PYRAZOLE DERIVATES AS CANNABINOID RECEPTOR MODULATORS

摘要

Compounds of formula (I), are cannabinoid CB1 receptors, useful, inter alia in the treatment of obesity: wherein A₁ is hydrogen, -COOH, or tetrazolyl, and A₂ is hydrogen, -COOH, tetrazolyl, -CN, -CF₃, -COR₆, -SO₂R₆, -OR₇, -NR₇R₈, -NHCOR₆, and -NR₇SO₂R₈ provided that one of A₁ and A₂ is either -COOH or tetrazolyl; p is 0 or 1 and A₃ is phenyl or cycloalkyl, either of which is optionally substituted with R₄ and/or R₅; q is 0 or 1; R₁ is a bond, or -(CH₂)_aB₁(CH₂)_b- wherein a and b are independently 0, 1, 2 or 3 provided that a+b is not greater than 4, and B₁ is -CO-, -O-, -S-, -SO-, -SO₂-, -CH₂-, -CHOH- or -NR₇-; R₂ is a bond, -CH₂)_aB₁(CH₂)_b- or -[(CH₂)_aB₁(CH₂)_b]_n-A₄-[(CH₂)_cB₂(CH₂)_d]_m- wherein a, b, and B₁ are as defined for R₁; B₂ is as defined for B₁, c and d are independently 0, 1, 2 or 3; with the proviso that a+b+c+d is not greater than 6, n and m are independently 0 or 1 and A₄ is a monocarbocyclic or monoheterocyclic ring, having 3 to 8 ring atoms, optionally substituted with one or more of -F, -Cl, -Br, -CN, -CF₃, C₁-C₄ alkyl, cycloalkyl, -OR₉, oxo or -NR₇R₈; R₃ is hydrogen, C₁-C₄ alkyl, cycloalkyl, -CF₃, -OR₉, -NR₇R₈, -(CH₂)_sCOR₆, -(CH₂)_sSO₂R₆, -(CH₂)_sNR₇COR₆, -(CH₂)_sNR₇COOR₈, -(CH₂)_sNR₇SO₂R₆, wherein s is 1, 2, 3 or 4; R₄ and R₅ independently -R₉, -CN, -F, -Cl, -Br, -OR₉, -NR₇R₈, -NR₇COR₆, -NR₇SO₂R₆, -COR₆, -SR₉, -SOR₉, -SO₂R₆, (C₁-C₄ alkyl)OR₉, -(C₁-C₄ alkyl)NR₇R₈, -(C₁-C₄ alkyl)NR₇COR₆, C₁-C₄ alkyl)NR₇COOR₈, -(C₁-C₄ alkyl)NR₇SO₂R₆, -(C₁-C₄ alkyl)COR₆, -(C₁-C₄ alkyl)SO₂R₆, -NR₇COOR₈, or [N-(C₁-C₄ alkyl)]-tetrazolyl; R₆ is C₁-C₄ alkyl, cycloalkyl, -CF₃ or -NR₇R₈; R₇ and R₈ are independently hydrogen, C₁-C₄ alkyl or cycloalkyl; and R₉ is hydrogen, C₁-C₄ alkyl, cycloalkyl, fully or partially fluorinated C₁-C₄ alkyl.