3-aminocyclopentane carboxamide derivatives

Abstract

Compounds of the formula I ##STR00001## in which R.sup.1, R.sup.4, R, X.sup.1, X.sup.2, X.sup.3, X.sup.4, q and W have the meanings indicated in Claim 1, are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.

Claims

1. A compound of the formula TABLE-US-00003 No. Name “A1” 4-(1,3-benzoxazol-2-yl)-N-[(1R,3S)-3- (ethylcarbamoyl)cyclopentyl]-N-methyl-benzamide “A2” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(1-methyl- 1H-benzoimidazol-2-yl)-benzamide “A3” 4-benzothiazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)- N-methyl-benzamide “A4” 4′-[(R)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide “A5” 4-benzoxazol-2-yl-N-((1R,3S)-3-isopropylcarbamoyl- cyclopentyl)-N-methyl-benzamide “A6” 4-benzoxazol-2-yl-N-((1R,3S)-3-cyclopropylcarbamoyl- cyclopentyl)-N-methyl-benzamide “A7” 4-benzoxazol-2-yl-N-((1R,3S)-3-cyclopentylcarbamoyl- cyclopentyl)-N-methyl-benzamide “A8” 4-benzoxazol-2-yl-N-((1R,3S)-3-(cyclohexylmethyl-carbamoyl)- cyclopentyl]-N-methyl-benzamide “A9” 4-benzoxazol-2-yl-N-methyl-N-[(1R,3S)-3-(pyrrolidine-1- carbonyl)-cyclopentyl]-benzamide “A10” 4-(1,3-benzoxazol-2-yl)-N-[(1S,3R)-3- (ethylcarbamoyl)cyclopentyl]-N-methyl-benzamide “A11” 4-(1H-benzimidazol-2-yl)-N-[(1R,3S)-3- (ethylcarbamoyl)cyclopentyl]-N-methyl-benzamide “A12” 4-benzoxazol-2-yl-N-ethyl-N-((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-benzamide “A13” 4-benzoxazol-2-yl-N-benzyl-N-((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-benzamide “A14” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4- oxazolo[5,4-b]pyridin-2-yl-benzamide “A15” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4- oxazolo[5,4-c]pyridin-2-yl-benzamide “A16” 4′-methoxy-biphenyl-4-carboxylic acid ((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-methyl-amide “A17” 4′-[(S)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide “A18” 4-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-2- fluoro-N-methyl-benzamide “A19” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(5-fluoro- benzoxazol-2-yl)-N-methyl-benzamide “A20” 4-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)- 2,6-difluoro-N-methyl-benzamide “A21” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(5- trifluoromethoxy-benzoxazol-2-yl)-benzamide “A22” 4-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N- methyl-3-trifluoromethyl-benzamide “A23” 4-(6-chloro-benzoxazol-2-yl)-N-((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-N-methyl-benzamide “A24” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4- naphthalen-2-yl-benzamide “A25” N-((1R,3S)-3-Ethylcarbamoyl-cyclopentyl)-4-isoquinolin-6-yl-N- methyl-benzamide “A26” 4-benzofuran-5-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N- methyl-benzamide “A27” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(1- methyl-1H-benzoimidazol-5-yl)-benzamide “A28” 4-benzoxazol-2-yl-N-[(1R,3S)-3-(4-ethyl-piperazine-1-carbonyl)- cyclopentyl]-N-methyl-benzamide “A29” 4-benzoxazol-2-yl-N-cyclopropylmethyl-N-((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-benzamide “A30” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(1H-indol-2-yl)-N- methyl-benzamide “A31” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-[5- (pyrrolidine-1-carbonyl)-benzoxazol-2-yl]-benzamide “A32” 4-benzoxazol-2-yl-N-[(1R,3S)-3-(cyclopentylmethyl-carbamoyl)- cyclopentyl]-N-methyl-benzamide “A33” 4-benzoxazol-2-yl-N-methyl-N-[(1R,3S)-3-(oxetan-3- ylcarbamoyl)-cyclopentyl]-benzamide “A34” 4-benzoxazol-2-yl-N-methyl-N-((1R,3S)-3-{[(S)-1-(tetrahydro- furan-2-yl)methyl]-carbamoyl}-cyclopentyl)-benzamide “A35” 4-benzoxazol-2-yl-N-methyl-N-((1R,3S)-3-{[(R)-1-(tetrahydro- furan-2-yl)methyl]-carbamoyl}-cyclopentyl)-benzamide “A36” 4-benzoxazol-2-yl-N-[(1R,3S)-3-(2-methoxy-ethylcarbamoyl)- cyclopentyl]-N-methyl-benzamide “A37” 4-benzoxazol-2-yl-N-methyl-N-{(1R,3S)-3-[(R)-(tetrahydro- furan-3-yl)carbamoyl]-cyclopentyl}-benzamide “A38” 4-benzoxazol-2-yl-N-methyl-N-{(1R,3S)-3-[(S)-(tetrahydro- furan-3-yl)carbamoyl]-cyclopentyl]-benzamide “A39” 6-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N- methyl-nicotinamide “A40” 5-benzoxazol-2-yl-pyridine-2-carboxylic acid ((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-methyl-amide “A41” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(5-methoxy- benzoxazol-2-yl)-N-methyl-benzamide “A42” 4-(5-chloro-benzoxazol-2-yl)-N-((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-N-methyl-benzamide “A43” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(5- trifluoromethyl-benzoxazol-2-yl)-benzamide “A44” 4-(1,3-benzoxazol-2-yl)-N-[(1R,3R)-3- (ethylcarbamoyl)cyclopentyl]-N-methyl-benzamide “A45” 4-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-3- methoxy-N-methyl-benzamide “A46” 4-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-2- methoxy-N-methyl-benzamide “A47” 4-benzoxazol-2-yl-N-[(1R,3S)-3-(ethyl-methyl-carbamoyl)- cyclopentyl]-N-methyl-benzamide “A48” 4-benzoxazol-2-yl-N-((1R,3S)-3-diethylcarbamoyl-cyclopentyl)- N-methyl-benzamide “A49” 4′-methyl-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-methyl-amide “A50” biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-methyl-amide “A51” 3-chloro-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-methyl-amide “A52” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(6-methoxy-4- methyl-pyridazin-3-yl)-N-methyl-benzamide “A53” 5-phenyl-pyridine-2-carboxylic acid ((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-methyl-amide “A54” 4-(4-chloro-phenylethynyl)-N-((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-N-methyl-benzamide “A55” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(4-fluoro- phenylethynyl)-N-methyl-benzamide “A56” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4- pyridin-4-yl-benzamide “A57” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-2-fluoro-N-methyl-4- pyridin-4-yl-benzamide “A58” 4′-ethyl-3,5-difluoro-biphenyl-4-carboxylic acid ((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-methyl-amide “A59” 2′-methanesulfonyl-biphenyl-4-carboxylic acid ((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-methyl-amide “A60” 2′-tert-butylsulfamoyl-biphenyl-4-carboxylic acid ((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-methyl-amide “A61” 2′-sulfamoyl-biphenyl-4-carboxylic acid ((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-methyl-amide “A62” 4′-chloro-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-methyl-amide “A63” 2′,4′-difluoro-biphenyl-4-carboxylic acid ((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-methyl-amide “A64” 2′-trifluoromethyl-biphenyl-4-carboxylic acid ((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-methyl-amide “A65” 2,2′-dimethyl-biphenyl-4-carboxylic acid ((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-methyl-amide “A66” 4′-(bis-trifluoromethyl-amino)-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide “A67” biphenyl-4-carboxylic acid methyl-[(1R,3S)-3-(1-methyl- cyclopropylcarbamoyl)-cyclopentyl]-amide “A68” 4-benzoxazol-2-yl-N-methyl-N-[(1R,3S)-3-(1-methyl- cyclopropylcarbamoyl)-cyclopentyl]-benzamide “A69” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(4-methoxy- phenylethynyl)-N-methyl-benzamide “A70” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4- pyridin-4-ylethynyl-benzamide “A71” 4-benzothiazol-2-yl-N-methyl-N-[(1R,3S)-3-(1-methyl- cyclopropylcarbamoyl)-cyclopentyl]-benzamide “A72” 4-(4-fluoro-phenylethynyl)-N-methyl-N-[(1R,3S)-3-(1-methyl- cyclopropylcarbamoyl)-cyclopentyl]-benzamide “A73” 4-benzoxazol-2-yl-N-methyl-N-[(1R,3S)-3-(1-propyl- cyclopropylcarbamoyl)-cyclopentyl]-benzamide “A74” 4-(1,3-benzoxazol-2-yl)-N-methyl-N-[(1R,3S)-3-[[(1S)-1- methylpropyl]carbamoyl] cyclopentyl]benzamide “A75” 4-(1,3-benzoxazol-2-yl)-N-methyl-N-[(1R,3S)-3[[(1R)-1- methylpropyl]carbamoyl]cyclopentyl]benzamide “A76” 4-(1,3-benzoxazol-2-yl)-N-[(1R,3S)-3- (cyclobutylcarbamoyl)cyclopentyl]-N-methyl-benzamide “A77” 4-(1,3-benzoxazol-2-yl)-N-[(1R,3S)-3-[(trans-3- hydroxycyclobutyl)carbamoyl]cyclopentyl]-N-methyl-benzamide “A78” 4-(1,3-benzoxazol-2-yl)-N-[(1R,3S)-3-[(cis-3-hydroxycyclo butyl)-carbamoyl]cyclopentyl]-N-methyl-benzamide “A79” 4-(1,3-benzoxazol-2-yl)-2-methoxy-N-methyl-N-[(1R,3S)-3[(1- methylcyclopropyl)carbamoyl]cyclopentyl]benzamide “A80” N-methyl-N-[(1R,3S)-3-[(1-methylcyclopropyl)- carbamoyl]cyclopentyl]-4-(4-pyridyl)benzamide “A81” 4-(4-cyanophenyl)-N-methyl-N-[(1R,3S)-3-[(1- methylcyclopropyl)carbamoyl]cyclopentyl]benzamide “A82” 4-benzoxazol-2-yl-N-((1R,3S)-3-dimethylcarbamoyl- cyclopentyl)-N-methyl-benzamide “A83” N-methyl-N-[(1R,3S)-3-(1-methyl-cyclopropylcarbamoyl)- cyclopentyl]-4-pyridin-3-yl-benzamide “A84” 4-benzoxazol-2-yl-N-methyl-N-[(1R,3S)-3-(1-methyl- cyclobutylcarbamoyl)-cyclopentyl]-benzamide “A85” 4-benzoxazol-2-yl-3-methoxy-N-methyl-N-[(1R,3S)-3-(1-methyl- cyclopropylcarbamoyl)-cyclopentyl]-benzamide “A86” 4-benzoxazol-2-yl-N-((1R,3S)-3-carbamoyl-cyclopentyl)-N- methyl-benzamide “A87” 4-(7-cyano-imidazo[1,2-a]pyridin-2-yl)-N-((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide “A88” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4- (5-methyl-[1,2,4]oxadiazol-3-yl)-benzamide “A89” 4-benzoxazol-2-yl-N-[(1R,3S)-3-(2-dimethylamino-1-methyl- ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide “A90” 4-benzoxazol-2-yl-N-[(1R,3S)-3((S)-2-hydroxy-1-methyl- ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide “A91” 4-benzoxazol-2-yl-N-[(1R,3S)-3-((R)-2-hydroxy-1-methyl- ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide “A92” 4-benzoxazol-2-yl-N-[(1R,3S)-3((S)-2-methoxy-1-methyl- ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide “A93” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(5- sulfamoyl-benzooxazol-2-yl)-benzamide “A94” 4-(5-ethanesulfonyl-benzooxazol-2-yl)-N-((1R,3S)-3- ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide “A95” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(1H-imidazol-2-yl)- N-methyl-benzamide “A96” 4-(5,7-difluoro-benzoxazol-2-yl)-N-((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-N-methyl-benzamide “A97” 4-benzoxazol-2-yl-N-[(1R,3S)-3-(2-hydroxy-ethylcarbamoyl)- cyclopentyl]-N-methyl-benzamide “A98” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(6-fluoro- benzooxazol-2-yl)-N-methyl-benzamide “A99” 4-benzoxazol-2-yl-N-[(1R,3S)-3-(2-hydroxy-1,1-dimethyl- ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide “A100” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(7-fluoro- benzooxazol-2-yl)-N-methyl-benzamide “A101” 4-(5,6-difluoro-benzoxazol-2-yl)-N-((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-N-methyl-benzamide “A102” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4- pyridin-3-yl-benzamide “A103” 4′-cyano-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-methyl-amide “A104” 4′-fluoro-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl- cyclopentyl)-methyl-amide “A105” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4- pyrimidin-5-yl-benzamide “A106” 4-benzoxazol-2-yl-N-[(1R,3S)-3-(2-hydroxy-ethylcarbamoyl)- cyclopentyl]-N-methyl-benzamide “A107” N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(1H-indazol-4- yl)-N-methyl-benzamide “A108” 4-benzoxazol-2-yl-N-[(1R,3S)-3-(1-hydroxymethyl- cyclopropylcarbamoyl)-cyclopentyl]-N-methyl-benzamide or pharmaceutically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios.

2. A pharmaceutical composition comprising at least one compound according to claim 1 and/or pharmaceutically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios, and an pharmaceutically acceptable carrier, excipient or vehicle.

3. A medicament comprising at least one compound of claim 1 and/or pharmaceutically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios, and at least one further medicament active ingredient.

4. A kit consisting of separate packs of (a) an effective amount of a compound of claim 1 and/or pharmaceutically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios, and (b) an effective amount of a further medicament active ingredient.

Description

EXAMPLE 1

4-(1,3-benzoxazol-2-yl)-N-[(1R,3S)-3-(ethylcarbamoyl)cyclopentyl]-N-methyl-benzamide (“A1”)

(1) ##STR00006##
1.1 (1S,3R)-3-(tert-Butoxycarbonyl-methyl-amino)-cyclopentanecarboxylic acid (Roberto J. Brea Angew. Chem. Int. Ed. 2005, 44, 5710-5713) (90 mg; 0.37 mmol), ethylamine (2.0 M solution in tetrahydrofurane) (555 μl; 1.11 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidhydrochlorid (142 mg; 0.74 mmol) and 1-hydroxybenzotriazol hydrat (56.65 mg; 0.37 mmol) are dissolved in 5 ml N,N-dimethylformamide. 4-Methylmorpholine (0.122 ml; 1.11 mmol) is added and the mixture is stirred at r.t. for 14 h. The reaction solution is diluted with water (10 ml) and extracted 2× with 10 ml of ethylacetate. The combined organic layer is washed 3× with 10 ml of water and 1× with 10 ml of brine, dried over Na.sub.2SO.sub.4, filtered and evaporated to dryness to yield 100 mg (100%) tert-butyl N-[(1R,3S)-3-(ethylcarbamoyl)cyclopentyl]-N-methyl-carbamate (1); LC/MS: 271 (M+H).
1.2 To tert-butyl N-[(1R,3S)-3-(ethylcarbamoyl)cyclopentyl]-N-methyl-carbamate (1) (100 mg; 0.37 mmol) in 15 ml of dichloromethane is added trifluoroacetic acid (1 ml; 13 mmol). The solution is stirred for 14 h at room temperature and then reduced to dryness under vacuo to afford 105 mg (100%) (1 S,3R)—N-ethyl-3-(methylamino)cyclopentanecarboxamide(2) as the TFA salt; LC/MS: 171 (M+H).
1.3 4-Benzoxazol-2-yl-benzoic acid (4) (Dinesh Kumar Aust. J. Chem. 2008 (61) 881-887) (50 mg; 0.21 mmol), (1S,3R)—N-ethyl-3-(methylamino)-cyclopentanecarboxamide trifluoroacetate (2) (59.42 mg; 0.21 mmol.), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride for synthesis (60.1 mg; 0.314 mmol), and 1-hydroxybenzotriazole (32 mg; 0.21 mmol) are dissolved in 3 ml of N,N-dimethylformamide and then was added 4-methylmorpholine for synthesis (91.9 μl; 0.84 mmol). The reaction mixture is stirred at r.t. for 14 h. The reaction solution is diluted with 10 ml of water and extracted 3× with 10 ml of ethylacetate. The combined organic layers are washed 3× with water and 1× with brine, dried over Na.sub.2SO.sub.4, filtered, evaporated to dryness and the residue is purified by flash chromatography (dichloromethane:methanol 95:5) to yield 65 mg (78./%) 4-(1,3-benzoxazol-2-yl)-N-[(1R,3S)-3-(ethylcarbamoyl)cyclopentyl]-N-methyl-benzamide (“A1”) as a white solid; LC/MS: 392 (M+H); .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.86-7.80 (m, 2H), 7.72 (br. s, 1H; NH), 7.65-7.55 (m, 2H), 7.45 (pd, J=7.4, 1.3 Hz, 2H), 4.89, 4.00 (2×br. s, 1H, ratio=1:1.8 mixture of rotamers), 3.06 (q, J=6.6 Hz, 2H, NCH2), 2.91 (br. s, 3H, CH3), 2,67, 2.49 (2×br.s, 1H, ratio=1:1.8 mixture of rotamers), 2.20-1.52 (m, 6H), 1.00 (t, J=7.1 Hz, 3H, CH3).

EXAMPLE 2

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(1-methyl-1H-benzoimidazol-2-yl)-benzamide (“A2”)

(2) ##STR00007##

(3) The compound is synthesized analogously to the method described above (example 1.3) with the amine (2) (example 1.2) and 4-(1-methyl-1H-benzoimidazol-2-yl)-benzoic acid as educts; LC/MS: M+H=405; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 7.97 (d, J=8.3 Hz, 2H), 7.88 (d, J=7.6 Hz, 1H), 7.80 (d, J=7.8 Hz, 1H), 7.73 (s, 1H; NH), 7.70-7.60 (m, 2H), 7.51 (dq, J=15.0, 7.0 Hz, 2H). 4.90, 4.00 (2×br. s, 1H, ratio=1.6:1, mixture of rotamers), 4.00 (s, 3H), 3.06 (q, J=7.0 Hz, 2H), 2.92 (s, 3H), 2.64, 2.44 (2×br. s, 1H, ratio=1.6:1 mixture of rotamers), 2.08-1.51 (m, 6H), 1.00 (t, J=7.1 Hz, 3H).

Synthesis of 4-(1-methyl-1H-benzoimidazol-2-yl)-benzoic acid

(4) 0.50 g (4.1 mmol) N-methyl-1,2-phenylenediamine and (0.67 g; 4.1 mmol) methyl 4-formylbenzoate for synthesis are dissolved in 20 ml methanol dried (max. 0.005% H.sub.2O). After addition of 1.17 ml acetic acid (glacial 100%) the mixture is stirred at r.t. for 14 h. The reaction solution is evaporated to dryness and the residue is dissolved in 10 ml of 5% NaHCO.sub.3-solution and extracted 2× with 10 ml ethyl acetate. The combined organic layer are washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated to dryness. The residue, 1.15 g, is purified by silica gel column chromatography with CombiFlash. Eluent: 100% dichlormethane to 65:35 dichlormethane:ethyl acetate to yield 367 mg (33.7%) 4-(1-methyl-1H-benzoimidazol-2-yl)-benzoic acid methyl ester as a beige solid; LC/MS: M+H 267. This solid is dissolved in 15 ml tetrahydrofuran and 5 ml warer. After addition of 99.02 mg lithiumhydroxid the reaction mixture is stirred 2 h at room temperature and concentrated under reduced pressure. The residue is diluted with 5 ml water, acidified (pH-3) using 1 N HCl and the resulting precipitate is filtered with suction, washed with water and dried at 50° C. in a vacuum cabinet dryer to yield 280 mg (80.5%) 4-(1-methyl-1H-benzoimidazol-2-yl)-benzoic acid as a beige solid; LC/MS: M+H 253.

EXAMPLE 3

4-benzothiazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A3”)

(5) ##STR00008##

(6) The compound is synthesized analogously to the method described above (example 1.3) with the amine (2) (example 1.2) and 4-benzothiazol-2-yl-benzoic (Lloyd J. Nadeau, Chem. Commun., 2006, 564-565) as educts. LC/MS: M+H=408; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm]8.17 (dd, J=12.1, 7.9 Hz, 3H), 8.09 (d, J=8.0 Hz, 1H), 7.73 (s, 1H; NH), 7.63-7.52 (m, 3H), 7.49 (t, J=7.6 Hz, 1H), 4.88, 4.02 (2×br. s, 1H, ratio=1:2 mixture of rotamers) 3.06 (q, J=7.0 Hz, 2H), 2.90 (s, 3H), 2,90, 2.44 (2×br.s, 1H, ratio=1:2 mixture of rotamers), 2.20-1.63 (m, 6H), 1.00 (t, J=7.2 Hz, 3H).

EXAMPLE 4

4′-[(R)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide

(7) ##STR00009##

(8) The compound is synthesized analogously to the method described above (example 1.3) with the amine (2) (example 1.2) and 4′-[(R)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid as educts.

(9) LC/MS: M+H=437; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 7.73 (s, 1H; NH), 7.70-7.61 (m, 4H), 7.41 (d, J=7.9 Hz, 2H), 7.02 (d, J=8.8 Hz, 2H), 5.11-5.05 (m, 1H), 4.83, 4.12 (2×br. s, 1H, ratio=1:1.6 mixture of rotamers) 3.92 (dd, J=10.1, 4.6 Hz, 1H), 3.86 (q, J=8.1 Hz, 1H), 3.81 (d, J=10.1 Hz, 1H), 3.77 (td, J=8.3, 4.6 Hz, 1H), 3.05 (q, J=7.2 Hz, 2H), 2.88 (s, 3H), 2.31-2.18 (m, 1H), 1.99 (dt, J=12.6, 5.8 Hz, 1H), 1.95-1.58 (m, 6H), 1.00 (t, J=7.2 Hz, 3H).

Synthesis of 4′-[(R)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid

(10) ##STR00010##
a) A mixture of 4′-hydroxy-biphenyl-4-carboxylic acid (R)-1-methyl-heptyl ester (269.5 mg; 0.825 mmol), toluene-4-sulfonic acid (R)-(tetrahydro-furan-3-yl) ester (200 mg; 0.825 mmol) and cesium carbonate (350 mg; 1.07 mmol) in of N,N-dimethylformamide (5 mL) is heated to 60° C. for 4 hours. The reaction mixture is diluted with 10 ml water and extracted 3× with 10 ml ethyl acetate. The organic layer is dried over Na.sub.2SO.sub.4, filtered and the solvent removed in vacuo. The residue is crystallized with methanol, filtered with suction, washed with cold methanol and dried at 40° C. under vacuo to give 300 mg (91.7%) 4′-[(R)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid (R)-1-methyl-heptyl ester as white powder; LC/MS: M+Na=419.
b) 4′-[(R)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid (R)-1-methyl-heptyl ester (300 mg) is dissolved in 15 ml tetrahydrofuran and 3 ml warer. After addition of 54.36 mg lithiumhydroxid the reaction mixture is stirred for 14 h at 70° C. and concentrated under reduced pressure. The residue is diluted with 5 ml water, acidified (pH-3) using 1 N HCl and the resulting precipitate is filtered with suction, washed with water and dried at 50° C. in a vacuum cabinet dryer to yield 210 mg (97.6%) 4′-[(R)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid as beige solid; LC/MS: M+H 285.

(11) The following compounds are synthesized analogously to methods 1.1 to 1.3 (example 1):

4-benzoxazol-2-yl-N-((1R,3S)-3-isopropylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A5”)

(12) ##STR00011##

(13) LC/MS: M+H 406; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.83 (dd, J=14.3, 7.3 Hz, 2H), 7.60 (m, 3H; 2×CH+NH), 7.53-7.37 (m, 2H), 4.89, 3.98 (2×br. s, 1H, ratio=1:1.6 mixture of rotamers), 3.82 (dq, J=13.2, 6.6 Hz, 1H), 2.91 (br. s, 3H, CH3), 2,63, 2.41 (2×br.s, 1H, ratio=1:1.6 mixture of rotamers) 2.00-1.61 (m, 6H), 1.03 (d, J=6.3 Hz, 6H);

4-benzoxazol-2-yl-N-((1R,3S)-3-cyclopropylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A6”)

(14) ##STR00012##

(15) LC/MS: M+H 404; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.25 (d, J=8.4 Hz, 2H), 7.92-7.70 (m, 3H; 2×CH+NH), 7.59 (br. d, J=5.6 Hz, 2H), 7.52-7.35 (m, 2H), 4.88, 3.98 (2×br. s, 1H, ratio=1:1.7 mixture of rotamers), 2.91 (br. s, 3H), 2.67, 2.38 (2×br. s, 1H, ratio=1:1.7 mixture of rotamers), 2.64-2.55 (m, 1H), 2.03-1.52 (m, 6H), 0.58 (d, J=5.2 Hz, 2H), 0.36 (br. s, 2H);

4-benzoxazol-2-yl-N-((1R,3S)-3-cyclopentylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A7”)

(16) ##STR00013##

(17) LC/MS: M+H 432; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.4 Hz, 2H), 7.83 (dd, J=14.3, 7.3 Hz, 2H), 7.68 (s, 1H; NH), 7.60 (d, J=7.0 Hz, 2H), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 4.89, 3.98 (2×br. s, 1H, ratio=1:2 mixture of rotamers), 3.97 (q, J=6.8 Hz, 2H), 2.91 (br. s, 3H), 2.73, 2.43 (2×br. s, 1H, ratio=1:2 mixture of rotamers), 2.10-1.54 (m, 10H), 1.53-1.41 (m, 2H), 1.40-1.24 (m, 2H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-(cyclohexylmethyl-carbamoyl)-cyclopentyl]-N-methyl-benzamide (“A8”)

(18) ##STR00014##

(19) LC/MS: M+H 460;

4-benzoxazol-2-yl-N-methyl-N-[(1R,3S)-3-(pyrrolidine-1-carbonyl)-cyclopentyl]-benzamide (“A9”)

(20) ##STR00015##

(21) LC/MS: M+H 418; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.83 (dd, J=14.2, 7.3 Hz, 2H), 7.60 (d, J=7.3 Hz, 2H), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 4.90, 4.00 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 3.51-3.24 (m, 4H), 2.91 (s, 3H), 303, 2.78 (2×br. s, 1H, ratio=1:1.8 mixture of rotamers), 2.09-1.56 (m, 10H);

4-(1,3-benzoxazol-2-yl)-N-[(1S,3R)-3-(ethylcarbamoyl)cyclopentyl]-N-methyl-benzamide (“A10”)

(22) ##STR00016##

(23) LC/MS: 392 (M+H); .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.86-7.80 (m, 2H), 7.72 (br. s, 1H; NH), 7.65-7.55 (m, 2H), 7.45 (pd, J=7.4, 1.3 Hz, 2H), 4.89, 4.00 (2×br. s, 1H, ratio=1:1.8 mixture of rotamers), 3.06 (q, J=6.6 Hz, 2H, NCH2), 2.91 (br. s, 3H, CH3), 2,67, 2.49 (2×br.s, 1H, ratio=1:1.8 mixture of rotamers) 2.20-1.52 (m, 6H), 1.00 (t, J=7.1 Hz, 3H, CH3);

4-(1H-benzimidazol-2-yl)-N-[(1R,3S)-3-(ethylcarbamoyl)cyclopentyl]-N-methyl-benzamide (“A11”)

(24) ##STR00017##

(25) LC/MS: M+H 391; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.23 (d, J=8.4 Hz, 2H), 7.75 (s, 1H, NH), 7.71 (dd, J=6.0, 3.2 Hz, 2H), 7.69-7.55 (m, 2H), 7.36 (dd, J=5.9, 3.0 Hz, 2H), 4.90, 4.00 (2×br. s, 1H, ratio=1:1.4, mixture of rotamers), 3.06 (q, J=7.2 Hz, 2H), 2.90 (s, 3H), 2.71, 2.46 (2×br. s, 1H, ratio=1:1.4 mixture of rotamers) 2.05-1.53 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

4-benzoxazol-2-yl-N-ethyl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-benzamide (“A12”)

(26) ##STR00018##

(27) LC/MS: M+H 406;

(28) .sup.1H NMR (500 MHz, DMSO-d.sub.6), mixture of rotamers, δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.83 (ddd, J=12.2, 7.3, 1.9 Hz, 2H), 7.72 (s, 1H; NH), 7.57 (d, J=8.3 Hz, 2H), 7.51-7.39 (m, 2H), 3.38 (br. s, 2H), 3.16-2.98 (m, 2H), 2.16-1.52 (m, 6H), 1.38-1.06 (m, 3H), 1.07-0.91 (m, 3H);

4-benzoxazol-2-yl-N-benzyl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-benzamide (“A13”)

(29) ##STR00019##

(30) LC/MS: M+H 468;

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-oxazolo[5,4-b]pyridin-2-yl-benzamide (“A14”)

(31) ##STR00020##

(32) LC/MS: M+H 393;

(33) .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.42 (dd, J=4.9, 1.5 Hz, 1H), 8.31 (dd, J=7.9, 1.5 Hz, 1H), 8.29 (d, J=8.3 Hz, 2H), 7.72 (s, 1H; NH), 7.62 (d, J=6.6 Hz, 2H), 7.53 (dd, J=7.8, 4.9 Hz, 1H), 4.89, 3.97 (2×br.s, 1H, ratio=1:1,9, mixture of rotamers), 3.05 (q, J=6.0, 1.0 Hz, 2H), 2.92 (s, 3H), 2.41 (br. s, 1H), 2.13-1.49 (m, 6H), 1.00 (t, J=7.0 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-oxazolo[5,4-c]pyridin-2-yl-benzamide (“A15”)

(34) ##STR00021##

(35) LC/MS: M+H 393;

4′-methoxy-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A16”)

(36) ##STR00022##

(37) LC/MS: M+H 381; .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.74 (s, 1H; NH), 7.66 (t, J=8.6 Hz, 4H), 7.41 (d, J=8.1 Hz, 2H), 7.04 (d, J=8.8 Hz, 2H), 4.41 (br. s, 1H), 3.81 (s, 3H; CH.sub.3O), 3.05 (dd, J=7.2, 5.6 Hz, 2H), 2.88 (s, 3H; CH.sub.3N), 1.94-1.58 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

4′-[(S)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A17”)

(38) ##STR00023##

(39) LC/MS: M+H 437;

4-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-2-fluoro-N-methyl-benzamide (“A18”)

(40) ##STR00024##

(41) LC/MS: M+H 410;

(42) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.10 (d, J=7.9 Hz, 1H), 8.04 (d, J=9.8 Hz, 1H), 7.85 (dd, J=14.2, 7.8 Hz, 2H), 7.72 (t, J=5.4 Hz, 1H; NH), 7.62 (q, J=8.0 Hz, 1H), 7.47 (pd, J=7.4, 1.4 Hz, 2H), 4.92, 3.91 (2×br.s, 1H, ratio=1:7, mixture of rotamers), 3.06 (dp, J=14.3, 7.2 Hz, 2H), 2.96, 2.79 (2×s, ratio=1:1,6, mixture of rotamers, 3H), 2.65, 2.43 (2×br. s, ratio=1:1,6, mixture of rotamers, 1H), 2.06-1.52 (m, 6H), 1.00 (dt, J=14.3, 7.2 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(5-fluoro-benzoxazol-2-yl)-N-methyl-benzamide (“A19”)

(43) ##STR00025##

(44) LC/MS: M+H 410;

(45) .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.25 (d, J=8.3 Hz, 2H), 7.85 (dd, J=8.9, 4.4 Hz, 1H), 7.72 (dd, J=8.7, 2.6 Hz, 1H+1H, NH), 7.60 (d, J=6.8 Hz, 2H), 7.32 (td, J=9.4, 2.6 Hz, 1H), 0.4.89, 3.97 (2×br.s, 1H, ratio=1:1,6, mixture of rotamers) 3.05 (q, J=6.7 Hz, 2H), 2.91 (br. s, 3H), 2.63, 2.42 (2×br.s, 1H, ratio=1:1,6, mixture of rotamers) 2.05-1.52 (m, 6H), 1.00 (t, J=7.1 Hz, 3H);

4-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-2,6-difluoro-N-methyl-benzamide (“A20”)

(46) ##STR00026##

(47) LC/MS: M+H 428;

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(5-trifluoromethoxybenzoxazol-2-yl)-benzamide (“A21”)

(48) ##STR00027##

(49) LC/MS: M+H 476;

4-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-3-trifluoromethyl-benzamide (“A22”)

(50) ##STR00028##

(51) LC/MS: M+H 460;

4-(6-chloro-benzoxazol-2-yl)-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A23”)

(52) ##STR00029##

(53) LC/MS: M+H 426;

(54) .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.24 (d, J=8.3 Hz, 2H), 8.03 (d, J=1.9 Hz, 1H), 7.86 (d, J=8.5 Hz, 1H), 7.72 (s, 1H; NH), 7.60 (d, J=6.8 Hz, 2H), 7.49 (dd, J=8.5, 2.0 Hz, 1H), 4.87, 3.96 (2×br.s, 1H, ratio=1:1,46, mixture of rotamers), 3.05 (q, J=6.6 Hz, 2H), 2.91 (br. s, 3H), 2.61, 2.43 (2×br.s, 1H, ratio=1:1,46, mixture of rotamers), 2.06-1.49 (m, 6H), 1.00 (t, J=7.1 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-naphthalen-2-yl-benzamide (“A24”)

(55) ##STR00030##

(56) LC/MS: M+H 401;

N-((1R,3S)-3-Ethylcarbamoyl-cyclopentyl)-4-isoquinolin-6-yl-N-methyl-benzamide (“A25”)

(57) ##STR00031##

(58) LC/MS: M+H 402;

(59) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 9.66 (s, 1H), 8.64 (d, J=6.2 Hz, 1H), 8.54 (s, 1H), 8.46 (d, J=8.7 Hz, 1H), 8.33-8.16 (m, 2H), 7.99 (d, J=8.3 Hz, 2H), 7.75 (s, 1H; NH), 7.57 (d, J=7.6 Hz, 2H), 3.06 (p, J=7.1 Hz, 2H), 2.91 (br. s, 3H), 2.09-1.54 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

4-benzofuran-5-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A26”)

(60) ##STR00032##

(61) LC/MS: M+H 391;

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(1-methyl-1H-benzoimidazol-5-yl)-benzamide (“A27”)

(62) ##STR00033##

(63) LC/MS: M+H 391;

4-benzoxazol-2-yl-N-[(1R,3S)-3-(4-ethyl-piperazine-1-carbonyl)-cyclopentyl]-N-methyl-benzamide (“A28”)

(64) ##STR00034##

(65) LC/MS: M+H 461;

4-benzoxazol-2-yl-N-cyclopropylmethyl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-benzamide (“A29”)

(66) ##STR00035##

(67) LC/MS: M+H 432;

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(1H-indol-2-yl)-N-methyl-benzamide (“A30”)

(68) ##STR00036##

(69) LC/MS: M+H 390;

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-[5-(pyrrolidine-1-carbonyl)-benzoxazol-2-yl]-benzamide (“A31”)

(70) ##STR00037##

(71) LC/MS: M+H 489;

4-benzoxazol-2-yl-N-[(1R,3S)-3-(cyclopentylmethyl-carbamoyl)-cyclopentyl]-N-methyl-benzamide (“A32”)

(72) ##STR00038##

(73) LC/MS: M+H 446;

(74) .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.4 Hz, 2H), 7.83 (dd, J=13.4, 8.0 Hz, 2H), 7.73 (s, 1H; NH), 7.60 (d, J=7.1 Hz, 2H), 7.49-7.37 (m, 2H), 4.89, 3.99 (2×br.s, 1H, ratio=1:1.7, mixture of rotamers) 3.11-2.72 (m, 5H), 2.10-1.34 (m, 13H), 1.23-0.97 (m, 2H);

4-benzoxazol-2-yl-N-methyl-N-[(1R,3S)-3-(oxetan-3-ylcarbamoyl)-cyclopentyl]-benzamide (“A33”)

(75) ##STR00039##

(76) LC/MS: M+H 420;

4-benzoxazol-2-yl-N-methyl-N-((1R,3S)-3-{[(S)-1-(tetrahydro-furan-2-yl)methyl]-carbamoyl}-cyclopentyl)-benzamide (“A34”)

(77) ##STR00040##

(78) LC/MS: M+H 448; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.27 (d, J=8.3 Hz, 2H), 7.98-7.72 (m, 3H), 7.61 (d, J=6.9 Hz, 2H), 7.46 (pd, J=7.4, 1.4 Hz, 2H), 4.91, 4.00 (2×br. s, 1H, ratio=1:1.8 mixture of rotamers) 3.89-3.78 (m, 1H), 3.75 (q, J=6.9 Hz, 1H), 3.61 (q, J=7.2 Hz, 1H), 3.16-3.06 (m, 2H), 2.92 (s, 3H), 2.90 (s, 3H), 2,72, 2.55 (2×br.s, 1H, ratio=1:1.8 mixture of rotamers), 2.03-1.58 m, 9H), 1.49 (dq, J=14.4, 7.2 Hz, 1H).

4-benzoxazol-2-yl-N-methyl-N-((1R,3S)-3-{[(R)-1-(tetrahydro-furan-2-yl)methyl]-carbamoyl}-cyclopentyl)-benzamide (“A35”)

(79) ##STR00041##

(80) LC/MS: M+H 448; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.27 (d, J=8.3 Hz, 2H), 7.98-7.72 (m, 3H), 7.61 (d, J=6.9 Hz, 2H), 7.46 (pd, J=7.4, 1.4 Hz, 2H), 4.91, 4.00 (2×br. s, 1H, ratio=1:1.8 mixture of rotamers) 3.89-3.78 (m, 1H), 3.75 (q, J=6.9 Hz, 1H), 3.61 (q, J=7.2 Hz, 1H), 3.16-3.06 (m, 2H), 2.92 (s, 3H), 2.90 (s, 3H), 2,72, 2.55 (2×br.s, 1H, ratio=1:1.8 mixture of rotamers), 2.03-1.58 m, 9H), 1.49 (dq, J=14.4, 7.2 Hz, 1H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-(2-methoxy-ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide (“A36”)

(81) ##STR00042##

(82) LC/MS: M+H 422; .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.27 (d, J=8.3 Hz, 2H), 7.89-7.79 (m, 3H), 7.61 (d, J=6.7 Hz, 2H), 7.46 (pd, J=7.4, 1.4 Hz, 2H), 4.90, 4.00 (2×br. s, 1H, ratio=1:2 mixture of rotamers) 3.34 (t, J=5.6 Hz, 2H), 3.31 (s, 3H; OCH.sub.3), 3.24-3.18 (m, 2H), 2.92 (s, 3H), 2.08-1.52 (m, 6H);

4-benzoxazol-2-yl-N-methyl-N-{(1R,3S)-3-[(R)-(tetrahydro-furan-3-yl)carbamoyl]-cyclopentyl}-benzamide (“A37”)

(83) ##STR00043##

(84) LC/MS: M+H 434;

(85) .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.98 (s, 1H; NH), 7.83 (ddd, J=12.7, 7.3, 1.8 Hz, 2H), 7.60 (d, J=6.9 Hz, 2H), 7.50-7.40 (m, 2H), 4.90, 3.99 (2×br.s, 1H, ratio=1:1.5, mixture of rotamers) 4.25-4.17 (m, 1H), 3.83-3.70 (m, 2H), 3.65 (q, J=8.1 Hz, 1H), 3.41 (dd, J=8.6, 3.3 Hz, 1H), 2.91 (br. s, 3H), 2.12-1.99 (m, 1H), 2.00-1.54 (m, 7H);

4-benzoxazol-2-yl-N-methyl-N-{(1R,3S)-3-[(S)-(tetrahydro-furan-3-yl)carbamoyl]-cyclopentyl}-benzamide (“A38”)

(86) ##STR00044##

(87) LC/MS: M+H 434;

(88) .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.98 (s, 1H; NH), 7.83 (ddd, J=12.7, 7.3, 1.8 Hz, 2H), 7.60 (d, J=6.9 Hz, 2H), 7.50-7.40 (m, 2H), 4.90, 3.99 (2×br.s, 1H, ratio=1:1.5, mixture of rotamers) 4.25-4.17 (m, 1H), 3.83-3.70 (m, 2H), 3.65 (q, J=8.1 Hz, 1H), 3.41 (dd, J=8.6, 3.3 Hz, 1H), 2.91 (br. s, 3H), 2.12-1.99 (m, 1H), 2.00-1.54 (m, 7H);

6-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methylnicotinamide (“A39”)

(89) ##STR00045##

(90) LC/MS: M+H 393;

(91) .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.79 (s, 1H), 8.39 (d, J=8.1 Hz, 1H), 8.07 (s, 1H), 7.90 (d, J=7.6 Hz, 1H), 7.86 (d, J=7.7 Hz, 1H), 7.73 (s, 1H; NH), 7.52 (td, J=7.8, 1.4 Hz, 1H), 7.47 (td, J=7.7, 1.2 Hz, 1H), 4.91, 3.99 (2×br.s, 1H, ratio=1:1.5, mixture of rotamers), 3.14-3.00 (m, 2H), 2.95 (s, 3H), 2.44 (br. s, 1H), 2.11-1.52 (m, 6H), 1.13-0.89 (m, 3H);

5-benzoxazol-2-yl-pyridine-2-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A40”)

(92) ##STR00046##

(93) LC/MS: M+H 393;

(94) .sup.1H NMR (500 MHz, DMSO-d.sub.6) mixture of rotamers: δ [ppm] 9.35 (s, 1H), 8.63 (d, J=8.1 Hz, 1H), 7.87 (dd, J=16.0, 7.1 Hz, 2H), 7.83-7.62 (m, 2H), 7.60-7.32 (m, 2H), 4.93, 4.00 (m, 1H), 3.11-3.01 (m, 2H), 2.96, 2.85 (s, 3H), 2.65, 2.44 (m, 1H), 2.08-1.53 (m, 6H), 1.10-0.93 (m, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(5-methoxy-benzoxazol-2-yl)-N-methyl-benzamide (“A41”)

(95) ##STR00047##

(96) LC/MS: M+H 422;

(97) .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.22 (d, J=8.1 Hz, 2H), 7.73 (br. s, 1H; NH), 7.70 (d, J=8.9 Hz, 1H), 7.58 (d, J=6.5 Hz, 2H), 7.38 (d, J=2.4 Hz, 1H), 7.03 (dd, J=8.9, 2.5 Hz, 1H), 4.89, 3.97 (2×br.s, 1H, ratio=1:2, mixture of rotamers), 3.84 (s, 3H), 3.14-2.99 (m, 2H), 2.90 (br. s, 3H), 2.33 (br. s, 1H), 2.07-1.49 (m, 6H), 1.00 (t, J=7.0 Hz, 3H);

4-(5-chloro-benzoxazol-2-yl)-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A42”)

(98) ##STR00048##

(99) LC/MS: M+H 426

(100) .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.25 (d, J=8.3 Hz, 2H), 7.95 (d, J=2.1 Hz, 1H), 7.86 (d, J=8.7 Hz, 1H), 7.72 (s, 1H; NH), 7.60 (d, J=6.4 Hz, 2H), 7.50 (dd, J=8.7, 2.1 Hz, 1H), 4.89, 3.97 (2×br.s, 1H, ratio=1:1.9, mixture of rotamers) 3.05 (q, J=6.7 Hz, 2H), 2.91 (br. s, 3H), 2.42 (br. s, 1H), 2.10-1.50 (m, 6H), 1.00 (t, J=7.1 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(5-trifluoromethylbenzoxazol-2-yl)-benzamide (“A43”)

(101) ##STR00049##

(102) LC/MS: M+H 460;

(103) .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ [ppm] 8.34-8.24 (m, 3H), 8.06 (d, J=8.5 Hz, 1H), 7.87-7.80 (m, 1H), 7.74 (s, 1H; NH), 7.63 (s, 2H), 4.90, 3.96 (2×br.s, 1H, ratio=1:1.7, mixture of rotamers) 3.05 (q, J=6.7, 5.8 Hz, 2H), 2.93 (br. s, 3H), 2.15-1.50 (m, 6H), 0.99 (t, J=6.4 Hz, 3H);

4-(1,3-benzoxazol-2-yl)-N-[(1R,3R)-3-(ethylcarbamoyl)cyclopentyl]-N-methyl-benzamide (“A44”)

(104) ##STR00050##

(105) LC/MS: M+H 392;

(106) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.88-7.78 (m, 2H), 7.74 (s, 1H; NH), 7.58 (d, J=7.3 Hz, 2H), 7.51-7.39 (m, 2H), 4.94, 4.17 (2×br.s, 1H, ratio=1:2.2, mixture of rotamers), 3.01 (br. s, 2H), 2.86 (br. s, 3H), 2.80-2.64 (m, 1H), 2.15-1.53 (m, 6H), 0.96 (br. s, 3H);

4-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-3-methoxy-N-methyl-benzamide (“A45”)

(107) ##STR00051##

(108) LC/MS: M+H 422;

(109) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.09 (d, J=7.9 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.80 (d, J=6.9 Hz, 1H), 7.75 (s, 1H; NH), 7.49-7.39 (m, 2H), 7.24 (s, 1H), 7.12 (d, J=7.3 Hz, 1H), 4.93, 4.07 (2×br.s, 1H, ratio=1:1.5, mixture of rotamers), 3.98 (s, 3H), 3.15-3.00 (m, 2H), 2.93 (br. s, 3H), 2.09-1.58 (m, 6H), 1.02 (t, J=7.0 Hz, 3H);

4-benzoxazol-2-yl-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-2-methoxy-N-methyl-benzamide (“A46”)

(110) ##STR00052##

(111) LC/MS: M+H 422;

(112) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] mixture of rotamers 7.90-7.78 (m, 4H), 7.69 (s, 1H, NH), 7.46 (td, J=7.2, 1.4 Hz, 2H), 7.39 (d, J=7.7 Hz, 1H), 4.95, 3.83 (2×m, 1H, ratio=1:1.8, mixture of rotamers), 3.95 (s, 3H), 3.15-2.98 (m, 2H), 2.92, 2.70 (2×s, 3H), 2.04-1.44 (m, 6H), 1.08-0.92 (m, 3H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-(ethyl-methyl-carbamoyl)-cyclopentyl]-N-methyl-benzamide (“A47”)

(113) ##STR00053##

(114) LC/MS: M+H 406;

(115) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] mixture of rotamers 8.26 (d, J=8.3 Hz, 2H), 7.83 (dd, J=13.7, 6.9 Hz, 2H), 7.60 (d, J=7.2 Hz, 2H), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 4.93, 4.04 (2×s, 1H, ratio=1:1.7, mixture of rotamers), 3.29-3.16 (m, 2H), 3.10-2.70 (m, 6H), 2.13-1.57 (m, 6H), 1.19-0.84 (m, 3H);

4-benzoxazol-2-yl-N-((1R,3S)-3-diethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A48”)

(116) ##STR00054##

(117) LC/MS: M+H 420;

(118) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.4 Hz, 2H), 7.87-7.78 (m, 2H), 7.60 (d, J=7.1 Hz, 2H), 7.45 (td, J=7.5, 1.5 Hz, 2H), 4.95, 4.04 (2×s, 1H, ratio=1:1.7, mixture of rotamers), 3.30-3.11 (m, 2H), 2.91 (br. s, 3H), 2.09-1.53 (m, 6H), 1.21-0.84 (m, 6H);

4′-methyl-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A49”)

(119) ##STR00055##

(120) LC/MS: M+H 365;

(121) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.73 (s, 1H; NH), 7.70 (d, J=8.3 Hz, 2H), 7.60 (d, J=8.1 Hz, 2H), 7.43 (d, J=7.9 Hz, 2H), 7.29 (d, J=7.9 Hz, 2H), 4.83, 4.09 (2×s, 1H, ratio=1:1.8, mixture of rotamers), 3.05 (p, J=7.2 Hz, 2H), 2.88 (s, 3H), 2.35 (s, 3H), 2.05-1.54 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A50”)

(122) ##STR00056##

(123) LC/MS: M+H 351;

(124) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.81-7.63 (m, 5H), 7.49 (t, J=7.7 Hz, 2H), 7.45 (d, J=7.9 Hz, 2H), 7.40 (t, J=7.4 Hz, 1H), 4.84, 4.08 (2×s, 1H, ratio=1:1.8, mixture of rotamers), 3.06 (p, J=7.2 Hz, 2H), 2.88 (br. s, 3H), 2.05-1.54 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

3-chloro-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A51”)

(125) ##STR00057##

(126) LC/MS: M+H 385;

(127) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.81 (d, J=6.9 Hz, 1H), 7.77-7.65 (m, 4H), 7.50 (t, J=7.6 Hz, 2H), 7.41 (q, J=7.4, 6.8 Hz, 2H), Hz, 2H), 7.40 (t, J=7.4 Hz, 1H), 4.95, 3.82 (2×m, 1H, ratio=1:1.6, mixture of rotamers), 3.15-2.98 (m, 2H), 2.94, 2,72 (2×s, 3H, ratio=1:1.6, mixture of rotamers), 2.65, 2.41 (2×m, 1H ratio=1:1.6, mixture of rotamers), 2.02-1.50 (m, 6H), 1.07-0.91 (m, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(6-methoxy-4-methyl-pyridazin-3-yl)-N-methyl-benzamide (“A52”)

(128) ##STR00058##

(129) LC/MS: M+H 397;

(130) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.74 (s, 1H; NH), 7.62 (d, J=8.2 Hz, 2H), 7.48 (d, J=7.7 Hz, 2H), 7.20 (s, 1H), 4.87, 4.04 (2×s, 1H, ratio=1:1.2, mixture of rotamers), 4.06 (s, 3H), 3.06 (p, J=7.1 Hz, 2H), 2.90 (br. s, 3H), 2.29 (s, 3H), 2.04-1.55 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

5-phenyl-pyridine-2-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A53”)

(131) ##STR00059##

(132) LC/MS: M+H 352;

(133) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.89 (s, 1H), 8.19 (dd, J=8.1, 2.3 Hz, 1H), 7.78 (d, J=7.5 Hz, 2H), 7.69 (t, J=4.2 Hz, 1H; NH), 7.66-7.57 (m, 1H), 7.53 (t, J=7.5 Hz, 2H), 7.45 (t, J=7.4 Hz, 1H), 4.93, 4.132 (2×m, 1H, ratio=1:1.5, mixture of rotamers), 3.17-2.97 (m, 2H), 2.94, 2.86 (2×s, 3H, ratio=1:1.5, mixture of rotamers; N—CH.sub.3), 2.64, 2.41 (2×m, 1H ratio=1:1.5, mixture of rotamers), 2.10-1.49 (m, 6H), 1.08-0.90 (m, 3H);

4-(4-chloro-phenylethynyl)-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A54”)

(134) ##STR00060##

(135) LC/MS: M+H 409;

(136) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.73 (br. s, 1H; NH), 7.61 (t, J=8.2 Hz, 4H), 7.51 (d, J=8.6 Hz, 2H), 7.41 (d, J=7.4 Hz, 2H), 4.86, 3.95 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 3.05 (p, J=7.1 Hz, 2H), 2.86 (br. s, 3H), 2.56, 2,43 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 2.08-1.46 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(4-fluoro-phenylethynyl)-N-methyl-benzamide (“A55”)

(137) ##STR00061##

(138) LC/MS: M+H 393;

(139) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.73 (br. s, 1H; NH), 7.64 (dd, J=8.9, 5.5 Hz, 2H), 7.60 (d, J=8.3 Hz, 2H), 7.41 (d, J=8.3 Hz, 2H), 7.29 (t, J=8.9 Hz, 2H), 4.87, 3.94 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 3.05 (p, J=7.1 Hz, 2H), 2.86 (br. s, 3H), 2.56, 2,43 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 2.11-1.50 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-pyridin-4-yl-benzamide (“A56”)

(140) ##STR00062##

(141) LC/MS: M+H 352;

(142) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.66 (d, J=6.1 Hz, 2H), 7.87 (d, J=8.3 Hz, 2H), 7.82-7.61 (m, 3H), 7.50 (d, J=7.6 Hz, 2H), 4.87, 4.04 (2×s, 1H, ratio=1:1.9, mixture of rotamers), 3.05 (p, J=7.1 Hz, 2H), 2.89 (br. s, 3H), 2.13-1.52 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-2-fluoro-N-methyl-4-pyridin-4-yl-benzamide (“A57”)

(143) ##STR00063##

(144) LC/MS: M+H 370;

(145) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.67 (d, J=4.6 Hz, 2H), 7.84-7.76 (m, 3H), 7.74 (dd, J=7.9, 1.6 Hz, 1H), 7.70 (t, J=5.2 Hz, 1H; NH), 7.50 (q, J=7.6 Hz, 1H), 4.93, 3.92 (2×p, J=8.2 Hz, 1H, ratio=1:1.8, mixture of rotamers), 3.17-2.97 (m, 2H), 2.94, 2.78 (2×s, 3H), 2.65, 2.40 (2×m, 1H, ratio=1:1.8, mixture of rotamers), 2.09-1.51 (m, 6H), 1.07-0.91 (m, 3H);

4′-ethyl-3,5-difluoro-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A58”)

(146) ##STR00064##

(147) LC/MS: M+H 415;

(148) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.84-7.66 (m, 3H), 7.54 (dd, J=9.3, 2.9 Hz, 2H), 7.34 (d, J=8.3 Hz, 2H), 4.93, 3.99 (2×m, 1H, ratio=1:1.7, mixture of rotamers), 3.14-2.99 (m, 2H), 2.96, 2.81 (2×s, 3H, ratio=1:1.7, mixture of rotamers), 2.66 (q, J=7.6 Hz, 2H), 2.04-1.54 (m, 6H), 1.28-1.17 (m, 3H), 1.07-0.91 (m, 3H);

2′-methanesulfonyl-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A59”)

(149) ##STR00065##

(150) LC/MS: M+H 429;

(151) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.11 (dd, J=8.0, 1.3 Hz, 1H), 7.82-7.72 (m, 2H), 7.70 (td, J=7.7, 1.4 Hz, 1H), 7.54-7.31 (m, 5H), 3.06 (p, J=7.1 Hz, 2H), 4.87, 4.02 (2×br. s, 1H, ratio=1:1.4, mixture of rotamers), 2.94-2.78 (m, 6H), 2.09-1.54 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

2′-tert-butylsulfamoyl-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A60”)

(152) ##STR00066##

(153) LC/MS: M+H 486;

(154) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.11-7.98 (m, 1H), 7.75 (s, 1H; NH), 7.65 (td, J=7.5, 1.3 Hz, 1H), 7.58 (td, J=7.7, 1.4 Hz, 1H), 7.46 (d, J=8.1 Hz, 2H), 7.38 (d, J=7.5 Hz, 2H), 7.34 (dd, J=7.5, 1.1 Hz, 1H), 6.67 (s, 1H; NH), 4.82, 4.13 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 3.06 (p, J=7.2 Hz, 2H), 2.90 (s, 3H), 2.04-1.48 (m, 6H), 1.05-0.92 (m, 12H);

2′-sulfamoyl-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A61”)

(155) ##STR00067##

(156) LC/MS: M+H 430;

(157) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.05 (dd, J=7.8, 1.3 Hz, 1H), 7.76 (s, 1H; NH), 7.67-7.55 (m, 2H), 7.44 (d, J=8.2 Hz, 2H), 7.37 (d, J=7.8 Hz, 2H), 7.34 (dd, J=7.4, 1.3 Hz, 1H), 7.27 (s, 2H), 4.87, 4.13 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 3.06 (p, J=7.1 Hz, 2H), 2.89 (s, 3H), 2.02-1.55 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

4′-chloro-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A62”)

(158) ##STR00068##

(159) LC/MS: M+H 385;

(160) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.80-7.69 (m, 5H), 7.55 (d, J=8.6 Hz, 2H), 7.47 (d, J=7.8 Hz, 2H), 4.84, 4.08 (2×br. s, 1H, ratio=1:2.1, mixture of rotamers), 3.07 (p, J=7.1 Hz, 2H), 2.89 (s, 3H), 2.09-1.50 (m, 6H), 1.01 (t, J=7.2 Hz, 3H);

2′,4′-difluoro-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A63”)

(161) ##STR00069##

(162) LC/MS: M+H 387;

(163) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.75 (s, 1H; NH), 7.65 (td, J=8.9, 6.6 Hz, 1H), 7.60 (d, J=6.8 Hz, 2H), 7.48 (d, J=7.8 Hz, 2H), 7.40 (ddd, J=11.6, 9.3, 2.6 Hz, 1H), 7.23 (td, J=8.8, 2.3 Hz, 1H), 4.84, 4.08 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 3.07 (p, J=7.1 Hz, 2H), 2.89 (s, 3H), 2.04-1.57 (m, 6H), 1.01 (t, J=7.2 Hz, 3H);

2′-trifluoromethyl-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A64”)

(164) ##STR00070##

(165) LC/MS: M+H 419;

(166) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.86 (d, J=7.7 Hz, 1H), 7.82-7.69 (m, 2H), 7.65 (t, J=7.7 Hz, 1H), 7.49-7.42 (m, 3H), 7.38 (d, J=8.0 Hz, 2H), 4.88, 4.05 (2×br. s, 1H, ratio=1:1.5, mixture of rotamers), 3.07 (p, J=7.1 Hz, 2H), 2.90 (s, 3H), 2.02-1.56 (m, 6H), 1.01 (t, J=7.2 Hz, 3H);

2,2′-dimethyl-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A65”)

(167) ##STR00071##

(168) LC/MS: M+H 379;

(169) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.77 (s, 1H; NH), 7.39-7.16 (m, 5H), 7.16-7.03 (m, 2H), 4.87, 4.14 (2×br. s, 1H, ratio=1:1.5, mixture of rotamers), 3.07 (p, J=7.2 Hz, 2H), 2.89 (s, 3H), 2.03 (s, 3H), 2.02 (s, 3H), 2.00-1.58 (m, 6H), 1.01 (t, J=7.2 Hz, 3H);

4′-(bis-trifluoromethyl-amino)-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A66”)

(170) ##STR00072##

(171) LC/MS: M+H 502;

(172) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.90 (d, J=8.6 Hz, 2H), 7.79 (d, J=8.3 Hz, 2H), 7.73 (s, 1H; NH), 7.63 (d, J=8.4 Hz, 2H), 7.49 (d, J=7.8 Hz, 2H), 4.82, 4.04 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 3.06 (p, J=7.1 Hz, 2H), 2.89 (s, 3H), 2.07-1.54 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

biphenyl-4-carboxylic acid methyl-[(1R,3S)-3-(1-methyl-cyclopropylcarbamoyl)-cyclopentyl]-amide (“A67”)

(173) ##STR00073##

(174) LC/MS: M+H 377;

(175) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.95 (s, 1H; NH), 7.75-7.67 (m, 4H), 7.49 (t, J=7.6 Hz, 2H), 7.45 (d, J=7.8 Hz, 2H), 7.40 (t, J=7.4 Hz, 1H), 4.83, 4.05 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 2.88 (s, 3H), 2.47-2.23 (m, 1H), 2.11-1.45 (m, 6H), 1.25 (s, 3H), 0.64-0.41 (m, 4H);

4-benzoxazol-2-yl-N-methyl-N-[(1R,3S)-3-(1-methyl-cyclopropylcarbamoyl)-cyclopentyl]-benzamide (“A68”)

(176) ##STR00074##

(177) LC/MS: M+H 418;

(178) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.25 (d, J=8.4 Hz, 2H), 7.94 (s, 1H; NH), 7.88-7.75 (m, 2H), 7.59 (d, J=5.8 Hz, 2H), 7.51-7.35 (m, 2H), 4.86, 3.96 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 2.90 (s, 3H), 2.45-2.23 (m, 1H), 2.09-1.42 (m, 6H), 1.25 (s, 3H), 0.66-0.36 (m, 4H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(4-methoxy-phenylethynyl)-N-methyl-benzamide (“A69”)

(179) ##STR00075##

(180) LC/MS: M+H 405;

(181) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.73 (s, 1H; NH), 7.56 (d, J=8.3 Hz, 2H), 7.51 (d, J=8.9 Hz, 2H), 7.39 (d, J=7.5 Hz, 2H), 7.00 (d, J=8.9 Hz, 2H), 4.84, 3.97 (2×br. s, 1H, ratio=1:1.9, mixture of rotamers), 3.80 (s, 3H; CH.sub.3O), 3.05 (p, J=7.1 Hz, 2H), 2.86 (s, 3H), 2.01-1.49 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-pyridin-4-ylethynyl-benzamide (“A70”)

(182) ##STR00076##

(183) LC/MS: M+H 376;

(184) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.65 (d, J=6.0 Hz, 2H), 7.73 (s, 1H; NH), 7.67 (d, J=8.4 Hz, 2H), 7.54 (d, J=6.1 Hz, 2H), 7.44 (d, J=7.7 Hz, 2H), 4.83, 3.94 (2×br. s, 1H, ratio=1:1.9, mixture of rotamers), 3.11-3.00 (m, 2H), 2.86 (br. s, 3H), 2.10-1.49 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

4-benzothiazol-2-yl-N-methyl-N-[(1R,3S)-3-(1-methyl-cyclopropylcarbamoyl)-cyclopentyl]-benzamide (“A71”)

(185) ##STR00077##

(186) LC/MS: M+H 434;

(187) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.18 (d, J=8.0 Hz, 1H), 8.15 (d, J=8.4 Hz, 2H), 8.09 (d, J=7.8 Hz, 1H), 7.94 (s, 1H; NH), 7.61-7.52 (m, 3H), 7.49 (t, J=7.6 Hz, 1H), 4.84, 3.97 (2×br. s, 1H, ratio=1:1.6, mixture of rotamers), 2.90 (br. s, 3H), 2.00-1.58 (m, 6H), 1.25 (s, 3H), 0.66-0.40 (m, 4H);

4-(4-fluoro-phenylethynyl)-N-methyl-N-[(1R,3S)-3-(1-methyl-cyclopropylcarbamoyl)-cyclopentyl]-benzamide (“A72”)

(188) ##STR00078##

(189) LC/MS: M+H 419;

(190) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.94 (s, 1H; NH), 7.68-7.56 (m, 4H), 7.40 (d, J=7.8 Hz, 2H), 7.28 (t, J=8.9 Hz, 2H), 4.83, 3.92 (2×br. s, 1H, ratio=1:1.3, mixture of rotamers), 2.86 (s, 3H), 1.99-1.48 (m, 6H), 1.25 (s, 3H), 0.64-0.39 (m, 4H);

4-benzoxazol-2-yl-N-methyl-N-[(1R,3S)-3-(1-propyl-cyclopropylcarbamoyl)-cyclopentyl]-benzamide (“A73”)

(191) ##STR00079##

(192) LC/MS: M+H 446;

(193) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.25 (d, J=8.4 Hz, 2H), 7.89 (br. s, 1H; NH), 7.86-7.79 (m, 2H), 7.59 (d, J=6.1 Hz, 2H), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 2.90 (s, 3H), 4.86, 3.95 (2×m, 1H, ratio=1:1.9, mixture of rotamers), 2.39 (br. s, 1H), 2.02-1.53 (m, 6H), 1.51-1.38 (m, 2H), 1.39-1.25 (m, 2H), 0.86 (t, J=7.3 Hz, 3H), 0.60-0.39 (m, 4H);

4-(1,3-benzoxazol-2-yl)-N-methyl-N-[(1R,3S)-3-[[(1S)-1-methylpropyl]-carbamoyl]cyclopentyl]benzamide (“A74”)

(194) ##STR00080##

(195) LC/MS: M+H 420;

(196) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.4 Hz, 2H), 7.83 (dd, J=14.4, 7.3 Hz, 2H), 7.60 (d, J=7.0 Hz, 2H), 7.50 (s, 1H; NH), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 4.85, 3.97 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 3.65 (dt, J=13.6, 6.7 Hz, 1H), 2.91 (br. s, 3H), 2.11-1.50 (m, 6H), 1.36 (p, J=6.5 Hz, 2H), 1.00 (d, J=6.2 Hz, 3H), 0.81 (t, J=7.4 Hz, 3H);

4-(1,3-benzoxazol-2-yl)-N-methyl-N-[(1R,3S)-3-[[(1R)-1-methylpropyl]-carbamoyl]cyclopentyl]benzamide (“A75”)

(197) ##STR00081##

(198) LC/MS: M+H 420;

(199) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.4 Hz, 2H), 7.83 (dd, J=14.4, 7.3 Hz, 2H), 7.60 (d, J=7.0 Hz, 2H), 7.50 (s, 1H; NH), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 4.85, 3.97 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 3.65 (dt, J=13.6, 6.7 Hz, 1H), 2.91 (br. s, 3H), 2.11-1.50 (m, 6H), 1.36 (p, J=6.5 Hz, 2H), 1.00 (d, J=6.2 Hz, 3H), 0.81 (t, J=7.4 Hz, 3H);

4-(1,3-benzoxazol-2-yl)-N-[(1R,3S)-3-(cyclobutylcarbamoyl)cyclopentyl]-N-methyl-benzamide (“A76”)

(200) ##STR00082##

(201) LC/MS: M+H 418;

(202) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.4 Hz, 2H), 7.99 (s, 1H; NH), 7.89-7.76 (m, 2H), 7.60 (d, J=7.2 Hz, 2H), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 4.86, 3.98 (2×br. s, 1H, ratio=1:1.9, mixture of rotamers), 4.17 (h, J=8.2 Hz, 1H), 2.90 (br. s, 3H), 2.22-2.04 (m, 2H), 2.02-1.48 (m, 10H);

4-(1,3-benzoxazol-2-yl)-N-[(1R,3S)-3-[(trans-3-hydroxycyclobutyl)-carbamoyl]cyclopentyl]-N-methyl-benzamide (“A77”)

(203) ##STR00083##

(204) LC/MS: M+H 434;

(205) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.4 Hz, 2H), 7.98 (s, 1H; NH), 7.88-7.77 (m, 2H), 7.60 (d, J=7.2 Hz, 2H), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 4.95 (d, J=5.4 Hz, 1H), 4.89, 3.98 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 4.22 (dt, J=13.0, 3.8 Hz, 1H), 4.16 (q, J=6.5 Hz, 1H), 2.90 (br. s, 3H), 2.19-1.95 (m, 4H), 1.99-1.53 (m, 6H);

4-(1,3-benzoxazol-2-yl)-N-[(1R,3S)-3-[(cis-3-hydroxycyclobutyl)-carbamoyl]cyclopentyl]-N-methyl-benzamide (“A78”)

(206) ##STR00084##

(207) LC/MS: M+H 434;

(208) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.4 Hz, 2H), 7.90 (s, 1H; NH), 7.83 (dd, J=13.8, 8.0 Hz, 2H), 7.59 (d, J=7.0 Hz, 2H), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 5.00 (d, J=5.7 Hz, 1H; OH), 4.88, 3.98 (2×br. s, 1H, ratio=1:1.5, mixture of rotamers), 3.77 (h, J=7.0 Hz, 1H), 3.65 (h, J=8.5 Hz, 1H), 2.90 (br. s, 3H), 2.46 (d, J=7.0 Hz, 2H), 2.03-1.49 (m, 8H);

4-(1,3-benzoxazol-2-yl)-2-methoxy-N-methyl-N-[(1R,3S)-3-[(1-methylcyclopropyl)carbamoyl]cyclopentyl]benzamide (“A79”)

(209) ##STR00085##

(210) LC/MS: M+H 448;

(211) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.92, 7.89 (2×s, 1H, NH; ratio=1:1.9, mixture of rotamers), 7.87-7.75 (m, 4H), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 7.41-7.33 (m, 1H), 4.91, 3.80 (2×m, 1H, ratio=1:1.9, mixture of rotamers) 3.97-3.90 (m, 3H), 2.90, 2.69 (2×s, 3H, ratio=1:1.9, mixture of rotamers), 1.96-1.46 (m, 6H), 1.29-1.19 (m, 3H), 0.65-0.39 (m, 4H);

N-methyl-N-[(1R,3S)-3-[(1-methylcyclopropyl)carbamoyl]cyclopentyl]-4-(4-pyridyl)benzamide (“A80”)

(212) ##STR00086##

(213) LC/MS: M+H 378;

(214) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.66 (d, J=6.1 Hz, 2H), 7.94 (s, 1H; NH), 7.86 (d, J=8.4 Hz, 2H), 7.75 (d, J=6.2 Hz, 2H), 7.50 (d, J=7.4 Hz, 2H), 4.85, 3.97 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 2.88 (br. s, 3H), 2.08-1.45 (m, 6H), 1.25 (s, 3H), 0.64-0.41 (m, 4H);

4-(4-cyanophenyl)-N-methyl-N-[(1R,3S)-3-[(1-methylcyclopropyl)-carbamoyl]cyclopentyl]benzamide (“A81”)

(215) ##STR00087##

(216) LC/MS: M+H 402;

(217) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.97-7.90 (m, 5H), 7.81 (d, J=8.4 Hz, 2H), 7.49 (d, J=7.5 Hz, 2H), 2.88 (br. s, 3H), 4.82, 4.02 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 2.08-1.45 (m, 6H), 1.25 (s, 3H), 0.63-0.40 (m, 4H);

4-benzoxazol-2-yl-N-((1R,3S)-3-dimethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A82”)

(218) ##STR00088##

(219) LC/MS: M+H 392;

(220) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.83 (ddd, J=12.4, 7.0, 1.6 Hz, 2H), 7.60 (d, J=7.3 Hz, 2H), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 4.92, 4.00 (2×br. s, 1H, ratio=1:2.5, mixture of rotamers), 3.16-2.83 (m, 6H), 2.82 (s, 3H), 2.10-1.57 (m, 6H);

N-methyl-N-[(1R,3S)-3-(1-methyl-cyclopropylcarbamoyl)-cyclopentyl]-4-pyridin-3-yl-benzamide (“A83”)

(221) ##STR00089##

(222) LC/MS: M+H 378;

(223) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.93 (dd, J=2.4, 0.7 Hz, 1H), 8.60 (dd, J=4.8, 1.6 Hz, 1H), 8.12 (ddd, J=8.0, 2.4, 1.7 Hz, 1H), 7.95 (s, 1H; NH), 7.79 (d, J=8.4 Hz, 2H), 7.59-7.33 (m, 3H), 4.83, 4.04 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 2.88 (s, 3H), 1.98-1.53 (m, 6H), 1.25 (s, 3H), 0.64-0.41 (m, 4H);

4-benzoxazol-2-yl-N-methyl-N-[(1R,3S)-3-(1-methyl-cyclobutylcarbamoyl)-cyclopentyl]-benzamide (“A84”)

(224) ##STR00090##

(225) LC/MS: M+H 432;

(226) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.4 Hz, 2H), 7.87-7.78 (m, 2H), 7.74 (s, 1H; NH), 7.60 (d, J=7.8 Hz, 2H), 7.51-7.37 (m, 2H), 2.90 (br. s, 3H), 4.84, 3.95 (2×br. s, 1H, ratio=1:1.5, mixture of rotamers), 2.26-2.12 (m, 2H), 2.01-1.60 (m, 10H), 1.34 (s, 3H);

4-benzoxazol-2-yl-3-methoxy-N-methyl-N-[(1R,3S)-3-(1-methyl-cyclopropylcarbamoyl)-cyclopentyl]-benzamide (“A85”)

(227) ##STR00091##

(228) LC/MS: M+H 448;

(229) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.09 (d, J=7.9 Hz, 1H), 7.96 (s, 1H; NH), 7.88-7.73 (m, 2H), 7.50-7.39 (m, 2H), 7.23 (s, 1H), 7.11 (d, J=7.9 Hz, 1H), 3.98 (s, 3H), 4.89, 4.02 (2×br. s, 1H, ratio=1:1.4, mixture of rotamers), 2.92 (br. s, 3H), 2.11-1.55 (m, 6H), 1.26 (s, 3H), 0.66-0.37 (m, 4H);

4-benzoxazol-2-yl-N-((1R,3S)-3-carbamoyl-cyclopentyl)-N-methyl-benzamide (“A86”)

(230) ##STR00092##

(231) LC/MS: M+H 364;

(232) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.83 (ddd, J=13.1, 7.3, 1.7 Hz, 2H), 7.60 (d, J=6.7 Hz, 2H), 7.45 (pd, J=7.4, 1.3 Hz, 2H), 7.23 (s, 1H; NH), 6.74 (s, 1H; NH), 4.89, 3.99 (2×br. s, 1H, ratio=1:2.0, mixture of rotamers), 2.91 (br. s, 3H), 2.45 (br. s, 1H), 2.15-1.51 (m, 6H);

4-(7-cyano-imidazo[1,2-a]pyridin-2-yl)-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A87”)

(233) ##STR00093##

(234) LC/MS: M+H 416;

(235) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.72 (d, J=7.0 Hz, 1H), 8.69 (s, 1H), 8.36 (s, 1H), 8.06 (d, J=8.3 Hz, 2H), 7.73 (s, 1H; NH), 7.47 (d, J=7.8 Hz, 2H), 7.22 (dd, J=7.0, 1.6 Hz, 1H), 4.85, 4.07 (2×br. s, 1H, ratio=1:2.0, mixture of rotamers), 3.05 (p, J=7.1 Hz, 2H), 2.88 (br. s, 3H), 2.01-1.51 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-benzamide (“A88”)

(236) ##STR00094##

(237) LC/MS: M+H 357;

(238) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.04 (d, J=8.3 Hz, 2H), 7.72 (s, 1H; NH), 7.54 (d, J=7.2 Hz, 2H), 4.88, 3.96 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 3.05 (p, J=7.1 Hz, 2H), 2.89 (br. s, 3H), 2.68 (s, 3H), 2.42 (br. s, 1H), 2.06-1.49 (m, 6H), 0.99 (t, J=7.1 Hz, 3H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-(2-dimethylamino-1-methyl-ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide (“A89”)

(239) ##STR00095##

(240) LC/MS: M+H 449;

(241) .sup.1H NMR (400 MHz, DMSO-d.sub.6+CF.sub.3COOD) δ [ppm] 8.31 (d, J=8.1 Hz, 2H), 7.84 (d, J=7.2 Hz, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.61 (d, J=7.4 Hz, 2H), 7.45 (p, J=7.3 Hz, 2H), 4.95, 4.09 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 4.35-4.17 (m, 1H), 3.13 (d, J=4.8 Hz, 2H), 2.95 (s, 3H), 2.85 (s, 3H), 2.83 (s, 3H), 2.18-1.60 (m, 6H), 1.19-1.03 (m, 3H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-((S)-2-hydroxy-1-methyl-ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide (“A90”)

(242) ##STR00096##

(243) LC/MS: M+H 422;

(244) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.2 Hz, 2H), 7.83 (dd, J=14.3, 7.3 Hz, 2H), 7.60 (d, J=6.4 Hz, 2H), 7.54-7.39 (m, 3H), 4.88, 3.99 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 4.61 (t, J=5.4 Hz, 1H; OH), 3.85-3.64 (m, 1H), 3.40-3.29 (m, 1H), 3.26-3.12 (m, 1H), 2.91 (br. s, 3H), 2.15-1.45 (m, 6H), 1.00 (d, J=6.0 Hz, 3H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-((R)-2-hydroxy-1-methyl-ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide (“A91”)

(245) ##STR00097##

(246) LC/MS: M+H 422;

(247) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.2 Hz, 2H), 7.83 (dd, J=14.3, 7.3 Hz, 2H), 7.60 (d, J=6.4 Hz, 2H), 7.54-7.39 (m, 3H), 4.88, 3.99 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 4.61 (t, J=5.4 Hz, 1H; OH), 3.85-3.64 (m, 1H), 3.40-3.29 (m, 1H), 3.26-3.12 (m, 1H), 2.91 (br. s, 3H), 2.15-1.45 (m, 6H), 1.00 (d, J=6.0 Hz, 3H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-((S)-2-methoxy-1-methyl-ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide (“A92”)

(248) ##STR00098##

(249) LC/MS: M+H 436;

(250) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.3 Hz, 2H), 7.87-7.78 (m, 2H), 7.71-7.53 (m, 3H), 7.45 (pd, J=7.4, 1.4 Hz, 2H), 4.87, 3.98 (2×br. s, 1H, ratio=1:1.9, mixture of rotamers), 3.91 (p, J=6.7 Hz, 1H), 3.27-3.24 (m, 1H), 3.24 (s, 3H; CH.sub.3O), 3.15 (dd, J=9.4, 6.1 Hz, 1H), 2.89 (br. s, 3H), 2.08-1.53 (m, 6H), 1.01 (d, J=6.4 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-(5-sulfamoyl-benzooxazol-2-yl)-benzamide (“A93”)

(251) ##STR00099##

(252) LC/MS: M+H 471;

(253) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.29 (d, J=8.3 Hz, 2H), 8.23 (d, J=1.6 Hz, 1H), 8.01 (d, J=8.6 Hz, 1H), 7.93 (dd, J=8.6, 1.8 Hz, 1H), 7.72 (s, 1H; NH), 7.62 (d, J=6.5 Hz, 2H), 7.47 (s, 2H; NH.sub.2), 1H; NH), 7.63 (d, J=6.6 Hz, 2H), 4.90, 3.97 (2×m, 1H, ratio=1:1.8, mixture of rotamers), 3.05 (p, J=6.9 Hz, 2H), 2.92 (bt. s, 3H), 2.42 (br. s, 1H), 2.12-1.46 (m, 6H), 1.00 (t, J=7.1 Hz, 3H);

4-(5-ethanesulfonyl-benzooxazol-2-yl)-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A94”)

(254) ##STR00100##

(255) LC/MS: M+H 484;

(256) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.34 (d, J=1.7 Hz, 1H), 8.30 (d, J=8.3 Hz, 1H), 8.10 (d, J=8.6 Hz, 1H), 7.98 (dd, J=8.6, 1.8 Hz, 1H), 7.72 (br. s, 1H; NH), 7.63 (d, J=6.6 Hz, 2H), 4.90, 3.97 (2×m, 1H, ratio=1:1.6, mixture of rotamers), 3.39 (q, J=7.3 Hz, 2H), 3.06 (p, J=6.9, 6.5 Hz, 2H), 2.92 (br. s, 3H), 2.41 (br. s, 1H), 2.07-1.50 (m, 6H), 1.14 (t, J=7.3 Hz, 3H), 1.00 (t, J=7.1 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(1H-imidazol-2-yl)-N-methyl-benzamide (“A95”)

(257) ##STR00101##

(258) LC/MS: M+H 341;

(259) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 12.59 (s, 1H; NH), 7.99 (d, J=8.3 Hz, 2H), 7.75 (s, 1H; NH), 7.44 (d, J=7.7 Hz, 2H), 7.29 (s, 1H), 7.07 (s, 1H), 4.85, 4.05 (2×br. s, 1H, ratio=1:2.0, mixture of rotamers), 3.07 (p, J=7.1 Hz, 2H), 2.88 (br. s, 3H), 2.46 (br. s, 1H), 2.00-1.55 (m, 6H), 1.01 (t, J=7.2 Hz, 3H);

4-(5,7-difluoro-benzoxazol-2-yl)-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A96”)

(260) ##STR00102##

(261) LC/MS: M+H 428;

(262) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.27 (d, J=8.4 Hz, 2H), 7.74 (s, 1H; NH), 7.66 (dd, J=8.4, 2.0 Hz, 1H), 7.61 (d, J=3.2 Hz, 2H), 7.51 (td, J=10.3, 2.3 Hz, 1H), 4.89, 3.96 (2×m, 1H, ratio=1:1.5, mixture of rotamers), 3.05 (q, J=7.0, 5.9 Hz, 2H), 2.91 (br. s, 3H), 2.43 (br. s, 1H), 2.09-1.48 (m, 6H), 0.99 (t, J=7.1 Hz, 3H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-(2-hydroxy-ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide (“A97”)

(263) ##STR00103##

(264) LC/MS: M+H 407;

(265) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.27 (d, J=8.4 Hz, 2H), 7.89-7.81 (m, 2H), 7.77 (s, 1H; NH), 7.61 (d, J=7.4 Hz, 2H), 7.53-7.39 (m, 2H), 4.63 (t, J=5.4 Hz, 1H; OH), 4.91, 4.00 (2×m, 1H, ratio=1:1.7, mixture of rotamers), 3.39 (q, J=5.7 Hz, 2H), 3.12 (q, J=5.8 Hz, 2H), 2.92 (br. s, 3H), 2.19-1.47 (m, 6H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(6-fluoro-benzooxazol-2-yl)-N-methyl-benzamide (“A98”)

(266) ##STR00104##

(267) LC/MS: M+H 410;

(268) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.22 (d, J=8.3 Hz, 2H), 7.86 (dd, J=8.8, 5.0 Hz, 1H), 7.82 (dd, J=8.4, 2.4 Hz, 1H), 7.72 (s, 1H; NH), 7.60 (d, J=6.8 Hz, 2H), 7.31 (ddd, J=9.9, 8.9, 2.5 Hz, 1H), 4.89, 3.97 (2×br. s, 1H, ratio=1:1.6, mixture of rotamers), 3.05 (p, J=6.8 Hz, 2H), 2.91 (br. s, 3H), 2.07-1.52 (m, 6H), 1.00 (t, J=7.1 Hz, 3H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-(2-hydroxy-1,1-dimethyl-ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide (“A99”)

(269) ##STR00105##

(270) LC/MS: M+H 436;

(271) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.27 (d, J=8.4 Hz, 2H), 7.90-7.78 (m, 2H), 7.61 (d, J=7.7 Hz, 2H), 7.54-7.40 (m, 2H), 7.20 (s, 1H; NH), 4.83 (s, 1H; OH), 4.86, 3.97 (2×m, 1H, ratio=1:1.7, mixture of rotamers), 3.38 (d, J=5.7 Hz, 2H), 2.91 (br. s, 3H), 2.12-1.46 (m, 6H), 1.17 (s, 6H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(7-fluoro-benzooxazol-2-yl)-N-methyl-benzamide (“A100”)

(272) ##STR00106##

(273) LC/MS: M+H 410;

(274) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.27 (d, J=8.3 Hz, 2H), 7.73 (s, 1H; NH), 7.69 (d, J=7.8 Hz, 1H), 7.61 (d, J=6.8 Hz, 2H), 7.48-7.34 (m, 2H), 4.89, 3.98 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 3.06 (p, J=6.6 Hz, 2H), 2.91 (br. s, 3H), 2.42 (br. s, 1H), 2.07-1.52 (m, 6H), 1.00 (t, J=7.1 Hz, 3H);

4-(5,6-difluoro-benzoxazol-2-yl)-N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-benzamide (“A101”)

(275) ##STR00107##

(276) LC/MS: M+H 428;

(277) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.22 (d, J=8.2 Hz, 2H), 8.14 (dd, J=9.8, 6.9 Hz, 1H), 8.02 (dd, J=10.2, 7.6 Hz, 1H), 7.74 (s, 1H; NH), 7.60 (d, J=7.1 Hz, 2H), 4.89, 3.97 (2×br. s, 1H, ratio=1:1.5, mixture of rotamers), 3.05 (p, J=6.9 Hz, 2H), 2.91 (br. s, 3H), 2.42 (br. s, 1H), 2.12-1.46 (m, 6H), 1.00 (t, J=7.1 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-pyridin-3-yl-benzamide (“A102”)

(278) ##STR00108##

(279) LC/MS: M+H 352;

(280) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.93 (d, J=1.9 Hz, 1H), 8.60 (dd, J=4.8, 1.6 Hz, 1H), 8.12 (dt, J=8.0, 2.0 Hz, 1H), 7.80 (d, J=8.3 Hz, 2H), 7.74 (s, 1H; NH), 7.54-7.44 (m, 3H), 4.84, 4.07 (2×br. s, 1H, ratio=1:2.0, mixture of rotamers), 3.06 (p, J=7.2 Hz, 2H), 2.89 (b. s, 3H), 2.00-1.55 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

4′-cyano-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A103”)

(281) ##STR00109##

(282) LC/MS: M+H 376;

(283) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.99-7.91 (m, 4H), 7.83 (d, J=8.4 Hz, 2H), 7.76 (s, 1H; NH), 7.51 (d, J=7.9 Hz, 2H), 4.87, 4.05 (2×br. s, 1H, ratio=1:1.6, mixture of rotamers), 3.07 (p, J=7.1 Hz, 2H), 2.90 (br. s, 3H), 2.01-1.59 (m, 6H), 1.01 (t, J=7.2 Hz, 3H);

4′-fluoro-biphenyl-4-carboxylic acid ((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-methyl-amide (“A104”)

(284) ##STR00110##

(285) LC/MS: M+H 369;

(286) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 7.85-7.67 (m, 5H), 7.46 (d, J=7.9 Hz, 2H), 7.32 (t, J=8.9 Hz, 2H), 4.82, 4.07 (2×br. s, 1H, ratio=1:1.6, mixture of rotamers), 3.07 (p, J=7.1 Hz, 2H), 2.89 (br. s, 3H), 1.98-1.51 (m, 6H), 1.01 (t, J=7.2 Hz, 3H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-N-methyl-4-pyrimidin-5-yl-benzamide (“A105”)

(287) ##STR00111##

(288) LC/MS: M+H 353;

(289) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 9.21 (s, 1H), 9.19 (s, 2H), 7.88 (d, J=8.4 Hz, 2H), 7.75 (s, 1H; NH), 7.52 (d, J=7.8 Hz, 2H), 4.85, 4.03 (2×br. s, 1H, ratio=1:1.7, mixture of rotamers), 3.18-2.97 (m, 2H), 2.89 (br. s, 3H), 1.99-1.52 (m, 6H), 1.11-0.89 (m, 3H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-(2-hydroxy-ethylcarbamoyl)-cyclopentyl]-N-methyl-benzamide (“A106”)

(290) ##STR00112##

(291) LC/MS: M+H 408;

(292) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.27 (d, J=8.4 Hz, 2H), 7.88-7.81 (m, 2H), 7.78 (s, 1H; NH), 7.61 (d, J=7.4 Hz, 2H), 7.51-7.40 (m, 2H), 4.89, 4.00 (2×br. s, 1H, ratio=1:1.8, mixture of rotamers), 4.63 (t, J=5.4 Hz, 1H; OH), 3.39 (q, J=5.7 Hz, 2H), 3.12 (q, J=5.8 Hz, 2H), 2.92 (br. s, 3H), 2.11-1.50 (m, 6H);

N-((1R,3S)-3-ethylcarbamoyl-cyclopentyl)-4-(1H-indazol-4-yl)-N-methyl-benzamide (“A107”)

(293) ##STR00113##

(294) LC/MS: M+H 391;

(295) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 13.25 (s, 1H; NH), 8.21 (s, 1H), 7.80 (d, J=8.2 Hz, 2H), 7.74 (s, 1H; NH), 7.58 (d, J=8.3 Hz, 1H), 7.52 (d, J=7.8 Hz, 2H), 7.48-7.43 (m, 1H), 7.28 (d, J=6.9 Hz, 1H), 4.85, 4.16 (2×br. s, 1H, ratio=1:2.4, mixture of rotamers), 3.06 (p, J=7.2 Hz, 2H), 2.91 (s, 3H), 2.04-1.58 (m, 6H), 1.00 (t, J=7.2 Hz, 3H);

4-benzoxazol-2-yl-N-[(1R,3S)-3-(1-hydroxymethyl-cyclopropylcarbamoyl)-cyclopentyl]-N-methyl-benzamide (“A108”)

(296) ##STR00114##

(297) LC/MS: M+H 434;

(298) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ [ppm] 8.26 (d, J=8.4 Hz, 2H), 8.04 (s, 1H; NH), 7.88-7.79 (m, 2H), 7.59 (d, J=7.1 Hz, 2H), 7.50-7.41 (m, 2H), 4.86, 3.96 (2×br. s, 1H, ratio=1:1.6, mixture of rotamers) 4.66 (t, J=5.6 Hz, 1H; OH), 3.40 (d, J=5.6 Hz, 2H), 2.90 (br. s, 3H), 2.42 (br. s, 1H), 2.11-1.47 (m, 6H), 0.65 (s, 2H), 0.52 (s, 2H).

(299) Pharmacological Data

(300) TABLE-US-00002 TABLE 2 Inhibition of FASN of some representative compounds of the formula I Compound IC.sub.50 FASN Compound IC.sub.50 FASN No. (enzyme assay) No. (enzyme assay) “A1” A “A61” A “A2” A “A62” A “A3” “A63” A “A4” B “A64” A “A5” A “A65” A “A6” A “A66” “A7” A “A67” A “A8” “A68” A “A9” “A69” A “A11” A “A70” A “A44” A “A71” A “A45” A “A72” A “A46” A “A73” B “A47” B “A74” A “A48” B “A75” A “A49” A “A76” A “A50” A “A77” A “A51” A “A78” A “A52” C “A79” B “A53” A “A80” A “A54” A “A81” A “A55” A “A82” B “A56” A “A83” A “A57” A “A84” A “A58” A “A85” A “A59” A “A86” B “A60” C “A87” B “A88” C “A101” A “A90” B “A102” A “A91” A “A103” A “A92” B “A104” A “A93” C “A106” A “A96” A “A107” A “A97” A “A108” B “A98” A “A99” B “A100” A IC.sub.50: <0.3 μM = A 0.3-3 μM = B 3-50 μM = C

(301) The compounds shown in Table 2 are particularly preferred compounds according to the invention.

(302) The following examples relate to medicaments:

EXAMPLE A: INJECTION VIALS

(303) A solution of 100 g of an active ingredient of the formula I and 5 g of disodium hydrogenphosphate in 3 l of bidistilled water is adjusted to pH 6.5 using 2 N hydrochloric acid, sterile filtered, transferred into injection vials, lyophilised under sterile conditions and sealed under sterile conditions. Each injection vial contains 5 mg of active ingredient.

EXAMPLE B: SUPPOSITORIES

(304) A mixture of 20 g of an active ingredient of the formula I with 100 g of soya lecithin and 1400 g of cocoa butter is melted, poured into moulds and allowed to cool. Each suppository contains 20 mg of active ingredient.

EXAMPLE C: SOLUTION

(305) A solution is prepared from 1 g of an active ingredient of the formula I, 9.38 g of NaH.sub.2PO.sub.4.2H.sub.2O, 28.48 g of Na.sub.2HPO.sub.4.12H.sub.2O and 0.1 g of benzalkonium chloride in 940 ml of bidistilled water. The pH is adjusted to 6.8, and the solution is made up to 1 l and sterilised by irradiation. This solution can be used in the form of eye drops.

EXAMPLE D: OINTMENT

(306) 500 mg of an active ingredient of the formula I are mixed with 99.5 g of Vaseline under aseptic conditions.

EXAMPLE E: TABLETS

(307) A mixture of 1 kg of active ingredient of the formula I, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate is pressed in a conventional manner to give tablets in such a way that each tablet contains 10 mg of active ingredient.

EXAMPLE F: DRAGEES

(308) Tablets are pressed analogously to Example E and subsequently coated in a conventional manner with a coating of sucrose, potato starch, talc, tragacanth and dye.

EXAMPLE G: CAPSULES

(309) 2 kg of active ingredient of the formula I are introduced into hard gelatine capsules in a conventional manner in such a way that each capsule contains 20 mg of the active ingredient.

EXAMPLE H: AMPOULES

(310) A solution of 1 kg of active ingredient of the formula I in 60 l of bidistilled water is sterile filtered, transferred into ampoules, lyophilised under sterile conditions and sealed under sterile conditions. Each ampoule contains 10 mg of active ingredient.