US2011201581A1PendingUtilityA1
Novel Compounds 010
Est. expiryDec 12, 2027(~1.4 yrs left)· nominal 20-yr term from priority
A61P 43/00A61P 37/08A61P 11/08A61P 11/02A61P 11/06A61P 11/00C07D 211/60C07D 205/04C07D 211/62C07D 413/12C07D 409/12C07D 417/12C07D 405/12C07D 207/16C07D 401/12
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Claims
Abstract
The present invention provides compounds of formula (I) in which n, y, X 1 , X 2 , A, B, R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the specification, a process for their preparation, pharmaceutical compositions containing them and their use in therapy.
Claims
exact text as granted — not AI-modified1 . A compound of formula (I)
wherein
n independently represents 0, 1, 2, 3 or 4;
X 1 represents a methylene group;
y represents 0, 1 or 2;
each R 1 independently represents halogen, hydroxyl, carboxyl, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, trifluoromethyl, NR 6 R 7 , C(O)NR 6 R 7 , NR 6a C(O)R 7a , SO 2 NR 6 R 7 , NR 6a SO 2 R 7a or S(O) m R 8 and R 1 is optionally substituted with hydroxy, halogen or C 1 -C 6 alkoxy;
R 2 represents a hydrogen atom or a C 1 -C 6 alkyl group optionally substituted by at least one substituent selected from halogen, hydroxyl, carboxyl, cyano, trifluoromethyl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, NR 9 R 10 , C(O)NR 11 R 12 , NR 13 C(O)R 14 , SO 2 NR 15 R 16 , NR 17 SO 2 R 18 and S(O) p R 19 ;
R 3 represents a hydrogen atom or a C 1 -C 6 alkyl group optionally substituted by at least one substituent selected from halogen, hydroxyl, carboxyl, cyano, trifluoromethyl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, NR 2 OR 21 , C(O)NR 22 R 23 , NR 24 C(O)R 25 , SO 2 NR 26 R 27 , NR 28 SO 2 R 29 and S(O) q R 30 ,
R 4 represents a hydrogen atom or a C 1 -C 6 alkyl group optionally substituted by at least one substituent selected from halogen, hydroxyl, carboxyl, cyano, trifluoromethyl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, NR 31 R 32 , C(O)NR 33 R 34 , NR 35 C(O)R 36 , SO 2 NR 37 R 38 , NR 39 SO 2 R 40 and S(O) r R 41 ,
R 5 represents a hydrogen atom or a C 1 -C 6 alkyl group optionally substituted by at least one substituent selected from halogen, hydroxyl, carboxyl, cyano, trifluoromethyl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, NR 42 R 43 , C(O)NR 44 R 45 , NR 46 C(O)R 47 , SO 2 NR 48 R 49 , NR 50 SO 2 R 51 and S(O) t R 52 , or
R 3 and R 4 together with the carbon atoms to which they are attached represent a cyclopropyl ring, or
R 4 and R 5 together with the carbon atom to which they are attached form a saturated or unsaturated, 3- to 6-membered carbocyclic or heterocyclic ring which ring may be optionally substituted with at least one substituent selected from halogen, hydroxyl, carboxyl and C 1 -C 6 alkyl;
A and B each independently represent a 5- to 10-membered aromatic ring system optionally comprising at least one ring heteroatom selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by at least one substituent selected from halogen, carboxyl, hydroxyl, oxo, nitro, cyano, mercapto, C 3 -C 6 cycloalkyl, C 2 -C 6 alkenyl, trifluoromethyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylcarbonyloxy, C 1 -C 6 alkoxycarbonyl, —NR 53 R 54 , —C(O)NR 55 R 56 , NR 57 C(O)R 58 , SO 2 NR 59 R 60 , NR 61 SO 2 R 62 , S(O) v R 63 , saturated 4- to 7-membered heterocyclyloxy, benzyloxy, C 1 -C 6 alkylpiperazinyl and a C 1 -C 6 alkyl group (itself optionally substituted by hydroxyl, C 1 -C 6 alkoxy, NR 64 R 65 , phenyl or morpholinyl);
m, p, q, r, t and v each independently represent 0, 1 or 2;
X 2 represents a bond, an oxygen or sulphur atom, SO, SO 2 , NR 66 , C(O)NR 66 , NR 66 C(O), SO 2 NR 66 , NR 66 SO 2 , C 1 -C 3 alkyl, ethenyl or ethynyl;
R 6 and R 7 independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 6 and R 7 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 9 and R 10 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 9 and R 10 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 11 and R 12 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 11 and R 12 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 15 and R 16 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 15 and R 16 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 20 and R 21 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 20 and R 21 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 22 and R 23 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 22 and R 23 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 26 and R 27 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 26 and R 27 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 31 and R 32 independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 31 and R 32 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 33 and R 34 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 33 and R 34 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 37 and R 38 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 37 and R 38 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 42 and R 43 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 42 and R 43 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 44 and R 45 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 44 and R 45 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 48 and R 49 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 48 and R 49 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 53 and R 54 independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 53 and R 54 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 55 and R 56 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 55 and R 56 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 59 and R 60 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 59 and R 60 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R 64 and R 65 each independently represent hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 64 and R 65 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
each group R 6a , R 7a , R 8 , R 13 , R 14 , R 17 , R 18 , R 19 , R 24 , R 25 , R 28 , R 29 , R 30 , R 35 , R 36 , R 39 , R 40 , R 41 , R 46 , R 47 , R 50 , R 51 , R 52 , R 57 , R 58 , R 61 , R 62 , and R 63 independently represents a hydrogen atom or a C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl group; and
R 66 represents a hydrogen atom or a C 1 -C 6 alkyl group; or
a pharmaceutically acceptable salt thereof.
2 . A compound according to claim 1 wherein n is 2.
3 . A compound according to claim 1 , wherein X 1 is methylene.
4 . A compound according to claim 1 , wherein R 2 represents a hydrogen atom.
5 . A compound according to claim 1 , wherein R 3 , R 4 and R 5 each represent a hydrogen atom.
6 . A compound according to claim 1 , wherein A represents phenyl.
7 . A compound according to claim 1 , wherein B represents a 5- to 10-membered aromatic ring system optionally comprising one or two ring heteroatoms independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by at least one substituent selected from halogen, carboxyl, hydroxyl, cyano, C 1 -C 6 alkoxy, —NR 53 R 54 , —C(O)NR 55 R 56 , NR 57 C(O)R 58 , SO 2 NR 59 R 60 , S(O) v R 63 , pyrrolidinyloxy, benzyloxy, methylpiperazinyl and C 1 -C 6 alkyl (itself optionally substituted by hydroxyl, C 1 -C 6 alkoxy, NR 64 R 65 , phenyl or morpholinyl).
8 . A compound according to claim 7 , wherein the aromatic ring system in B is selected from phenyl, pyrazolyl, pyridinyl, indolyl, oxazolyl, quinolinyl, pyrimidinyl and thienyl,
9 . A compound according to claim 1 , wherein X 2 represents a bond.
10 . A compound according to claim 1 being:
(S)—N—((S)-2-(3′-Chlorobiphenyl-4-yl)-1-cyanoethyl)piperidine-2-carboxamide,
(S)—N-45)-1-Cyano-2-(3′-(piperidin-1-ylmethyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-2-(biphenyl-4-yl)-1-cyanoethyl)pyrrolidine-2-carboxamide,
(S)—N—((S)-2-(4-(1-Benzyl-1H-pyrazol-4-yl)phenyl)-1-cyanoethyl)-piperidine-2-carboxamide,
(S)—N—((S)-2-(4′-Carbamoylbiphenyl-4-yl)-1-cyanoethyl)piperidine-2-carboxamide,
(S)—N-45)-1-Cyano-2-(3′-cyanobiphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-2-(3′-(Aminomethyl)biphenyl-4-yl)-1-cyanoethyl)piperidine-2-carboxamide,
(S)—N—((S)-2-(3′-Acetamidobiphenyl-4-yl)-1-cyanoethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-(morpholinomethyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4-(pyridin-3-yl)phenyl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-hydroxy-2′-methylbiphenyl-4-yl)ethyl)piperidine-2-carboxamide,
4′-((S)-2-Cyano-2-((S)-piperidine-2-carboxamido)ethyl)biphenyl-3-carboxylic acid,
(S)—N—((S)-1-Cyano-2-(2′-((R)-pyrrolidin-3-yloxy)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-2-(4-(1H-Indol-2-yl)phenyl)-1-cyanoethyl)piperidine-2-carboxamide,
(2S)—N-[(1S)-1-cyano-2-(3′-methoxybiphenyl-4-yl)ethyl]piperidine-2-carboxamide,
Piperidine-2-carboxylic acid (2-biphenyl-4-yl-1-cyano-ethyl)-amide,
(2S,4R)—N—((S)-2-(biphenyl-4-yl)-1-cyanoethyl)-4-hydroxypyrrolidine-2-carboxamide,
(R)—N—((S)-2-(biphenyl-4-yl)-1-cyanoethyl)thiazolidine-4-carboxamide,
S)—N—((S)-1-cyano-2-(3′-cyanobiphenyl-4-yl)ethyl)azetidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-[4-(dimethylsulfamoyl)phenyl]phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-(4-1,2-oxazol-4-ylphenyl)ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(3-methylsulfanylphenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(4-hydroxyphenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(4-cyanophenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(4-methoxyphenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(1-methylpyrazol-4-yl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-[4-(3-hydroxypropyl)phenyl]phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-2-(4-Benzo[1,3]dioxol-5-ylphenyl)-1-cyano-ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(3,4-difluorophenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(4-fluoro-2-phenylmethoxy-phenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(3-fluoro-4-methoxy-phenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(3,4-dimethoxyphenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(2,4-dimethoxyphenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-2-[4-(3-Carbamoylphenyl)phenyl]-1-cyano-ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(2,5-dioxabicyclo [4.4.0]deca-7,9,11-trien-8-yl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-2-[4-[4-(Aminomethyl)phenyl]phenyl]-1-cyano-ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(2-dimethylaminopyrimidin-5-yl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(4-methylthiophen-3-yl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(3-fluoro-4-propoxy-phenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(2-methoxypyridin-3-yl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(2-methylpyrazol-3-yl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-[3-(dimethylcarbamoyl)phenyl]phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(4-ethylsulfonyl-2-methyl-phenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(3,5-difluoro-2-methoxy-phenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-[3-(hydroxymethyl)phenyl]phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(2-methoxypyrimidin-5-yl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(2-hydroxyphenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-(4-quinolin-8-ylphenyl)ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(2-methylphenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(2-phenylmethoxyphenyl)phenyl]ethyl]piperidine-2-carboxamide,
(2S)—N-[(1S)-1-Cyano-2-[4-(2-methylpyridin-3-yl)phenyl]ethyl]piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4-(6-cyanopyridin-3-yl)phenyl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4-(3-(2-hydroxyethyl)-2-oxo-2,3-dihydrobenzo[d]thiazol-5-yl)phenyl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-cyano-2-(4-(3-(2-methoxyethyl)-2-oxo-2,3-dihydrobenzo[d]thiazol-5-yl)phenyl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-cyano-3′-fluorobiphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-cyano-3′-(methylthio)biphenyl-4-yl)ethyl)-piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-cyano-3′-(methylsulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-cyano-3′-(ethylsulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-cyano-3′-(propylsulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(2S)—N-((1S)-2-(4′-Carbamoyl-3′-(methylsulfinyl)biphenyl-4-yl)-1-cyanoethyl)piperidine-2-carboxamide,
(2S)—N-((1S)-1-Cyano-2-(4′-cyano-3′-(2-methyl-1H-imidazol-1-yl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-cyano-2-(3 ′-cyano-4′-(methylthio)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(3′-cyano-4′-(methylsulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)-tert-Butyl 2-((S)-1-cyano-2-(3′-cyano-4′-(propylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)piperidine-1-carboxylate,
(S)—N—((S)-1-Cyano-2-(4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]thiazol-5-yl)phenyl)ethyl)piperidine-2-carboxamide,
(2S)—N-{(1S)-1-Cyano-2-[4-(1,1-dioxido-2,3-dihydro-1,2-benzisothiazol-5-yl)phenyl]ethyl}piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-yl)phenyl)ethyl)piperidine-2-carboxamide,
2S)—N-{(1S)-1-Cyano-2-[4-(2-methyl-1,1-dioxido-2,3-dihydro-1,2-benzisothiazol-5-yl)phenyl]ethyl}piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-ethylbiphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4′-(N-methylsulfamoyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-2-(4′-(Azetidin-1-ylsulfonyl)biphenyl-4-yl)-1-cyanoethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4′-(N-(2-hydroxyethyl)sulfamoyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-(methylcarbamoyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4′-(pyrrolidine-1-carbonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4′-(4-methylpiperazine-1-carbonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(6-(4-cyanophenyl)pyridin-3-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(6-(3-cyanophenyl)pyridin-3-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(6-(2-hydroxyphenyl)pyridin-3-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(6-(4-(N,N-dimethylsulfamoyl)phenyl)pyridin-3-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-2-(6-(3-Chloro-5-(dimethylcarbamoyl)phenyl)pyridin-3-yl)-1-cyanoethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4′-(trifluoromethyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(3′-(piperidine-1-carbonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(3′-(thiazol-2-ylcarbamoyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(3′-(2-cyanoethylcarbamoyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-2-(3′-(2-amino-2-oxoethyl)biphenyl-4-yl)-1-cyanoethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(3′-(N,N-dimethylsulfamoyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(3′-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(3′-(methylsulfonamidomethyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-2-(3′-(Acetamidomethyl)biphenyl-4-yl)-1-cyanoethyl)-piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4′-(4-cyanopiperidin-1-ylsulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4′-(morpholinosulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4′-(4-methylpiperazin-1-ylsulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4-(3-(2-methoxyethyl)-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]thiazol-6-yl)phenyl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4-(3-(2-hydroxyethyl)-2-oxo-2,3-dihydrobenzo[d]thiazol-6-yl)phenyl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-cyanobiphenyl-3-yl)ethyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4′-(cyanomethyl)-3′-(methylsulfonyl)biphenyl-4-yl)ethyl)-piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4-(phenylsulfonyl)phenyl)ethyl)piperidine-2-carboxamide,
(S)—N-((1R,2R)-1-Cyano-2-(4′-cyanobiphenyl-4-yl)cyclopropyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N-((1R,2R)-2-(4′-(Azetidin-1-ylsulfonyl)biphenyl-4-yl)-1-cyanocyclopropyl)piperidine-2-carboxamide trifluoroacetate,
(S)—N—((S)-1-Cyano-2-(4′-(trifluoromethoxy)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
(S)—N—((S)-1-Cyano-2-(4′-(methylsulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide,
((2S)—N-(1-Cyano-2-(4′-(4-ethylpiperazin-1-ylsulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide ditrifluoroacetate,
(2S)—N-(1-Cyano-2-(4′-(4-methyl-1,4-diazepan-1-ylsulfonyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide ditrifluoroacetate,
(S)—N—((S)-1-Cyano-2-(3′-(morpholinomethyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide ditrifluoroacetate, or
(S)—N—((S)-1-Cyano-2-(4-(1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl)ethyl)piperidine-2-carboxamide ditrifluoroacetate
or a pharmaceutically acceptable salt thereof.
11 . A process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in claim 1 which comprises reacting a compound of formula (II)
wherein R 3 , R 4 , R 5 , A, X 2 and B are as defined in formula (I), with a compound of formula (III)
wherein PG 1 represents a protecting group and n, X 1 , y, R 1 and R 2 are as defined in formula (I), and optionally thereafter carrying out one or more of the following procedures:
converting a compound of formula (I) into another compound of formula (I)
removing any protecting groups
forming a pharmaceutically acceptable salt.
12 . A pharmaceutical composition comprising a compound of formula (I) as claimed in claim 1 or a pharmaceutically acceptable salt thereof in association with a pharmaceutically acceptable adjuvant, diluent or carrier.
13 . The method of claim 15 , wherein the obstructive airways disease asthma, chronic obstructive pulmonary disease or allergic rhinitis.
14 . (canceled)
15 . A method of treating an obstructive airways disease in a patient suffering from, or at risk of, said disease, which comprises administering to the patient a therapeutically effective amount of a compound of formula (I) as claimed in claim 1 or a pharmaceutically acceptable salt thereof.
16 . A combination of a compound of formula (I) as claimed in claim 1 or a pharmaceutically acceptable salt thereof and one or more agents independently selected from:
a non-steroidal glucocorticoid receptor agonist;
a selective β 2 adrenoceptor agonist;
a phosphodiesterase inhibitor;
a protease inhibitor;
a glucocorticoid;
an anticholinergic agent;
a modulator of chemokine receptor function; and
an inhibitor of kinase function.Join the waitlist — get patent alerts
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