| abstract |
Pyrazole compounds and compositions comprising them. The compounds and compositions are useful as modulators of monoacylglycerol lipase (MAGL). In addition, they are useful for the treatment of pain. Claim 1: A compound of formula (1); characterized in that: R¹ is -C (O) OR¹⁵ or -C (O) NR¹⁰R¹¹; R² is H, halogen, C₁₋₆ alkyl, or C₁₋₆ haloalkyl; R³ is a compound selected from the group of formulas (2); A is N or C (H); X is -O-, -N (R¹⁶) -, or -CH₂N (R¹⁶) CH₂-; Y is -CH₂- or -C (O) -; Z is -S-, -O-, or -N (R¹⁸) -; R⁴ is H, halogen, -OR⁷, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ haloalkyl, -C (O) NR⁸R⁹, C₃₋₈ cycloalkyl, C₂₋₉ heterocycloalkyl, -C₁₋₆ alkyl-C₂₋₉ heterocycloalkyl, C₆₋₁₀ aryl, or C₁₋₉ heteroaryl, where C₃₋₈ cycloalkyl, C₂₋₉ heterocycloalkyl, -C₁₋₆ alkyl-C₂₋₉ heterocycloalkyl, C₆₋₁₀ aryl, or C₁₋₉ heteroaryl are optionally substituted with 1 or 2 R¹⁴; R⁵ is H, halogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ haloalkoxy, or phenyl; R⁶ is H, halogen, or C₂₋₆ alkyl; R⁷ is H, C₁₋₆ alkyl, C₁₋₆ haloalkyl, -C₁₋₆ alkyl-OH, C₂₋₉ heterocycloalkyl, C₆₋₁₀ aryl, or C₁₋₉ heteroaryl, where C₂₋₉ heterocycloalkyl, C₆₋₁₀ aryl, or C₁₋₉ heteroaryl is optionally substituted with 1 or 2 R¹⁴; each R⁸ and each R⁹ are independently selected from H and C₁₋₆ alkyl; or R⁸ and R⁹ together with the nitrogen to which they are attached, combine to form a heterocycloalkyl ring; R¹⁰ and R¹¹ are independently from each other H or C₁₋₆ alkyl; R¹² is H, halogen, or C₁₋₆ alkyl; R¹³ is H or C₁₋₆ alkyl; each R¹⁴ is independently selected from halogen, -OH, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy, -C₁₋₆ alkyl-OH, C₃₋₈ cycloalkyl, -C (O) OH, -C (O ) NR⁸R⁹, -SO₂-C₁₋₆ alkyl, and -N (R¹⁷) C (O) -C₁₋₆ alkyl; R¹⁵ is H or C₁₋₆ alkyl; R¹⁶ is H, C₁₋₆ alkyl, -C (O) -C₁₋₆ alkyl, -C₁₋₆ alkyl-OH, or -CH₂CO₂H; R¹⁷ is H or C₁₋₆ alkyl; R¹⁸ is H or C₁₋₆ alkyl; v is 0 or 1; n is 0 or 1; m is 0 or 1; p is 0, 1 or 2; and q is 0, 1 or 2; or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or a pharmaceutically acceptable salt thereof. |