Title of Invention	SULFONYLAMINO-ACETIC DERIVATIVES AND THEIR USE AS OREXIN RECEPTOR ANTAGONISTS
Abstract	The invention relates to novel sulfonylamino-acetic acid derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of such compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as orexin receptor antagonists.

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ACTELION 26A/OR4 Sulfonvlamino-acetic acid Derivatives The present invention relates to novel sulfonylamino-acetic acid derivatives of the general formula (I) and their use as pharmaceuticals. The invention also concerns related aspects including pharmaceutical compositions containing one or more compounds of formula I, and especially their use as orexin receptor antagonists. The orexins (hypocretins) comprise two neuropeptides produced in the hypothalamus: the orexin A (OX-A) (a 33 aminoacid peptide) and the orexin B (OX-B) (a 28 aminoacid peptide) (Sakurai T. et al9 Cell, 1998, 92, 573-585). Orexins are found to stimulate food consumption in rats suggesting a physiological role for these peptides as mediators in the central feedback mechanism that regulates feeding behavior (Sakurai T. et aL9 Cell, 1998, 92, 573-585). On the other hand, it was also proposed that orexins regulate states of sleep and wakefulness opening potentially novel therapeutic approaches for narcoleptic patients (Chemelli R.M. et al> Cell, 1999, 98, 437-451). Two orexin receptors have been cloned and characterized in mammals which belong to the G-protein coupled receptor superfamily (Sakurai T. et al9 Cell, 1998, 92, 573-585), the orexin-1 receptor (OXi) which is selective for OX-A and the orexin-2 receptor (OX2) which is capable to bind OX-A as well as OX-B. Orexin receptors are found in the mammalian host and may be responsible for many pathologies including, but not limited to, depression; anxiety; addictions; obsessive compulsive disorder; affective neurosis; depressive neurosis; anxiety neurosis; dysthymic disorder; behaviour disorder; mood disorder; sexual dysfunction; psychosexual dysfunction; schizophrenia; manic depression; delerium; dementia; severe mental retardation and dyskinesias such as Huntington's disease and Tourette syndrome; feeding disorders such as anorexia, bulimia, cachexia and obesity; diabetes; appetite/taste disorders; vomiting/nausea; asthma; cancer; Parkinson' s disease; Cushing' s syndrome/disease; basophil adenoma; prolactinoma; hyperprolactinemia; hypopituitarism; hypophysis tumor/adenoma; hypothalamic diseases; inflammatory bowel disease; gastric diskinesia; gastric ulcus; Froehlich's syndrome; adrenohypophysis disease; hypophysis disease; pituitary growth hormone; adrenohypophysis hypoftmction; adrenohypophysis hyperfunction; hypothalamic hypogonadism; Kallman's syndrome (anosmia, hyposmia); functional or psychogenic amenorrhea; hypopituitarism; hypothalamic hypothyroidism; hypothalamic-adrenal dysfunction; idiopathic hyperprolactinemia; hypothalamic disorders of growth hormone deficiency; idiopathic growth deficiency; dwarfism; gigantism; acromegaly;-disturbed biological and circadian rhythms; sleep disturbances associated with deseases such as neurological disorders, neuropathic pain and restless leg syndrome; heart and lung diseases, acute and congestive heart failure; hypotension; hypertension; urinary retention; osteoporosis; angina pectoris; myocardinal infarction; ischaemic or haemonhagic stroke; subarachnoid haemorrhage; ulcers; allergies; benign prostatic hypertrophy; chronic renal failure; renal disease; impaired glucose tolerance; migraine; hyperalgesia; pain; enhanced or exaggerated sensitivity to pain such as hyperalgesia, causalgia, and allodynia; acute pain; burn pain; atypical facial pain; neuropathic pain; back pain; complex regional pain syndrome I and II; arthritic pain; sports injury pain; pain related to infection e.g. by HIV; post-chemotherapy pain; post-stroke pain; post-operative pain; neuralgia; conditions associated with visceral pain such as irritable bowel syndrome, migraine and angina; urinary bladder incontinence e.g. urge incontinence; tolerance to narcotics or withdrawal from narcotics; sleep disorders;-sleep apnea; narcolepsy; insomnia; parasomnia; jet-lag syndrome; delayed or advanced sleep phase syndrome; sleep related dystonias; and neurodegerative disorders including nosological entities such as disinMbition-dementia-parkinsonism-amyotrophy complex; pallido-ponto-nigral degeneration epilepsy, seizure disorders including febrile seizures and other hyperthermia disorders; and other diseases related to orexin. Up to now some low molecular weight compounds are known which have a potential to antagonise either specifically OXi or 0X2, or both receptors at the same time. In WO 99/09024, WO 99/58533, WO 00/47576, WO 00/47577 and WO 00/47580 formerly SmithKline Beecham reported phenylurea, phenylthiourea and cinnamide derivatives as OXi selective antagonists. More recently WO 01/85693 from Banyu Pharmaceuticals has been published wherein N-acyltetrahydroisoquinoline derivatives are disclosed. 2-Amino-methylpiperidine derivatives (WO 01/96302), 3-aminomethyl- s morpholine derivatives (WO 02/44172) and N-aroyl cyclic amines (WO 02/89800, WO 02/90355, WO 03/51368 and WO 03/51871) have been suggested by formerly SmithKline Beecham as orexin receptor antagonists. Related compounds are disclosed in WO 03/02559, WO 03/02561, WO 03/32991, WO 03/41711, WO 03/51872 and WO 03/51873. In WO 03/37847 formerly SmithKline Beecham reported benzamide derivatives as orexin receptor antagonists. International patent applications WO 01/68609 and WO 02/51838 disclose 1,2,3,4-tetrahydroisoquinoline and novel benzazepine derivatives as orexin receptor antagonists. The novel compounds of the present invention belong to an entirely different class of low molecular weight compounds as compared to all prior art orexin receptor antagonists so far published. The present invention comprises sulfonylamino-acetic acid derivatives which are non-peptide antagonists of the human orexin receptors, in particular the human orexin-2 receptor. These compounds, therefore, are of potential use in the treatment of disturbed homeostasis and eating disorders (e.g. bulimia, obesity, food abuse, compulsive eating or irritable bowel syndrome), as well as disturbed sleep/wake schedule, sleep disorders (e.g. insomnias, apneas, dystonias) or stress-related diseases (e.g. anxiety, mood and blood pressure disorders) or any other disease related to orexin dysfunction. WO 00/50391 discloses certain sulfonamide derivatives as modulators of the production of amyloid p-protein. WO 02/32864 discloses certain sulfanilide derivatives useiiil in the treatment of diseases mediated by oxytocin and/or vasopressin. The present invention relates to novel sulfonylamino-acetic acid derivatives of the general formula (I). wherein: A represents 4~ethylphenyK 4-isopropylphenyl, 4-fe/?.-butylphenyK 2-methylphenyl-, 3-methylphenyl-, 4-cyclopropylphenyl, 3-fluorophenyl-, 2-chIorophenyI-, 3-chlorophenyI-, 4-bromophenyl-, 2-trifluoromethylphenyl-, 3-trifluoromethylphenyl-, 4-(l-hydroxy-l-methyl-ethyl)-phenyl-, 3-chloro-4-methylphenyl-, 2-methoxy~4-methylphenyl-, 3,4-difluorophenyl-, 1,2,3,4-tetrahydroisoquinolin-7-yl, 2-methyl-l,2,3,4-tetrahydroisoquinolin-7-yl, 2-formyl-l,2,3,4-tetrahydroisoquinolin-7-yl, phenylethenyl-, 1-naphthyl-, 2-naphthy!-, 3-methyl-pyridin-2-yI, 5-methyl-pyridin-2-yl, 5-isopropyl-pyridin-2-yl, 6-dimethylamino-pyridin-3-yl, 6-bromo-5-cMoro-pyridin-3-yl or 8-quinolinyl-; B represents a phenyl, a 6-membered heteroaryl or a nine- or ten-membered bicyclic heteroaryl group, which groups are unsubstituted or independently mono- or di- substituted with cyano, halogen, hydroxy, lower alkyl, hydroxy lower alkyl, amino lower alkyl, aminocarbonyl lower alkyl, sulfonylamino lower alkyl, lower alkenyl, lower alkoxy, trifluoromethyl, trifluoromethoxy, cycloalkyloxy, aryloxy, aralkyloxy, heterocyclyloxy, heterocyclyl lower alkyloxy, amino, aminocarbonyl or sulfonylamino; or a cyclohexyl, 3-piperidinyl or 4-piperidinyl group, which groups are unsubstituted or mono-substituted with hydroxy, lower alkyl, hydroxy lower alkyl, aminocarbonyl lower alkyl, sulfonylamino lower alkyl, amino, aminocarbonyl or sulfonylamino; with the proviso that in case A represents 2-methylphenyl- or 4-bromophenyl the phenyl ring as represented by B is substituted; Rl represents lower alkyl, cycloalkyl, hydroxy lower alkyl or cyano lower alkyl; R2 represents lower alkyl, lower alkenyl, hydroxy lower alkyl, amino lower alkyl, sulfonylamino lower alkyl, cycloalkyl; an unsubstituted or mono- or disubstituted phenyl group substituted independently with cyano, halogen, hydroxy, lower alkyl, lower alkoxy, cycloalkyloxy, amino, amino lower alkyl, aminocarbonyl or sulfonylamino; an unsubstituted or mono- or di-substituted five- or six-membered heteroaryl group substituted independently with cyano, halogen, hydroxy, lower alkyl, lower alkoxy, cycloalkyloxy, amino, amino lower alkyl, aminocarbonyl or sulfonylamino; an unsubstituted or mono- or di-substituted nine- or ten-membered bicyclic heteroaryl group substituted independently with cyano, halogen, hydroxy, lower alkyl, lower alkoxy, cycloalkyloxy, amino, amino lower alkyl, aminocarbonyl or sulfonylamino; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutical^ acceptable salts, solvent complexes, and morphological forms, thereof. In the present description the term "lower alkyl", alone or in combination, means a straight-chain or brancheri-chain alkyl group with 1-5 carbon atoms as for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tart-butyl, isobutyl and the isomeric pentyls. The term "lower alkenyl" means a straight-chain or branched-chain alkenyl group with 2 to 5 carbon atoms, preferably allyl and vinyl. The term "lower alkoxy", alone or in combination, means a group of the formula lower alkyl-O- in which the term "lower alkyl" has the previously given significance, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy, preferably methoxy and ethoxy. The term "cycloalkyl", alone or in combination, means a cycloalkyl ring with 3 to 6 carbon atoms. Examples of C3-C6 cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, preferably cyclopropyl, cyclohexyl and particularly cyclohexyl or lower alkyl substituted cycloalkyl which may preferably be substituted with lower alkyl such as methyl-cyclopropyl, dimethyl-cyclopropyl, methyl-cyclobutyl, methyl-cyclopentyl, mefhyl-cyclohexyl or dimethyl-cyclohexyl. The term "aryl" means a phenyl or naphthyl group which optionally carries one or more substituents, preferably one or two substituents, each independently selected from cyano, halogen, hydroxy, lower alkyl, lower alkenyl, lower alkoxy, lower alkenyloxy, trifluoromethyl, trifluoromethoxy, amino, or carboxy. The term "aralkyl" means a lower alkyl group as previously defined in which one hydrogen atom has been replaced by an aryl group as previously defined. The term "heterocyclyl" means a 5- to 10-membered monocyclic or bicyclic ring, which may be saturated, partially unsaturated or aromatic containing for example 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulphur which may be the same or different. Examples of such heterocyclyl groups are pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, thienyl, thiazolyl, isothiazolyl, furyl, imidazolyl, pyrazolyl, pyrrolyl, indazolyl, indolyl, isoindolyl, isoxazolyl, oxazolyl, quinoxalinyl, phthalazinyl, cinnolinyl, dihydropyrrolyl, pyrrolidinyl. isobenzofiiranyl, tetrahydrofiiranyl, dihydropyranyl. The heterocyclyl group may have up to 5, preferably 1, 2 or 3 optional substituents. Examples of suitable substituents include halogen, lower alkyl, amino, nitro, cyano, hydroxy, lower alkoxy, carboxy and lower alkyloxy-caibonyls. The term "6-membered heteroaryl group" means e.g. a pyridyl, pyrimidinyl, pyrazinyl or a pyridazinyl group. The term "nine- or ten-membered bicyclic heteroaryl group" means e.g. an indazolyl, indolyl, isoindolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl," quinolinyl, isoquinolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, quinazolinyl or a naphthyridinyl group. The term "5-membered heteroaryl group" means e.g. a pyrrolyl, furyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl or thiadiazolyl group. The term "amino" in terms like "amino", "amino lower alkyl", "aminocarbonyl" or "aminocarbonyl lower alkyl" represents a NH2-» NHR3- or a NR3R4-group. R3 and R4 are lower alkyl groups, which might be equal or different. The term "sulfonylamino" in terms like "sulfonylamino" or "sulfonylaminoalkyl" represents a R5S(0)2NR3-group. R5 represents a lower alkyl group, a phenyl group, a 6-mernbered heteroaryl group or a 5-membered heteroaryl group. The term "halogen" means fluorine, chlorine, bromine or iodine and preferably chlorine and bromine and particularly chlorine. A preferred group of compounds of formula (T) are those in which B, R1 and R2 have the meaning given in formula (I) above and A represents a 4-ethylphenyl group; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. Another preferred group of compounds of formula (I) are those in which B, R and R have the meaning given in formula (T) above and A represents a 4-isopropylphenyl group; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. Another preferred group of compounds of formula (I) are those in which B, R1 and R2 have the meaning given in formula (I) above and A represents a 4-ter*.-butylphenyl group; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and phannaceutically acceptable salts, solvent complexes, and morphological forms, thereof. Another preferred group of compounds of formula (I) are those in which B, R1 and R2 have the meaning given in formula (I) above and A represents a 2-methylphenyl group; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and phannaceutically acceptable salts, solvent complexes, and morphological forms, thereof. Another preferred group of compounds of formula (T) are those in which B, R1 and R2 have the meaning given in formula (I) above and A represents a 3-methylphenyl group; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric -racemates, mixtures of diastereoisomeric racemates and the meso-form and phannaceutically acceptable salts, solvent complexes, and morphological forms, thereof. Another preferred group of compounds of formula (T) are those in which B, R1 and R2 have the meaning given in formula (I) above and A represents a 4-(l-hydroxy-l-methyl-ethyl)-phenyl group; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and phannaceutically acceptable salts, solvent complexes, and morphological forms, thereof. Another preferred group of compounds of formula (I) are those in which B, R and R have the meaning given in formula (I) above and A represents a 3-chloro-4-methylphenyl group: and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and phannaceutically acceptable salts, solvent complexes, and morphological forms, thereof. Another preferred group of compounds of formula (I) are those in which B, R1 and R2 have the meaning given in formula (I) above and A represents a 2~formyl-l,2,3,4-tetrahydroisoquinolin-7-yl group; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof." Another preferred group of compounds of formula (J) are those in which B, R1 and R2 have the meaning given in formula (I) above and A represents a 2-naphthyl group; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. Another preferred group of compounds of formula (I) are those in which B, R1 and R2 have the meaning given in formula (I) above and A represents a 3-methyl-pyridin-2-yl group; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. Another preferred group of compounds of formula (I) are those in which B, R1 and R2 have the meaning given in formula (I) above and A represents a 5-isopropyl-pyridin-2-yl group; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. Another preferred group of compounds of formula Q) are those in which B, R and R have the meaning given in formula (T) above and A represents a 6-dimethylamino-pyridin-3-yl group; The present invention encompasses physiologically usable or pharmaceutical^ acceptable salts of compounds of formula (I). This encompasses salts with physiologically compatible mineral acids such as hydrochloric acid, sulphuric or phosphoric acid; or with organic acids such as formic acid, methanesulphonic acid, acetic acid, trifluoroacetic acid, citric acid, fumaric acid, maleic acid, tartaric acid, succinic acid or salicylic acid and the like. The compounds of formula (I) which are acidic can also form salts with physiologically compatible bases. Examples of such salts are alkali metal, alkali earth metal, ammonium and alkylammoniumsalts such as Na, K, Ca or tetraalkylammonium salt. The compounds of formula (I) can also be present in the form of a zwitterion. The present invention encompasses also solvation complexes of compounds of general formula (I). The solvation can be effected in the course of the manufacturing process or can take place separately, e.g. as a consequence of hygroscopic properties of an initially anhydrous compound of general formula (I). The present invention further encompasses different morphological forms, e.g. crystalline forms, of compounds of general formula (I) and their salts and solvation complexes. Particular heteromorphs may exhibit different dissolution properties, stability profiles, and the like, and are all included in the scope of the present invention. The compounds of formula (I) might have one or several asymmetric centres and .can be present in the form of optically pure enantiomers, mixtures of enantiomers such as, for example, racemates, optically pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates or mixtures of diastereoisomeric racemates and the meso- forms. Preferred compounds as described above have IC50 values below 100 nM, particularly preferred compounds have IC50 values below 20 nM which have been determined with the FLIPR (Fluorometric Imaging Plates Reader) method described in the beginning of the experimental section. The compounds of formula (T) and their pharmaceutically usable salts can be used for the treatment of diseases or disorders where an antagonist of a human orexin receptor is required such as obesity, diabetes, prolactinoma, narcolepsy, insomnia, sleep apnea, parasomnia, depression, anxiety, addictions, schizophrenia and dementia or any other disease related to orexin dysfunction. The compounds of formula (I) and their pharmaceutically usable salts are particularly useful for the treatment of disturbed homeostasis and eating disorders (e.g. bulimia, obesity, food abuse, compulsive eating or irritable bowel syndrome), as well as disturbed sleep/wake schedule, sleep disorders (e.g. insomnias, apneas, dystonias), stress-related diseases (e.g. anxiety, mood and blood pressure disorders), or any other disease related to orexin dysfunction. The compounds of formula (I) and their pharmaceutically usable salts can be used as medicament (e.g. in the form of pharmaceutical preparations). The pharmaceutical preparations can be administered enterally, such as orally (e.g. in the form of tablets, coated tablets, dragees, hard and soft gelatine capsules, solutions, emulsions or suspensions), nasally (e.g. in the form of nasal sprays) or rectaily (e.g. in the form of suppositories). However, the administration can also be effected parenterally, such as intramuscularly or intravenously (e.g. in the form of injection solutions), or topically, e.g. in the form of ointments, creams or oils. The compounds of formula (I) and their pharmaceutically usable salts can be processed with pharmaceutically inert, inorganic or organic adjuvants for the production of tablets, coated tablets, dragees, and hard gelatine capsules. Lactose, corn starch or derivatives thereof talc, stearic acid or its salts etc. can be used, for example, as such adjuvants for tablets, dragees, and hard gelatine capsules. Suitable adjuvants for soft gelatine capsules, are, for example, vegetable oils, waxes, fats, semi-solid substances and liquid polyols, etc. Suitable adjuvants for the production of solutions and syrups are, for example, water, polyols, saccharose, invert sugar, glucose, etc. Suitable adjuvants for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils, etc. Suitable adjuvants for suppositories are, for example, natural or hardened oils, waxes, fats, semi-solid or liquid polyols, etc. Morever, the pharmaceutical preparations can contain preservatives, solubilizers, viscosity-increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. The compounds of formula (I) may also be used in combination with one or more other therapeutically useful substances. Examples are anorectic drugs like fenfluramine and related substances; lipase inhibitors like orlistat and related substances; antidepressants like fluoxetine and related substances; anxiolytics like alprazolam and related substances; sleep-inducers like zopiclone and related substances; or any other therapeutically useful substance. The dosage of compounds of formula (I) can vary within wide limits depending on the disease to be controlled, the age and the individual condition of the patient and the mode of administration, and will, of course, be fitted to the individual requirements in each particular case. For adult patients a daily dosage of about 1 mg to 1000 mg, especially about 50 mg to about 500 mg, comes into consideration. The pharmaceutical preparations conveniently contain about 1 - 500 mg, preferably 5 - 200 mg of a compound of formula (T). The compounds of general formula (T) of the present invention are prepared according to the general sequence of reactions outlined in the schemes below, wherein A, B, R1, R2 are as defined in formula (T) above. As the case may be any compound obtained with one or more optically active carbon atom may be resolved into pure enantiomers or diastereomers, mixtures of enantiomers or diastereomers, diastereomeric racemates and the meso-forms in a maimer known per se. The compounds obtained may also be converted into a pharmaceutically acceptable salt thereof in a manner known per se. The compounds of formula (I) may be prepared as single compounds or as libraries of compounds comprising at least 2, typically 5 to 200 compounds of formula (T). Compound libraries are prepared by multiple parallel synthesis using solution phase chemistry. The compounds of formula (I) have been prepared by following one out of three possible synthetic pathways. The first pathway starts with the reaction of an amine B-NH2 with an a-bromoacetamide, which might be synthesised starting from bromoacetyl bromide and an amine NHR!(CH2R2) either in situ or separately. In a second step the respective aminoacetamide was reacted with a sulfonyl chloride A-S02C1 (Scheme 7). 1 The second synthetic route starts with the reaction of an amine B-NH2 with a sulfonyl chloride A-SQ2CI. From the intermediate sulfonamides the target molecules can be obtained by reaction with the respective a-bromoacetamide (Scheme 2). In a third pathway a sulfonamide is synthesized starting from an amine B-NH2 and a sulfonyl chloride A-SO2CI. The obtained sulfonamide is transformed to a t-butyl- or methyl acetate derivative by reaction with either tert-butyl bromoacetate or methyl bromoacetate. rhe ester is hydrolyzed and the obtained acid is coupled with an amine NHR (CEfeR ) to jive the desired amide (Scheme 3). Experimental Section Abbreviations: bp Boiling point BSA Bovine serum albumine CHO Chinese hamster ovary d Day(s) DCM Dichloromethane DMSO Dimethylsulfoxide DIPEA i^tf-Diisopropylethylamine EDC 1 -(3-Dimethylaminopropyl)-3-ethylcarbodiimide ES Electron spray ether Diefhylether FCS Foetal calf serum FLPR Fluorescent imaging plate reader h Hpur(s) HBSS Hank's balanced salt solution HEPES 4-(2-Hydroxyethyl)-piperazine-1 ^ethanesulfonic acid HPLC High pressure/performance liquid chromatography MS Mass spectroscopy LC Liquid chromatography min Minute(s) Rt retention time RT Room temperature TBTU O-Benzotriazol-1-yl-A^A^A^'A^-tetramethyliironiumtetrafl TFA Trifluoroacetic acid THF Tetrahydrofuran I. Biology Determination of Orexin receptor antagonistic activity The Orexin receptor antagonistic activity of the compounds of formula (I) was determined in accordance with the following experimental method. Experimental method: Intracellular calcium measurements Chinese hamster ovary (CHO) cells expressing the human orexin-1 receptor and the human orexin-2 receptor, respectively, were grown in culture medium (Ham F-12 with L- Glutamine) containing 300 jig/ml G418,100 U/ml penicillin, 100 jxg/ml streptomycin and 10 % inactivated foetal calf serum (FCS). The cells were seeded at 80'000 cells / well into 96-well black clear bottom sterile plates (Costar) which had been precoated with 1% gelatine in Hanks5 Balanced Salt Solution (HBSS). All reagents were from Gibco BRL. The seeded plates were incubated overnight at 37°C in 5% C02. Human oresdn-A as an agonist was prepared as 1 mM stock solution in methanoi:water (1:1), diluted in HBSS containing 0.1 % bovine serum albumin (BSA) and 2 mM HEPES for use in the assay at a final concentration of 10 nM. Antagonists were prepared as 10 mM stock solution in DMSO. then diluted in 96-well plates, first in DMSO, then in HBSS containing 0.1 % bovine serum albumin (BSA) and 2 mM HEPES, On the day of the assay, 100 ^1 of loading medium (HBSS containing 1% FCS, 2 mM HEPES, 5 mM probenecid (Sigma) and 3 \JM of the fluorescent calcium indicator fluo-3 AM (1 mM stock solution in DMSO with 10% pluronic acid) (Molecular Probes) was added to each well. The 96-well plates were incubated for 60 min at 37° C in 5% CO2. The loading solution was then aspirated and cells were washed 3 times with 200 jil HBSS containing 2.5 mM probenecid, 0.1% BSA, 2 mM HEPES. 100 pi of that same buffer was left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), antagonists were added to the plate in a volume of 50 pi, incubated for 20 min and finally 100 JLXI of agonist was added. Fluorescence was measured for each well at 1 second intervals, and the height of each fluorescence peak was compared to the height of the fluorescence peak induced by 10 nM orexin-A with buffer in place of antagonist. For each antagonist, IC50 value (the concentration of compound needed to inhibit 50 % of the agonistic response) was determined. Selected compounds are displayed in Table L II. Chemistry:„ The following examples illustrate the preparation of pharmacologically active compounds of the invention but do not at all limit the scope thereof. All temperatures are stated in °C. All analytical and preparative HPLC investigations were performed using RP-C18 based columns. A Synthesis of starting materials A, 1 Synthesis of amines Al.l Synthesis of amines via reductive animation (general procedure): A solution of the respective amine in THF (2.0 mol/L, 5.0 mL) was added to a solution of the respective aldehyde (10r0 mmol) in methanpl (20 mL). Activated molecular sieves (4A) were added and the reaction mixture was stirred for 16 h. After addition of sodium borohydride (12 mmol) the solution was stirred for 3 h. treated with water (10 mL), stirred for 1 h and purified by ion-exchange chromatography [amberlyst 15, methanol / ammonium hydroxide solution (10 mol/L) 1:1]. After removal of methanol in vacuo the aqueous layer was extracted with ethyl A1.2 Synthesis of 6-Ethylaminomethyl-pyridin-2-ylamines: Al.2.1 Synthesis of 6-Bromo-pyridine-2~carboxylic acid ethylamide: TBTU (6.5 mmol) was added to a solution of 6-bromo-pyridine-2-carboxylic acid (5.0 mmol) in DMF (30 mL). A solution of ethylamine in THF (1.0 mol/L, 5.0 mL) and DIPEA (15.0 mmol) were added and the reaction mixture was stirred for 16 h. Water (100 mL) and ethyl acetate (100 mL) were added, the layers were separated, and the aqueous layer was extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2S04> and concentrated in vacuo to give 1.1 g (4.8 mmol, 96%) of the desired amide as a yellow oil which was used without further purification. LC-MS: rt = 0.85 min, 229 (M+l, ES+). Al.2.2 Synthesis of 6-Amino-pyridine-2-carboxylic acid ethylamides (general procedure): A solution of the respective amine in methanol (2.0 mol/L, 5.0 mL) was added to 6-bromo-pyridine-2-carboxylic acid ethylamide (4,38 mmol). The reaction mixture was heated for 5 min in a microwave oven at 150W and purified by preparative HPLC chromatography to give the following aminopyridines: 6-(Ethyl-methy]-amino)-pyridine-2-carboxylic acid ethylamide: prepared by reaction of ethyl-methyl-amine with 6-bromo-pyridine-2-carboxylic acid ethylamide LC-MS: rt = 0.82 min, 208 (M+l, ES+). 6-Dimethylamino-pyridine-3-thiol: At -78°C a solution of (5-bromo-pyridin-2-yl)-dimefhyl-amine (15.0 mmol) in THF (50 mL) was added dropwise to a solution of n-BuIi in Hexane (1.6 mol/L, 10.0 mL). The reaction mixture was stirred for 15 ™-m and sulfur (20.0 mmol) was added. After 1 min a solution of n-BuIi in Hexane (1.6 mol/L, 20.0 ml) was added. The reaction mixture was stirred for 10 min at -78°C and purified immediately by flash-chromatography (ethyl acetate/heptane 1:3) without previous work-up. A second flash-chromatography (gradient: ethyl acetate/heptane 1:19 to 1:9) yielded 0.50 g (3.24 mmol, 21%) of 6-dimethylamino-pyridine-3-thiol as a yellow oil. LC-MS: rt ~ 0.46 min, 155 (M+l, ES+). 6-Dimethylamino-pyridine-3-sulfonyl chloride: Hydrochloric acid (25%, 1.13 mL) was added to a solution of 6-dimethylamino-pyridine-3-thiol (0.50 mmol) in DCM (10 mL) at -78°C. A solution of sodium hypochlorite in water (6-14%, 5.2 mL) was added, at -78°C and the reaction mixture was stirred for additional 2 rain. The layers were separated and the aqueous layer was extracted with DCM (3 x 20 mL). The solvents were removed in vacuo and the obtained 6-dimethylamino-pyridine-3-sulfonyl chloride was used immediately in the next synthetic step. L2.2 Synthesis of 5-Isopropyl-pyridine-2-sulfonyl chloride Hydrochloric acid (25%, 63 mL) was added to a suspension of 5-isopropyl-pyridine-2-thiol (90 mmol) in DCM (150 mL) at RT. The reaction mixture was cooled to -15°C, a solution of sodium hypochlorite in water (6-14%, 240 mL) was added dropwise and the reaction mixture was stirred for additional 15 min. After separation of the layers DCM (150 mL) was added to the aqueous layer. Another portion of a solution of sodium hypochlorite in water (6-14%, 90 mL) was added at -15°C. The layers were separated and the aqueous layer was extracted with DCM (2 x 150 mL). All organic layers were combined and dried with Na2SC>4. The solvents were removed in vacuo and the obtained 5-isopropyl-pyridine-2-sulfonyl chloride was used immediately in the next synthetic step. A.23 Synthesis of 5-Methyl-pyridine*2-sulfonyl chloride xa^uruwiuuiiv; awu \*5%9 21 mL) was added to a suspension of 5-methyl-pyridine-2-thiol (30 mmol) in DCM (50 mL) at RT. The reaction mixture was cooled to -15°C, a solution of sodium hypochlorite in water (6-14%, 80 mL) was added dropwise and the reaction mixture was stirred for additional 15 min. After separation of the layers DCM (150 mL) was added to the aqueous layer. Another portion of a solution of sodium hypochlorite in water (6-14%, 30 mL) was added at -15°C. The layers were separated and the aqueous layer was extracted with DCM (3 x 100 mL). All organic layers were combined and dried with Na2SC>4. The solvents were removed in vacuo and the obtained 5-mefhyl-pyridine-2-sulfonyl chloride was used immediately in the next synthetic step. A.2.4 Synthesis of 3-Methyl-pyridine-2-sulfonyl chloride M 3-Methyl-pyridine-2-thiol: Thiourea (174 mmol) was added to a solution of 2-bromo-3-methylpyridine (87 mmol) in ethanol (500 mL). The reaction mixture was refiuxed for 5 h, cooled to RT, treated with an aqueous solution of sodium hydroxide (25%, 1.0 mL) and refiuxed for additional 60 min. The mixture was concentrated in vacuo to 50 mL, water (300 mL) and ethyl acetate (300 mL) were added, the layers were separated and the aqueous layer was extracted with ethyl acetate (3 x 100 mL). Brine (50 mL) was added to the combined organic layers, the layers were separated and the solvents were removed in vacuo. The crude oil was crystallized from ether to give 7.1 g (56.7 mmol, 65%) of the thiol as pale yellow crystals. LC-MS: rt = 0.48 min, 126 (M+l, ES+). 3-Methyl-pyridine-2-sulfonyl chloride: Hydrochloric acid (25%, 9.0 mL) was added to a solution of 3-methyl-pyridine-2-thiol (16 mmol) in DCM (60 mL) at RT. The reaction mixture was cooled to -15°C, a solution of sodium hypochlorite in water (6-14%, 42 mL) was added dropwise and the reaction mixture was stirred for additional 10 min. After separation of the layers the aqueous layer was extracted with DCM (3 x 50 mL). The organic layers were combined and dried with Na2SC>4. The solution of the obtained 3-methyl-pyridine-2-sulfonyl chloride was used immediately in the next synthetic step. A3 Synthesis of other intermediates A.3.1 Synthesis of A^Ethyl-A^pyridin-Z-ylmethyl-Z-p-tolylamino-acetamide p-Tolylamino-acetic acid tert-butyl ester: A solution ofp-toluidine (200 mmol) in THF (500 mL) was treated with tert-butyl bromoacetate (220 mmol) and DPEA (440 mmol) at RT. The reaction mixture was heated to reflux for 16 h and cooled to RT. Water (200 mL) and EE (500 mL) were added, the layers were separated and the aqueous layer was extracted twice with ethyl acetate (100 mL). The combined organic layers were washed with water and brine. The solvents were removed in vacuo and the residue (44 g) was used without further purification. LC-MS: rt = 0.96 min, 222 (M+l, ES+). p-Tolylamino-acetic acid: A solution of crude prtolylamino-acetic acid tert-butyl ester (200 mmol) in DCM (600 mL) was cooled to 0°C and treated with TFA (150 mL). The reaction mixture was allowed to reach RT and stirred for 4 d. Water (200 mL) was added, the layers were separated and the aqueous layer was extracted with DCM (4 x 200 mL). The aqueous layer was adjusted to pH 8 by addition of saturated NaHCC>3 solution and extracted with ethyl acetate (4 x 200 mL). The combined organic layers were dried with Na2SC>4 and the solvents were removed in vacuo to give the crude acid (18 g) which was used in the next step without further purification. LC-MS: rt - 0.54 min, 166 (M+l, ES+). iV"-Ethyl-AT-pyridin-2-ylme^ A suspension of ethyl-pyridin-2-ylmethyl-amine (29.0 mmol) and DIPEA (78.0 mmol) in DMF (50 mL) was cooled to -20°C and added to a cold (-20°C) solution of p-tolylamino-acetic acid (26.0 mmol) and TBTU (34.0 mmol) in DMF (100 mL). The reaction mixture was stirred for 15 min at -20°C. Water (300 mL) and ethyl acetate (400 mL) were added, the layers were separated and the organic layer was washed with water (4 x 100 mL). The combined aqueous layers were extracted with ethyl acetate (200 mL). The combined organic layers were washed with NaOH solution (1.0 mol/L, 100 mL) and brine (100 mL) and dried with Na2S04. The solvents were removed in vacuo and the obtained solid was dissolved in ethanol. By addition of a solution of hydrogen chloride in ether a byproduct precipitated which was filtered off. Dilution of the remaining solution with ether led to precipitation of the desired acetamide, which was obtained as a white solid (5.3 g). LC-MS: rt = 0.64 min, 284 (M+l, ES+). A*3.2 Synthesis of 6-Methyl-pyridin-3-yIamine (6-Methyl-pyridm-3-yl)-carbamic acid benzyl ester: To a suspension of 6-methylnicotinic acid (36,4 mmol) in toluene (100 mL) was added DIPEA (120 mmol) and Diphenylphosphoryl azide (91.1 mmol). The reaction mixture was heated to reflux for 1 h, cooled to RT and treated with benzyl alkohol (120 mmol). After 30 min ethyl acetate (200 mL) and water (200 mL) were added, the layers were separated and the organic layer was washed with water (3x100 mL). The solvents were removed in vacuo and the residue was purified by preparative HPLC chromatography to give (6-methyl-pyridin-3-yl)-carbamic acid benzyl ester (5.2 g, 21.5 mmol, 59%) as a colourless oil. LC-MS: rt - 0.68 mm, 243 (M+l, ES+). 6-Methyl-pyridin-3-ylamine: To a solution of (6-methyl-pyridin-3-yl)-caibamic acid benzyl ester (21.5 mmol) in methanol (100 mL) was added ammonium formate (107 mmol) and palladium on activated carbon (10%, wet, 1.0 g). The reaction mixture was stirred under nitrogen for 1 h and filtered over Celite. The solvents were removed in vacuo and the residue was dissolved in ethyl acetate. The organic layer was washed with water (2x100 mL) and the combined aqueous layers were extracted with ethyl acetate (3 x 100 mL). The organic layers were combined and dried with Na2S(>4. The solvents were removed in vacuo and the crude 6-methyl-pyridm-3-ylamine (0.80 g, 7.40 mmol, 34%) was used without further purification. LC-MS: rt - 0.16 min, 109 (M+l, ES+). B Synthesis of sulfonylamino-acetic acid derivatives via a-aminoacetamide intermediates (one-pot procedure) General Procedure: A solution of 2-bromoacetyl bromide (0.30 mmol) in THF (0.50 mL) was cooled to 0°C and treated dropwise with the respective dialkylamine (0.30 mmol). After addition of ethyldiisopropylamine (1.80 mmol) the reaction mixture was allowed to reach RT and was stirred for 60 min. A solution of the primary amine B-NHo (0.30 mmol) in THF (0.50 mL) was added. The suspension was stirred at 60°C for 16 h, cooled to RT and treated with a solution of the respective sulfonyl chloride (0.30 mmol) in THF (0.50 mL). After 60 min the solvent was removed in vacuo and the residue was purified by preparative HPLC chromatography to give the following sulfonamides: the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were concentrated in vacuo and the residue was purified by preparative HPLC chromatography to give 66.7 mg (0.14 mmol, 29%) of the desired product. LC-MS: rt - 0.65 min, 493 (M+l, ES+). (3-jJimeffiyiamino-pnenyiaminoj-aceticacid metayl ester: To a solution of A^iV-dimethyl-m-phenylenediamine (120 mmol) in THF (500 mL) was added methyl bromoacetate (132 mmol) and DIPEA (264 mmol). The reaction mixture was refluxed for 16 h. Water (200 mL) and ethyl acetate (300 mL) were added, the layers were separated and the aqueous layer was extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with water (4 x 100 mL) and brine (100 mL) and dried over Na2S04. The solvents were removed in vacuo and the residue was purified by flash-chromatography (ethyl acetate/heptane 1:4) to give 17.5 g (84.0 mmol, 70%) of an oily product which crystallized slowly. LC-MS: rt = 0.51 min, 209 (M+l, ES+). (3-Dimethylamino-phenylamino)-acetic acid: To a solution of (3-dimethylamino-phenylamino)-acetic acid methyl ester (84 mmol) in methanol (300 mL) was added a solution of sodium hydroxide in water (2.0 mol/L. 150 mL) at 0°C. The reaction mixture was stirred at RT for 16 h and methanol was removed in vacuo. Water (200 mL) and ethyl acetate (300 mL) were added, the layers were separated and the aqueous layer was acidified to pH 2 by addition of hydrochloric acid (2.0 mol/L). The aqueous layer was extracted with ethyl acetate (3 x 200 mL) and concentrated in vacuo. Methanol (100 raL) was added and the obtained suspension was filtered. The filtrate was concentrated in vacuo and the obtained solid was crystallized from methanol / ethyl acetate to give 15.0 g (56.2 WE CLAIM: 1. Compounds of formula (I) wherein: A represents 4-ethylphenyl-, 4-isopropylphenyI, 4-tert. -butylphenyl-, 2-methylphenyl-, 3-methylphenyl-, 4-cyclopropylphenyl, 3-fluorophenyl-, 2-chlorophenyl-, 3-chlorophenyl-, 4-bromophenyl-, 2-trifluoromethylphenyl-, 3 -trifluoromethylphenyl-, 4-( 1 -hydroxy-1 - methyl-ethyl)-phenyl-, 3-chloro-4-methylphenyl-, 2-methoxy-4-methylphenyl-, 3,4- difluorophenyl-, 1 ,2,3,4-tetrahydroisoquinolin-7-yl, 2-methyl-l ,2,3,4-tetrahydroisoquinolin- 7-yl, 2-formyl-l,2,3,4-tetrahydroisoquinolin-7-yl, phenylethenyl-, 1-naphthyl-, 2-naphthyl-, 3-methyl-pyridin-2-yl, 5-methyl-pyridin-2-yl, 5-isopropyl-pyridin-2-yl, 6-dimethylamino- pyridin-3-yl, 6-bromo-5-chloro-pyridin-3-yI or 8-quinolinyl-; B represents a phenyl, a 6-membered heteroaiyl or a nine- or ten-membered bicyclic heteroaryl group, which groups are unsubstituted or independently mono- or di- substituted with cyano, halogen, hydroxy, lower alkyl, hydroxy lower alkyl, amino lower alkyl, aminocarbonyl lower alkyl, sulfonylamino lower alkyl, lower alkenyl, lower alkoxy, trifluoromethyl, trifluoromethoxy, cycloalkyloxy, aryloxy, aralkyloxy, heterocyclyloxy, heterocyclyl lower alkyloxy, amino, aminocarbonyl or sulfonylamino; or a cyclohexyl, 3- piperidinyl or 4-piperidinyl group, which groups are unsubstituted or mono-substituted with hydroxy, lower alkyl, hydroxy lower alkyl, aminocarbonyl lower alkyl, sulfonylamino lower alkyl, amino, aminocarbonyl or sulfonylamino; with the proviso that in case A represents 2-methylphenyl- or 4-bromophenyl the phenyl ring as represented by B is substituted; R1 represents lower alkyl, cycloalkyl, hydroxy lower alkyl or cyano lower alkyl; R represents lower alkyl, lower alkenyl, hydroxy lower alkyl, amino lower alkyl, sulfonylamino lower alkyl, cycloalkyl; an unsubstituted or mono- or disubstituted phenyl group substituted independently with cyano, halogen, hydroxy, lower alkyl, lower alkoxy, cycloalkyloxy, amino, amino lower alkyl, aminocarbonyl or sulfonylamino; an unsubstituted or mono- or di-substituted five- or six-membered heteroaryl group substituted independently with cyano, halogen, hydroxy, lower alkyl, lower alkoxy, cycloalkyloxy, amino, amino lower alkyl, aminocarbonyl or sulfonylamino; an unsubstituted or mono- or di-substituted nine- or ten-membered bicyclic heteroaryl group substituted independently with cyano, halogen, hydroxy, lower alkyl, lower alkoxy, cycloalkyloxy, amino, amino lower alkyl, aminocarbonyl or sulfonylamino; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. 2. Compounds of formula (I) wherein: A represents a 4-ethylphenyl group; 1 J B, R and R have the meaning given m claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. 3. Compounds of formula (I) wherein: A represents a 4-isopropylphenyl group; B, R and R have the meaning given in claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. 4. Compounds of formula (I) wherein: A represents a 4-/erf.-butylphenyl group; B, R1 and R2 have the meaning given in claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. 5. Compounds of formula (I) wherein: A represents a 2-methylphenyl group; B has the meaning given in claim 1 with the proviso that the phenyl group is substituted; R1 and R2 have the meaning given in claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. 6. Compounds of formula (I) wherein: A represents a 3-methylphenyl group; 1 7 B, R and R have the meaning given in claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. 7. Compounds of formula (I) wherein: A represents a 4-(l-hydroxy-l-methyl-ethyl)-phenyl group; B, R1 and R2 have the meaning given in claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. 8. Compounds of formula (I) wherein: A represents a 3-chloro-4-methylphenyl group; B, R and R have the meaning given in claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. 9. Compounds of formula (I) wherein: A represents a 2-formyl-l,2,3,4-tetrahydroisoquinolin-7-yl group; B, R1 and R2 have the meaning given in claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. 10. Compounds of formula (I) wherein: A represents a 2-naphthyl group; B, R and R have the meaning given in claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutical^ acceptable salts, solvent complexes, and morphological forms, thereof. 11. Compounds of formula (I) wherein: A represents a 3-methyl-pyridin-2-yl group; B, R1 and R2 have the meaning given in claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, and morphological forms, thereof. 12. Compounds of formula (I) wherein: A represents a 5-isopropyl-pyridin-2-yl group; B, R1 and R2 have the meaning given in claim 1; and pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and

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