| abstract |
Formula (I) [wherein Q is —O— (CHR 6 ) 1-3 or —S— (CHR 6 ) 1-3 —; R 1 and each R 6 are optionally substituted with H [C 1-6 alkyl, C 1-4 alkaryl, C 1-4 alkheterocyclyl, C 2-9 heterocyclyl, C 3-8 cycloalkyl, C 1-4 alkcycloalkyl] or — (CR 1A R 1B ) n NR 1C R 1D ; R 1A , R 1B , R 1C and R 1D are independently hydrogen, optionally substituted [C 1-6 alkyl, C 1-4 alkaryl, C 1- 4 alkheterocyclyl, C 2-9 heterocyclyl, C 3-8 cycloalkyl, etc.], R 1A and R 1B together form ═O, or R 1C and R 1D are optionally substituted together A C 2-9 heterocyclyl or N-protecting group; n is an integer 1-6; each of R 2 and R 3 is H, hal, optionally substituted [C 1-6 alkyl, C 6-10 aryl, C 1-6 alkaryl, C 2-9 heterocyclyl , C 1-6 alkoxy, C 1-6 thioalkoxy, (CH 2 ) r2 NHC (NH) R 2A , (CH 2 ) r2 NHC (S) NHR 2A , C 1-4 alkheterocyclyl] or hydroxy, Where r2 is an integer 0-2 and R 2A is optionally substituted [C 1-6 alkyl, C 6-10 aryl, C 1-4 alkaryl, C 2-9 heterocyclyl, C 1-4 Alkheterocyclyl, C 1-6 thioalkoxy, C 1-4 thioalkaryl, aryloyl, C 1-4 thioalkheterocyclyl, or amino]; each of R 4 and R 5 is H, hal, (CH 2 ) r2 NHC (NH) R 2A , or (CH 2 ) r2 NHC (S) NHR 2A ; Y 1 and Y 2 are ═O together, or Y 1 and Y 2 are independently H, optional [C 1-6 alkyl, C 6-10 aryl, C 1-6 alkaryl, C 2-9 heterocyclyl, C 1-6 alkoxy, C 1-6 thioalkoxy, or C 1-4 alkheterocyclyl substituted with ] Or hydroxy Yes, where only one of R 2 , R 3 , R 4 , and R 5 is (CH 2 ) r2 NHC (NH) R 2A or (CH 2 ) r2 NHC (S) NHR 2A ] Benzoxazines, benzothiazines or pharmaceutically acceptable salts or prodrugs thereof are disclosed. The benzoxazines and benzothiazines inhibit nitric oxide synthase (NOS) and selectively inhibit neuronal nitric oxide synthase (nNOS), especially compared to other NOS isomers. The NOS inhibitor represented by Formula I can be used alone or in combination with other drugs to treat or prevent various medical conditions. [Selection figure] None |