Spirochromanone derivatives as acetyl coenzyme A carboxylase (ACC) inhibitors

1. A method for the treatment of, insulin resistance in a subject in need thereof which comprises administering to said subject a therapeutically effective amount of a compound of formula (I):

wherein R 1 and R 5 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 -Q 1 -N(R a )-Q 2 -R b ,

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(R c )R d , or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;

R 2 , R 3 and R 4 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—R k or a group of —N(R e )R f , or

a lower alkoxy group substituted by the group of —N(R e )R f , 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;

Q 1 and Q 2 each independently represent a single bond, or a group of —CO—, —SO 2 — or —C(R g )(R h )—, when Q 2 represents the group of —C(R g )(R h )—, R a and R g , taken together, may represent a group of -Q 1 -N═C(R h )—R b ;

R a and R b 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(R i )R j , 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;

R c , R d , R g , R h , R i and R j each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;

R e and R f 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;

R k represents a pyrrolidinyl, tetrahydrofuranyl, piperidyl group optionally substituted by a lower alkyl group or a halo-lower alkyl group;

T, U and W are each methine;

Y is a nitrogen atom; and

V represents an oxygen atom;

or a pharmaceutically acceptable salt or ester thereof.

2. The method of claim 1 , wherein the compound of formula I is selected from the group consisting of:

5-{1′-[(1-Cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxo-spiro[chromane-2,4′-piperidin]-6-yl}nicotinic acid;

Methyl 5-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxo-spiro[chromane-2,4′-piperidin]-6-yl}nicotinate;

sodium 5-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxo-spiro [chromane-2,4′-piperidin]-6-yl}-2-fluorobenzoate;

sodium 2-{1′-[(8-cyclopropyl-4-ethoxyquinolin-2-yl)carbonyl]-4-oxo-spiro [chromane-2,4′-piperidin]-6-yl}isonicotinate; and

sodium 4-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxo-spiro [chromane-2,4′-piperidin]-6-yl}pyridine-2-carboxylate.