Benzimidazole derivatives useful as CB-1 inverse agonists

A compound of formula (I)

• wherein
• R0 is selected from the group consisting of hydrogen, —OH, —C(O)OH, —C(O)O—(C1-4alkyl), —CH2—OH, —CH2—O—(C1-2alkyl) and —CH2—O—(C1-2alkyl)-CO2H;
• is selected from the group consisting of cylopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, furyl, thienyl, thiazolyl, benzothiazolyl and benzo[d][1,3]dioxolyl;
• wherein the phenyl, furyl, thienyl, thiazolyl or benzothiazolyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-2alkyl, C1-4alkoxy, fluorinated C1-2alkoxy, cyano, —C(O)OH, —C(O)O—(C1-4alkyl), —C(O)NRARB and NRARB;
• wherein RA and RB are each independently selected from the group consisting of hydrogen, alkyl and hydroxy substituted C1-2alkyl;
• provided that each substituent is bound to a carbon atom;
• is selected from the group consisting of cylopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, furyl, thienyl, thiazolyl, benzothiazolyl and benzo[d][1,3]dioxolyl;
• wherein the phenyl, furyl, thienyl, thiazolyl or benzothiazolyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-2alkyl, C1-4alkoxy, fluorinated C1-2alkoxy, cyano, —C(O)OH, —C(O)O—(C1-4alkyl), —C(O)NRCRD and NRCRD;
• wherein RC and RD are each independently selected from the group consisting of hydrogen, alkyl and hydroxy substituted C1-2alkyl;
• provided that each substituent is bound to a carbon atom;
• R1 is selected from the group consisting of hydrogen, hydroxy and C1-4alkoxy;
• R2 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, fluorinated C1-2alkyl, —(C1-2alkyl)-OH, —(C1-2alkyl)-C(O)OH, —(C1-2alkyl)-NRERF, —(C2-4alkenyl)-OH, —C(O)OH, —C(O)O—(C1-2alkyl), —NRERF, C3-6cycloalkyl, phenyl, furyl, thienyl, pyridyl, azetidin-3-yl, oxetan-3-yl, tetrahydrofuran-2-yl and tetrahydropyran-4-yl;
• wherein the phenyl is optionally substituted with one to two halogen;
• wherein the azetidin-3-yl is optionally substituted with —C(O)O—(C1-4alkyl);
• and wherein RE and RF are each independently selected from the group consisting of hydrogen and C1-4alkyl;
• provided that when R2 is selected from the group consisting of pyridyl, furyl and thienyl, then the R2 is bound to the benzimidazole core through a carbon atom;
• R3 is selected from the group consisting of (a) through (k);
• wherein
• (a) is
• wherein R4 is selected from the group consisting of hydrogen, —C(O)OH, —C(O)O—(C1-2alkyl), —C(O)NRGRH, —NH-(phenyl), and —NH—SO2-(phenyl);
• wherein the phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy and carboxy;
• and wherein RG and RH are each independently selected from the group consisting of hydrogen and C1-4alkyl;
• (b) is
• (c) is
• (d) is
• (e) is
• (f) is
• wherein a is an integer from 0 to 1;
• wherein L1 is selected from the group consisting of —CH2—, —CH2—CH2, —CH2CH2CH2—, —CH(CH3)CH2— and —CH2—CH(CH3)—;
• wherein R5 is selected from the group consisting of hydrogen, C1-2alkyl, fluorinated C1-2alkyl, C2-4alkenyl, —(C1-2alkyl)-C(O)OH, —(C1-2alkyl)-C(O)O—(C1-2alkyl), —(C2-3alkyl)-O-(phenyl), —C(O)—(C1-2alkyl)-OH, —C(O)—(C1-2alkyl)-C(O)OH, —C(O)—(C1-2alkyl)-C(O)O—(C1-2alkyl), —C(O)—(C1-2alkyl)-C(O)—NH2, —C(O)OH, —C(O)O—(C1-4alkyl), —C(O)O—(C3-5cycloalkyl), —C(O)—NRJRK, —C(O)NH—(C3-5cycloalkyl), —C(O)NH-(phenyl), —C(O)NH—(C1-2alkyl)-(phenyl), —SO2—(C1-2alkyl), —SO2-(fluorinated C1-2alkyl), —SO2—(C1-2alkyl)-C(O)OH, —SO2—(C1-2alkyl)-C(O)O—(C1-2alkyl), —SO2—NRJRK, —SO2—(C1-2alkyl)-C(O)NRJRK, phenyl, —(C1-3alkyl)-phenyl, —C(O)-(phenyl), —C(O)O-(phenyl), —C(O)O—(C1-2alkyl)-(phenyl), —SO2-(phenyl), pyrimidin-2-yl, pyridyl, —(C1-2alkyl)-pyridyl, —C(O)-(pyridyl), —SO2-(pyridyl), furyl, —(C1-2alkyl)-furyl, —C(O)-furyl, —SO2-(furyl), thienyl, —(C1-2alkyl)-thienyl, —C(O)-thienyl, —SO2-(thienyl), —C(O)-(1,2,3-triazol-4-yl), —C(O)-(1,2,4,-triazol-3-yl) and —SO2—(C1-2alkyl)-(piperazin-1-yl);
• wherein the phenyl, pyrimidin-2-yl, pyridyl, furyl, thienyl or pyridyl, is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-2alkyl, —(C1-2alkyl)-OH, —(C1-2alkyl)-C(O)OH, —(C1-2alkyl)-C(O)O—(C1-2alkyl), —C(1-2alkyl)-C(O)OH, —(C1-2alkyl)-C(O)O—(C1-2alkyl), —(C1-2alkyl)-C(O)—NRLRM, —O—(C1-4alkyl), —O-(fluorinated C1-2alkyl), —O—(C2-6alkenyl), —O—(C1-2alkyl)-C(O)OH, —O—(C1-2alkyl)-C(O)O—(C1-2alkyl), —O—(C1-2alkyl)-C(O)NRLRM, —O—(C1-2alkyl)-C(O)—NRLRM, —C(O)OH, —C(O)O—(C1-4alkyl), —C(O)—NRLRM, —C(O)—NH—(C1-3alkyl)-OH, —C(O)—NH—(C1-2alkyl)-C(O)OH, —C(O)—NH—(C1-2alkyl)-C(O)O—(C1-2alkyl), —NRLRM and —SO2—NRLRM;
• wherein RJ and RK are each independently selected from the group consisting of hydrogen and C1-4alkyl;
• and wherein RL and RM are each independently selected from the group consisting of hydrogen and C1-4alkyl;
• (g) is
• wherein b is an integer from 0 to 1;
• wherein L2 is selected from the group consisting of —CH2—, —CH2CH2—, —CH(CH3)—, —CH(CH3)—CH2—, —CH2—CH(CH3)—, —CH2CH2—O—, —CH2—CH(OH)—, —CH(CH3)—CH(OH) and —CH2CH2CH2—NH—SO2—;
• wherein R6 is selected from the group consisting of hydrogen, halogen, hydroxy, C1-2alkyl, fluorinated C1-2alkyl, C1-2alkoxy, fluorinated C1-2alkoxy, —C(O)OH, —C(O)O—(C1-2alkyl), —O—(C1-2alkyl)-O—(C1-2alkyl), —O—(C1-2alkyl)-C(O)OH, —O—(C1-2alkyl)-C(O)O—(C1-2alkyl), —C(O)—NRNRP, —O—(C1-2alkyl)-C(O)—NRNRP, phenyl, furyl and thienyl;
• wherein the phenyl, furyl or thienyl is optionally substituted with a substituent selected from the group consisting of halogen, C1-4alkyl and carboxy;
• and wherein RN and RP are each independently selected from the group consisting of hydrogen and C1-4alkyl;
• wherein R7 is selected from the group consisting of hydrogen, halogen, hydroxy, C1-4alkyl, fluorinated C1-2alkyl, C1-4alkoxy, fluorinated C1-2alkoxy, —C(O)OH and —C(O)O—(C1-4alkyl);
• (h) is
• wherein L3 is selected from the group consisting of —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH(CH3)CH2—, —CH2CH(CH3)— and —CH2CH2—O—;
• wherein R8 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, C1-4alkoxy, —C(O)OH and —C(O)O—(C1-4alkyl);
• (i) is
• wherein c is an integer from 0 to 1;
• and wherein L4 is selected from the group consisting of —CH2— and —CH2—CH2—;
• (j) is
• and (k) is
• or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.