl}amino)adamantane-l-carboxamide; E-4-{2-[4-Chloro-2-(pyrrolidin-l-ylsulfonyl)phenoxy]-2-methylpropanoyl} amino)adamantane- 1 -carboxamide; E-4-{2-Methyl-2-[4-(methylsulfonyl)phraioxy]propanoyl}amino)adamantane-l-carboxamide; E-4-({2-Methyl-2-[2-(methylsulfonyl)phenoxy]propanoyl}amino)adamantane-l-carboxamide; E-4-[(2-{4-Chloro-2-[(diethylamino)sulfonyl]phenoxy}-2-methylpropanoyl)amino]adamantane-l-carboxamide; 5-4-({2-Methyl-2-[4-(pyrrolidin-l-ylsulfonyl)phenoxy]propanoyl}amino)adamantane-l-carboxamide; 2-(2-Chloro-4-fluorophenoxy)-N-[(E)-5-hydroxy-2-adamantyl]-2-methylpropanamide; 2-(2-Chloro-4-fluorophenoxy)-2-methyl-N-[(E)-5-(2H-tetraazol-5-yl)-2- adamantyl]propanamide; 2-(2-Chloro-4-fluorophenoxy)-2-methyl-N-[(E)-5-(methylthio)-2-adamantyl]propanamide; 2-(2-Chloro-4-fluorophenoxy)-2-methyl-N-[(E)-5-(methyIsulfonyl)-2-adamantyl]propanamide; 2-(2-Chloro-4-fluorophenoxy)-2-methyl-N-[(E)-5-(methylsulfinyl)-2-adamantyl]propanamide; N-[(E)-5-(Aminosulfonyl)-2-adamantyl]-2-(4-chlorophenoxy)-2-methylpropanamide E-4-{[l-(4Chlophenoxy)cyclobutyl]carbonyl}amino)adamantane-l-arboxamide; adamantyl)methyl]sulfonyl}amino)methyl]benzoic acid; 2-(4-Chlorophenoxy)-N-[(E)-5-(lH-imidazol-2-yl)-2-adamantyl]-2-methylpropanamide; (2E)-3-(E)-4-{[2-(4-Chlorophenoxy)-2-methylpropanoyl]ainino}-l-adamantyl)acrylic acid; (E)-4-[(2-Methyl-2-{[5-(lH-pyrazol-l-yl)pyridin-2-yl]oxy}propanoyl)amino]adamantane-l-carboxamide; 2-(4-Chlorophenoxy)-N-[(E)-5-isoxazol-5-yl-2-adamantyl]-2-methylpropanamide; 2-(4-Chlorophraoxy)-2-methyl-N-{(E)-5-[(2-morpholm-4-ylethoxy)methyl]-2-adamantyl}propanamide; N-[(E)-5-(Aminosulfonyl)-2-adamantyl]-2-(2chlorophenoxy)-2-methylpropanamide N-[(E)-5-(Aminosulfonyl)-2-adamantyl]-2-methyl-2-(2-methylphenoxy)propanamide; N-[(E)-5-Aminosulfonyl)-2-adamantyl]-2-methyl-2-(4-methylpheaoxy)propanamide N-[(E)-5-(Aminosulfonyl)-2-adamantyl]-2-methyl-2-[2-(trifluoromethyl)phenoxy]propanaimide; N-[(E)-5-(Aminosulfonyl)-2-adamantyl]-2-methyl-2-[2-(trifluoromethoxy)phenoxy]propanamide; N-[(E)-5-(Aminosulfonyl)-2-adamantyl]-2-(2-chloro-4-fluorophenoxy)-2-methylpropanamide; E-4-{[2-(2-Chlorophenoxy)-2-methyl-3-phraylpropanoyl]amino}adamantane-l-carboxamide; 2-(4-chlorophenoxy)-N-[(E)-5-hydroxy-2-adamantyl]-2-methylpropanamide; E-4-({2-methyl-2-[(5-morpholin-4-ylpyridin-2-yl)oxy]propanoyl}amino)adamantane-1-carboxamide; E-4-{[2-methyl-2-(pyridin-2-yloxy)propanoyl]amino}adamantane-l-carboxamide; 2-(4-chlorophenoxy)-2-methyl-N-(E)-5-[(methylamino)sulfonyl]-2-adamantyl}propanamide; 3_((E)-4-{[2-(4-chlorophenoxy)-2-methylpropanoyl]amino}-l-adamantyl)propanoic acid; 2-(4-chlorophenoxy)-N-{(E)-5-[(dimethylamino)sulfonyl]-2-adamantyl}-2-methylpropanamide; E-4-[(2-{[5-(lH-imidazol-l-yl)pyridin-2-yl]oxy}-2-methylpropanoyl)amino]adamanatane-l-carboxamide; 2-(4-chlorophenoxy)-2-methyl-N-[(E)-5-(lH-pyrazol-3-yl)-2-adamantyl]propanamide; N-[(E)-5-(aminosulfonyl)-2-adamantyl]-2-(3-chlorophenoxy)-2-methylpropanamide; N-[(E)-5-(aminosulfonyl)-2-adamantyl]-2-methyl-2-(3-methylphenoxy)propanamide; N-[(E)-5-(anmiosulfonyl)-2-adamantyl]-2-(2-methoxyphenoxy)-2-methylpropanamide; N-[(E)-5-(aminosulfonyl)-2-adamantyl]-2-(3-methoxyphenoxy)-2-methylpropanamide; N-[(E)-5-(aminosulfonyl)-2-adamantyl]-2-(4-methoxyphenoxy)-2-methylpropanamide; N-[(E)-5-(aminosulfonyl)-2-adamantyl]-2-(4-cyanophenoxy)-2-methylpropanamide; E-4-{[2-methyl-2-(3-methylphenoxy)propanoyl]amino}adamantane-l-carboxamide; E-4-[(2-methyl-2-{[(lS,2S)-2-methylcyclohexyl]oxy}propanoyl)amino]adamantane-1-carboxylic acid; E-4-( {2-methyl-2-[(2-methylcyclohexyl)oxy]propanoyl} amino)adamantane- 1 -carboxamide E-4-{[2-(cycloheptyloxy)-2-methylpropanoyl]amino}adamantane-l-carboxamide; E-4- {[2-(cyclohexylmethoxy)-2-methylpropanoyl]amino} adamantane-1-carboxamide; E-4-({2-methyl-2-[(3-methylcyclohexyl)oxy]propanoyl}amino)adamantane-l- carboxamide; E-4-{[2-(2-chlorophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxamide; 4-{[({(E)-4-[(2-methyl-2-phenoxypropanoyl)amino]-l-adamantyl}carbonyl)amino]methyl}benzoic acid; E-4-({2-[(4,4-dimethylcyclohexyl)oxy]-2-methylpropanoyl}amino)adamantane-l-carboxylic acid; E-4-{[2-methyl-2-(l,2,3,4-tetrahydronaphthalen-2-yloxy)propanoyl]amino}adamantane-l-carboxylic acid; E-4-{[2-(4-bromophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4-{[2-methyl-2-(1-naphthyloxy)propanoyl]amino}adamantane-l-carboxyIic acid; E-4-{[2-(2,3,-dichlorophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4-{[2-(2,4-dichlorophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4- {[2-(2,5-dichlorophenoxy)-2-methylpropanoyl]amino} adamantane-1 -carboxylic acid; E-4-{[2-(2,4-dimethylphenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4-{[2-(2,5-dimethylphenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4-{[2-methyl-2-(2-naphthyloxy)propanoyl]amino} adamantane-1-carboxylic acid; E-4- {[2-(4-bromo-2-fluorophenoxy)-2-methylpropanoyl]amino} adamantane-1 -carboxylic acid; E-4-({2-methyl-2-[(7-methyl-2,3-dihydro-lH-inden-4-yl)oxy]propanoyl} amino)adamantane-l-carboxylic acid; E-4-{[2-(4-bromo-2-chlorophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxylic acid; E-4- {[2-(l, 1 -biphenyl-3-yloxy)-2-methylpropanoyl]amino} adamantane-1 -carboxylic acid; E-4- {[2-(2-bromophenoxy)-2-me1hylpropanoyl]amino} adamantane-1 -carboxylic acid; E-N-[4-(aminocarbonyl)benzyl]-4-[(2-methyl-2-phenoxypropanoyl)amino]adamantane-l-carboxamide; ylmethyl)adamantane-l-carboxamide; E-4- {[2-(4-chlorophenoxy)-2-methylpropanoyl]amino} -N-(pyridin-4-ylmethyl)adamanantane-l-carboxamide; E-4-{[2-(4-aminophenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxamide; E-4-{2-methyl-2-[2-(trifluoromethoxy)phenoxy]propanoyl}amino)adamanatane-l-carboxamide; E-4-( {2-methyl-2-[2-(trifluoromethyl)phenoxy]propanoyl} amino)adamantane- 1 -carboxamide; E-4-({2-methyl-2-[4-(pyrrolidin-l-ylsulfonyl)phenoxy]propanoyl}amino)adamantane-l -carboxamide; 2-(2-cbloro-4-fluorophenoxy)-N-[(E)-5-hydroxy-2-adamantyl]-2-melhylpropanamide; 2-(2-chloro-4-fluorophenoxy)-N-[(E)-5-cyano-2-adamantyl]-2-methylpropanamide; E-4-[(2-methyl-2- {4-[(trifluoroacetyl)amino]phenoxy}propanoyl)amino] adamantane-1 -carboxamide; E-4-{[2-(3-bromo-4-methoxyphenoxy)-2-methyrpropanoyl]amino}adamantane-l-carboxamide; E-4- {[2-(2,5-dibromo-4-methoxypheooxy)-2-methylpropanoyl]amino} adamantane-1-carboxamide; E-4-{[2-(2-bromo-4-methoxyphenoxy)-2-methylpropanoyl]amino}adamantane-l-carboxamide; dimethyladamantane-1-carboxamide; 2-(4-chlorophenoxy)-N-((E)-5- {[(4-methoxy-6-methylpyrimidin-2-yl)arnino]methyl} 2-adamantyl)-2-methylpropanamide; E-4- {[2-(4- {[(tert-butylamino)carbonyl]amino}phenoxy)-2-methylpropanoyl]amino} adamantane-1-carboxamide; ethyl 4-(2-{[(E)-5-(aminocarbonyl)-2-adamantyl]amino}-1,1dimethyl-2-oxoethoxy)phenylcarbamate; E-4-[(2-methyl-2-{4-[(propylsulfonyl)amino]phenoxy}propanoyl)amino] adamantane-1-carboxamide; E-4-[(2-{4-[(3,3-dimethylbutanoyl)amino]phenoxy}-2-methylpropanoyl)arnino] adamantane-1-carboxamide; E-4-{[2-methyl-2-(phenylsulfinyl)propanoyl]amino}adamantane-l-carboxylic acid; E-4-{[2-methyl-2-(penylsulfonyl)propanoyl]amino} adamantane-1-carboxylic acid; N-[(E)-5-cyano-2-adamantyl]-2-[(4-methoxyphenyl)sulfonyl]-2-methylpropanamide; 2-[(4-methoxyphenyl)sulfonyl]-2-methyl-N-[(E)-5-(2H-tetraazol-5-yl)-2-adamantyl]propanamide; and E-4-( {2-[4-(benzyloxy)phenoxy]-2-methy]propanoyl} amino)adamantane-l -carboxamide. 31. A method of inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme, comprising administering to a mammal, a therapeutically effective amount of the compound of formula (I) of claim 1. 32. A method of treating disorders in a mammal by inhibiting 11 -beta-hydroxysteroid dehydrogenase Type I enzyme, comprising administering to a mammal, a therapeutically effective amount of the compound of formula 0) of claim 1. 33. A method of treating non-insulin dependent type 2 diabetes in a mammal by inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effective amount of the compound of formula (I) of claim 1. 34. A method of treating insulin resistance in a mammal by inhibiting 11-beta- hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effective amount of the compound of formula (I) of claim 1. 35. A method of treating obesity in a mammal by inhibiting 11 -beta-hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effective amount of the compound of formula (I) of claim 1. 36. A method of treating lipid disorders in a mammal by inhibiting 11-beta- hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effective amount of the compound of fonnula (I) of claim 1. 37. A method of treating metabolic syndrome in a mammal by inhibiting 11-beta- hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effective amount of the compound of formula (I) of claim 1. 38. A method of treating diseases and conditions that are mediated by excessive glucocorticoid action in a mammal by inhibiting 11-beta-hydroxysteroid dehydrogenase Type I enzyme comprising administering to a mammal, a therapeutically effective amount of the compound of formula (I) of claim 1. 39. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) of claim 1 in combination with a pharmaceutically suitable carrier. |
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| Patent Number | 270073 | ||||||||||||||||||||||||||||||
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| Indian Patent Application Number | 5144/DELNP/2007 | ||||||||||||||||||||||||||||||
| PG Journal Number | 49/2015 | ||||||||||||||||||||||||||||||
| Publication Date | 04-Dec-2015 | ||||||||||||||||||||||||||||||
| Grant Date | 27-Nov-2015 | ||||||||||||||||||||||||||||||
| Date of Filing | 03-Jul-2007 | ||||||||||||||||||||||||||||||
| Name of Patentee | ABBOTT LABORATORIES | ||||||||||||||||||||||||||||||
| Applicant Address | 100 ABBOTT PARK ROAD, ABBOTT PARK, ILLINOIS 60064-6008 USA. | ||||||||||||||||||||||||||||||
Inventors:
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| PCT International Classification Number | C07C 235/14 | ||||||||||||||||||||||||||||||
| PCT International Application Number | PCT/US2006/000210 | ||||||||||||||||||||||||||||||
| PCT International Filing date | 2006-01-05 | ||||||||||||||||||||||||||||||
PCT Conventions:
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