Hydroxylamine and oxime substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines

摘要

Imidazo-quinoline, -pyridine, and -naphthyridine ring systems substituted at the 1-position, pharmaceutical compositions containing the compounds, intermediates, and methods of use of these compounds as immunomodulators, for inducing cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases are disclosed.

主权项

1. A compound of the Formula (II):wherein:
Z is —C(═N—O—R1-2)— X is:
—CH(R9)—, or—CH(R9)-alkylene-; R1-1 is selected from the group consisting of:
hydrogen,alkyl, andaryl; R1-2 is selected from the group consisting of:
hydrogen,alkyl,heterocyclyl,aryl,heteroaryl, andalkyl, heterocyclyl, aryl, or heteroaryl, substituted by one or more substituents selected from the group consisting of:
halogen,cyano,alkyl,hydroxy,hydroxyalkyl,alkoxy,dialkylamino,heterocyclyl,aryl, andheteroaryl; R is selected from the group consisting of:
halogen,hydroxy,alkyl,alkenyl,haloalkyl,alkoxy,alkylthio, and—N(R9)2; R2 is selected from the group consisting of:
hydrogen;alkyl;alkoxyalkyl; andhydroxyalkyl; R3 is selected from the group consisting of:
aryl,heteroaryl, andaryl and heteroaryl substituted by one or more of the groups selected from halogen, hydroxyl, alkoxy, hydroxyalkyl, cyano, dialkylamino, heterocyclyl, —C(O)NH2, —NHS(O)2-alkyl, —C(O)NH-alkyl, —NHC(O)-alkyl, —C(O)NH-heterocyclyl, and R6 is selected from the group consisting of ═O and ═S; R8 is selected from the group consisting of hydrogen, C1-10 alkyl, C2-10 alkenyl, C1-10 alkoxy-C1-10 alkylenyl, hydroxy-C1-10 alkylenyl, heteroaryl-C1-10 alkylenyl, and aryl-C1-10 alkylenyl; R9 is selected from the group consisting of hydrogen and alkyl; A is selected from the group consisting of —O—, —C(O)—, —S(O)0-2—, and —CH2—; V is selected from the group consisting of —C(R6)—, —O—C(R6)—, —N(R8)—C(R6)—, and —S(O)2—; a and b are each independently integers from 1 to 6 with the proviso that a+b is ≦7; n′ is an integer from 0 to 4; and m is 0 or 1; with the proviso that when m is 1, then n′ is 0 or 1;or a pharmaceutically acceptable salt thereof.