11-Beta-hydroxysteroid dehydrogenase 1 inhibitors useful for the treatment of diabetes, obesity and dyslipidemia

A compound represented by Formula I:

• 296
• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• A and B may be taken separately or together;
• when taken separately,
• A represents halo, C1-6alkyl, OC1-6alkyl or phenyl, said alkyl, phenyl and the alkyl portion of OC1-6alkyl being optionally substituted with 1-3 halo groups;
• and
• B represents represents H, halo, C1-6alkyl, —OC1-6alkyl, —SC1-6alkyl, C2-6alkenyl, phenyl or naphthyl, said alkyl, alkenyl, phenyl, naphthyl, and the alkyl portions of —OC1-6alkyl and —SC1-6alkyl being optionally substituted with 1-3 groups selected from halo, OH, CH3O, CF3 and OCF3;
• and
• when taken together,
• A and B together represents (a) C1-4alkylene optionally substituted with 1-3 halo groups, and 1-2 Ra groups wherein Ra represents C1-3alkyl, OC1-3alkyl, C6-10arC1-6alkylene or phenyl optionally substituted with 1-3 halo groups, or (b) C2-5alkanediyl such that they form a 3-6 membered ring with the carbon atom to which they are attached, said ring optionally containing 1 double bond or 1-2 heteroatoms selected from O, S and N, said 3-6 membered ring being optionally substituted with C1-4alkylene, oxo, ethylenedioxy or propylenedioxy, and being further optionally substituted with 1-4 groups selected from halo, C1-4alkyl, haloC1-4alkyl, C1-3acyl, C1-3acyloxy, C1-3alkoxy, C1-6alkylOC(O)—, C2-4alkenyl, C2-4alkynyl, C1-3alkoxyC1-3alkyl, C1-3alkoxyC1-3alkoxy, phenyl, CN, OH, D, NH2, NHRa and N(Ra)2 wherein Ra is as previously defined;
• each R1 represents H or is independently selected from the group consisting of:
• OH, halo, C1-10alkyl, C1-6alkoxy and C6-10aryl, said C1-10alkyl, C6-10aryl and the alkyl portion of C1-6alkoxy being optionally substituted with 1-3 halo, OH, OC1-3alkyl, phenyl or naphthyl groups, said phenyl and naphthyl being optionally substituted with 1-3 substituents independently selected from halo, OCH3, OCF3, CH3, CF3 and phenyl, wherein said phenyl is optionally substituted with 1-3 halo groups,
• or two R1 groups taken together represent a fused C5-6alkyl or aryl ring, which may be optionally substituted with 1-2 OH or Ra groups, wherein Ra is as defined above;
• R2 and R3 are taken together or separately;
• when taken together, R2 and R3 represent (a) a C3-8 alkanediyl forming a fused 5-10 membered non-aromatic ring optionally interrupted with 1-2 double bonds, and optionally containing 1-2 heteroatoms selected from O, S and N;
• or (b) a fused 6-10 membered aromatic monocyclic or bicyclic group, said alkanediyl and aromatic monocyclic or bicyclic group being optionally substituted with 1-6 halo atoms, and 1-4 of OH, C1-3alkyl, OC1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, and phenyl, said phenyl being optionally substituted with 1-4 groups independently selected from halo, C1-3alkyl, OC1-3alkyl, and said C1-3alkyl and the C1-3alkyl portion of OC1-3alkyl being optionally substituted with 1-3 halo groups;
• when taken separately,
• R2 is selected from the group consisting of:
• (a) C1-14alkyl optionally substituted with 1-6 halo groups and 1-3 substituents selected from OH, OC1-3alkyl, and phenyl, said phenyl being optionally substituted with 1-4 groups independently selected from halo, OCH3, OCF3, CH3 and CF3, and said C1-3alkyl portion of OC1-3alkyl being optionally substituted with 1-3 halo groups;
• (b) phenyl or pyridyl optionally substituted with 1-3 halo, OH or Ra groups, with Ra as previously defined;
• (c) C2-10 alkenyl, optionally substituted with 1-3 substituents independently selected from halo, OH and OC1-3alkyl, said C1-3alkyl portion of OC1-3alkyl being optionally substituted with 1-3 halo groups;
• (d) CH2CO2H;
• (e) CH2CO2C1-6alkyl;
• (f) CH2C(O)NHRa wherein Ra is as previously defined;
• (g) NH2, NHRa and N(Ra)2 wherein Ra is as previously defined;
• and R3 is selected from the group consisting of:
• C1-4alkyl, C2-10alkenyl, SC1-6alkyl, C6-10aryl, heterocyclyl and heteroaryl, said alkyl, alkenyl, aryl, heterocyclyl, heteroaryl and the alkyl portion of SC1-6alkyl being optionally substituted with (a) R;
• (b) 1-6 halo groups and (c) 1-3 groups selected from OH, NH2, NHC1-4alkyl, N(C1-4alkyl)2, C1-4alkyl, OC1-4alkyl, CN, C1-4alkylS(O)x— wherein x is 0, 1 or 2, C1-4alkylSO2NH—, H2NSO2—, C1-4alkyl NHSO2— and (C1-4alkyl)2NSO2—, said C1-4alkyl and the C1-4alkyl portions of said groups being optionally substituted with phenyl and 1-3 halo groups, and
• R is selected from heterocyclyl, heteroaryl and aryl, said group being optionally substituted with 1-4 groups selected from halo, C1-4alkyl, C1-4alkylS(O)x—, with x as previously defined, C1-4alkylSO2NH—, H2NSO2—, C1-4alkylNHSO2—, (C1-4alkyl)2NSO2—, CN, OH, OC1-4alkyl, and, said C1-4alkyl and the C1-4alkyl portions of said groups being optionally substituted with 1-5 halo and 1 group selected from OH and OC1-3alkyl.