Patent IL-125796-A (IL)
Title: Substituted 4-hydroxyphenylalkanoic acid derivatives with agonist activity to ppar-gamma
IPC: C07C229/56
Filed: 1997-02-26
Abstract: A compound of the formula wherein A is selected from the group consisting of: (i) phenyl, wherein said phenyl is optionally substituted by one or more halogen atoms, C1-6 alkyl, C1-3 alkoxy, C1-3 fluoroalkoxy, nitrile, or -NR7R8 where R7 and R8 are independently 1395 כ" ג בסיון התשס" א - June 14, 2001 hydrogen or C1-3; alkyl; (ii) a 5- or 6-membered heterocyclic group containing at least one heteroatom selected from oxygen, nitrogen and sulfur; and (iii) a fused bicyclic ring wherein ring C represents a heterocyclic group as defined in point (ii) above, which bicyclic ring is attached to group B via a ring atom of ring C; B is selected from the group consisting of: (iv) C1-6 alkylene; (v) -MC1-6 alkylene or C1-6 alkyleneMC1-6 alkylene, wherein M is O, S, or -NR2 wherein R2 represents hydrogen or C1-3 alkyl; (vi) a 5- or 6-membered heterocylic group containing at least one nitrogen heteroatom and optionally at least one further heteroatom selected from oxygen, nitrogen and sulfur and optionally substitued by C1-3 alkyl; and (vii) Het-C1-6 alkylene, wherein Het represents a heterocyclic group as defined in point (vi) above; Alk represents C1-3 alkylene; R1 represents hydrogen or C1-3 alkyl; Z is selected from the group consisting of: (viii) -(C1-3 alkylene) phenyl, which phenyl is optionally substituted by one or more halogen atoms; and (ix) -NR3R4, wherein R3 represents hydrogen or C1-3 alkyl, and R4 represents -Y- (C=O)-T-R5, or -Y-(CH(OH))-T-R5, wherein: (a) Y represents a bond, C1-6 alkylene, C2-6 alkenylene, C4-6 cycloalkylene or cycloalkenylene, a heterocyclic group as defined in point (vi) above, or phenyl optionally substituted by one or more C1-3 alkyl groups and/or one or more halogen atoms; (b) T represents a bond, C1-3 alkyleneoxy, -O- or -N(R6)-, wherein R6 represents hydrogen or C1-3 alkyl; (c) R5 represents C1-6 alkyl, C4-6 cycloalkyl or cycloalkenyl, phenyl (optionally substituted by one or more: halogen atoms, C1-3 alkyl, C1-3 alkoxy groups, C0-3 alkylene NR9R10 where each R9 and R10 is independently hydrogen, C1-3 alkyl, -SO2C1-3 alkyl, or -CO2C1-3 alkyl, -SO2NHC1-3 alkyl, C0-3 alkylene CO2H, C0-3 alkylene CO2C1-3 alkyl, or -OCH2C(O)NH2), a 5- or 6-membered heterocyclic group as defined in point (ii) above, or a bicyclic fused ring wherein ring D represents a 5- or 6-membered heterocyclic group containing at least one heteroatom selected from oxygen, nitrogen and sulfur and optionally substituted by (=O), which bicyclic ring is attached to T via a ring atom of ring D, or -C1-6 alkyleneMR11, M is O, S, or -NR2 wherein R2 and R11 are independently hydrogen or C1-3 alkyl; or a tautomeric form thereof, and/or a pharmaceutically acceptable salt or solvate thereof for the treatment of hyperglycaemia, dyslipidemia, Type II diabetes, Type I diabetes, hypertriglyceridemia, syndrome X, insulin resistance, heart failure, diabetic dyslipidemia, hyperlipidemia, hypercholesteremia, hypertension, obesity, anorexia bulimia, anorexia nervosa, and cardiovascular disease, especially atherosclerosis. 1396 כ" ג בסיון התשס" א - June 14, 2001