US 7,410,976 B2Granted

Spirochromanone derivatives

AssigneeMerck & Co., Inc.

InventorsTakeru Yamakawa, Hideki Jona, Kenji Niiyama, Koji Yamada, Tomoharu Iino, Mitsuru Ohkubo, Hideaki Imamura, Jun Shibata, Jun Kusunoki, Lihu Yang

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Abstract

The invention relates to a compound of a formula (I): or a pharmaceutically acceptable salt or ester thereof, useful as a therapeutic agent for various ACC-related disorders.

Claims29

Dependent claims

A compound of formula (I):

wherein R1 represents a halogen atom, a cyano group, a lower alkenyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Q1-N(Ra)-Q2-Rb,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group,
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of —CO—N(Rc)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R5 represents a hydrogen atom, a halogen atom, a cyano group, a lower alkenyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Ql-N(Ra)-Q2-Rb, a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group, an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of -CO-N(RC)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R2, R3 and R4 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a hydroxy-lower alkoxy group, a lower alkoxy-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, a group of —O—Rk or a group of —N(Re)Rf, or
a lower alkoxy group substituted by the group of —N(Re)Rf, or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group;
Q1 and Q2 each independently represent a single bond, or a group of —CO—, —SO2— or —C(Rg)(Rh)—, when Q2 represents the group of —C(Rg)(Rh)—, Ra and Rg, taken together, may represent a group of -Q1-N═C(Rh)—Rb;
Ra and Rb each independently represent a hydrogen atom, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group, a carbamoyl group, a lower alkoxycarbonyl group or a group of —N(Ri)Rj, or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or
a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group;
Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
Re and Rf each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
Rk represents a pyrrolidinyl, tetrahydrofuranyl, piperidyl group optionally substituted by a lower alkyl group or a halo-lower alkyl group;
T, U, W and Y each independently represent a nitrogen atom or a methine group;
and
V represents an oxygen atom or a sulfur atom;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.

15 more elements

A compound selected from the group consisting of:

(1) N-{1′-[(4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}acetamide,
(2) N-{1′-[(4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}acetamide hydrochloride,
(3) N-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}acetamide,
(4) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-spiro[chroman-2,4′-piperidin]-4-one,
(5) 6-amino-1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-spiro[chroman-2,4′-piperidin]-4-one,
(6) N-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}urea,
(7) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidine]-6-sulfonamide,
(8) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-N-methyl-4-oxospiro[chroman-2,4′-piperidine]-6-sulfonamide,
(9) 6-bromo-1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-spiro[chroman-2,4′-piperidin]-4-one,
(10) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-[(1-methyl-1H-pyrazol-5-yl)amino]spiro[chroman-2,4′-piperidin]-4-one,
(11) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-[(1-ethyl-1H-pyrazol-5-yl)amino]spiro[chroman-2,4′-piperidin]-4-one,
(12) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-pyrimidin-2-yl-spiro[chroman-2,4′-piperidin]-4-one,
(13) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-pyridin-3-yl-spiro[chroman-2,4′-piperidin]-4-one,
(14) 5-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinamide,
(15) 6-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinamide,
(16) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidine]-6-carbonitrile,
(17) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(18) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one sodium salt,
(19) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1-methyltetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(20) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(2-methyltetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(21) (5-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-2H-tetrazol-2-yl)-methyl pivalate,
(22) (5-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-2H-tetrazol-1-yl)-methyl pivalate,
(23) 1′-[(8-cyclopropyl-4-ethoxy-1,7-naphthyridin-2-yl)-carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(24) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)spiro[chroman-2,4′-piperidin]-4-one,
(25) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)spiro[chroman-2,4′-piperidin]-4-one,
(26) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(benzyloxycarbonyl)spiro[chroman-2,4′-piperidin]-4-one,
(27) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(carboxy)spiro[chroman-2,4′-piperidin]-4-one,
(28) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)spiro[chroman-2,4′-piperidin]-4-one,
(29) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1H-1,2,4-triazol-3-yl)spiro[chroman-2,4′-piperidin]-4-one,
(30) 3-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-1H-1,2,4-triazole-5-carboxamide,
(31) 6-(4-acetylpiperazin-1-yl)-1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-spiro[chroman-2,4′-piperidin]-4-one,
(32) 6-(4-acetylpiperazin-1-yl)-1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]spiro[chroman-2,4′-piperidin]-4-one,
(33) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-[4-(methylsulfonyl)piperazin-1-yl]spiro[chroman-2,4′-piperidin]-4-one,
(34) sodium 3-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-5-oxo-1,2,4-oxadiazol-4-ide,
(35) 1′-[4-(2-hydroxyethoxy)-8-methoxy-2-naphthoyl]-6-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)spiro[chroman-2,4′-piperidin]-4-one,
(36) 1′-[8-methoxy-4-(1H-tetrazol-5-yl)-2-naphthoyl]-6-(1-methyl-1H-pyrazol-4-yl)spiro[chroman-2,4′-piperidin]-4-one,
(37) 3-1′-[(8-cyclopropyl-4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-1H-1,2,4-triazole-5-carboxamide,
(38) 5-{1′-[(8-cyclopropyl-4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinic acid,
(39) N-(2-amino-2-oxoethyl)-1′-{[1-cyclopropyl-5-(2-hydroxyethoxy)isoquinolin-7-yl]carbonyl}-4-oxospiro[chroman-2,4′-piperidine]-6-carboxamide,
(40) 5-(1′-{[8-cyclopropyl-4-(2-hydroxyethoxy)-1,7-naphthyridin-2-yl]carbonyl}-4-oxospiro[chroman-2,4′-piperidin]-6-yl)nicotinamide,
(41) 5-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinic acid sodium salt,
(42) 3-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}benzoic acid,
(43) 1′-(4,8-dimethoxy-2-naphthoyl)-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(44) 1′-(8-methoxy-4-morpholin-4-yl-2-naphthoyl)-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(45) 1′-[(8-methoxy-4-phenylquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(46) 1′-[(8-cyclopropyl-4-methoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(47) 1′-[(4-ethoxy-8-ethylquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(48) 1′-[(4-ethoxy-8-ethylquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(49) 1′-[(5,8-dichloro-4-ethoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(50) 1′-[(1,5-dimethoxyisoquinolin-7-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(51) 1′-[(1-cyclopropyl-5-ethoxyisoquinolin-7-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(52) sodium 5-{1′-[(1-cyclopropyl-5-ethoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}tetrazol-1-ide,
(53) 1′-{[1-cyclopropyl-5-(2-hydroxyethoxy)isoquinolin-7-yl]carbonyl}-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(54) 1′-[(4-cyclopropyl-8-ethoxyisoquinolin-6-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(55) 1′-[(4-cyclopropyl-8-methoxyquinolin-6-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(56) sodium 5-{1′-[(1-cyclopropyl-5-ethoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinate,
(57) sodium 5-{1′-[(8-cyclopropyl-4-methoxy-quinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinate,
(58) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1H-pyrazol-4-yl)spiro[chroman-2,4′-piperidin]-4-one,
(59) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1-methyl-1H-pyrazol-4-yl)spiro[chroman-2,4′-piperidin]-4-one,
(60) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1,1-dioxidothiomorpholin-4-yl)spiro[chroman-2,4′-piperidin]-4-one,
(61) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(3-oxopiperazin-1-yl)spiro[chroman-2,4′-piperidin]-4-one,
(62) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(4H-1,2,4-triazol-3-ylamino)spiro[chroman-2,4′-piperidin]-4-one,
(63) 1′-[(4-hydroxy-8-methoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(64) 1′-[(8-hydroxy-4-methoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(65) 1-[(8-cyclopropyl-4-methoxyquinolin-2-yl)carbonyl]-6′-(1H-tetrazol-5-yl)spiro[piperidine-4,2′-thiochroman]-4′-one,
(66) 6′-tert-butyl-1-[(4,8-dimethoxyquinolin-2-yl)carbonyl]spiro[piperidine-4,2′-pyrano[2,3-c]pyridin]-4′(3′H)-one,
(67) sodium 5-{1′-[(8-cyclopropyl-4-ethoxy-1,7-naphthyridin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinate,
(68) sodium 2-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxo-spiro[chroman-2,4′-piperidin]-6-yl}isonicotinate,
(69) sodium 2-{1′-[(1-cyclopropyl-5-ethoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}isonicotinate,
(70) 4,8-dimethoxy-2-({6-[(methoxycarbonyl)amino]-4-oxospiro[chroman-2,4′-piperidin]-1′-yl}carbonyl)quinoline hydrochloride,
(71) 2-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-2-methylpropanoic acid, and
(72) 1′-[(1,5-dimethoxyisoquinolin-3-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.

70 more elements

A compound of formula (I):

wherein R1 and R5 each independently represent a hydrogen atom, a halogen atom, a cyano group, a lower alkenyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Q1-N(Ra)-Q2-Rb,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group,
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of -CO-N(Rc)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R2, R3 and R4 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a hydroxy-lower alkoxy group, a lower alkoxy-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, a group of -O-Rk or a group of -N(Re)Rf, or
a lower alkoxy group substituted by the group of -N(Re)Rf, or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group, provided that at least one of R2, R3 and R4 is lower alkoxy, hydroxy-lower alkoxy, cyclo-lower alkyl, or aryl substituted with at least one lower alkoxy;
Q1 and Q2 each independently represent a single bond, or a group of -CO-, -SO2- or -C(Rg)(Rh)-, when Q2 represents the group of C(Rg)(Rh)-, Ra and Rg, taken together, may represent a group of-Q1-N=C(Rh)-Rb;
Ra and Rb each independently represent a hydrogen atom, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group, a carbamoyl group, a lower alkoxycarbonyl group or a group of -N(Ri)Rj, or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group;
Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
Re and Rf each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
Rk represents a pyrrolidinyl, tetrahydrofuranyl, piperidyl group optionally substituted by a lower alkyl group or a halo-lower alkyl group;
T, U, W and Y each independently represent a nitrogen atom or a methine group;
and V represents an oxygen atom or a sulfur atom;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.

12 more elements

A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I):

wherein R1 and R5 each independently represent a hydrogen atom, a halogen atom, a cyano group, a lower alkenyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Q1-N(Ra)-Q2-Rb,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group,
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of -CO-N(Rc)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R2, R3 and R4 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a hydroxy-lower alkoxy group, a lower alkoxy-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, a group of -O-Rk or a group of -N(Re)Rf, or
a lower alkoxy group substituted by the group of -N(Re)Rf, or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group;
Q1 and Q2 each independently represent a single bond, or a group of -CO-, -SO2- or -C(Rg)(Rh)-, when Q2 represents the group of -C(Rg)(Rh)-, Ra and Rg, taken together, may represent a group of -Q1-N=C(Rh)-Rb;
Ra and Rb each independently represent a hydrogen atom, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group, a carbamoyl group, a lower alkoxycarbonyl group or a group of -N(Ri)Rj, or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or
a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group;
Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo- lower alkyl group;
Re and Rf each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
Rk represents a pyrrolidinyl, tetrahydrofuranyl, piperidyl group optionally substituted by a lower alkyl group or a halo-lower alkyl group;
T, U, W and Y each independently represent a nitrogen atom or a methine group;
and
V represents an oxygen atom or a sulfur atom;
or a pharmaceutically acceptable salt thereof;
or a pharmaceutically acceptable ester of a carboxylic group thereof,
and a pharmaceutically acceptable additive.

16 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/487,029Filed 14 Jul 2006 · us provisional application
Priority: 19 Jul 2005
Published: US 2007/0021453 A125 Jan 2007
Granted: 12 Aug 2008
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07D 491/10
In which the condensed system contains two hetero rings: spiro-condensed systems
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents

Family

Application60/700,382Us provisional application · filed 19 Jul 2005
US 2007/0021453 A1Pre-grant publication · published 25 Jan 2007
US 7,410,976 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

The invention relates to a compound of a formula (I): or a pharmaceutically acceptable salt or ester thereof, useful as a therapeutic agent for various ACC-related disorders.

A compound of formula (I):

wherein R1 represents a halogen atom, a cyano group, a lower alkenyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Q1-N(Ra)-Q2-Rb,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group,
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of —CO—N(Rc)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R5 represents a hydrogen atom, a halogen atom, a cyano group, a lower alkenyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Ql-N(Ra)-Q2-Rb, a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group, an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of -CO-N(RC)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R2, R3 and R4 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a hydroxy-lower alkoxy group, a lower alkoxy-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, a group of —O—Rk or a group of —N(Re)Rf, or
a lower alkoxy group substituted by the group of —N(Re)Rf, or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group;
Q1 and Q2 each independently represent a single bond, or a group of —CO—, —SO2— or —C(Rg)(Rh)—, when Q2 represents the group of —C(Rg)(Rh)—, Ra and Rg, taken together, may represent a group of -Q1-N═C(Rh)—Rb;
Ra and Rb each independently represent a hydrogen atom, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group, a carbamoyl group, a lower alkoxycarbonyl group or a group of —N(Ri)Rj, or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or
a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group;
Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
Re and Rf each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
Rk represents a pyrrolidinyl, tetrahydrofuranyl, piperidyl group optionally substituted by a lower alkyl group or a halo-lower alkyl group;
T, U, W and Y each independently represent a nitrogen atom or a methine group;
and
V represents an oxygen atom or a sulfur atom;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.

15 more elements

Facts

Application

11/487,029Filed 14 Jul 2006 · us provisional application

Priority

19 Jul 2005

Published

US 2007/0021453 A125 Jan 2007

Granted

12 Aug 2008

Term ends

Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07D 491/10
In which the condensed system contains two hetero rings: spiro-condensed systems
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents