Patent US6303659B2 successfully refreshed from Google Patents.
US6303659B2
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Compounds
Assignee: AstraZeneca AB
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Filing: 2000-12-26
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Granted: 2001-10-16
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Expires: 2020-12-26
Abstract
Abstract The invention provides adamantane derivatives, a process for their preparation, pharmaceutical compositions containing them, a process for preparing the pharmaceutical compositions, and their use in therapy.
Inventors
- 👤 Andrew Baxter
- 👤 Thomas McInally
- 👤 Michael Mortimore
- 👤 David Cladingboel
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 13:09
CPC Classifications
C; C07; C07D; C07D203/00; C07D203/04; C07D203/06; C07D203/08; C07D203/14; A; A61; A61P; A61P19/00; A61P19/02; A61P29/00; A61P37/00; A61P37/02; A61P37/06; C07C; C07C233/00; C07C233/64; C07C233/65; C07C235/00; C07C235/42; C07C235/44; C07C235/46; C07C235/58; C07C235/60; C07C237/00; C07C237/28; C07C237/30; C07C323/00; C07C323/50; C07C323/62; C07D209/00; C07D209/02; C07D209/04; C07D209/08; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/78; C07D213/81; C07D213/82; C07D233/00; C07D233/54; C07D233/64; C07D295/00; C07D295/04; C07D295/12; C07D295/125; C07D295/13; C07C2603/00; C07C2603/56; C07C2603/58; C07C2603/70; C07C2603/74
Claims Analysis
Total Claims: 6
Claim 1
Independent Claim
373 words
A method of treating rheumatoid arthritis which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I) wherein x represents 1 or 2; A represents a group CH 2 ; B represents a hydrogen or halogen atom; R represents a phenyl, pyridyl, indolyl, indazolyl, pyrimidinyl or thienyl group, each of which may be optionally substituted by one or more substituents independently selected from (i) halogen, amino, cyano, hydroxyl, nitro, C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, —N(R 1 )—C(═O)—R 2 , —NR 5 R 6 , C 3 -C 8 -cycloalkyl, 3- to 8-membered heterocyclyl, C 3 -C 8 -cycloalkyloxy, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylsulphinyl, C 1 -C 6 -alkylsulphonyl, and (ii) C 1 -C 6 -alkoxy, C 1 -C 6 -alkylamino, phenoxy, benzyl, C 1 -C 6 -alkylthio and phenylthio each of which may be optionally substituted by one or more substituents independently selected from halogen, amino, cyano, carboxyl, hydroxyl, nitro, 1-pyrrolidinyl, 1-piperidinyl, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, (di)C 1 -C 6 -alkylamino, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxycarbonyl, R 1 represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; R 2 represents a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; R 5 represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; R 6 represents a C 3 -C 8 -cycloalkyl group and, additionally, a C 1 -C 6 -alkyl group when R 5 is not a hydrogen atom; R 7 represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; R 8 represents a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; R 9 represents a hydrogen atom or a hydroxyl group; and R 10 represents a hydrogen atom or a phenyl or imidazolyl group; with the proviso that when B represents a hydrogen atom and R is a phenyl- or pyridyl-containing group, the phenyl or pyridyl moiety is substituted as defined above; or a pharmaceutically acceptable salt or solvate thereof.
Claim 2
Independent Claim
373 words
A method of treating rheumatoid arthritis which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I) wherein x represents 1 or 2; A represents a group CH 2 ; B represents a hydrogen or halogen atom; R represents a phenyl, pyridyl, indolyl, indazolyl, pyrimidinyl or thienyl group, each of which may be optionally substituted by one or more substituents independently selected from (i) halogen, amino, cyano, hydroxyl, nitro, C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, —N(R 1 )—C(═O)—R 2 , —NR 5 R 6 , C 3 -C 8 -cycloalkyl, 3- to 8-membered heterocyclyl, C 3 -C 8 -cycloalkyloxy, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylsulphinyl, C 1 -C 6 -alkylsulphonyl, and (ii) C 1 -C 6 -alkoxy, C 1 -C 6 -alkylamino, phenoxy, benzyl, C 1 -C 6 -alkylthio and phenylthio each of which may be optionally substituted by one or more substituents independently selected from halogen, amino, cyano, carboxyl, hydroxyl, nitro, 1-pyrrolidinyl, 1-piperidinyl, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, (di)C 1 -C 6 -alkylamino, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxycarbonyl, R 1 represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; R 2 represents a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; R 5 represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; R 6 represents a C 3 -C 8 -cycloalkyl group and, additionally, a C 1 -C 6 -alkyl group when R 5 is not a hydrogen atom; R 7 represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; R 8 represents a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; R 9 represents a hydrogen atom or a hydroxyl group; and R 10 represents a hydrogen atom or a phenyl or imidazolyl group; with the proviso that when B represents a hydrogen atom and R is a phenyl- or pyridyl-containing group, the phenyl or pyridyl moiety is substituted as defined above; or a pharmaceutically acceptable salt or solvate thereof.
Claim 3
Dependent Claim
124 words
A method according to claim 1 , wherein R represents a phenyl, pyridyl or indolyl group, each of which may be optionally substituted by one or two substituents independently selected from a fluorine, chlorine, bromine or iodine atom or an amino, hydroxyl, nitro, aziridinyl, pyrrolidinyl, C 1 -C 4 -alkyl, trifluoromethyl, —NR 5 R 6 , C 1 -C 4 -alkylsulphinyl or C 1 -C 4 -alkylsulphonyl group, or a C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, benzyl, C 1 -C 4 alkylthio or phenylthio group optionally substituted by one or two substituents independently selected from a halogen atom or an amino, cyano, carboxyl, hydroxyl, 1-pyrrolidinyl, 1-piperidinyl, methyl, methoxy, dimethylamino, C 1 -C 4 -alkoxycarbonyl or one of the following groups:
Claim 4
Dependent Claim
22 words
A method according to claim 1 , wherein R 5 represents a hydrogen atom or a C 1 -C 4 -alkyl group.
Claim 5
Dependent Claim
26 words
A method according to claim 1 , wherein R 6 represents a C 1 -C 4 -alkyl group when R 5 is not a hydrogen atom.
Claim 6
Dependent Claim
303 words
A method according to claim 1 , wherein the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof is: 2,4-Dichloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 3,5-Dichloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-Chloro-N-(tricyclo[3.3 1.1 3,7 ]dec-1-methyl)-benzamide, 2.6-Dichloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-Methoxy-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-Methyl-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-Bromo-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-Iodo-N-(tricyclo[3.3.1.1 3,7 ]dec- 1-methyl)-benzamide, 2-Nitro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2,6-Dimethoxy-N-(tricyclo[3.3.1.1 3.7 ]dec-1-methyl)-benzamide, 2-(Trifluoromethyl)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2,6-Difluoro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-(Trifluoromethyl)-6-flouro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-Amino-6-chloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-Chloro-4-nitro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-(2-Cyanophenylthio)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-(4-Methlyphenylthio)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-3-pyridine carboxamide, 2-(Methylthio)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-(Methylthio)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-3-pyridine carboxamide, 3-Chloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2,3-Dichloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2,5-Dimethyt-N-(tricyclo[3.3.1.1 3,7 ]de-1-methyl)-benzamide, 2-(Phenylmethyl)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, 2-(2-(N,N-Dimethylamino)ethyloxy)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-benzamide, hydrochloride, 2-[[(Tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)amino]carbonyl]phenyl-1-oxyacetic acid, 1,1-dimethylethyl ester 2-[[(Tricyclo[3.3.1.1 3,7 ]dec-1ylmethyl)amino]carbonyl]phenyl-1-oxyacetic acid, 2-(Methylsulphoxide)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-3-pyridine carboxamide, N-(tricyclo[3.3.1.1 3,7 ]dec-1-methyl)-5-indole carboxamide, 2-Amino-6-chloro-N-(2-[tricyclo[3.3.1.1 3,7 ]dec-1-yl]ethyl)-benzamide, 2-(2-Methylsulphonyl)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, 2-(2-Aminoethylthio)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxaride, trifluoroacetate 2-(2-(N,N-Dimethylamino)ethylamino)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, dihydrochloride, 2-(2-(Pyrrolidin-1-yl)ethylamino)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, dihydrochloride, 2-(Methylamino)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, dihydrochloride, 2-(Dimethylamino)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, hydrochloride, 2-(Pyrrolidin-1-yl)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, dihydrochloride, 2-(2,5-Dimethoxyphenylthio)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, 2-Chloro-5-methylthio-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-(2-(N,N-Dimethylamino)ethylthio)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-(4-Methoxyphenylthio)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, 2-Chloro-3-fluoro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Bromo-5-fluoro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-5-fluoro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-(2,5-Dihydroxyphenylthio)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, 3-[[(Tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)amino]carbonyl]pyridyl-2-thioacetic acid, (2-Chloro-6-methyl)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, 3-[[(Tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)amino ]carbonyl]pyridyl-2-(4-phenylthio)oxyacetic acid, 2-(4-(3-N,N-dimethylamino)propyloxyphenylthio)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, dihydrochloride, (2-Methylthio-6-methyl)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-3-pyridine carboxamide, 2-[[(Tricyclo[3.3 1.1 3,7 ]dec-1-ylmethyl)amino]carbonyl]phenyl-1-oxybutyric acid, 2-Chloro-5-hydroxy-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-3-nitro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-5-nitro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 3-Amino-2-chloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 5-Amino-2-chloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-3-(N,N-dimethylamino)ethylamino-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-5-(N,N dimethylamino)ethylamino-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-5-(N,N-dimethylamino)ethylthio-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, fumarate, 2-Chloro-3-hydroxy-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-5-(N,N-dimethylamino)ethyloxy-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2,5-Dichloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-5-methylamino-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-5-(2chloromethyl)amino-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 5-Aziridin-1-yl-2-chloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Methyl-3,5-dinitro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 3,5-Diamino-2-methyl-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 3,5-Dimethoxy-2-methyl-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 3,5-Dimethoxy-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 5-(N-(2-Hydroxy-2-phenylethyl)-2-aminoethyl)amino-2-chloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-5-(2-(piperdin-1-yl)ethylamino)-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, hydrochloride, 5-((N-(2-Hydroxyethyl)-2-aminoethyl)amino-2-chloro-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, dihydrochioride, 2-Chloro-N-(2-[tricyclo[3.3.1.1 3,7 ]dec-1-yl]ethyl)-benzamide, 2,3-Dichloro-N-(2-[tricyclo[3.3.1.1 3,7 ]dec-1-yl]ethyl)-benzamide, 5-Amino-2-chloro-N-(2-[tricyclo[3.3.1.1 3,7 ]dec-1-yl]ethyl)-benzamide, 2,5-Dimethyl-N-(2-[tricyclo[3.3.1.1 3,7 ]dec-1-yl]ethyl)-benzamide 2-Chloro-N-(3-chloro-tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2-Chloro-3-(N-(2-[imidazoyl-2-yl]ethyl)-2-aminoethyl)amino-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide, 2,5-Dimethyl-N-(3-chloro-tricyclo[3.3.1.1 3,7 ]dec-1ylmethyl)-benzamide, 3,5-Dimethoxy-2-methyl-N-(3-chloro-tricyclo[3.3.1.1 3,7 ]dec-1ylmethyl)-benzamide, or 2-Chloro-5-iodo-N-(tricyclo[3.3.1.1 3,7 ]dec-1-ylmethyl)-benzamide.
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