Bicyclic pyrazole compounds as allosteric modulators of mglur5 receptors

A method for the treatment of a neurological and/or psychiatric disorder associated with glutamate dysfunction in a mammal comprising the step of administering to the mammal a therapeutically effective amount of at least one compound having a structure represented by a formula:

• wherein Ar1 is phenyl with 0-3 substituents selected from halogen, cyano, C1-C4 alkyl, C1-C4 alkyloxy, monohalo C1-C4 alkyl, and polyhalo C1-C4 alkyl, or Ar1 is pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and has 0-3 substituents selected from halogen, cyano, C1-C4 alkyl, C1-C4 alkyloxy, monohalo C1-C4 alkyl, and polyhalo C1-C4 alkyl;
• wherein each of R1a and R1b is independently selected from hydrogen, C1-C4 alkyl, monohalo C1-C4 alkyl, and polyhalo C1-C4 alkyl;
• wherein R2 is selected from hydrogen, halogen, cyano, —NH2, C1-C4 alkyl, monohalo C1-C4 alkyl, C1-C4 alkoxy, and polyhalo C1-C4 alkyl;
• wherein each of R3a and R3b is independently selected from hydrogen, C1-C4 alkyl, monohalo C1-C4 alkyl, and polyhalo C1-C4 alkyl, or are covalently bonded and, together with the intermediate carbon, comprise an optionally substituted 3- to 7-membered spirocycloalkyl;
• wherein each of R4a and R4b is independently selected from hydrogen, C1-C4 alkyl, monohalo C1-C4 alkyl, and polyhalo C1-C4 alkyl, or are covalently bonded and, together with the intermediate carbon, comprise an optionally substituted 3- to 7-membered spirocycloalkyl;
• wherein each of R5a and R5b is independently selected from hydrogen, C1-C4 alkyl, monohalo C1-C4 alkyl, and polyhalo C1-C4 alkyl, or are covalently bonded and, together with the intermediate carbon, comprise an optionally substituted 3- to 7-membered spirocycloalkyl;
• and
• wherein Ar2 is phenyl with 0-3 substituents selected from halogen, cyano, C1-C4 alkyl, C1-C4 alkyloxy, monohalo C1-C4 alkyl, and polyhalo C1-C4 alkyl, or Ar2 is pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and has 0-3 substituents selected from halogen, cyano, C1-C4 alkyl, C1-C4 alkyloxy, monohalo C1-C4 alkyl, and polyhalo C1-C4 alkyl;
• or a pharmaceutically acceptable salt thereof.