Substituted imidazo[2,1-A]isoindoles as PDE10 inhibitors

摘要

This invention is directed to compounds with the structure;
which are PDE10A enzyme inhibitors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. The present invention also provides processes for the preparation of the compounds of formula I. The present invention further provides a method of treating a subject suffering from a neurodegenerative disorder comprising administering to the subject a therapeutically effective amount of a compound of formula I. The present invention also provides a method of treating a subject suffering from a drug addiction comprising administering to the subject a therapeutically effective amount of a compound of formula I. The present invention further provides a method of treating a subject suffering from a psychiatric disorder comprising administering to the subject a therapeutically effective amount of a compound of formula I.

主权项

1. A method of treating a subject suffering from a psychiatric disorder, comprising administering to said subject a therapeutically effective amount of a compound having the structure I: wherein X is selected from the group consisting of CH, CF, COCH3 and COH; R1 and R2 are each selected independently from the group consisting of hydrogen; C1-C6 alkyl; C1-C6 alkyl(C3-C8) cycloalkyl; C1-C6 hydroxyalkyl; C1-C6 alkoxy; CH2CN; CH2C(O)NH2; C1-C6 arylalkyl; C1-C6 alkyl-heterocycloalkyl; 4-chlorobenzyl; halogen; and hydroxy; L is a linker selected from the group consisting of —CH2—CH2—, —CH═CH—, —CH2—S—, and —S—CH2—; and HET is a heteroaromatic group of formula II containing 2 to 4 nitrogen atoms: wherein
Y is N or CH, Z is N or C; andHET optionally is substituted with up to three substituents R5, R6 and R7 individually selected from the group consisting of hydrogen; C1-C6 alkyl; halogen; cyano; halo(C1-C6)alkyl; aryl; C1-C6 alkoxy; and C1-C6 hydroxyalkyl; wherein“*” denotes the attachment point; and wherein the psychiatric disorder is selected from the group consisting of schizophrenia, schizophreniform disorder and schizoaffective disorder.