NOVEL ACETYL-COA CARBOXYLASE (ACC) INHIBITORS AND THEIR USE IN DIABETES, OBESITY AND METABOLIC SYNDROME

摘要

The present invention is directed to compounds of formula (I), or a pharmaceutically acceptable salt, prodrug, salt of a prodrug, or combination thereof, wherein Y is selected from the group consisting of-CR_xR_y-, -C(O)-, -O-, -N(H)-, -N(alkyl)- and -S-; wherein each of R_x and R_y is independently selected from the group consisting of hydrogen. alkyl, hydroxyalkyl, and haloalkyl; or R_x and R_y together with the carbon to which they are attached form a monocyclic cycloalkyl or heterocycle ring, Ar₁ is selected from the group consisting of phenyl and a monocyclic, five or six- membered heteroaryl, Ar₃ is phenyl or monocyclic heteroaryl, wherein Ar₃ is substituted with 1, 2, 3 or 4 substituents Ar₂ is a group of formula (a), (b), (c), (d), or (e); wherein R is hydrogen, cycloalkyj, alkyl or haloalkyl, Z₁, Z₂, Z₃ and Z₄ are C(R₁₀₁), or one or two of Z₁, Z₂, Z₃ and Z₄ is N and the others are C(R₁₀₁); Z₅, Z₆ and Z₇ are C(₁₀₂). or one or two of Z₅, Z₆ and Z₇ are N, and the others are C(R₁₀₂), Z is selected from the group consisting of -OR₅, -alkylenyl-OR₅, -N(R₆)(R₇) and -alkylenyI-N(R₆)(R₇), which inhibit acetyl-CoA carboxylase (ACC) and are useful for the prevention or treatment of metabolic syndrome, type II diabetes, obesity, atherosclerosis and cardiovascular diseases in humans.