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US 9,206,200 B2Granted
N-linked lactam M1 receptor positive allosteric mogulators
AssigneeMerck Sharp & Dohme Corp.
InventorsScott D. Kuduk, Douglas C. Beshore, Zhi-Qiang Yang, Youheng Shu, Daniel Pitts
Life of this patent
Estimating the term…
Abstract
The present invention is directed to N-linked lactam compounds of general formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
Claims13
A compound of formula (I):
- and pharmaceutically acceptable salts thereof, wherein
- X=CH
- R1 represents C3-10cycloalkyl that is cyclohexyl, C6-10 aryl that is phenyl, and C5-10 heterocyclyl that is pyranyl, said cycloalkyl, aryl and heterocyclyl optionally substituted with 1 Ra,
- R2 and R2a together with the nitrogen to which they are attached combined to form a C3-10 heterocyclic ring wherein 1 to 2 carbon atoms on the ring are optionally interrupted by 1 to 2 heteroatoms selected from N, O and S, said heterocyclic ring optionally substituted with 1 to 3 groups of Ra,
- R3 and R4 independently represent:
- (1) hydrogen,
- (2) —C1-6 alkyl, optionally substituted with 1 to 3 groups of Ra,
- Ra represents:
- (1) hydroxyl,
- (2) halogen,
- (3) C1-6alkyl,
- (4) (CH2)nC6-10 aryl, which is unsubstituted or substituted with 1 to 3 groups of Rb,
- (5) (CH2)nheterocyclyl, which is unsubstituted or substituted with 1 to 3 groups of Rb, and
- (6) —CN,
- (7) (CH2)nC1-4 haloalkyl,
- (8) COOR3,
- (9) C3-10cycloalkyl,
- (10) C(O)C1-6alkyl,
- (11) S(O)2C1-6alkyl,
- (12) C2-4 alkynyl,
- (13) C2-4 alkenyl, and
- (14) 2 adjacent Ra's on the C3-10 heterocyclic ring formed when R2 and R2a combine may combine with the atoms to which they are attached to form a 3-10 carbocyclic ring with 1 to 2 carbons atoms on the ring optionally interrupted by 1 to 2 heteroatoms selected from N, O, and S,
- wherein said alkyl, aryl, heterocyclyl, cycloalkyl, alkynyl, alkenyl, and carbocyclic ring are optionally substituted with 1 to 3 groups of Rb,
- Rb represents:
- (1) hydroxyl,
- (2) halogen,
- (3) C1-6alkyl, and
- (4) C1-4 haloalkyl,
- (5) —OC1-6alkyl,
- (6) C3-10cycloalkyl,
- (7) C2-6 alkenyl, and
- (8) S(O)2C1-6alkyl,
- n is 0-2.
30 more elements
A compound which is
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(pyridine-2-yl)piperidine-4-carbonitrile,
- 5-{[4-Fluoro-4-(pyridine-2-yl)piperidine-1-yl]methyl}-2-[(1S,2S)-2-hydroxycyclohexyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 1-({2-[(1S,2S)-2-Hydroxycyclohexyl]-1-methyl-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(pyridine-2-yl)piperidine-4-carbonitrile,
- 1-({2-[(1S,2S)-2-Hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(6-methylpyridin-2-yl)piperidine-4-carbonitrile,
- 4-(6-Ethylpyridin-2-yl)-1-({2-[(1S,2S)-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)piperidine-4-carbonitrile,
- 1-({2-[(1S,2S)-2-Hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(6-methoxypyridin-2-yl)piperidine-4-carbonitrile,
- 1,5-Anhydro-2,3-dideoxy-3-{5-[(4,4-difluoropiperidin-1-yl)methyl]-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}-L-threo-pentitol,
- 1,5-Anhydro-2,4-dideoxy-2-{5-[(4,4-difluoropiperidin-1-yl)methyl]-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}-L-threo-pentitol,
- 5-[(4-Ethenyl-4-fluoropiperidin-1-yl)methyl]-8-[(1S,2S)-2-hydroxycyclohexyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 3-{5-[(4,4-Difluoropiperidin-1-yl)methyl]-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}phenyl dimethylcarbamate,
- 2-(2-Hydroxycyclohexyl)-5-(piperidin-1-ylmethyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-[(4-methylpiperazin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-[(4-methyl-3-oxopiperazin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-[(4-acetylpiperazin-1-yl)methyl]-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-{[4-(methylsulfonyl)piperazin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-[(3-methylpiperidin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-[(3-fluoropiperidin-1-yl)methyl]-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-[(3,3-difluoropiperidin-1-yl)methyl]-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 4-fluoro-1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)piperidine-4-carbonitrile,
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)piperidine-4-carbonitrile,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-[(4-methylpiperidin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-[(4-hydroxypiperidin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-Hydroxycyclohexyl)-5-(pyrrolidin-1-ylmethyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-(morpholin-4-ylmethyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-[(4,4-difluoropiperidin-1-yl)methyl]-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-[(4-fluoropiperidin-1-yl)methyl]-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-{[4-(trifluoromethyl)piperidin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-[(3-fluoro-4-hydroxypyrrolidin-1-yl)methyl]-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-{[trans-3,4-difluoropyrrolidin-1-yl]methyl}-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-{[2-(trifluoromethyl)pyrrolidin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-{[3-(fluoromethyl)pyrrolidin-1-yl]methyl}-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-{[(3S)-3-fluoropyrrolidin-1-yl]methyl}-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-[(3,3-difluoropyrrolidin-1-yl)methyl]-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- ethyl 4-fluoro-1-{[2-(2-hydroxycyclohexyl)-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl]methyl}piperidine-4-carboxylate,
- 2-(2-hydroxycyclohexyl)-5-(2-oxa-7-azaspiro[3.5]non-7-ylmethyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-[(4-hydroxy-4-methylpiperidin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-[(4,4-dimethylpiperidin-1-yl)methyl]-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-[(4-cyclopropylpiperidin-1-yl)methyl]-2-(2-hydroxycyclohexyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-(1′H-spiro[1-benzofuran-3,4′-piperidin]-1′-ylmethyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-[(4-phenylpiperidin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-[(4-(4-pyridinyl)piperidin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-hydroxycyclohexyl)-5-[(4-hydroxy-4-pyridin-4-ylpiperidin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-1-methyl-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(pyridin-2-yl)piperidine-4-carbonitrile,
- 1-({2-[(1R,2R)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile,
- 1-({2-[(1R,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile,
- 4-(6-chloropyridin-2-yl)-1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)piperidine-4-carbonitrile, 4-(6-ethenylpyridin-2-yl)-1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)piperidine-4-carbonitrile,
- 4-(6-ethenylpyridin-2-yl)-1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)piperidine-4-carbonitrile,
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(pyrazin-2-yl)piperidine-4-carbonitrile,
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(pyrimidin-4-yl)piperidine-4-carbonitrile,
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(pyridazin-3-yl)piperidine-4-carbonitrile, 5-[(4-fluoro-4-phenylpiperidin-1-yl)methyl]-2-[(1R,2R)-2-hydroxycyclohexyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 1-{[3-oxo-2-(tetrahydro-2H-pyran-4-yl)-2,3-dihydro-1H-benzo[e]isoindol-5-yl]methyl}-4-pyridin-2-ylpiperidine-4-carbonitrile,
- 1-{[3-oxo-2-(tetrahydro-2H-pyran-3-yl)-2,3-dihydro-1H-benzo[e]isoindol-5-yl]methyl}-4-pyridin-2-ylpiperidine-4-carbonitrile,
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-phenylpiperidine-4-carbonitrile,
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-pyridin-3-ylpiperidine-4-carbonitrile,
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-pyridin-4-ylpiperidine-4-carbonitrile,
- 4-(2-chlorophenyl)-1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)piperidine-4-carbonitrile,
- 4-(2-fluorophenyl)-1-({2-[(1R,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)piperidine-4-carbonitrile,
- 1-({2-[(1R,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(2-methylphenyl)piperidine-4-carbonitrile,
- 1-{[2-(2-fluorophenyl)-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl]methyl}-4-pyridin-2-ylpiperidine-4-carbonitrile,
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(4-methylpyridin-2-yl)piperidine-4-carbonitrile,
- 5-{[4-(4-fluorophenyl)piperazin-1-yl]methyl}-2-[(1S,2S)-2-hydroxycyclohexyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-({4-[4-(methylsulfonyl)phenyl]piperazin-1-yl}methyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-{[4-(4-methoxyphenyl)-2-methylpiperazin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-{[5-(4-methoxyphenyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-[(4-phenylpiperazin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1R,2S)-2-hydroxycyclohexyl]-1-methyl-5-[(4-phenylpiperazin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-[(4-pyridin-3-ylpiperazin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-[(4-pyridin-4-ylpiperazin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-[(3-methyl-4-phenylpiperazin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-{[4-(1-methyl-1H-pyrazol-4-yl)piperazin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1S,2S)-2-hydroxycyclohexyl]-5-{[4-(1-methyl-1H-pyrazol-4-yl)piperazin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-[(1R,2R)-2-hydroxycyclohexyl]-5-{[4-(1-methyl-1H-pyrazol-4-yl)piperazin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-{[4-(1-methyl-1H-pyrazol-4-yl)piperazin-1-yl]methyl}-2-(tetrahydro-2H-pyran-4-yl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-{[4-(1-methyl-1H-pyrazol-4-yl)piperazin-1-yl]methyl}-2-(tetrahydro-2H-pyran-3-yl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-fluorophenyl)-5-[(4-isoquinolin-3-ylpiperazin-1-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 5-{[4-(1,3-benzothiazol-6-yl)piperazin-1-yl]methyl}-2-(2-fluorophenyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 8-[(1S,2S)-2-hydroxycyclohexyl]-5-(piperidin-1-ylmethyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-[(1S,2S)-2-hydroxycyclohexyl]-5-[(4-methylpiperidin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(diethylamino)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-[(4-hydroxypiperidin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4-cyclopropylpiperidin-1-yl)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4-fluoropiperidin-1-yl)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 1-({8-[(1S,2S)-2-hydroxycyclohexyl]-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)piperidine-4-carbonitrile,
- 5-[(4-fluoropiperidin-1-yl)methyl]-8-[(1S,2S)-2-hydroxycyclohexyl]-9-methyl-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 1-({8-[(1S,2S)-2-hydroxycyclohexyl]-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)piperidine-4-carbonitrile,
- 8-(2-hydroxycyclohexyl)-5-(1′H-spiro[1-benzofuran-3,4′-piperidin]-1′-ylmethyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-(2-oxa-7-azaspiro[3.5]non-7-ylmethyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-(pyrrolidin-1-ylmethyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(3,3-difluoropyrrolidin-1-yl)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-(morpholin-4-ylmethyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4,4-dimethylpiperidin-1-yl)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-[(4-hydroxy-4-methylpiperidin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4-fluoro-4-methylpiperidin-1-yl)methyl]-8-[(1S,2S)-2-hydroxycyclohexyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4-ethynyl-4-fluoropiperidin-1-yl)methyl]-8-[(1S,2S)-2-hydroxycyclohexyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4,4-difluoropiperidin-1-yl)methyl]-8-[(1R,2S)-2-hydroxycyclohexyl]-9-methyl-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4,4-difluoropiperidin-1-yl)methyl]-9-ethyl-8-[(1R,2S)-2-hydroxycyclohexyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 1,5-anhydro-2,4-dideoxy-4-{5-[(4,4-difluoropiperidin-1-yl)methyl]-9-methyl-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}-D-erythro-pentitol,
- 1,5-anhydro-3,4-dideoxy-3-{5-[(4,4-difluoropiperidin-1-yl)methyl]-9-methyl-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}-D-erythro-pentitol,
- 1,5-anhydro-3-{5-[(4-cyano-4-pyridin-2-ylpiperidin-1-yl)methyl]-9-methyl-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}-2,3-dideoxypentitol,
- 1,5-anhydro-3-(5-{[4-cyano-4-(4-methylpyridin-2-yl)piperidin-1-yl]methyl}-9-methyl-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl)-2,3-dideoxypentitol,
- 1,5-anhydro-3-{5-[(4-cyano-4-fluoropiperidin-1-yl)methyl]-9-methyl-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}-2,3-dideoxypentitol,
- 1,5-anhydro-3-{5-[(4-fluoropiperidin-1-yl)methyl]-9-methyl-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}-2,3-dideoxypentitol,
- 1,5-anhydro-3-{5-[(4-cyanopiperidin-1-yl)methyl]-9-methyl-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}-2,3-dideoxypentitol,
- 1,5-anhydro-2,3-dideoxy-3-{5-[(4-ethynylpiperidin-1-yl)methyl]-9-methyl-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}pentitol,
- 1,5-anhydro-2,3-dideoxy-3-{5-[(4-ethynyl-4-fluoropiperidin-1-yl)methyl]-9-methyl-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}pentitol,
- 1,5-anhydro-2,3-dideoxy-3-{5-[(4-fluoro-4-prop-1-yn-1-ylpiperidin-1-yl)methyl]-9-methyl-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}pentitol,
- 5-[(4,4-difluoropiperidin-1-yl)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 4-fluoro-1-({8-[(1S,2S)-2-hydroxycyclohexyl]-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)piperidine-4-carbonitrile,
- 4-fluoro-1-{[8-(2-hydroxycyclohexyl)-9-methyl-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl]methyl}piperidine-4-carbonitrile,
- 4-fluoro-1-{[8-(2-hydroxycyclohexyl)-9-methyl-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl]methyl}piperidine-4-carbonitrile,
- 1-({9-ethyl-8-[(1R,2S)-2-hydroxycyclohexyl]-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)-4-fluoropiperidine-4-carbonitrile,
- 5-[(3-fluoropiperidin-1-yl)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(3,3-difluoropiperidin-1-yl)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-{[4-(trifluoromethyl)piperidin-1-yl]methyl}-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4-ethynylpiperidin-1-yl)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4-fluoro-4-pent-1-yn-1-ylpiperidin-1-yl)methyl]-8-[(i S,2S)-2-hydroxycyclohexyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 4-fluoro-1-{[8-(3-hydroxyphenyl)-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl]methyl}piperidine-4-carbonitrile,
- 5-[(4-ethynyl-4-fluoropiperidin-1-yl)methyl]-8-(3-hydroxyphenyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 3-{5-[(4-cyano-4-fluoropiperidin-1-yl)methyl]-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}phenyl dimethylcarbamate,
- 3-{5-[(4-ethynyl-4-fluoropiperidin-1-yl)methyl]-7-oxo-7,9-dihydro-8H-pyrrolo[3,4-h]quinolin-8-yl}phenyl dimethylcarbamate,
- 5-[(4-fluoro-4-prop-1-yn-1-ylpiperidin-1-yl)methyl]-8-[(1S,2S)-2-hydroxycyclohexyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-{[4-(cyclopropylethynyl)-4-fluoropiperidin-1-yl]methyl}-8-[(1S,2S)-2-hydroxycyclo-hexyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-({4-fluoro-4-[(4-fluorophenyl)ethynyl]piperidin-1-yl}methyl)-8-(2-hydroxycyclo-hexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4-benzyl-4-fluoropiperidin-1-yl)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 1-{[8-(2-hydroxycyclohexyl)-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl]methyl}-4-(pyridin-4-ylmethyl)piperidine-4-carbonitrile,
- 1-({8-[(1S,2S)-2-hydroxycyclohexyl]-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)-4-phenylpiperidine-4-carbonitrile,
- 1-{[8-(2-hydroxycyclohexyl)-9-methyl-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl]methyl}-4-phenylpiperidine-4-carbonitrile,
- 8-(2-hydroxycyclohexyl)-5-[(4-phenylpiperidin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-9-methyl-5-[(4-phenylpiperidin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-[(4-pyridin-4-ylpiperidin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-[(4-hydroxy-4-pyridin-4-ylpiperidin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-9-methyl-5-[(4-pyridin-4-ylpiperidin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 1-({8-[(1S,2S)-2-hydroxycyclohexyl]-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile,
- 5-[(4-fluoro-4-pyridin-2-ylpiperidin-1-yl)methyl]-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-[(4-fluoro-4-pyridin-2-ylpiperidin-1-yl)methyl]-8-[(1R,2S)-2-hydroxycyclohexyl]-9-methyl-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 1-{[8-(2-hydroxycyclohexyl)-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl]methyl}-4-(4-methylpyridin-2-yl)piperidine-4-carbonitrile,
- 1-({(9R)-8-[(1S,2S)-2-hydroxycyclohexyl]-9-methyl-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile,
- 1-({(9R)-8-[(1S,2S)-2-hydroxycyclohexyl]-9-methyl-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile,
- 1-({(9R)-8-[(1S,2S)-2-hydroxycyclohexyl]-9-methyl-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)-4-(4-methylpyridin-2-yl)piperidine-4-carbonitrile,
- 1-({(9R)-8-[(1S,2S)-2-hydroxycyclohexyl]-9-methyl-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)-4-(4-methylpyridin-2-yl)piperidine-4-carbonitrile,
- (9R)-5-[(4-fluoro-4-pyridin-2-ylpiperidin-1-yl)methyl]-8-[(1S,2S)-2-hydroxycyclohexyl]-9-methyl-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 1-({8-[(1S,2S)-2-hydroxycyclohexyl]-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)-4-(6-methoxypyridin-2-yl)piperidine-4-carbonitrile,
- 1-({8-[(1S,2S)-2-hydroxycyclohexyl]-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)-4-(6-methoxypyridin-2-yl)piperidine-4-carbonitrile,
- 1-({8-[(1S,2S)-2-hydroxycyclohexyl]-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-5-yl}methyl)-4-(6-methoxypyridin-2-yl)piperidine-4-carbonitrile,
- 8-[(1S,2S)-2-hydroxycyclohexyl]-5-{[4-(1-methyl-1H-pyrazol-4-yl)piperazin-1-yl]methyl}-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-9-methyl-5-{[4-(1-methyl-1H-pyrazol-4-yl)piperazin-1-yl]methyl}-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-[(4-pyridin-4-ylpiperazin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-9-methyl-5-[(4-pyridin-4-ylpiperidin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-[(4-pyridin-3-ylpiperazin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-9-methyl-5-[(4-pyridin-3-ylpiperazin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-9-methyl-5-[(4-pyridin-3-ylpiperazin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-9-methyl-5-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-9-methyl-5-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-9-methyl-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-9-methyl-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-{[4-(4-fluorophenyl)piperazin-1-yl]methyl}-8-(2-hydroxycyclohexyl)-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-{[4-(4-fluorophenyl)piperazin-1-yl]methyl}-8-(2-hydroxycyclohexyl)-9-methyl-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 5-{[4-(4-fluorophenyl)piperazin-1-yl]methyl}-8-(2-hydroxycyclohexyl)-9-methyl-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-5-[(4-phenylpiperazin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-9-methyl-5-[(4-phenylpiperazin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one,
- 8-(2-hydroxycyclohexyl)-9-methyl-5-[(4-phenylpiperazin-1-yl)methyl]-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one
- 1-({2-[(1S,2S)-2-hydroxycyclohexyl]-1-methyl-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)-4-(pyridin-2-yl)piperidine-4-carbonitrile,
- 1-{[2-(2-fluorophenyl)-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl]methyl}-4-(4-methylpyridin-2-yl)piperidine-4-carbonitrile,
- 2-(2-fluorophenyl)-5-{[1-(pyridin-4-yl)-3,4-dihydroisoquinolin-2(1H)-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-fluorophenyl)-5-{[4-(pyridin-2-yl)piperazin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- 2-(2-fluorophenyl)-5-{[4-(pyridin-2-yl)piperazin-1-yl]methyl}-1,2-dihydro-3H-benzo[e]isoindol-3-one,
- and pharmaceutically acceptable salts thereof.
169 more elements
Dependencies are inferred from the claim text.