Title of Invention

SUBSTITUTED 2-AMINO PHENYL DERIVATIVES

Abstract

ABSTRACT OF THE DISCLOSURE The present invention provides " activity inhibitor comprising as an active ingredient a compound" represented by the formula (I): wherein R represents a straight chain or branched alkyl group; a straight chain or branched alkenyl group; a lower haloalkyl group; a substituted or unsubstituted cycloalkyl group; a substituted or unsubstituted cycloalkenyl group; a substituted or unsubstituted cycloalkylalkyl group; a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, X<SUB>1</SUB>( X<SUB>2</SUB>, X<SUB>3</SUB>, and X, may be the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower haloalkyl group; a lower alkoxy group; a cyano group; a nitro group; an acyl group; or an aryl group, Y represents -CO- or -S02, and Z represents a hydrogen atom or a mercapto-protecting group, or a prodrug compound^ a pharmaceutically acceptable salt, or hydrate or solvate thereof. The compounds represented by the formula (I) can increase HDL and at the same time decrease LDL through selective inhibition of CETP activity and, therefore, is expected to be useful as a new type of a preventive or therapeutic agent for atherosclerosis or hyperlipidemia.

Full Text

-SPECIFICATION CETP ACTIVITY INHIBITOR JfegHHICAL FIELD —- This invention relates to a novel CETP activity inhibitor which comprises as an active ingredient a compound having a bis-(2-aminophenyl) disulfide structure or a 2-amino-phenylthio structure and more particularly to a pharmaceutical composition for treating or preventing atherosclerosis or hyperlipidemia. This invention also relates to a compound having a bis-(2-aminophehyl) disulfide structure or a 2-aminophenylthio structure, a prodrug compound/ a pharmaceutically acceptable salt, hydrate or solvates of these compounds. BA£££fi2QH2Z£EX From the results of many epidemiological studies, it has been considered that there exists certain relation between atherosclerotic diseases and serum lipoprotein. For example, Badimon et al. (J. Clin. Invest, fll, 1234-1241 (1990)) reported that not only the prevention of development but also regression of atherosclerotic lesions were observed after intravenous injection of fractions containing HDL {high density lipoprotein) and VHDL (very high density lipoprotein) to cholesterol-loaded rabbits. Thus, regarding the relation between atherosclerotic diseases and serum lipoproteins, it is expected that HDL and VHDL may have antiatherosclerotic activity. Recently, it has been elucidated that there are proteins that transfer lipids among serum lipoproteins, i.e., CETP (cholesterol ester transfer protein). The presence of CETP was first indicated by Nichols and Smith in 1965 (J. Lipid Res. £, 206 (1965)). cDNA of the compound was later cloned by Drayna et al. in 1987. Molecular weight of the compound as glycoprotein is 74,000 Da. It is about 58,000 after complete removal of sugar chain- cDNA of this compound is composed of 1656 residues and codes for 476 amino acids following signal peptide of 17 residues. Since around 44 % of these amino acids are hydrophobic, the protein is highly hydrophobic and liable to be inactivated by oxidation. CETP is synthesized in organs like liver, spleen, adrenal, fat tissue, small intestine, kidney, skeletal muscle, and myocardium. It has been confirmed that CETP is synthesized in cells like macrophages derived from human monocytes, B lymphocytes, fat cells, small intestinal epithelial cells, CaCo2 cells, and liver cells (for example, HepG2 cells derived from human hepatoma cells) . In addition to these tissues, it is present in cerebrospinal fluid and seminal fluid, too. The presence is also confirmed in culture media of neuroblastoma and neuroglioma cells, and in chorioid plexus of sheep. It has become apparent that CETP participates in metabolism of all the lipoproteins in vivo and plays important roles in reverse transfer system of cholesterol. It attracted attention a.s a system that prevents the accumulation of cholesterol into peripheral cells and functions as protective mechanism against atherosclerosis. In relation to HDL, which plays important roles in the reverse transfer system of cholesterol, a great number of epidemiological studies have shown that a decrease in CE (cholesterol esters) of HDL in blood represents one of the risk factors for coronary artery diseases. Activity of CETP differ depending on the species of animals and it has become apparent that cholesterol load does not bting about atherosclerosis in animals with low CETP activity, while it is easily produced in animals with high CETP activity. Absence of CETP results in high HDL-emia + low LDL (low density lipoprotein)-emia and brings about a state resistant to atherosclerosis. Thus, the importance of CETP as mediators of transfer of CE in HDL to blood LDL has become recognized in addition to the importance of HDL in blood. Free cholesterol (FC) synthesized in the liver and secreted therefrom is taken up into very low density lipoprotein ( VLDL ). Next, VLDL is metabolized in the blood to LDL via intermediate density lipoprotein (IDL) by the action of lipoprotein lipase (LPL) and liver triglyceride lipase (HTGL). LDL is taken up to peripheral cells mediated by LDL receptor and, thus, FC is supplied to the cells. Contrary to this flow from the liver to peripheral cells, there exists another flow of cholesterol from peripheral cells to the liver called cholesterol reverse transfer system. FC accumulated in peripheral cells is extracted by HDL, esterified on HDL through the action of LCAT (Lecithin: cholesterol acyltransferase) to form CE, tranferred to the hydrophobic core portion of HDL, and HDL becomes matured to globular HDL particles. CE in HDL is transferred to apoB-containing lipoproteins such as VLDL, IDL, and LDL by CETP present in the blood. In exchange, TG is transferred to HDL in mole ratio of 1:1. CE that is transferred to apoB-containing lipoprotein is taken up by the liver via LDL receptor on it and, thus, cholesterol is transferred indirectly to the 1 iver. There is mechanisms, too, by which HDL becomes CE-rich, apoprotein E-containing HDL by taking up apoprotein E secreted by macrophages and the like, which is then taken up directly to the liver via LDL receptor or remnant receptor. In another, the liver cells do not take up HDL particles, but take up selectively only CE in HDL. in still another, HDL particles are taken up by the liver cells via so-called HDL receptor. In a state, in which CETP activity is augmented, CE in HDL is decreased and CE in VLDL, IDL and LDL is increased due to augmentation of CE transfer from HDL. increases in uptake of IDL, and LDL to the liver result in down-regulation of LDL receptor and increases in LDL in the blood. In contrast, in a state of CETP deficiency, HDL removes cholesterol from peripheral cells with the aid of LCAT, increases its size gradually and acquires apoE. HDL that becomes apoE-rich is taken up by the liver via LDL receptor of the liver and catabolized. However, as the operation of this mechanism is not adequate in the human, retention of large HDL in the blood occurs and, as a result, cholesterol pool in the liver becomes smaller. LDL receptor becomes up-regulated and LDL is decreased. Hence, by selectively inhibiting CETP, it is possible to decrease IDL, VLDL and LDL that accelerate atherosclerosis and increase HDL that exhibits inhibitory action. Thus, it is anticipated that hitherto non-existent drugs useful for prevention or therapy of atherosclerosis may be provided. Very recently there have been reports on chemical compounds that aim at inhibition of such CETP activity. For example, in Biochemical and Biophysical Research Communications 221, 42-47 (1996), dithiodipyridine derivatives and substituted dithiobenzene derivatives are disclosed as compounds capable of inactivating CETP through modification of cysteine residues. However, the literature neither discloses nor suggests the compounds such as those of the present invention which have a bis-(2-aminophenyl) disulfide structure or a 2-aminophenylthio structure. WO95/06626 discloses Wiedendiol-A and Wiedendiol^B as CETP activity inhibitors, but there is no description suggesting the compounds of the present invention. Furthermore, in JP-B-Sho 45-11132, JP-B-Sho 45-2892, JP-B-Sho 45-2891, JP-B-Sho 45-2731, and JP-B-Sho 45-2730, mercaptoanilides substituted with higher fatty acids such as o-isostearoylamino thiophenol are disclosed. However, in these publications , the atherosclerosis-preventing action is only referred to and there is no description of test examples that substantiate the action. There is also no description of CETP inhibitory activity. Nor is there description suggestive of compounds of the present invention. There are several reports on the compounds having a bis-{2-aminophenyl) disulfide structure or a 2-aminophenylthio structure similar to those of the present application of invention. For example, WO96/09406 discloses disulfide compounds such as 2-acetylaminophenyl disulfide and the like. However, the compounds of the publication are the ones that are useful for retrovirus, i.e., Hiv-l, and usefulness as regards inhibitors of CETP activity has not been disclosed. There also is no description suggestive of the usefulness. In JP-A-Hei 8-253454, disulfide compounds such as 2,2' -di(pyrimidylamino)diphenylsulfide and the like are disclosed. However, the compounds in this publication are the ones that have inhibitory action on production of IL-lp and on release of TNFa and there are no disclosure as regards the usefulness as inhibitors of CETP activity. There is even no description suggestive of the usefulness. In JP-A-Hei 2-155937, bis-(acylaminophenyl) disulfide compounds such as 2 ,2 ' -diacetylaminodiphenyl disulfide and the like are disclosed. However, the compounds in this publication relates to the method of making vulcanized rubber filled with carbon black and there are no disclosure as regards the usefulness as inhibitors of CETP activity. There is also no description suggestive of the usefulness. In the claims recited in the publication, C5-C12 cycloalkyl and cycloalkenyl are defined as R9, and R10, and as specific examples cyclohexyl and cyclohexenyl are described. However, in the publication no example that substantiates the use of the compound is shown and there is no description of the general method of production of the compounds. JP-A-Hei 2-501772 discloses acylamino phenyl disulfide derivatives such as o-pivaloylaminophenyl disulfide and the like as intermediates for production of pyrrazolone photocoupler. However, the invention described in this publication relates to the photo-element and not suggestive of the present invention. This publication also describes 2-cyclohexane carbonylamino phenylthio group as an example of coupling-off group of the coupler, but there is no description of examples that substantiate the use of the compound. jp-A-Hei 8-171167 discloses thiophenol derivatives or disulfide derivatives such as 2-acetylamino thiophenol. However, the invention described in this publication relates to the silver halide emulsion and not suggestive of the present invention. In JP-A-Hei 4-233908, disulfide derivatives such as bis-(2-acetoamidephenyl) disulfide and the like are disclosed. However, the compounds of this publication is disclosed as chain transfer agents and, thus, the publication does not suggest the present invention. As specific examples of R3 in X,Y, a cyclohexyl group is disclosed, but the example substantiating the use and the general method of production are not described. JP-A-Sho 63-157150 discloses amidophenyl disulfide derivatives such as o-pivalamidophenyl disulfide and the like as stabilizers. However, the invention of this publication relates to photo-element and is not suggestive of the present invention. In the claim recited in this publication, a cycloalkyl group is defined as R in the substituents V or Y of the stabilizer compounds, but the example substantiating the use and the general method of production are not described. Bis-(amidophenyl) disulfide derivatives are also disclosed in JP-A-Hei 8-59900, JP-A-Hei 7-258472, JP-A-Hei 7-224028, JP-A-Hei 7-49554, JP-A-Hei 6-19037, JP-A-Hei 6-19024, JP-A-Hei 3-226750, JP-A-Hei 2-284146, JP-A-Hei 2-23338, JP-A-Hei 1-321432, JP-A-Hei 1-278543, and JP-B-Sho 47-357786. However, none of them discloses usefulness as inhibitors of CETP activity and there is no description suggestive of the usefulness. DISCLOSURE OF THE TNVEHTIOH As described above, the present inventors studied ardently in order to provide the compounds that selectively inhibit CETP activity and, as a result, found compounds useful as novel preventive or therapeutic agents of atherosclerosis or hyperlipidemia which could increase HDL and at the same time decrease LDL, thereby completing the present invention. The present invention relates to the compounds and medicaments as shown in the following {1) to (19) which have CETP activity inhibitory effect: (1) A CETP activity inhibitor comprising as an active ingredient a compound represented by the formula (I): wherein R represents a straight chain or branched CW1 alkyl group; a straight chain or branched c2.10 alkenyl group; a halo-Ci., lower alkyl group; a substituted or unsubstituted C3.l(, cycloalkyl group; a substituted or unsubstituted C5_„ cycloalkenyl group; a substituted or unsubstituted C3.10 cycloalkyl C,.1( alky! group; a substituted or unsubstituted aryl group; a substituted or unsubstituted aralkyl group; or a substituted or unsubstituted 5- or 6-membered heterocyclic group having 1-3 nitrogen, oxygen or sulfur atoms, Xlf X2, X3, and X4 may be the same or different and represents a hydrogen atom; a halogen atom; a Cj.4 lower alkyl group; a halo-C^ lower alkyl group; a cw lower alkoxy group; a cyano group; a nitro group; an acyl group; or an aryl group, Y represents -CO-; or -SO,, and Z represents a hydrogen atom; or a mercapto-protecting group, or a prodrug compound, a pharmaceutical^ acceptable salt, or hydrate or solvate thereof. (2) A CETP activity inhibitor comprising as an active ingredient the compound described in the above (1), wherein R represents a straight chain or branched Cj_10 alkyl group; a straight chain or branched C2_10 alkenyl group; a halo-Cj., lower alkyl group substituted with 1-3 halogen atoms selected from fluorine, chlorine, and bromine; a C3-io cycloalkyl group, a C5.8 cycloalkenyl group, or a C3_10 cycloalkyl Cj_10 alkyl group, each of which may have 1-4 sur>stituents selected from the group consisting of a straight chain or branched CX_J0 alkyl group, a straight chain or branched C2.10 alkenyl group, a C3-io cycloalkyl group. a CS.B cycloalkenyl group, a CJ-IO cycloalkyl C^^ alkyl group, an aryl group selected from phenyl, biphenyl, and naphthyl, an oxo group, and an aralkyl group having an aryl group selected from phenyl, biphenyl, and naphthyl; an aryl, aralkyl, or 5- or 6-membered heterocyclic group with 1-3 nitrogen, oxygen or sulfur atoms, each of which may have 1-4 substituents selected from the group consisting of a straight chain or branched Cj.^, alkyl group, a straight chain or branched C2_1D alkenyl group, a halogen atom selected from fluorine, chlorine, or bromine, a nitro group, and a halo-C^ lower alkyl group having a halogen atom selected from fluorine, chlorine, and bromine; Z represents a hydrogen atom; a mercapto-protecting group selected from the group consisting of a Cj., lower alkoxymethyl group, a C^, lower alkylthiomethyl group, an aralkyloxymethyl group having an aryl group selected from phenyl, biphenyl, and naphthyl, an aralkylthiomethyl group having an aryl group selected from phenyl, biphenyl, and naphthyl, a C3-ia cycloalkyloxymethyl group, a Cs.e cycloalkenyloxymethyl group, a C3-io cycloalkyl cl_ia alkoxymethyl group, an aryloxymethyl group having an aryl group selected from phenyl, biphenyl, and naphthyl, an arylthiomethyl group having an aryl group selected from phenyl, biphenyl, and naphthyl, an acyl group, an acyloxy group, an aminocarbonyloxymethyl group, a thiocarbonyl group, and a thio group, or a prodrug compound thereof, or a pharmaceutically acceptable salt, or hydrate or solvate thereof. (3) A CETP activity inhibitor comprising as an active ingredient the compound as described in the above (2), which is represented by the formula (1-1): wherein R, xlf X2, X3, X,, and Y are the same as in the above (2) and Z, represents a hydrogen atom; a group represented by the formula wherein R, XH X3, X}, X,, and Y are the same as described above; wherein Y1 represents -CO-; or -CS-, Ry represents a substituted or unsubstituted straight chain or branched C^u, alkyl group; a Cl_i lower alkoxy group; a CU4 lower alkylthio group; a substituted or unsubstituted amino group; a substituted or unsubstituted ureido group; a substituted or unsubstituted Cj.l0 cycloalkyl group; a substituted or unsubstituted C3_10 cycloalkyl c^^ alkyl group; a substituted or unsubstituted aryl group; a substituted or unsubstituted aralkyl group; a substituted or unsubstituted arylalkenyl group; a substituted or unsubstituted arylthio group; a substituted or unsubstituted 5- or 6-membered heterocyclic group having 1-3 nitrogen, oxygen, or sulfur atoms; or a substituted or unsubstituted 5- or 6-membered heteroarylalkyl group; or -S~R; , wherein R2 represents a substituted or unsubstituted C,.( lower alkyl group; or a substituted or unsubstituted aryl group, or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (4) A CETP activity inhibitor comprising as an active ingredient the compound as described in the above (3), wherein R! represents a straight chain or branched C^^ alkyl group which may have 1-3 substituents selected from the group consisting of a halogen atom selected from iluorine, chlorine, and bromine, a C1_4 lower alkoxy group, an amino group that may be substituted with a c^ lower alkyl, acyl, or hydroxyl group, a C^ lower alkylthio group, a carbamoyl group, a hydroxyl group, an acyl group, an acyloxy group having an acyl group, a carboxyl group, an aryloxy group that may be substituted with a halogen atom selected from fluorine, chlorine, and bromine; a Ci-« lower alkoxy group; a d_« lower alkylthio group; an amino or ureido group that may have 1-2 substituents selected from the group consisting of a Cu a hydroxy1 group, an acyl group, and an aryl group that may be substituted with a lower c^, alkoxy group; a CJ-IO cycloalkyl or C3_10 cycloalkyl C1_l0 alkyl group that may have substituents selected from the group consisting a straight or branched Cj.1B alkyl group, a CJ-ID cycloalkyl group, a cs-s cycloalkenyl group, an aryl group, an amino group, a C^ lower alkylamino group having a CM lower alkyl group, and an acylamino group having an acyl group; an aryl group, an aralkyl group, an arylalkenyl group, or an arylthio group, each of which may have 1-4 substituents selected from the group consisting of a Cx.la alkyl group, a halogen atom selected from fluorine, chlorine, and bromine; a nitro group, a hydroxyl group, a Cl_i lower alkoxy group, a C^ lower alkylthio group, an acyl group, a halo-C^ lower alkyl group having a halogen atom selected from fluorine, chlorine, and bromine, and an amino group that may be substituted with a C^, lower alkyl or acyl group; a 5- or 6-membered heterocyclic group having 1-3 nitrogen, oxygen or sulfur atoms or a 5- or 6-membered heteroarylalkyl group that may have 1-4 substituents selected from the group consisting of a straight chain or branched C,.10 alkyl group, a halogen atom selected from fluorine, chlorine, anci bromine, an acyl group, an oxo group, and an halo-C^ lower alkyl group having a halogen atom selected from fluorine, chlorine, and bromine; R2 represents a Cn lower alkyl group that may have 1-3 substituents selected from th£ group consisting of a Cj.4 lower alkoxy groups, an amino group that may be substituted with a Cj_4 lower alkyl or acyl group, a C,., lower alkylthio group, a carbamoyl group, a hydroxy1 group, a carboxyl group, an acyl group, and a 5- or 6-membered heterocyclic group having 1-3 nitrogen, oxygen, or sulfur atoms; an aryl group that may have 1-4 substituents selected from the group consisting of a Cj_4 lower alkyl group, a halogen atom selected from fluorine, chlorine, and bromine, a nitro group, a hydroxy1 group, a C1_i lower alkoxy group/ a C1-4 lower alkylthio group, an acyl group, an amino group that may be substituted with a c1-4 lower alkyl or acyl group, and a halo-Cj.j lower alkyl group having a halogen atom selected from fluorine, chlorine, and bromine; or a prodrug compound, a pharmaceutical^ acceptable salt, or hydrate or solvate thereof. (5) A CETP activity inhibitor comprising as an active ingredient the compound as described in the above (1), which is selected from the group consisting of bis-[2-(pivaloylamino)phenyl] disulfide; bis-[2-(2-propylpentanoylamino)phenyl] disulfide; bis-[2-(l-methylcyclohe#anecarbonylamino)phenyl] disulfide; bis-[2-(1-isopentylcyclopentanecarbonylamino)phenyl] disulfide; bis-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] disulfide; N-(2-mercaptophenyl)-2,2-dimethylpropionamide; N-(2-mercaptophenyl)-1-isopentylcyclohexanecarboxamide; N-( 2-mercaptophenyl )-l-inethylcyclohexanecarboxamide; N-(2-mercaptophenyl)-l-isopentylcyclopentanecarboxamide; N-(2-mercaptophenyl)-1-isopropylcyclohexanecarboxamide; N- (4,5-dichloro-2-mercaptophenyl)-1-isopentylcyclohexane-carboxamide; N-(4,5-dichloro-2-mercaptophenyl)-1-isopentylcyclopentane-carboxamide; N-(2-mercapto-5-methylphenyl)-l-isopentylcyclohexane- carboxamide; N-(2-mercapto-4-methylphenyl)-1-isopentylcyclohexane-carboxamide; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl]thio-acetate; S-[2-(1-methylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[2-(pivaloylamino)phenyl]phenylthioacetate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2-acetylamino-3-phenylthiopropionate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 3-pyridinethiocarboxylate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] chloro-thioacetate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] methoxy-thioacetate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] thio-propionate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] phenoxy- thioacetate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2-methylthiopropionate; S-[2-( 1-isopentylcyclohexanecarbonylami.no) phenyl] 4-chlorophenoxythioacetate; S-[2-( 1-isopenty lcyclohexanecarbonylami.no) phenyl] cyclo-propanethiocarboxylate; S-[2-(1-isopentylcyclohexanecarbonylami.no) phenyl ] 2-acetylamino-4-carbamoylthiobutyrate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2-hydroxy-2-methylthiopropionate; S-[2-(1-isopentylcyclopentanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[2-(1-isopentylcyclopentanecarbonylamino)phenyl] thio¬acetate; S-[4,5-dichloro-2-{1-isopentylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-isopentylcyclopentanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[2-(l-isopentylcyclohexanecarbonylamino)-4-trifluoro-methylphenyl] 2,2-dimethylthiopropionate; O-methyl S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl monothiocarbonate; S-[2-(1-methylcyclohexanecarbonylamino)phenyl] S-phenyl dithiocarbonate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] N-phenylthiocarbamate; S-[2-(pivaloylamino)-4-trifluoromethylphenyl] 2,2- dimethylthiopropionate; S-[4,5-dichloro-2-(1-cyclopropylcyclohexanecarbonylamino) phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(2-cyclohexylpropionylamino)phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-pentylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-cyclopropylmethylcyclohexane carbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(l-cyclohexylmethylcyclohexanecarbonyl-amino)phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-isopropylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-isopentylcycloheptanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-isopentylcyclobutanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[2-(1-isopentylcyclohexanecarbonylamino)-4-nitrophenyl] 2,2-dimethylthiopropionate; , S-[4-cyano-2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[4-chloro-2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[5-chloro-2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[4-fluoro-2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[4,5-difluoro-2-(1-isopentylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[5-fluoro-2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; bis-[4,5-dichloro-2-(1-isopentylcyclohexanecarbonylamino)-phenyl] disulfide; 2-tetrahydrofurylmethyl 2-(1-isopentylcyclohexanecarbonyl amino)phenyl disulfide; N-(2-mercaptophenyl)-l-ethylcyclohexanecarboxamide; N-{2-mercaptophenyl)-1-propylcyclohexanecarboxamide; N-(2-mercaptophenyl)-1-butylcyclohexanecarboxamide; N-(2-mercaptophenyl)-l-isobutylcyclohexanecarboxamide; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] cyclo-hexanethiocarboxylate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] thio-benzoate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 5- carboxythiopentanoate; S-[2-{l~isopentylcyclohexanecarbonylamino)-4-methylphenyl] thioacetate; bis-[2-[1-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] disulfide; N-(2-mercaptophenyl)-1-(2-ethylbutyl)cyclohexane-carboxamide; S-[2-[l-{2-ethylbutyl)cyclohexanecarbonylamino]phenyl] 2-methylthiopropionate; S-[2-(1-isobutylcyclohexanecarbonylamino)phenyl] 2-methyl-thiopropionate; S-[2-[l-{2-ethylbutyl)cyclohexanecarbonylamino]phenyl] 1-acetylpiperidine-4-thiocarboxylate; S-[2-[l-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] thioacetate; S-[2-[1-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] 2,2-dimethylthiopropionate; S-[2-[1-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] methoxythioacetate; S-[2-[l-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] 2-hydroxy-2-methylthiopropionate; S-[2-[1-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] 4-chlorophenoxythioacetate; S- [ 2-(1-isobutylcyclohexanecarbonylamino)phenyl] 4-chloro-phenoxythioacetate; S-[2-(1-isobutylcyclohexanecarbonylamino)phenyl] 1-acetyl-piperidine-4-thiocarboxylate; or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (6) A prophylactic or therapeutic agent for hyperlipidemia comprising as an active ingredient the compound as described in the above in (l)-(5), a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (7) A prophylactic or therapeutic agent for atherosclerosis comprising as an active ingredient the compound as described in the above in (l)-{5), a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (8) A Compound represented by the formula (1-2): wherein R' represents a substituted or unsubstituted C^.^ cycloalkyl group or a substituted or unsubstituted C5_a cycloalkenyl group; X,, X,, X3, and X4 are as in the above (1); Zt' represents a hydrogen atom; a group represented by the formula: wherein R" , Xlf X;, Xj, and X4 are as described above; wherein Y1 and Rx are the same as in the above (3) or -S-R,, wherein R, is the same as in the above (3), or a prodrug compound, a pharmaceutical^ acceptable salt, or hydrate or solvate thereof. (9) A compound as described above in (8), which is represented by the formula (1-3): wherein R'■ represents a l-substituted-C3_10 cycloalkyl group, or a l-substituted-C5_B cycloalkenyl group; Xw X2, X3, and X4 are the same as in the above (1); Zx ' represents a hydrogen atoms; a group represented by the formula: wherein R' ' , Xw X,, X3, and X wherein Yi and Rj are the same as in the above (3), or -S-R2 , wherein R2 is the same as in the above (3), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (10) A compound as described in the above (8), which is represented by the formula (II): wherein R' , Xlf X2, X3, and X4 are the same as in the above (8), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (11) A compound as described in the above (9), which is represented by formula (II-l): wherein R', XL, X2, X3, and X, are the same as in the above (9), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (12) A compound as described in the above (8), which represented by the formula (III): wherein R', Xw X2, X,, and X4 are the same as in the above (8), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (13) A compound as described in the above (9), which is represented by formula (III-l) : wherein R" ' , X,, X2, X3, and X, are the same as in the above (9), or a prodrug compound, a pharmaceutical^ acceptable salt, or hydrate or solvate thereof. (14) A compound as described in the above (8), which is represented by formula (IV): wherein R" , xl( X2, X3, Xa, Y,, and Rt are the same as in the above (8), or a prodrug compound, a pharmaceutical^ acceptable salt, or hydrate or solvate thereof. {15) A compound as described in the above (9), which is represented by formula (IV-1): wherein R' ', X1( X2, Xa, x4/ Yw and ^ are the same as in the above (9), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (16) A compound as described in the above ( 8), which is represented by formula (V); wherein R' , x1( X3, X}, xif and R, are the same as in the above (8), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (17 ) A compound as described in the above { 9 ), which is represented by formula (V-l): wherein R', X,, x2, X3, X,, and R2 are the same as in the above (9), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (19) A compound as described in the above (8), which is selected from the group consisting of bis-[2-(1-methylcyclohexanecarbonylamino)phenyl] disulfide; bis-(2-(1-isopentylcyclopentanecarbonylamino)phenyl] disulfide; bis-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] disulfide; N-(2-mercaptophenyl)-l-isopentylcyclohexanecarboxamide; N- N-(4,5-dichloro-2-mercaptopheny1)-1-isopentylcyclopentane-carboxamide; N-(2-mercapto-5-methylphenyl)-1-isopentylcyclohexane-carboxamide; N-(2-mercapto-4-methylphenyl)-1-isopentylcyclohexane-carboxamide; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] thio-acetate; S-[2-{1-methylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2-acetylamino-3-phenylthiopropionate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 3-pyridinethiocarboxylate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] chloro-thioacetate; S-£ 2-(1-isopentylcyclohexanecarbonylamino)phenyl] methoxy- thioacetate; S-[2-{1-isopentylcyclohexanecarbonylamino)phenyl] thio-propionatej S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] phenoxy-thioacetate; S-[2-{1-isopentylcyclohexanecarbonylamino)phenyl] 2-methylthiopropionate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 4-chlorophenoxythioacetate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] cyclo- propanethiocarboxylate; S- [ 2- (1-isopentylcyclohexanecarbonylami.no) phenyl ] 2 -acetylamino-4-carbamoylthiobutyrate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2 -hydroxy-2-methylthiopropionate; S-[2-(1-isopentylcyclopentanecarbonylamino)phenyl] 2,2-dimethylpropionatej S-[2-(1-isopentylcyclopentanecarbonylamino)phenyl] thio-acetate; S-[ 4,5-dichloro-2-(1-isopentylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-isopentylcyclopentanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[2-(l-isopentylcyclohexanecarbonylamino)-4-trifluoro-methylphenyl] 2,2-dimethylthiopropionate; O-methyl S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] monothiocarbonate; S-[2-(1-methylcyclohexanecarbonylamino)phenyl] S-phenyl dithiocarbonate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] N-phenylthiocarbamate; S-[4,5-dichloro-2-{1-cyclopropylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-pentylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-cyclopropylmethylcyclohexanecarbonyl-amino)phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-cyclohexylmethylcyclohexanecarbonyl-amino)phenyl] 2,2-dimethylthiopropioate; S-[4,5-dichloro-2-(1-isopropylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-isopentylcycloheptanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(1-isopentylcyclobutanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[2-(1-isopentylcyclohexanecarbonylamino)-4-nitrophenyl] 2,2-dimethylthiopropionate; S-[4-cyano-2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[4-chloro-2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[5-chloro-2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[4-fluoro-2-(1-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[4,5~difluoro-2-(1-isopentylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[5-fluoro-2-(1-isopentylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; bis-[4,5-dichloro-2-(1-isopentylcyclohexanecarbonylamino)-phenyl] disulfide; 2-tetrahydrofurylmethyl 2-(1-isopentylcyclohexanecarbonyl-amino)phenyl disulfide; N-(2-mercaptophenyl)-1-ethylcyclohexanecarboxamide; N-(2-mercaptopheny1)-1-propylcyclohexanecarboxaroide; N-(2-mercaptophenyl)-l-butylcyclohexanecarboxamide; N-(2-mercaptophenyl)-1-isobutylcyclohexanecarboxamide; S-[2-{1-isopentylcyclohexanecarbonylamino)phenyl] cyclo-hexanethiocarboxylate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] thio-benzoate; S-[2-(1-isopentylcyclohexanecarbonylamino)phenyl] 5-carboxythiopentanoate; S-[2-(1-isopentylcyclohexanecarbonylamino)-4-methylphenyl] thioacetate; bis-[2-[1-(2-ethyIbutyl)cyclohexanecarbonylamino]phenyl]-disulfide; N-(2-mercaptophenyl)-1-(2-ethyIbutyl)cyclohexane-carboxamide; S-[2-[l-(2-ethyIbutyl)cyclohexanecarbonylamino]phenyl] 2-methylthiopropionate; S-[2-(1-isobutylcyclohexanecarbonylamino]phenyl] 2-methyl- thiopropionate; S-[2-[1-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] 1-acetylpiperidine-4-thiocarboxylate; S-[2 -[1-(2-ethyIbutyl)cyclohexanecarbonylamino]phenyl] thioacetate; S-[2-[1-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] 2,2-dimethylthiopropionate; S-[2-[1-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] methoxythioacetate; S-[2-[l-{2-ethylbutyl)cyclohexanecarbonylamino]phenyl] 2-hydroxy-2-methylpropionate; S-[2-[1-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] 4-chlorophenoxythioacetate; S-[2-(1-isobutylcyclohexanecarbonylamino)phenyl] 4-chloro-phenoxythioacetate; and S-[2-(1-isobutylcyclohexanecarbonylamino)phenyl] 1-acetylpiperidine-4-thiocarboxylate, or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (19) A phamaceutical composition comprising as an active ingredient the compound as described in the above (8)-{18), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (20) Use of the compound represented by the above formula (I), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof, for production of a CETP activity inhibitor. (21) Use of the compound represented by the above formula (I), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof, for production of a prophylactic or therapeutic agent for hyperlipidemia. (22) Use of the compound represented by the above formula (I), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof, for production of a prophylactic or therapeutic agent for atherosclerosis. (23) A method for inhibition of CETP activity comprising administering to patients the compound represented by the above formula (I), or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. (24) A method for prevention or therapy of hyperlipidemia comprising administering to patients the compound represented by the above formula (I), or a prodrug compound/ a pharmaceutical^ acceptable salt, or hydrate or solvate thereof. (25) A method for prevention or therapy of atherosclerosis comprising administering to patients the compound represented by the above formula {I), or a prodrug compound, a pharmaceutical^ acceptable salt, or hydrate or solvate thereof. The term "straight chain or branched c^,,, alJcyl group" used herein means an alJcyl group having 1-10 carbon atoms which may be straight or branched. Specific examples thereof include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, 1-ethylbutyl, 2-ethylbutyl, 1-propylbutyl, 1,1-dimethylbutyl, l-isobutyl-3-methylbutyl, 1-ethylpentyl, 1-propylpentyl, 1-isobutylpentyl, 2-ethylpentyl, 2-isopropylpentyl, 2-tert-butylpentyl, 3-ethylpentyl, 3-isopropylpentyl, 4-methylpentyl, 1,4-dimethylpentyl, 2,4-dimethylpentyl, l-ethyl-4-methylpentyl, hexyl, 1-ethylhexyl, 1-propylhexyl, 2-ethylhexyl, 2-isopropylhexyl, 2-tert-butylhexyl, 3-ethylhexyl, 3-isopropylhexyl, 3-tert-butylhexyl, 4-ethylhexyl, 5-methylhexyl, heptyl, 1-ethylheptyl, 1-isopropylheptyl, 2-ethylheptyl, 2-isopropylheptyl, 3-propylheptyl, 4-propylheptyl, 5-ethylheptyl, 6-methylheptyl, octyl, 1-ethyloctyl, 2-ethyloctyl, nonyl, 1-methylnonyl, 2-methylnonyl, decyl, and the like groups. A straight chain or branched alkyl group having 1-8 carbon atoms is preferred. The term "C,^ lower alkyl group" used herein means an alkyl group having 1-4 carbon atoms, and specifically includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, and the like groups. The term "straight chain or branched C2_10 alkenyl group" means an alkenyl group having 2-10 carbon atoms with at least one or more double bonds, which may be straight or branched. Specific examples thereof include allyl, vinyl, isopropenyl, 1-propenyl, 1-methyl- 2-propenyl, 2-methyl-2-propenyl, 1-methyl-l-butenyl, crotyl, 1-methyl-3-butenyl, 3-methyl-2-butenyl, 1,3-dimethyl-2-butenyl, 1-pentenyl, l-methyl-2-pentenyl, l-ethyl-3-pentenyl, 4-pentenyl, L,3-pentadienyl, 2,4-pentadienyl, 1-hexenyl, l-methyl-2-hexenyl, 3-hexenyl, 4-hexenyl, l-butyl-5-hexenyl, 1,3-hexadienyl, 2,4-hexadienyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 1,3-heptadienyl, 2,4-heptadienyl, 1-octenyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 4-nonenyl, 5-nonenyl, 6-nonenyl, 7-nonenyl, 8-nonenyl, 9-decenyl, and the like groups. An alkenyl group having 2-8 carbon atoms, which may be straight or branched, is preferred. The term "halogen atom" means fluorine, chlorine, and bromine atoms. The term "halo-C^ alkyl group" means the above-described C^ lower alkyl group substituted with 1-3 halogens, which may be the same or different. Specific examples thereof include fluoromethyl, chloromethyl, bromomethyl, difluoromethyl, dichloromethyl, trifluoromethyl, trichloromethyl, chloroethyl, difluoroethyl, trifluoroethyl, pentachloroethyl, bromopropyl, dichloropropyl, trifluorobutyl, and the like groups. Trifluoromethyl and chloroethyl are preferred. The term "CM lower alkoxy group" means the alkoxy group containing the C^ lower alkyl group as described above. Examples thereof include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, and the like groups. The term "C^, lower alkylthio group" means the alkylthio group containing the cl_i lower alkyl group as described above. Examples thereof include methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, sec-butylthio, tert-butylthio, and the like groups. The term "C3.10 cycloalkyl group" means a cycloalkyl group having 3-10 carbon atoms, which may be monocyclic or polycyclic. Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, octahydroindenyl, decahydronaphthyl, bicyclo[2.2.1]heptyl, adamantyl, and the like groups . Preferred are those having 5-7 carbon atoms, including cyclopentyl, cyclohexyl, and cycloheptyl. The term "C5.8 cycloalkenyl group" means a cycloalkenyl group having 5-8 carbon atoms with one or more double bonds on the ring. Examples thereof include cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclopentadienyl, cyclohexadienyl, cycloheptadienyl, cyclooctadienyl, and the like groups. Preffered are those with 5-7 carbon atoms, including cyclopentenyl, cyclohexenyl, and cycloheptenyl. The term "C3_1D cycloalkyl C^,, alkyl group" means the above-described straight chain or branched c^,, alkyl group substituted with the above-described C,.^ cycloalkyl group. Specific examples thereof include cyclopropyImethyl, cyclopentylmethyl, cyclohexylmethyl, cyclohexyl cyclopentylmethyl, dicyclohexyImethyl, 1-cyclopentylethyl, 1-cyclohexylethyl, 2-cyclopropy1ethyl, 2-cyclopentylethyl, 2-cyclohexylethyl, 2-cycloheptylethyl, 1-cyclohexyl-1-methylethyl,1-cyclohexylpropyl, 2-cyclopentylpropyl, 3-cycXobutylpropyl, 3-cyclopentylpropyl, 3-cyclohexylpropyl, 3-cycloheptylpropyl, 1-cyclopropy1-1-methylpropyl, l-cyclohexyl-2-methylpropyl, 1-cyclopentylbutyl, 1-cyclohexylbutyl, 3-cyclohexylbutyl, 4-cyclopropylbutyl, 4-cyclobutylbutyl, 4-cyclopentylbutyl, 1-cyclohexyl-l-methylbutyl, l-cyclopentyl-2-ethylbutyl, l-cyclohexyl-3-methylbutyl, 1-cyclopentylpentyl, 1-cyclohexylpentyl, 1-cyclohexylraethylpentyl, 2-cyclohexylpentyl, 2-cyclohexylmethylpentyl, 3-cyclopentylpentyl, l-cyciohexyl-4-methylpentyl, 5-cyclopentylpentyl, 1-cyclopentylhexyl, 1-cyclohexylhexyl, l-cyclopentylmethylhexyl, 2-cyclopentylhexyl, 2-cyclopropylethylhexyl, 3-cyclopentylhexyl, 1-cyclohexylheptyl, 1-cyclopentyl-l-methylheptyl, 1-cyclohexyl-1,6-dimethylheptyl, 1-cycloheptyloctyl, 2-cyclopentyloctyl, 3-cyclohexyloctyl, 2-cyclopentylmethyloctyl, 1-cyclopentylnonyl, 1-cyclohexylnonyl, 3-cyclopropylnonyl, 1-cyclopentyldecyl, 1-cyclohexylunciecyl, 1-cyclopentyltridecyl, 2-cyclohexyltridecyl, and the like groups. The "aryl group" includes phenyl, naphthyl, anthryl, phenanthryl, biphenyl, and the like groups. Phenyl, naphthyl, and biphenyl groups are preferred. The "aralkyl group" means the above-described C^ lower alkyl group substituted with one or more aryl groups as described above. Examples thereof include benzyl, benzhydryl, trityl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl, naphthylmethy1, 2-naphthylethyl, 4-biphenylmethyl, 3 -(4-biphenyl) propyl, and the like groups. The "arylalkenyl group" means an alkenyl group having 2-4 carbon atoms substituted with the above-described aryl group. Examples thereof include 2-phenylvinyl, 3-phenyl-2-propenyl, 3-phenyl-2-methyl-2-propenyl, 4-phenyl-3-butenyl, 2-(1-naphthyl)vinyl, 2-(2-naphthyl)vinyl, 2-{4-biphenyl)vinyl, and the like groups. The "arylthio group" means an arylthio group containing the above-described aryl group and specifically include phenylthio, naphthylthio, and the like groups. The "heterocyclic ring group" means 5- and 6-membered aromatic or non-aromatic heterocyclic ring groups containing at least one or more, specifically 1-4, preferably 1-3, hetero atoms selected from nitrogen, oxygen, and sulfur atoms. Specific examples thereof include aromatic heterocyclic rings such as thiatriazolyl, tetrazolyl, dithiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, oxazolyl, pyrazolyl, pyrrolyl, furyl, thienyl, tetrazinyl, triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridyl, or the like groups and non-aromatic heterocyclic rings such as dioxoranyl, pyrrolidinyl, tetrahydrofuryl, tetrahydrothienyl, dithiadiazinyl, thiadiazinyl, morpholino, morpholinyl, oxazinyl, thia2inyl, piperazinyl, piperidyl, piperidino, pyranyl, thiopyranyl, or the like groups. Preferable groups are aromatic heterocyclic (heteroaryl) groups including furyl, thienyl, pyrrolyl, pyridyl, and the like and non-aromatic heterocyclic groups containing at least one nitrogen atom, including pyrrolidinyl, tetrahydrofuryl, piperazinyl, piperidyl, piperidino, and the like groups. The "heteroarylalkyl group" means the above-described C^ lower alkyl group substituted with the above-described 5- or 6-membered aromatic heterocyclic (heteroaryl) group and specifically include 2-thienylmethyl, 2-furylmethyl, 2-pyridylmethyl, 3-pyridylmethyl, 2-thienyl-2-ethyl, 3-furyl-l-ethyl, 2-pyridyl-3-propyl, and the like groups. The "acyl group" specifically includes formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, acryloyl, propioloyl, metacryloyl, crotonoyl, benzoyl, naphthoyl, toluoyl, hydroatropoyl, atropoyl, cinnamoyl, furoyl, thenoyl, nicotinoyl, isonicotinoyl, glucoloyl, lactoyl, glyceroyl, tropoyl, benzyloyl, salicyloyl, anisoyl, vaniloyl, veratoroyl, piperoniroyl, protocatechoyl, galloyl, cyclopentanecarbonyl, cyclohexanecarbonyl, cycloheptanecarbonyl, 1-methyl cyclohexanecarbonyl, 1-isopentylcyclopentanecarbonyl, 1-isopentyl cyclohexanecarbonyl, tert-butoxycarbonyl, methoxycarbonyl, ethoxycarbonyl, 2-(l-isopentylcyclohexanecarbonylamino)phenyl-thiocarbonyl, and the like groups. preferred are acetyl, tert-butoxycarbonyl , benzoyl, 1-methylcyclohexanecarbonyl, 1-isopentylcyclopentanecarbonyl, 1-isopentylcyclohexanecarbonyl, and 2-(l-isopentylcyclohexanecarbonylamino)phenylthiocarbonyl. The term "substituted or unsubstituted" of the "substituted or unsubstituted C3.10 cycloalkyl group", the "substituted or unsubstituted C5.a cycloalkenyl group", and the "substituted or unsubstituted C3.1D cycloalkyl Cj_10 alkyl group" described for R, R,, and the like means that the group may be substituted with 1-4 substituents which may be the same or different and any position may be arbitrarily substituted without any limitation. Specific examples of these groups are the above-described straight chain or branched C^^ alkyl group; the above-described straight chain or branched C2_10 alkenyl group; the above-described C3.10 cycloalkyl group; the above-described C5,8 cycloalkenyl group; the above-described C3,10 cycloalkyl C^la alkyl group; the above-described aryl group; an amino group; a Cj_, lower alkylamino group such as methylamino, ethylamino, or the like groups; an acylamino group such as acetylamino, propionylamino, benzylamino, or the like groups; an oxo group; the above-described aralkyl group; the above-described arylalkenyl group, and the like. The above substituents are recommended as substituents for R. Among these, preferred for Rx are the above-described straight chain orbranchedC[.10 alkyl group, the above-described C3_1D cycloalkyl group, the above-described C5_B cycloalkenyl group, the above-described aryl group, and the above-described amino group. The term "substituted or unsubstitueted" of the "substituted or unsubstitueted aryl group", the "heterocyclic group containing 1-3 nitrogen, oxygen, or sulfur atoms", the "substituted or unsubstitueted aralkyl group", the "substituted or unsubstitueted arylalkenyl group", the "substituted or unsubstitueted arylthio group", and the "substituted or unsubstitueted 5- or 6-membered heteroarylalkenyl group" described with respect to R, Rlf and the like means that the groups may be substituted with 1-4, preferably 1-3, substituents which may be the same or different and any position may be arbitrarily substituted without particular restriction. Examples of these groups include the above-described straight chain or branched C^K, alkyl group, preferably a straight chain or branched CLU aralkyl group; the above-described straight chain or branched Cs.10 alkenyl group, preferably a straight chain or branched c2_6 alkenyl group; the above-described halogen atom; a nitro group; the above-described amino group that may be substituted with the above-described CM lower alkyl group or the above-described acyl group; a hydroxyl group; the above-described c:,4 lower alkoxy group; the above-described C^ lower alkylthio group; the above-described halo-Ci.4 lower alkyl group; the above-described acyl group; an oxo group, and the like. The above substituents are recommended as substituents mainly for Rj. Among these, preferred foe R the above-described straight chain or branched Cj_6 alkyl group, the above-described halogen atom; and a nitro group. The "substituted or unsubstituted" of the "substituted or unsubstituted straight chain or branched Cj_1D alkyl group" described for R: and the like means that the group may be substituted with 1-3 substituents which may be the same or different and any position may be arbitrarily substituted without particular restriction. Examples of these groups are the above-described C^ lower alkoxy group; the above-described C^ lower alkyl group; the above-described amino group that may be substituted with an acyl or hydroxyl group; the above-described lower C^, alkylthio group; a carbamoyl group; a hydroxy1 group; the above-described halogen atom; the above-described acyloxy group containing an acyl group; a carboxyl group; the above-described acyl group; the above-described aryloxy group containing an aryl group that may be substituted; and the like. The "substituted or unsubstituted" of the "C1_i lower alkyl group" described with respect to R2 and the like means that the group may be substituted with 1-3 substituents which may be the same or different and any position may be arbitrarily substituted without particular restriction. Examples of the group include the above-described C1.A lower alkoxy group; the above-described amino group that may be substituted with the above-described C^ lower alkyl group or the above-described acyl group; the above-described C,_4 lower alkylthio group; a carbamoyl group; a hydroxyl group; a carboxyl group; the above-described acyl group; the above-described heterocyclic group {particularly aromatic heterocyclic groups such as thienyl or non-aromatic heterocyclic group such as tetrahydrofuryl); and the like. The term "substituted or unsubstituted" of the "substituted or unsubstituted amino group" and the "substituted or unsubstituted ureido group" described with respect to R: means that the groups may be substituted with one or more, preferably 1-2, substituents which may be the same or different and any position may be arbitrarily substituted without particular restriction. Examples of these groups are the above-described C,^ lower alkyl group; a hydroxyl group; the above-described acyl group; the above-described aryl group which may be substituted with the above-described CH lower alkoxy group; and the like. The "mercapto-protecting group" described with respect to 1 means commonly used mercapto protecting groups . Any organic residues that can be dissociated in vivo may be used without particular restriction. It may form a disulfide structure, that is dimer. Examples thereof include Cj_4 lower alkoxymethyl; C^, lower alkylthiomethyl; aralkyloxymethyl; aralkylthiomethyl; C3.lfl cycloalkyloxymethyl; C5.B cycloalkenyloxymethyl; C3_10 cycloalkyl c,.,0 alkoxymethyl; aryloxymethyl; arylthiomethyl; acyl; acyloxy; aminocarbonyloxymethyl; thiocarbonyl; and thio groups. Specific examples thereof include a C^, lower alkoxymethyl group with the above-described C,.4 lower alkoxy group; a Cj_ substituted or unsubstituted aralkyl group, the above-described substituted or unsubstituted arylalkenyl group, the above-described substituted or unsubstituted arylthio group, the above-described substituted or unsubstituted 5- or 6-membered heterocyclic group with 1-3 nitrogen, oxygen, or sulfur atoms, or the above-described substituted or unsubstituted 5- or 6-membered heteroarylalkyl group; an aminocarbonyloxymethyl group that may be substituted with the above-described substituted or unsubstituted straight chain or branched C^^ alkyl group, the above-described halo-Cj_4 alkyl group, the above-described Cj_4 lower alkoxy group, the above-described CM lower alkylthio group, the above-described substituted or unsubstituted Cj.1D cycloalkyl group, the above-described substituted or unsubstituted C3_1D cycloalkyl C^^ alkyl group, the above-described substituted or unsubstituted aryl group, the above-described substituted or unsubstituted aralkyl group, the above-described substituted or unsubstituted arylalkenyl group, the above-described substituted or unsubstituted 5- or 6-membered heterocyclic group with 1-3 nitrogen, oxygen, or sulfur atoms, or the above-described substituted or unsubstituted 5- or 6-membered heteroarylalkyl group; a thiocarbonyl group containing the above-described substituted or unsubstituted straight chain or branched C,.1(1 alkyl group, the above-described halo-Cj,4 lower alkyl group, the above-described CM lower alkoxy group, the above-described C^, lower alkylthio group, the above-described substituted or unsubstituted amino group, the above-described substituted or unsubstituted ureido group, the above-described substituted or unsubstituted C3_10 cycloalkyl group, the above-described substituted or unsubstituted C3.10 cycloalkyl C^^ alkyl group, the above-described substituted or unsubstituted aryl group, the above-described substituted or unsubstituted aralkyl group, the above-described substituted or unsubstituted arylalkenyl group, the above-described substituted or unsubstituted arylthio group, the above-described substituted or unsubstituted 5- or 6-membered heterocyclic group with 1-3 nitrogen, oxygen, or sulfur atoms , or the above-described substituted or unsubstituted 5- or 6-membered heteroarylalkyl group; and a thio group containing the above-described substituted or unsubstituted C^ lower alkyl or aryl group. More specifically, preferred as the "straight chain or branched C^u alkyl group" for R are methyl, ethyl, isopropyl, butyl, isobutyl, tert-butyl, heptyl, 1-propylbutyl, and l-isobutyl-3-methylbutyl. The "straight chain or branched C2_10 alkenyl group" referred to as Rare preferably allyl, vinyl, isopropenyl, l-methyl-2-propenyl, 2-methyl-2-propenyl, 1-methyl-1-butenyl, crotyl, l,3-dimethyl-2-butenyl, 1-penteny1, and 1-methyl-2-pentenyl. The Mhalo-Cj_4 lower alkyl group" for R means a c1.t lower alkyl group, particularly preferably a methyl group, substituted with the above-described halogen atom, particularly preferably fluorine, and chlorine, with being a trifluoromethyl group preferred. The "substituted or unsubstituted C3.1D cycloalkyl group" for R means a C3.10 cycloalkyl group (particularly preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, octahydroindenyl, decahydronaphthyl, adamantyl, and bicyclo[2.2 .1 ]-heptyl)that may be substituted with 1-4 substituents selected from the above-described straight chain or branched C1.1B alkyl group, {particularly preferably a Ci_B alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, 2,2-dimethylpropyl, 4-methylpentyl, 2-ethylbutyl, or the like), the above-described straight chain or branched C3.10 alkenyl group (particularly preferably a C2_B alkenyl group such as 1-methylvinyl, 2-methylvinyl, 3-methyl-3-propenyl, or the like), the above-described C3.l0 cycloalkyl group (particularly preferably a C3.7 cycloalkyl group such as cyclopropyl, cyclopentyl, cyclohexyl, or the like), the above-described C5_8 cycloalkenyl group (particularly preferably a C5.6 cycloalkenyl group such as cyclopentenyl, cyclohexenyl, or the like), the above-described C3_10 cycloalkyl CW() alkyl group (particularly preferably a C3_7 cycloalkyl Cw alkyl group such as cyclopropylmethyl, 2-cyclopropylethyl, 2-cyclopentylethyl, cyclohexylmethyl, 2-cyclohexylethyl, or the like), the above-described aryl group (particularly preferably a phenyl group), an oxo group, the above described aralkyl group (particularly preferably a phenyl Ci,i lower alkyl group such as benzyl, phenethyl, or the like), and the above-described arylalkenyl group (particularly preferably a 2-phenylvinyl group). Preferable examples thereof include 2,2,3,3-tetramethylcyclopropyl, 1-isopentylcyclobutyl, 1- isopropylcyclopentyl, X-isobutylcyclopentyl, 1- isopentylcyclopentyl, 1-cyclohexylmethylcyclopentyl, cyclohexyl, 1-methylcyclohexyl, 1-ethylcyclohexyl, 1-propylcyclohexyl, 1-isopropylcyclohexy1, 1-butylcyclohexyl, 1-isobutylcyclohexyl, 1 -pentylcyclohexyl, 1-isopentylcyclohexyl, l-(2,2-dimethylpropyl)-cyclohexyl, 1-(4-methylpentyl)cyclohexyl, 1-(2-ethylbutyl) cyclohexyl, 4-tert-butyl-1-isopentylcyclohexyl, 1-cyclopropylcyclohexyl, 1-bicyclohexyl, 1-phenylcyclohexyl, 1-cyclopropylmethylcyclohexyl, 1-cyclohexylmethylcyclohexyl, 1- (2~ cyclopropylethy1) cyclohexyl, 1-(2-cyclopentylethy1)cyclohexyl, l-(2-cyclohexylethyl)cyclohexyl, 4-methylcyclohexyl, 4-propyl-cyclohexyl, 4-isopropylcyclohexyl, 4-tert-butylcyclohexyl, 4-pentylcyclohexyl, 4-bicyclohexyl, 1-isopentylcycloheptyl, 3a-octahydroindenyl, 4a-decahydronaphthyl, 1-adamantyl, and 7,7-dimethyl-l-(2-oxo)-bicyclo[2.2.l]heptyl. The site of substitution is not specifically limited, but particularly preferably at position 1. Any substitution group as described above may be used, but the straight chain or branched C^^ alkyl group is particularly preferred. The substituent for the "substituted or unsubstituted C5_9 cycloalkenyl group" for H is the same as that for the above "substituted or unsubstituted C3,10 cycloalkyl group" . Specifically, it means a cycloalkenyl group {especially cyclopentenyl and cyclohexenyl) that may have 1-4 substituents selected from the above-described straight chain or branched c^^ alkyl group {particularly preferably a C^g alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, 2,2-dimethylpropyl, 4-methylpentyl, or the like), the above-described straight chain or branched C;.J0 alkenyl group (particularly preferably a C2_B alkenyl group such as 1-methylvinyl, 2-methylvinyl, 3-methyl-3-propenyl, and the like), the above-described C3_10 cycloalkyl group {particularly preferably a C3,7 cycloalkyl group such as cyclopropy1, cyclopentyl, cyclohexyl, or the like), the above-described C5_B cycloalkenyl group (particularly preferably a cs-6 cycloalkenyl group like cyclopentenyl, cyclohexenyl, or the like), the above-described C3,10 cycloalkyl C^o alkyl group {particularly preferably a C3_7 cycloalkyl C,.( lower alkyl group such as cyclopropyl methyl, 2-cyclopropylethyl, 2-cyclopentylethyl, cyclohexylmethyl, 2-cyclohexylethyl, or the like), the above-described aryl group (particularly preferably a phenyl group), an oxo group, the above-described aralkyl group (particularly preferably a phenyl cI-4 lower alkyl group such as benzyl, phenethyl, or the like), and arylalfcenyl group (particularly preferably 2-phenylvinyl). Preferable examples of the cycloalkenyl group includes 1- isopropyl-2-cyclopentenyl, l-isopropyl-3-cyclopentenyl, l- isobutyl-2-cyclopentenyl, l-isobutyl-3-cyclopentenyl, l- isopentyl-2-cyclopentenyl, l-isopentyl-3-cyclopentenyl, 1- cyclohexylmethyl-2-cyclopentenyl, l-cyclohexylmethyl-3- cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyciohexenyl, l-methyl-2-cyclohexenyl, l-methyl-3-cyclohexenyl, l-ethyl-2- cyclohexenyl, l-ethyl-3-cyclohexenyl, 1-propyl-2-cyciohexenyl, l-propyl-3-cyclohexenyl, 1-isopropy1-2-cyciohexenyl, 1- isopropyl-3-cyclohexenyl, l-butyl-2-cyclohexenyl, l-butyl-3- cyclohexenyl, l-isobutyl-2-cyclohexenyl, l-isobutyl-3- cyclohexenyl, 1-penty1-2-cyciohexenyl, l-pentyl-3-cyciohexenyl, l-isopentyl-2-cyclohexenyl, l-isopentyl-3-cyclohexenyl, l-(2,2- dimethylpropyl)-2-cyclohexenyl, 1-{2,2-dimethylpropyl)-3- cyclohexenyl, 1-(4-methylpentyl)-2-cyclohexenyl, 1- (4- methylpentyl)-3-cyciohexenyl, l-cyclopropyl-2-cyciohexenyl, 1- cyclopropyl-3-cyclohexenyl, l-cyclohexyl-2-cyclohexenyl, 1- cyclohexy1-3-cyciohexenyl, 1-pheny1-2-cyciohexenyl, l-phenyl-3- cyclohexenyl, l-cyclopropylmethyl-2-cyclohexenyl, 1-cyclo propylmethy1-3-cyciohexenyl, 1-cyclohexylmethy1-2-cyciohexenyl, l-cyclohexylmethyl-3-cyclohexenyl, 1-(2-cyclopropylethyl)-2- cyclohexeny1, 1-(2-cyclopropylethyl)-3-cyciohexenylf 1- (2- cyclopentylethyl)-2-cyclohexenyl, 1-(2-cyclopentylethyl)-3- cyclohexenyl, 1-(2-cyclohexylethyl)-2-cyclohexenyl, and 1 - (2- cyclohexylethyl) -3-cyclohexenyl. There is no special restriction on the substitution position, but the particularly preferred position is position 1. Any one of the above substituents may be used, but the straight chain or branched c^^ alkyl group or the C}_1B cycloalkyl The "substituted or unsubstituted C3.I0 cycloalkyl C^,, alkyl group" for R means a c3_10 cycloalkyl CUD alkyl group (particularly preferably cyclohexylmethyl, 1-cyclohexylethyl, 1-cyclohexyl-l-methylethyl, l-cyclohexyl-2-methylpropyl, l-cyclohexyl-3-methylbuty1, 1-cyclohexylhexyl, l-cyclohexyl-4-methylp^ntyl, and 1-cyclohexylheptyl) alkyl group of which is straight chain or branched and which may have 1-4 substituents selected from the above-described C3-io cycloalkyl group (particularly preferably a C3_7 cycloalkyl group such as cyclopentyl or cyclohexyl), the above-described CS_B cycloalkenyl group (particularly preferably a C5_7 cycloalkenyl group such as cyclopentenyl or cyclohexenyl), and the above-described aryl group (particularly preferably a phenyl group). There is no special restriction on the substitution position. The above--described substituents may be placed at the straight chain or branched C,.,j alkyl moiety. Preferable examples of the C3_10 cycloalkyl C^,, aJkyl group include cyclohexylmethyl, 1-cyclohexylethyl, cyclohexylcyclo-pentylmethyl, dicyclohexylmethyl, 1-cyclohexyl-1-methyiethyl, 1-cyclohexyl-2-methylpropyl, l-cyclohexyl-3-methylbutyl, 1-cyclohexyl-4-methylpentyl, 1-cyclohexylhexyl, and 1-cyclohexylheptyl. The " substituted or unsubstit.-at.ed aryl group" for ^ -means an aryl group (particularly preferably a phenyl group) that may have 1-4 substituents selected from the above-described straight chain or branched C1_6 alkyl group (particularly preferably a tert-butyl group), the above-described halogen atom (particularly preferably fluorine and chlorine), and a nitro group. Preferable examples of the aryl group are phenyl, 2-chlorophenyl, 4-nitrophenyl, and 3,5-di-tert-butylphenyl. The "substituted or unsubstituted aralkyl" for R means an aralkyl group (particularly preferably benzyl, benzhydryl, and trityl) which may have substituents selected from the above^described halogen atom (particularly preferably fluorine and chlorine), a nitro group, and a hydroxy group, and in which the C:_4 lower alkyl group is straight chain or branched. There is no special restriction on the position of substitution. The straight chain or branched c,_, lower alkyl moiety may be substituted. Preferable examples of the aralkyl group are benzyl and trityl. The "substituted or unsubstituted 5- or 6-membered heterocyclic group having 1-3 nitrogen, oxygen or sulfur atoms" for R means the above-described heterocyclic group that may have 1-4 substituents selected from the above-described straight chain or branched C^s alkyl group (particularly preferably a tert-butyl group), the above-described halogen atom (particularly preferably fluorine and chlorine), and a nitro group. The heterocyclic group is preferably an aromatic heterocyclic group, particularly preferably furyl, thienyl, and pyridyl. The " substituted or unsubstituted straight chain or branched C[_lD alkyl group" for R: means a straight chain or branched C^10 alkyl group that may have a substituent selected from the above-described halogen atom (particularly preferably fluorine and chlorine), the above-described c1-4 lower alkoxy group (particularly preferably a methoxy group), an amino group that may be substituted with the above-described c,.( lower alkyl group (particularly preferably a methyl group), the above-described acyl group (particularly preferably an acetyl group), or a hydroxyl group, the above-described Cj.4 lower alkylthio group (particularly preferably a methylthio group), a carbamoyl group, a hydroxyl group, an acyloxy group having the above-described acyl group (particularly preferably an acetyloxy group), a carboxyl group, an acyl group (particularly preferably a methoxycarbonyl group), and an aryloxy group having the above-described substituted or unsubstituted aryl group (particularly preferably a phenoxy group and a 4-chlorophenoxy group) . preferable examples of the alkyl group include methyl, chloromethyl, ethyl, isopropyl, l-methyl-2-pentyl, octyl, methoxymethyl, dimethylaminomethyl, acetylaminomethyl, 1-acetyl aminoethyl, 1-acetylamino-2-methylpropyl, l-acetylamino-3-methylbutyl, 1-acetylamino-3-methylthiopropyl, 1-acetylamino-3-carbamoylpropyl, 1-hydroxy-1-methylethyl/ 1-acetyloxy-1-methylethyl, 4-carboxybutyl, 2-methoxycarbonylethyl, phenoxymethyl, and 4-chlorophenoxymethyl. The "Cl_i lower alkoxy group" for Rx is preferably a methoxy group and a tert-butoxy group. The "Cn lower alkylthio group" for RL is preferably a methyl-thio group. The "substituted or unsubstituted amino group" for RX means an amino group that may have a substituent selected from the above-described C1_i lower alkyl group (particularly preferably ethyl, isopropyl, and tert-butyl), the above-described acyl group {particularly preferably acetyl and benzoyl), and the above-described aryl group (particularly preferably phenyl and 4-methoxyphenyl) that may be substituted with the above-described C^ lower alkoxy group. Preferable examples of the amino group are ethylamino, isopropylamino, tert-butylamino, phenylamino, and 4-methoxyphenylamino. The "substituted or unsubstituted ureido group" for RL means a ureido group that may have a substituent selected from the above-described C1_, lower alkyl group (particularly preferably methyl and ethyl), the above-described acyl group (particularly preferably acetyl and benzoyl), and the above-described aryl group (particularly preferably phenyl and 4-methoxyphenyl) that may be substituted with the above-described c,_« lower alkoxy group, with an N,N' -diphenylureido group being preferred. The "substituted or unsubstituted C3_10 cycloalkyl group" for Rt means a C3_10 cycloalkyl group (particularly preferably cyclopropyl and cyclohexyl) that may have a substituent selected from the above-described straight chain or branched C,.10 alkyl group (particularly preferably methyl, tert-butyl, and isopentyl), an amino group, an amino group (particularly preferably methylamino, ethylamino, acetylamino, and benzylamino) that may be substituted with the above-described C^ lower alkyl or acyl groups. Preferable examples the cycloalkyl group are cyclopropyl, cyclohexyl, 1-methylcyclohexyl, 1-isopentylcyclohexyl, 1-aminocyclohexyl, 1-acetylaminocyclohexyl, and 4-tert-butylcyclohexyl. The "substituted or unsubstituted C3_10 cycloalkyl c,.1( alkyl group" for RL means a C3_10 cycloalkyl Cl_1D alkyl group which may have a substituent selected from the above-described C3_1D cycloalkyl group (particularly preferably cyclopentyl and cyclohexyl), the above-described c5.B cycloalkenyl group (particularly preferably cyclopentenyl and cyclohexenyl), and the above-described aryl group {particularly preferably a phenyl group) and in which the cl.l0 alkyl moiety is straight chain or branched. There is no special restriction on the position of substitution. The straight chain or branched C^o alkyl moiety may be substituted. A cyclohexylmethyl group is preferred as the C3_,0 cycloalkyl C^^ alkyl group. The "substituted or unsubstituted aryl group " for Rt means an aryl group (particularly preferably phenyl and naphthyl) that may have a substituent selected from the above-described straight chain or branched c>6 alkyl group (particularly preferably methyl and tert-butyl group), the above-described halogen atom (particularly preferably fluorine and chlorine), a nitro group, a hydroicyl group, the above-described C^ lower alkoxy group (particularly preferably a methoxy group), and the above-described acyl group (particularly preferably a 2-(1-isopentylcyclohexanecarbonylamino)phenylthio-carbonyl group). Preferable examples of the aryl group include phenyl, 1-naphthyl, 2-naphthyl, 2-chlorophenyl, 2,6-dichlorophenyl, 2,6-dimethylphenyl, 2-methoxyphenyl, 2-nitrophenyl, 4-nitrophenyl, 3,5-di-tert-butyl-4-hydroxyphenyl, and 4-[2-(1-isopentylcyclo-hexanecarbonylamino)phenylthiocarbonyl]phenyl. The "substituted or unsubstituted aralkyl group " for Rj means an aralkyl group (particularly preferably benzyl, phenethyl, 3-phenylpropyl, naphthylmethyl, and biphenylmethyl) that may have a substituent selected from the above-described halogen atom (particularly preferably fluorine and chlorine), a nitro group, an amino group (particularly preferably amino, acetylamino, pivaloylamino, 1-methylcyclohexanecarbonyl-amino, tert-butoxycarbonylamino, and benzoylamino) that may be substituted with the above-described C%_, lower alkyl group or the above-described acyl group ,and a hydroxyl group, and in which the C1-4 lower alkyl group are straight chain or branched. There is no special restriction on the position of substitution. The straight chain or branched cw lower alkyl moiety may be substituted. Preferable examples of the aralkyl group include benzyl, phenethyl, 3-phenylpropyl, 2-naphthylmethyl, 4-biphenylmethyl, benzhydryl, 2-chlorophenylmethyl, 3-chloro phenylmethyl, 4-chlorophenylmethyl, 2-nitrophenylmethyl, 4-nitrophenylmethyl, 2-pivaloylaminophenylmethyl, 2-(l-methylcyclohexanecarbonylamino)phenylmethyl, 2-tert-butoxy-carbonylaminophenylmethyl, 3-acetylaminophenylmethyl, 3-(l-methylcyclohexanecarbonylamino)phenylmethyl, a-aminobenzyl, a-acetylaminobenzyl, a-{1-methylcyclohexanecarbonylamino)benzyl, a-benzoylaminoben2yl, a-aminophenethy1, a-acetylaminophenethyl, and l-acetylamino-2-(4-hydorxyphenyl) ethyl. The "substituted or unsubstituted arylalkenyl group" for R2 means an arylalkenyl group (particularly phenylvinyl) that may have a substituent selected from the above-described straight chain or branched CH lower alkyl group (particularly preferably methyl and tert-butyl), the above-described halogen atom (particularly preferably fluorine and chlorine), anitrogroup, and a hydroxyl group, with a 2-phenylvinyl group being preferred. The "substituted or unsubstituted arylthio group" for R: means an arylthio group (particularly preferably a phenylthio group) that may have a substituent selected from the above-described halogen atom (particularly preferably fluorine and chlorine), a nitro group, and an amino group that may be substituted with the above-described C^, lower alkyl group or the above-described acyl group (particularly preferably The "substituted or unsubstituted 5- or 6-membered heterocyclic ring groups with 1-3 nitrogen, oxygen, or sulfur atoms" for Ri means heterocyclic ring groups (particularly preferably an aromatic heterocyclic group such as pyridyl or a non-aromatic heterocyclic group such as piperidyl or pyrrolidinyl) tha.t may have substituents selected from the above-described straight chain or branched C^s alkyl group (particularly preferably a methyl group), a halogen atom (particularly preferably fluorine and chlorine), the above-described acyl group (particularly preferably Acetyl and benzoyl), and an oxo group. Preferable examples thereof are 3- pyridyl, l-methyl-4-piperidyl, l-acetyl-4-piperidyl, 5-oxo-2-pyrroJidinyl, l-acetyl-2-pyrrolidinyi, and l-benzoyl-2-pyrrolidinyl. A 4-piperidyl group such as l-methyl-4-piperidyl or l-acetyl-4-piperidyl group is particularly preferred. The "substituted or unsubstituted 5- or 6-membered heteroarylalkyl group" for R: means the above-described heteroarylalkyl group (particularly preferably a 2-tenyl group) that may be substituted with the above-described straight chain or branched ci-6 alkyl group (particularly preferably a methyl group) and the above-described halogen atom (particularly preferably fluorine and chlorine). A 2-tenyl group is preferred. The "substituted or unsubstituted d.4 lower alkyl group" for R2 means a Cw lower alkyl group {particularly preferably a methyl group) that may have 1-3 substituents selected from the above-described C^A lower alkoxy group (particularly preferably a methoxy group), an amino group that may be substituted with the above-described CM lower alkyl or acyl group (particularly preferably a dimethylamino group), the above-described C^, lower alkylthio group (particularly preferably a methylthio group), a carbamoyl group, a hydroxy1 group, a carboxyl group, the above-described acyl group (particularly preferably a methoxyc^rbonyl group), and the above-described heterocyclic group (particularly preferably an aromatic heterocyclic group such as thienyl or a non-aromatic heterocyclic group such as tetrahydrofuryl). A tetrahydro-furylmethyl group is preferred. The "substituted or unsubstituted a.ryl group" for R2 is the same as that for R,. Preferable examples thereof are a phenyl group, a halogenated phenyl group, an acylamino-substituted phenyl group, and the like. The "halogen atom" for Xlf X2, X;, x4 means a halogen atom including fluorine, chlorine, bromine, and the like, with fluorine and chlorine being preferred. The "C,.4 lower alkyl group" for Xlf x;, X3, X4 is preferably a methyl group. The "halo-Cj_4 lower alkyl group" for Xj, X2, X3, X4 means a C,.4 lower alkyl group (particularly preferably a methyl group) substituted with the above-described halogen atom (particularly preferably fluorine and chlorine). A trifluoromethyl group is preferred. The "Cl-4 lower alkoxy group" for X:, x2, X3, X4 is preferably a methoxy group. The "acyl group" for xw X3, X,, X4 is preferably a benzoyl group. The "aryl group" for Xir X2, X3, X, is preferably a phenyl group. The "l-substituted-C3_10 cycloalkyl group" for R1 ' means a cycloalkyl group (for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, preferably a C5_7 cycloalKyl group, particularly preferably a cyclohexyl group) that is substituted at position 1 with substituents selected from the above-described straight chain or branched Ci_10 alkyl group (particularly preferably a C,_„ alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, 2,2-dimethylpropyl, 4-methylpentyl, or 2-ethylbutyl), the above-described straight chain or branched C2_ ,„ alkenyl group (particularly preferably a C2_e alkenyl group such as 1-methylvinyl, 2-methylvinyl, or 3-methyl-3-propenyl), the above-described C3_1D cycloalkyl (particularly preferably a C3_7 cycloalkyl group such as cyclopropyl, cyclopentyl, or cyclohexyl), the above-described C5.B cycloalkenyl group (particularly preferably a C5_6 cycloalkenyl group such as cyclopentenyl or cyclohexenyl), the above-described C3_10 cycloalkyl C,.10 alkyl group (particularly preferably a C3.7 cycloalkyl Cj_4 lower alkyl group such as cyclopropylmethyl, 2-cyclopropylethyl, 2-cyclopentylethyl, cyclohexylmethyl, or 2-cyclohexylethyl), the above-described aryl group {particularly preferably a phenyl group), the above^described aralkyl group (particularly preferably a phenyl C^ lower alkyl group such benzyl and phenethyl), and an arylalkenyl group (particularly preferably 2-phenylvinyl). Preferable examples of the 1-substituted-C3_10 cycloalkyl group include 1-isopentylcyclobutyl, 1-isopropylcyclopentyl, 1-isobutylcyclopentyl, 1-isopentyl cyclopentyl, 1-cyclohexylmethylcyclopentyl, 1-methylcyclohexyl, 1-ethylcyclohexyl, 1-propylcyclohexyl, 1-isopropylcyclohexyl, 1-butylcyclohexyl, 1-isobutylcyclohexyl, 1-pentylcyclohexyl, 1-isopentylcyclohexyl, 1-(2,2-dimethylpropyl)cyclohexyl, 1-(4- methylpentyl)cyclohexyl, l-(2-ethylbutyl)cyclohexyl, 1-cyclopropylcyclohexyl, 1-bicyclohexyl, 1-phenylcyclohexyl, 1-cyclopropylmethylcyclohexyl, 1-cyclohexylmethylcyclohexyl, l-(2-cyclopropylethy1)cyclohexyl, 1-(2-cyclopentylethyl)cyclohexyl, l-(2-cyclohexylethyl)cyclohexyl, and 1-isopentylcycloheptyl. The straight chain or branched Cj.10 alkyl group is particularly preferable as a substituent at position 1. The " l-substituted-C5_B cycloalkenyl group" for R' ' means a cycloalkenyl groups{particularly preferably a Cs_6 cycloalkenyl group such as cyclopentenyl or cyclohexenyl) that is substituted at position 1 with substituents selected from the above-described straight chain or branched C1-10 alkyl group (particularly preferably a C,_e alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, 2,2-dimethyl propyl, and 4-methylpentyl), the above-described straight chain or branched C3_10 alkenyl group (particularly preferably a C3_e alkenyl group such as 1-methylvinyl, 2-methylvinyl, or 3-methyl-3-propenyl), the above-described C3_10 cycloalkyl group (particularly preferably a C3.7 cycloalkyl group such as cyclopropyl, cyclopentyl, or cyclohexyl), the above-described C5.B cycloalkenyl group (particularly preferably a C5.6 cycloalkenyl group such as cyclopentenyl or cyclohexenyl), the above-described C3.1(1 cycloalkyl CLK, alkyl group (particularly preferably a C3_, cycloalkyl C1-4 lower alkyl group such as cyclopropylmethyl, cyclopropylethyl, 2-cyclopentylethyl, cyclohexylmethyl, or 2-cyclohexylethyl), the above-described aryl group (particularly preferably a phenyl group), the above-described aralkyl group (particularly preferably a phenyl Cj_4 lower alkyl group such as benzyl or phenethyl), and the above-described arylalkenyl group (particularly preferably a 2-phenylvinyl group). Preferable examples of the l-substituted-C5.B cycloalkenyl group include l-isopropyl-2-cyclopentenyl, 1-isopropyl-3-cyclopentenyl, l-isobutyl-2-cyclopentenyl, 1-isobuty1-3-cyclopentenyl, 1-isopenty1-2-cyclopentenyl, 1-isopentyl-3-cyclopentenyl, l-cyclohexylmethyl-2-cyclopentenyl, l-cyclohexylmethyl-3-cyclopentenyl, 1-methyl-2-cyclohexenyl, 1-methyl-3-cyclohexenyl, l-ethyl-2-cyclohexenyl, l-ethyl-3-cyclohexenyl, 1-propyl-2-cyclohexenyl, 1-propy1-3-cyclohexenyl, l-isopropyl-2-cyclohexenyl, l-isopropyl-3-cyclohexenyl, 1-butyl- 2-cyclohexenyl, l-butyl-3-cyclohexenyl, l-isobutyl-2-cyclohexenyl, l-isobutyl-3-cyclohexenyl, l-pentyl-2-cyclohexenyl, l-pentyl-3- cyclohexenyl, i-igopentyl-2-cyclohexenyl, l-isopentyl-3- cyclohexenyl, l-{2,2-dimethylpropyl)-2-cyclohexenyl, 1-(2,2- dimethylpropyl)-3-cyclohexenyl,l-{4-methylpentyl)-2-cyclohexenyl, 1-(4-methylpentyl)-3-cyclohexenyl, l-cyclopropyl-2-cyclohexenyl, l-cyclopropyl-3-cyclohexenyl, l-cyclohexyl-2-cyclo'nexenyl, 1- cyclohexyl-3-cyclohexenyl, l-phenyl-2-cyclohexenyl, l-phenyl-3- cyclohexenyl, i-cyclopropylmethyl-2-cyclohexenyl, 1- cyclopropylmethyl-3-cyclohexenyl, l-cyclohexylmethyl-2- cyclohexenyl, i-cyclohexylmethyl-3-cyclohexenyl, l-(2-cyclopropylethyl)-2-cyClohexenyl, 1-(2-cyclopropylethyl)-3-cyclohexenyl, 1-(2-cyclopentylethyl)-2-cyclohexenyl, 1- (2-cyclopentylethyl)-3-cydohexenyl, l-(2-cyclohexylethyl)-2-cyclohexenyl, and 1-(2-cyclohexylethyl)-3-cyclohexenyl. The straight chain or branched C1-10 alkyl group is particularly preferable as a substituent at position 1. The "prodrug compound" means the derivatives of compounds of the present invention having a chemically or metabolically degradable group, which exhibit pharmaceutical activity by degradation through hydrolysis or solvolysis, or under physiological conditions. The "pharmaceutically acceptable salt" means any compound that is an atoxic salt formed with the compound represented by the above formula (I). Examples of such a salt include inorganic acid salts such as hydrochloride^, hydrobromides, hydroiodides, sulfates, nitrates, phosphates, carbonates, bicarbonates, or perchlorates; organic acid salts sucti as formates, acetates, trifluoroacetates, propionates, tartrates, glycolates, succinates, lactates, maleates, hydroxymaleates, methylmaleates, fumarates, adipiates, tartrates, malates, citrates, benzoates, cinnamates, ascorbates, salicylates, 2-acetoxybenzoates, nicotinates, or isonicotinates; sulfonates such as methane sulfonates, ethane sulfonates, isethionates, benzene sulfonates, p-toluene sulfonates, or naphthalene sulfonates-, salts of acidic amino acids such as aspargates or glutamates; alkali metal salts such as sodium salts or potassium salts, alkaline earth metal salts such as magnesium salts or calcium salts; ammonium salts; organic base salts such as trimethylamines, triethylamines, pyridine salts, picoline salts, dicyclohexylamine salts or N,N'-dibenzyl ethylenediamine salts; and salts of amino acids such as lysine salts or and arginine salts. Depending on the circumstances, hydrates or solvates with alcohols may be used. More specifically, a 1-isobutylcyclohexyl group, a l-(2-ethylbutyl) cyclohexyl group, and a 1-isopentylcyclohexyl group are particularly preferable as R in the formula (I), -CO- is particularly preferable as Y, a hydrogen atom is particularly preferable as xif X2, X3, X,, and an isobutyryl group and a 1-acety 1-4-piperidine carbonyl group are particularly preferable as Z. The compound of the present invention inhibits CETP activity and is expected as a conventionally unknown, new type of a preventive or therapeutic agent for hyperlipidemia or atherosclerotic diseases. When used as a pharmaceutical preparation, the compound of the present invention represented by the formula (I) or a pharmaceutical^ acceptable salt thereof can be usually used together with known pharmacologically acceptable carriers, excipients, diluents, extenders, disintegrators, stabilizers, preservatives, buffers, emulsifiers, aromatics, colorants, sweeteners, viscosity increasing agents, flavor improving agents, solubilizers, and other additives. More specifically, the compound can be formulated into dosage forms, such as tablets, pills, powders, granules, suppositories, injections, eye drops, liquid drugs, capsules, troches, aerosols, elixirs, suspensions, emulsions, or syrup, together with water, plant oil, alcohols such as ethanol or benzyl alcohol, polyethylene glycol, glyceroltriacetate gelatin, lactose, carbohydrates such as starch, magnesium stearates, talc, lanolin, and vaseline, which can be administered orally or parenterally. The above pharmaceutical preparations contain the compound of the present invention represented by the formula (I) or a pharmaceutical^ acceptable salt thereof in an amount effective to inhibit CETP activity and prevent or treat hyperlipidemia, atherosclerotic diseases, or the like diseases attributable to CETP activity. One skilled in the art can easily determine such an effective amount. Doses may vary depending on the type and degree of diseases, the compounds to be administered, the route of administration/ the age, sex, and body weight of the patients. In the case of oral administration, it is usually desirable to administer the compound (I) to an adult 1-1000 mg, particularly 50-800 mg per day. The compound of the present invention....can be produced using the following method, but it is needless to say that the method of producing the compound of the present invention is not limited to this method. tStep 1] The compound (II-2) {in the formula R, Xlf X2, X3, X,, and Y are as described above) can be synthesized by reacting the compound (VI) (in the formula X:, x;, X3, and X« are as described above) with the compound (XII) (in the formula X represents a halogen atom and R and Y are as described above) in the presence of a base such as pyridine, triethylamine, N-methylmorpholine, or N-methylpiperazine in an organic solvent such as methylene chloride, chloroform, toluene, ether, tetrahydrofuran, dioxane, diisopropyl ether, dimethoxyethane, or hexane, water, or a mixture of these solvents, or in the absence of a solvent, under cooling through heating temperature. The compound (III-2 ) can be synthesized from the compound (II-2 ) by the following step 2. [Step 2] The compound (III-2) (in the formula R, Xj, X2, X3, X4,and Y are as described above) can be synthesized by allowing the compound (II-2 ) (in the formula R, X:, X2, X3, x The compound (II-2) or (IV-2) can also be synthesized from the compound (III-2) using the following step 3 or 4. [Step 3] The compound (II-2) (in the formula R, x1# X3, X3, X,, and Y are as described above) can be synthesized by allowing the compound (III-2) (in the formula R, K:, X2, X3, X4, and Y are as described above) to react in the presence of an oxidizing agent such as iodine, hydrogen peroxide, potassium permanganate, or dimethylsulfoxide, in an organic solvent such as methanol, ethanol, ether, dioxane, tetrahydrofuran, diisopropyl ether, dimethoxyethane, acetone, toluene, hexane, dimethylformamide, or acetic acid, water, or a mixture of these solvents, or in the absence of a solvent, under cooling through heating temperature. [Step 4] The compound (IV-2) (in the formula R, R1( xlf X,, X3, x Y are as described above), or thiocarbonic halides R,-S-YX (Rlf X and Y are as described above) in the presence of a base such as pyridine, triethylamine, N-methylmorpholine, or N-methylbipiperazine, in an organic solvent such as methylene chloride, chloroform, toluene, ether, dioxane, tetrahydro furan, diisopropyl ether, dimethoxy ethane, or hexane, water, or a mixture of these solvents, or in the absence of a solvent, under cooling through heating temperature. Alternatively, the compound (IV-2) can be synthesized by reacting the compound (III-2) with carboxylic acid Rj-COOH (in the formula Rt is as described above) or thiocarboxylic acid Rj-YSH (in the formula Rj and Y are as described above) using a coupling agent such as l-ethyl-3-(3-dimethylaminopropylJcarbodiimide hydro-chloride, dicycloYiexylcarbodiimide, diphenylphosphorylazide, or carbonyldiimidazole, in the presence of an activating agent, if required, such as 1-hydroxybenzotriazole, hydroxysuccinimide, or N-hydroxy-5-norbornene-2,3-dicarboxylic acid imide, in an organic solvent such as dimethylformamide, dichloromethane, chloroform, acetonitrile, tetrahydrofuran, dimethylsufoxide, carbon tetrachloride, or toluene, or a mixture of these solvents, under cooling through heating temperature(The reaction may be carried out in the presence of a base such as pyridine or triethylamine). Furthermore, the compound (IV-2) can be synthesized by reacting the compound {III-2) with carboxylic acid R^COOH (in the formula Rj is as described above) in the presence of a base such as triethylamine or pyridine and in the presence of ethyl chlorocarbonate or the like, in a organic solvent such as ethyl acetate or tetrahydrofuran, or a mixture of these solvents, under cooling through heating temperature. When Rj has a carboxyl group, this above step may be conducted using the corresponding ester to obtain the compound by hydrolysis with acid using the known method. The compound (IV-2) can also be synthesized by subsequently conducting the step 4 following the above step 2 or the step 7 below, or the step 10 below, without isolating the compound (ln-2). The compound (V-2) can be synthesized by conducting the following step 5 or 5'. The step 5 is suitable especially when R2 is the lower alkyl group that may have substituents and the step 5' is suitable especially when R2 is the aryl group that may have substituents. [Step 5] The compound (V-2) (in the formula R, R2, XW X2, X3, x4,and Y are as described above) can be synthesized by allowing R2-x (in the formula R2 and X is as described above) and a sulfur compound like sodium thiosulfate to react in an organic solvent such as ethanol, methanol, tetrahydrofuran, dioxane, dimethoxyethane, acetone, or acetonitrile, water, or a mixture of these solvents, at room temperature through heating temperature, and adding the compound (111-2) (in the formula R, X,, X2, X3, X,, and Y are as described above) and a basic aqueous solution such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, or sodium bicarbonate to the resulting solution under ice-cooling through heating temperature. [Step 5'] The compound (V-2) (in the formula R, R2, x1# X2, X3, x,, and Y are as described above) can be synthesized by reacting R;-SH (in the formula R2 is as described above) with trimethylsilane-imidazole in carbon tetrachloride under ice-cooling through room temperature, adding to the resulting solution a reaction mixture resulted from reacting the compound (II-2) (in the formula R, Xlt X2, Xif X4, and Y are as described above) with sulfuryl chloride in carbon tetrachloride in the presence of a base such as triethylamine, pyridine, N-methylmorpholine, or N-methylpiperazine under ice- cooling through room temperature, and allowing the resulting mixture to react. The compound (III-2) can also be synthesized using the following scheme. [Step 6] The compound (XI) {in the formula R, Xw X;, x3, X4, and Y are as described above) can be synthesized by reacting the compound (X) (in the formula X:, X2, X3, and X, are as described above) with the compound (XII) (in the formula R, X, and Y are as described above) in the presence of a base such as pyridine, triethylamine, N-methylmorpholine, or N-methylpiperazine, in an organic solvent such as methylene chloride, chloroform, toluene, ether, dioxane, tetrahydrofuran, diisopropyl ether, dimethoxyethane, or hexane, water, or a mixture of these solvents, or in the absence of a solvent, under cooling through heating temperautre. [Step 7] The compound (III-2) (in the formula R, Xlf X:, X3, x4, and Y are as described above) can be synthesized by allowing the compound (XI) (in the formula R, Xx, X2, X3, X4, and Y are as described above) to react in the presence of a base such as sodium acetate, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, or sodium bicarbonate, in an organic solvent such as methanol, ethanol, tetrahydrofuran, dioxane, dimethoxyethane, ether, or diisopropyl ether, water, or a mixture of these solvents, under ice-cooling through heating temperature. The compound (III-2) can also be synthesized by the following scheme. [Step 8] The compound (VIII) (in the formula R„ and R1; may be the same or different and are a lower alkyl group such as methyl or ethyl, and Xw X2, X3, and X, are as described above) can be synthesized by reacting the compound (VII) (in the formula Xlf X2, X3, and X4 are as described above) with the compound (XIII) (in the formula Ru, R12, and X are as described above) in the presence of a base such as sodium hydride, triethylamine, or N-methylmorpholine, in an organic solvent such as dimethylformamide, tetrahydrofuran, dioxane, or dimethoxyethane or a mixture of these solvents, under cooling through heating temperature, and allowing the resulting product to react in an organic solvent such as phenylether or sulfolane or a mixture of these solvents, or in the absence of a solvent, under heating. [Step 9] The compound (IX) (in the formula R, Ru, R12, xlt X2, x3, x4, and Y are as described above) can be synthesized by allowing the compound (VIII) (in the formula Ru, R„, xlt X2, X3, and X4 are as described above) to react in the presence of a reducing agent such as stannous chloride, zinc, iron, sodium dithionite, sodium sulfide, or sodium disulfide, in an organic solvent such as ethyl acetate, acetic acid, methanol, ethanol, tetrahydrofuran, dioxane, diisopropy1 ether, dimethoxyethane, or toluene, water, or a mixture of these solvents, under cooling through heating temperature, and reacting the resulting product with the compound (XII) (in the formula R, X, and Y are as described above) in the presence of a base such as pyridine, triethylamine, N-methylmorpholine, or N-methylpiperazine, in an organic solvent such as chloroform, methylene chloride, tetrahydrofuran, ether, dioxane, diisopropy1 ether, dimethoxyethane, toluene, or hexane, water or a mixture of these solvents, or in the absence of a solvent, under cooling through heating temperature. [Step 10] The compound (III-2) (in the formula R, xlf Xj, X3, x4, and Y are as described above) can be synthesized by allowing the compound (IX) (in the formula R, Rn, RI2, X1# X2, X3/ X,, and Y are as described above) to react in the presence of a base such as potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, or sodium bicarbonate, in an organic solvent such as methanol, ethanol, tetrahydrofuran, dioxane, dimethoxyethane, ether, or diisopropy1 ether, water, or a mixture of these solvents, under cooling through heating temperature. The compound (VI) can also be synthesized from the compound (VIII) by the following step 11. (Step 11] The compound (VI) (in the formula X:, X2, X3, and x^ are as described above) can be synthesized by allowing the compound (VIII) (in the formula R1W Rn, x1( Xir X,, and x4 are as described above) to react in the presence of a reducing agent such as stannous chloride, WE CLAIM: 1. Substituted 2-amino phenyl derivatives represented by the formula (1-2) : wherein R' represents a substituted or unsubstitutcd C3-10 cycloalkyl group or a substituted or unsubstituted C5.g cycloalkenyl group; Xi, X2, X3, and X4 may be the same or different and represents a hydrogen atom; a halogen atom; a CM lower alkyl group; a halo-CM lower alkyl group; a CM lower alkoxy group; a cyano group; a nitro group; an acyl group; or an aryl group; Zi' represents a hydrogen atom; a group represented by the formula: wherein R', X[, X2, X3, and X4 are as described above; -Y,R,, wherein Yi represents -CO-; or -CS-, Ri represents a substituted or unsubstituted straight chain or branched CMQ alkyl group; a CM lower alkoxy group; a CM lower alkylthio group; a substituted or unsubstituted amino group; a substituted or unsubstituted ureido group; a substituted or unsubstituted C3.10 cycloalkyl group; a substituted or unsubstituted C3_io cycloalkyl CMO alkyl group; a substituted or unsubstituted aryl group; a substituted or unsubstituted aralkyl group; a substituted or unsubstituted arylalkenyl group; a substituted or unsubstituted arylthio group; a substituted or unsubstituted 5- or 6-membeied heterocyclic group having 1 -3 nitrogen, oxygen, or sulfur atoms; or a substituted or unsubstituted 5- or 6-membered heteroarylalkyl group; or -S-Ri, wherein R2 represents a substituted or unsubstituted CM lower alkyl group; or a substituted or unsubstituted aryl group, and a pharmaceutically acceptable salt selected from inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic base salts, salts of amino acids, or hydrate or solvate thereof. 2. The compound as claimed in claim 1, which is represented by the formula (1-3): wherein R" represents a l-substituted-C3.io cycloalkyl group, or a l-substituted-C5.g cycloalkeny) group; Xb X2, X3. and X4 are the same as in claim 1; Zi" represents a hydrogen atoms; a group represented by the formula: wherein R" is as described above; Xi, X2, Xj, and X4 are the same as in claim I; -Y,Rj, wherein Y[ and Ri are the same as in claim 1; or -S-Rj, wherein R2 is the same as in claim 1, and a pharmaceutical^ acceptable salt such as inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic base salts, salts of amino acids, or hydrate or solvate thereof. 3. The compound as claimed in claim 1, which is represented by the formula (II): wherein R', Xi, X2, X3, and X4 are the same as in claim 1, or a prodrug compound which is a derivative having a chemically or metabolically degradable group, which exhibit pharmaceutical activity by degradation through hydrolysis or solvolysis, or under physiological conditions, a pharmaceutically acceptable salt such as inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic base salts, salts of amino acids, or hydrate or solvate thereof. wherein R" is the same as in claim 2; Xj, X2, X3, and X4 are the same as in claim 1, and a pharmaceutically acceptable sail such as inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic base salts, salts of amino acids, or hydrate or solvate thereof. 5 The compound as claimed in claim 1, which represented by the formula (III): wherein R',Xi,X2,X3, and X4 are the same as in claim 1, and a pharmaceutical^ acceptable salt such as inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic base salts, salts of amino acids, or hydrate or solvate thereof. wherein R" is the same as in claim 2; Xi, X2, X3, and X4 are the same as in claim 1, and a pharmaceutically acceptable salt such as inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic base salts, salts of amino acids, or hydrate or solvate thereof. 7 The compound as claimed in claim 1, which is represented by formula (IV): wherein R', Xj, X2, X3, X4, Yh and Rj are the same as in claim 1, and a pharmaceutically acceptable sale such as inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic base salts, salts of amino acids, or hydrate or solvate thereof. wherein R" is the same as in claim 2; Xi, X2, X3, X4, Y], and Ri are the same as in claim 2, and a pharmaceutically acceptable salt such as inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic base salts, salts of amino acids, or hydrate or solvate thereof. 9. The compound as claimed in claim 1, which is represented by formula (V): wherein R\ Xj, X2, X3, X4, and R2 are the same as in claim 1, and a pharmaceutically acceptable salt such as inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic hase salts, salts of amino acids, or hydrate or solvate thereof. wherein R" is the same as in claim 2; X], X2, X3, X4, and R2 are the same as in claim 2, and a pharmaceutically acceptable salt such as inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic base salts, salts of amino acids, or hydrate or solvate thereof. 11. The compound as claimed in claim 1, which is selected from the group consisting of bis-[2-(l-methylcyclohexanecarbonylamino)phenylj disulfide; bis-[2-(l -isopentylcyclopentanecarbonylamino)phenyl] disulfide; bis-[2-(l-isopentylcycloheKatiecarbonylaminQ)phenyl] disulfide; N-(2-mercaptopheny])-l-isopentylcyclohexanecarboxamide; N-(2-mercaptophenyl(-l-methylcycIohexanecarboxamide; N-(2-mercaptopheny\)-l-isopenty\cyclopentanecarboxamide; N-(2-mercaptophenyl)-l-isopropylcyclohexanecarboxamide; N-(4,5-dichloro-2-mercaptophenyl)-l-isopentylcyclohexane-carboxamide; ■N-(4,5-dichloro-2-mercaptophenyl)-l-isopentylcyclopentane-carboxaniide; N-(2-mercapto-5-methylphenyl)-l-isopentylcyclohexane-carboxamide; N-{2-mercapto-4-methylphenyl(-l-isopentylcyclohexane-carboxamide; S-[2-( 1 -isopentylcyclohexanecarbonylamino)pbenyl] thio-acetate; S-[2-(l-methylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[2-(l-isopentylcyclohexanecarbonylamino)pheny]] 2,2-dimethylthiopropionate; S-[2-(l-isopentylcyclohexanecarbonylamino (phenyl] 2-acetyIamino-3-phenylthiopropionate; S-[2-(l-isopentylcyclohexanecarbonylamino (phenyl] 3-pyridinethiocarboxylate; S-[2-(l-isopentylcyclohexanecarbonylamino)phenyl] chloro-thioacetate; S-[2-(l-isopentylcyclohexanecarbonylamino)phenyl] methoxy-thioacelate; S-t2-(l-isopentylcyclohexanecarbonylaraino)phenyl] thio-propionate; S-[2-(l-isopentylcyclohexanecarbonylamino (phenyl] phenoxy-thioacetate; S-[2-(l-isopentylcyclohexanecarbonylamino (phenyl] 2-methylthiopropionate; S-[2-{l-isopentylcyclohexanecarbonylamino(phenyl] 4-chlorophenoxythioacetate; S-[2-(l-isopentylcyclohexanecarbonylamino (phenyl] eye lo-propanethiocarboxylate; S-[2-(l-isopentylcyclohexanecarbonylamino)phenylj 2-acetylamino-4-carbamoylthiobutyrate; S-[2-( 1 -isopentylcyclohexanccarbonylamino)phenyl] 2-hydroxy-2-methylthiopropionate; S-[2-(l-isopentylcyclopentanecarbonylamino)phenyl] 2,2-dimethylpropionate; S-[2-(l-isopentylcyclopentanecarbonylamino)phenyl] thio-acetate; S-[4,5-dichloro-2-(l-isopentylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(l-isopentylcyclopentanccarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[2-(l-isopentylcyclohexanecarbonylamino(-4-trifluoro-methylphenyl] 2,2-dimethylthiopropionate; O-methyl S-[2-(l-isopentylcyclohexanecarbonylamino(-phenyl] monothiocarbonate; S-[2-(l-methylcyclohexanecarbonylamino)phenyl] S-phenyl dithiocarbonate; S-[2-(l-isopentylcyclohexanecarbonylamino)phenyl] N-phenylthiocarbamate; S-[4,5-dichloro-2-(l-cyclopropylcyclohexanecarbonylamino)-phenyl] 2,2-dimethy lthi opropionate; S-[4,5-dichloro-2-(l-pentylcyclohexanecarbonylamino)-phenyl] 1,2-dimethy lthiopropionate; S-[4,5-dichloro-2-(l-cyclopropylmethylcyclohexanecarbonyl-amino)phenyl] 2,2-dimethy lthi opropionate; S-[4,5-dichloro-2-(l-cyclohexylmethylcyciohexanecarbonyl-amino)phenyl] 2,2-dimethy lthi opropioate; S-[4,5-dichloro-2-(l-isopropylcyclohexanecarbonylamino)-phenyl] 2,2-dimethy lthi opropionate; S-[4,5-dichloro-2-(l-isopentylcycloheptanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; S-[4,5-dichloro-2-(l-isopentylcyclobutanecarbonylamino)-phenyl] 2,2 -dimethy lthi opropi onate; S-[2-(I-isopentylcyclohexanecarbonyIamino)-4-nitrophenyl] 2,2-dimethylthiopropionate; S-[4-cyano-2-(l-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethy lthiopropionate; S-[4-chloro-2-(l-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-[5-chloro-2-(l-isopentylcyclohexanecarbonylamino)phenyl] 2,2-dimethylthiopropionate; S-(4-fluoro-2-(l-isopentylcyclohexanecarhonylamino)phenyl] 2,2-dimethylthiopropionate; S- [4,5-difluoro-2-( 1 -isopentylcyclohexanecarbony lamino)-pheny t] 2,2-dimethylthiopropionate; S-[5-fluoro-2-(l-isopentylcyclohexanecarbonylamino)-phenyl] 2,2-dimethylthiopropionate; bis-[4,5-dichloro-2-(l-isopentylcyc]ohexanecarbonylamino)-phenyl] disulfide; 2-tetrahydrofurylmethyl 2-(l -isopentylcyclohexanecarbonyl-amino)phenyl disulfide; N-(2-mercaptophenyl)-1 -ethylcyclohexanecarboxarmde; N-(2-mercaptophenyl)-1-propylcyclohexanecarboxamide; N-(2-mercaptophenyl)-l-butyfcyclohexanecarboxamide; N-(2-mercaptophenyl)-l-isobutylcycIohexanecarboxamide; S-[2-(l-isopentylcyclohexanecarbonylamino)phenyl] cyclo-hexaneth;ocarbaxylate; S-[2-(l-isopentylcyclohexanecarbony]amino)phenyl] thio-benzoate; S-[2-(l-isopentylcycIohexanecarbonylamino)phenyl] 5-carboxythiopentanoate; S-[2-(l-isopentylcyclohexanecarbonylamino)-4-methylphenyl] thioacetate; bis-[2-[l-(2-ethylbutyl)cyclohexanecarbonyIamino]phenyl] disulfide; N-(2-mercaptophenyl)-l-(2-ethylbutyl)cyclohexane-carboxamide; S-[2-[l-(2-ethy!butyl)cyclohexanecarbonylamino]phenyl] 2-methyIthiopropionate; S-[2-(l-isobutylcyclohexanecarbonylamino)phenyl) 2-methyl-thiopropionate; S-[2-[l-(2-ethylbutyl)cyclohexanecarbonyIamino]phenyIl l-acetylpiperidine-4-thiocarboxyiale; S-[2-[l-(2-ethylbuty])cyclohexanecarbonylaraino]phenyl] thioacetate; S-[2-[l-(2-ethylbutyl)cycIohexanecarbonylamino]phenyl] 2,2-dimethy lthiopropionate; S-[2-[I-(2-ethyIbutyI)cyclohexanecarbonylamino]phenyI] methoxythioacetate; S-[2-[l-(2-ethylbutyl)cyclohexanecarbonylamino]phenyl] 2-hydroxy-2-methylpropionate; S-l2-[l-(2-ethylbutyl)cyclohexanecarbonylamino]phenylJ 4-chlorophenoxythioacetate-, S-[2-(l-isobutylcyclohexanecarbonylarnino)phenyl] 4-chloro-phenoxythioacelate; and S-[2-(l-isobutylcyclohexanecarbonylamino)phenyl] l-acetylpiperidine-4-thiocarboxylate, and a pharmaceutically acceptable salt such as inorganic acid salts, organic acid salts, sulfonates, salts of acidic amino acids, alkali metal salts, alkaline earth metal salts, ammonium salts, organic base salts, salts of amino acids, or hydrate or solvate thereof.

Documents:

1209-mas-1998 abstract-duplicate.pdf

1209-mas-1998 abstract.pdf

1209-mas-1998 claims-duplicate.pdf

1209-mas-1998 claims.pdf

1209-mas-1998 correspondence-others.pdf

1209-mas-1998 correspondence-po.pdf

1209-mas-1998 description(complete) 2.pdf

1209-mas-1998 description(complete)-duplicate 2.pdf

1209-mas-1998 description(complete)-duplicate.pdf

1209-mas-1998 description(complete).pdf

1209-mas-1998 form-13.pdf

1209-mas-1998 form-19.pdf

1209-mas-1998 form-2.pdf

1209-mas-1998 form-26.pdf

1209-mas-1998 form-4.pdf

1209-mas-1998 form-6.pdf

1209-mas-1998 others.pdf

1209-mas-1998 petition.pdf

1209-mas-1998.rtf