Claims for Patent: 8,357,693

Summary for Patent: 8,357,693

Title:	Pharmacokinetically improved compounds
Abstract:	The present invention relates to inhibitors of ROCK1 and ROCK2 and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCK1 and or ROCK2 that are useful for the treatment of disease.
Inventor(s):	Bartolozzi; Alessandra (Somerville, MA), Campbell; Stewart (Framingham, MA), Foudoulakis; Hope (Framingham, MA), Kirk; Brian (Sudbury, MA), Ram; Siya (Winchester, MA), Sweetnam; Paul (Marblehead, MA)
Assignee:	Surface Logix, Inc. (Brighton, MA)
Application Number:	11/887,218
Patent Claims:	1. A compound of formula I: ##STR00303## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of --O--(CH.sub.2).sub.y--CO.sub.2R.sup.12, --O--(CH.sub.2).sub.y--C(.dbd.O)NR.sup.13R.sup.14, --O--(CH.sub.2).sub.y-heteroaryl, --O--(CH.sub.2).sub.y-cycloalkyl, --O--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --O--(CH.sub.2).sub.z--NR.sup.13R.sup.14, --NH--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --NH--C(.dbd.O)--X--R.sup.15, --NH--(CH.sub.2).sub.y--NR.sup.13R.sup.14; R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; X is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.15 is selected from the group consisting of heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl, or R.sup.15 is selected from --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --CO.sub.2R.sup.18, --O--(CH.sub.2).sub.x--CO.sub.2R.sup.18, and --C(.dbd.O)NR.sup.16R.sup.17; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; x is selected from 0 to 6; y is selected from 0 to 6; z is selected from 2 to 6; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; R.sup.4 is selected from H, --(CH.sub.2).sub.a--NR.sup.43R.sup.44, --Y--R.sup.42, --O--(CH.sub.2).sub.a--CO.sub.2R.sup.42, --O--(CH.sub.2).sub.a--C(.dbd.O)NR.sup.43R.sup.44,--O--(CH.sub.2).sub.a-h- eteroaryl, --O--(CH.sub.2).sub.a-cycloalkyl, --O--C(.dbd.O)--(CH.sub.2).sub.a--NR.sup.43R.sup.44, --O--(CH.sub.2).sub.c--NR.sup.43R.sup.44, --NH--C(.dbd.O)--(CH.sub.2).sub.a--NR.sup.43R.sup.44, --NH--C(.dbd.O)--Y--R.sup.45, --NH--C(.dbd.O)--(CH.sub.2).sub.a--NR.sup.43R.sup.44; R.sup.42 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.43 and R.sup.44 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.46R.sup.47, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.43 and R.sup.44 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; Y is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.45 is selected from the group consisting of H, aryl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.46R.sup.47, --CO.sub.2R.sup.48, --O--(CH.sub.2).sub.b--CO.sub.2R.sup.48, and --C(.dbd.O)NR.sup.46R.sup.47, R.sup.46 and R.sup.47 independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.46 and R.sup.47 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.48 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; a is selected from 0 to 6; b is selected from 0 to 6; c is selected from 2 to 6; R.sup.5 is selected from the group consisting of H, C.sub.1-C.sub.6 alkyl, --(CH.sub.2).sub.d--C(.dbd.O)--NR.sup.53R.sup.54, --C(.dbd.O)--(CH.sub.2).sub.d--NR.sup.53R.sup.54, --C(.dbd.O)--X--R.sup.55, and --C(.dbd.O)--(CH.sub.2).sub.d--NR.sup.53R.sup.54; R.sup.53 and R.sup.54 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.56R.sup.57, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.56R.sup.57, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.53 and R.sup.54 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.55 is selected from the group consisting of H, aryl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.56R.sup.57, --CO.sub.2R.sup.58, --O--(CH.sub.2).sub.e--CO.sub.2R.sup.58, and --C(.dbd.O)NR.sup.56R.sup.57, R.sup.56 and R.sup.57 independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.56 and R.sup.57 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.58 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.56R.sup.57, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; d is selected from 0 to 6; e is selected from 0 to 6; R.sup.6 is selected from the group consisting of H, C.sub.1-C.sub.6 alkyl, --(CH.sub.2).sub.r--C(.dbd.O)--NR.sup.63R.sup.64, --C(.dbd.O)--(CH.sub.2).sub.r--NR.sup.63R.sup.64, --C(.dbd.O)--X--R.sup.65, and --C(.dbd.O)--(CH.sub.2).sub.r--NR.sup.63R.sup.64; R.sup.63 and R.sup.64 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.66R.sup.67, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.66R.sup.67, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.63 and R.sup.64 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.65 is selected from the group consisting of H, aryl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.66R.sup.67, --CO.sub.2R.sup.68, --O--(CH.sub.2).sub.s--CO.sub.2R.sup.68, and --C(.dbd.O)NR.sup.66R.sup.67, R.sup.66 and R.sup.67 independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.66 and R.sup.67 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.68 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.66R.sup.67, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; r is selected from 0 to 6; s is selected from 0 to 6; n is selected from 0 to 4; m is selected from 0 to 3; and p is selected from 0 and 1. 2. The compound of claim 1, wherein R.sup.4 and R.sup.5 are independently selected from H and C.sub.1-C.sub.6 alkyl. 3. The compound of claim 1, wherein R.sup.4 and R.sup.5 are H. 4. The compound of claim 1, having the formula II: ##STR00304## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, n and m are as for the compound of the formula I. 5. The compound of claim 1, having the formula III: ##STR00305## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, n and m are as for the compound of the formula I. 6. The compound of claim 1, having the formula IV, ##STR00306## or a pharmaceutically acceptable salt thereof, wherein: R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; X is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; n is selected from 0 to 4; and m is selected from 0 to 3. 7. The compound of claim 1, having the formula IV.sub.a: ##STR00307## or a pharmaceutically acceptable salt thereof, wherein: R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl. 8. The compound of claim 1, having the formula V: ##STR00308## or a pharmaceutically acceptable salt thereof, wherein: R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; n is selected from 0 to 4; and m is selected from 0 to 3. 9. The compound of claim 1, having the formula V.sub.a: ##STR00309## or a pharmaceutically acceptable salt thereof, wherein: R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl. 10. A compound of formula VI: ##STR00310## or a pharmaceutically acceptable salt thereof, wherein: R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; n is selected from 0 to 4; and m is selected from 0 to 3. 11. The compound of claim 10, having the formula VI.sub.a: ##STR00311## or a pharmaceutically acceptable salt thereof, wherein: R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl. 12. The compound of claim 1, having the formula VII: ##STR00312## or a pharmaceutically acceptable salt thereof, wherein: R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; n is selected from 0 to 4; and m is selected from 0 to 3. 13. The compound of claim 1, having the formula VII.sub.a: ##STR00313## or a pharmaceutically acceptable salt thereof, wherein: R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl. 14. The compound of claim 1, having the formula VIII: ##STR00314## or a pharmaceutically acceptable salt thereof, wherein: X is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.15 is selected from the group consisting of heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl, or R.sup.15 is selected from --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, CO.sub.2R.sup.18, --O--(CH.sub.2).sub.x--CO.sub.2R.sup.18, and --C(.dbd.O)NR.sup.16R.sup.17; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O---(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; x is selected from 0 to 6, each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; n is selected from 0 to 4; and m is selected from 0 to 3. 15. The compound of claim 1, having the formula VIII.sub.a: ##STR00315## or a pharmaceutically acceptable salt thereof, wherein: X is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.15 is selected from the group consisting of H, aryl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl, or R.sup.15 is selected from --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --CO.sub.2R.sup.18, --O--(CH.sub.2).sub.x--CO.sub.2R.sup.18, and --C(.dbd.O)NR.sup.16R.sup.17; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; and x is selected from 0 to 6. 16. A compound of formula IX: ##STR00316## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of aryl, --(CH.sub.2).sub.y--NR.sup.13R.sup.14, --X--R.sup.12, --O--(CH.sub.2).sub.y--CO.sub.2R.sup.12, --O--(CH.sub.2).sub.y--C(.dbd.O)NR.sup.13R.sup.14, --O--(CH.sub.2).sub.y-heteroaryl, --O--(CH.sub.2).sub.y-cycloalkyl, --O--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --O--(CH.sub.2).sub.z--NR.sup.13R.sup.14, --NH--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --NH--C(.dbd.O)--X--R.sup.15, --NH--(CH.sub.2).sub.y--NR.sup.13R.sup.14; R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; X is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.15 is selected from the group consisting of H, aryl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl, or R.sup.15 is selected from --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --CO.sub.2R.sup.18, --O--(CH.sub.2).sub.x--CO.sub.2R.sup.18, and --C(.dbd.O)NR.sup.16R.sup.17; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; x is selected from 0 to 6; y is selected from 0 to 6; z is selected from 2 to 6; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; R.sup.43 and R.sup.44 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.46R.sup.47, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.43 and R.sup.44 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.46 and R.sup.47 independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.46 and R.sup.47 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; c is selected from 2 to 6; n is selected from 0 to 4; and m is selected from 0 to 3. 17. The compound of claim 1, having the formula X: ##STR00317## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of --O--(CH.sub.2).sub.y--CO.sub.2R.sup.12, --O--(CH.sub.2).sub.y--C(.dbd.O)NR.sup.13R.sup.14, --O--(CH.sub.2).sub.y-heteroaryl, --O--(CH.sub.2).sub.y-cycloalkyl, --O--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --O--(CH.sub.2).sub.z--NR.sup.13R.sup.14, --NH--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --NH--C(.dbd.O)--X--R.sup.15, --NH--(CH.sub.2).sub.y--NR.sup.13R.sup.14; R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; X is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.15 is selected from the group consisting of heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl, or le is selected from --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --CO.sub.2R.sup.18, --O--(CH.sub.2).sub.x--CO.sub.2R.sup.18, and --C(.dbd.O)NR.sup.16R.sup.17; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; x is selected from 0 to 6; y is selected from 0 to 6; z is selected from 2 to 6; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; R.sup.42 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.46 and R.sup.47 independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.46 and R.sup.47 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; n is selected from 0 to 4; and m is selected from 0 to 3. 18. A compound of formula XI: ##STR00318## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of aryl, --(CH.sub.2).sub.y--NR.sup.13R.sup.14, --X--R.sup.12, --O--(CH.sub.2).sub.y--CO.sub.2R.sup.12, --O--(CH.sub.2).sub.y--C(.dbd.O)NR.sup.13R.sup.14, --O--(CH.sub.2).sub.y-heteroaryl, --O--(CH.sub.2).sub.y-cycloalkyl, --O--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --O--(CH.sub.2).sub.z--NR.sup.13R.sup.14, --NH--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --NH--C(.dbd.O)--X--R.sup.15, --NH--(CH.sub.2).sub.y--NR.sup.13R.sup.14; R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; X is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.15 is selected from the group consisting of H, aryl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl, or R.sup.15 is selected from --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --CO.sub.2R.sup.18, --O--(CH.sub.2), CO.sub.2R.sup.18, and --C(.dbd.O)NR.sup.16R.sup.17; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; x is selected from 0 to 6; y is selected from 0 to 6; z is selected from 2 to 6; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; R.sup.43 and R.sup.44 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.46R.sup.47, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.43 and R.sup.44 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.46 and R.sup.47 independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.1-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.46 and R.sup.47 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; n is selected from 0 to 4; and m is selected from 0 to 3. 19. A compound of formula XII: ##STR00319## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of --O--(CH.sub.2).sub.y--CO.sub.2R.sup.12, --O--(CH.sub.2).sub.y--C(.dbd.O)NR.sup.13R.sup.14, --O--(CH.sub.2).sub.y-heteroaryl, --O--(CH.sub.2).sub.y-cycloalkyl, --O--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --O--(CH.sub.2).sub.z--NR.sup.13R.sup.14, --NH--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --NH--C(.dbd.O)--X--R.sup.15, --NH--(CH.sub.2).sub.y--NR.sup.13R.sup.14; R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; X is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.15 is selected from the group consisting of heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl, or R.sup.15 is selected from --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --CO.sub.2R.sup.18, --O--(CH.sub.2).sub.x--CO.sub.2R.sup.18, and --C(.dbd.O)NR.sup.16R.sup.17; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; x is selected from 0 to 6; y is selected from 0 to 6; z is selected from 2 to 6; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; R.sup.4 is selected from H, --(CH.sub.2).sub.a--NR.sup.43R.sup.44, --Y--R.sup.42, --O--(CH.sub.2).sub.a--CO.sub.2R.sup.42, --O--(CH.sub.2).sub.a--C(.dbd.O)NR.sup.43R.sup.44, --O--(CH.sub.2).sub.a-heteroaryl, --O--(CH.sub.2).sub.a-cycloalkyl, --O--C(.dbd.O)--(CH.sub.2).sub.a--NR.sup.43R.sup.44, --O--(CH.sub.2).sub.c--NR.sup.43R.sup.44, --NH--C(.dbd.O)--(CH.sub.2).sub.a--NR.sup.43R.sup.44, --NH--C(.dbd.O)--Y--R.sup.45, --NH--C(.dbd.O)--(CH.sub.2).sub.a--NR.sup.43R.sup.44; R.sup.42 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.43 and R.sup.44 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.46R.sup.47, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.43 and R.sup.44 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; Y is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.45 is selected from the group consisting of H, aryl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.46R.sup.47, --CO.sub.2R.sup.48, --O--(CH.sub.2).sub.b--CO.sub.2R.sup.48, and --C(.dbd.O)NR.sup.46R.sup.47, R.sup.46 and R.sup.47 independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.46 and R.sup.47 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.48 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.16 alkyl)-NR.sup.46R.sup.47, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.16 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; a is selected from 0 to 6; b is selected from 0 to 6; c is selected from 2 to 6; R.sup.5 is selected from the group consisting of H, C.sub.1-C.sub.6 alkyl, --(CH.sub.2).sub.d--C(.dbd.O)--NR.sup.53R.sup.54, --C(.dbd.O)--(CH.sub.2).sub.d--NR.sup.53R.sup.54, --C(.dbd.O)--X--R.sup.55, and --C(.dbd.O)--(CH.sub.2).sub.d--NR.sup.53R.sup.54; R.sup.53 and R.sup.54 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.56R.sup.57, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.56R.sup.57, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.53 and R.sup.54 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.55 is selected from the group consisting of H, aryl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.56R.sup.57, --CO.sub.2R.sup.58, --O--(CH.sub.2).sub.e--CO.sub.2R.sup.58, and --C(.dbd.O)NR.sup.56R.sup.57, R.sup.56 and R.sup.57 independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.56 and R.sup.57 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.58 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.16 alkyl)-NR.sup.56R.sup.57, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.16 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; d is selected from 0 to 6; e is selected from 0 to 6; R.sup.6 is selected from the group consisting of H, C.sub.1-C.sub.6 alkyl, --(CH.sub.2).sub.r--C(.dbd.O)--NR.sup.63R.sup.64, --C(.dbd.O)--(CH.sub.2), NR.sup.63R.sup.64, --C(.dbd.O)--X--R.sup.65, and --C(.dbd.O)--(CH.sub.2).sub.r--NR.sup.63R.sup.64; R.sup.63 and R.sup.64 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.66R.sup.67, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.66R.sup.67, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.63 and R.sup.64 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.65 is selected from the group consisting of H, aryl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.66R.sup.67, --CO.sub.2R.sup.68, --O--(CH.sub.2).sub.s--CO.sub.2R.sup.68, and --C(.dbd.O)NR.sup.66R.sup.67, R.sup.66 and R.sup.67 independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.66 and R.sup.67 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.68 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.66R.sup.67, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; r is selected from 0 to 6; s is selected from 0 to 6; n is selected from 0 to 4; m is selected from 0 to 3; and p is selected from 0 and 1. 20. A compound of formula XII.sub.a: ##STR00320## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of --O--(CH.sub.2).sub.y--CO.sub.2R.sup.12, --O--(CH.sub.2).sub.y--C(.dbd.O)NR.sup.13R.sup.14, --O--(CH.sub.2).sub.y-heteroaryl, --O--(CH.sub.2).sub.y-cycloalkyl, --O--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --O--(CH.sub.2).sub.z--NR.sup.13R.sup.14, --NH--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --NH--C(.dbd.O)--X--R.sup.15, --NH--(CH.sub.2).sub.y--NR.sup.13R.sup.14; R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; X is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.15 is selected from the group consisting of heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl, or R.sup.15 is selected from --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --CO.sub.2R.sup.18, --O--(CH.sub.2), CO.sub.2R.sup.18, and --C(.dbd.O)NR.sup.16R.sup.17; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; x is selected from 0 to 6; y is selected from 0 to 6; z is selected from 2 to 6; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; n is selected from 0 to 4; and m is selected from 0 to 3. 21. The compound of claim 20, wherein R.sup.1 is selected from --NH--C(.dbd.O)--(CH.sub.2).sub.y--NR.sup.13R.sup.14, --NH--C(.dbd.O)--X--R.sup.15, and --NH--(CH.sub.2).sub.y--NR.sup.13R.sup.14. 22. The compound of claim 1, having the formula XII.sub.b: ##STR00321## or a pharmaceutically acceptable salt thereof, wherein: R.sup.7 is selected from the group consisting of --(CH.sub.2).sub.y--NR.sup.13R.sup.14, and X--R.sup.15; R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; X is selected from a covalent bond, O, NH, and C.sub.1-C.sub.6 alkyl; R.sup.15 is selected from the group consisting of heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl, or R.sup.15 is selected from --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --CO.sub.2R.sup.18, --O--(CH.sub.2).sub.x--CO.sub.2R.sup.18, and --C(.dbd.O)NR.sup.16R.sup.17; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C.sub.1-C.sub.6 alkyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoroalkyl; x is selected from 0 to 6; y is selected from 0 to 6; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; n is selected from 0 to 4; and m is selected from 0 to 3. 23. The compound according to claim 1, wherein the compound is selected from the group consisting of 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isopropylacetami- de, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-(2-methoxyeth- yl)acetamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-(pyridin-3-yl)ac- etamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-1-(4-methy- lpiperazin-1-yl)ethanone, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-1-morpholinoethano- ne, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-methylacetami- de, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N--((R)-pyrroli- din-3-yl)acetamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N--((S)-pyrrolidin- -3-yl)acetamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N--((R)-tetrahydro- furan-3-yl)acetamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-1-(piperidin-1-yl)- ethanone, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-tert-bu- tylacetamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-ethylacetamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-(cyanomethyl)ace- tamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-cyclobuty- lacetamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isobutylacetamid- e, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-(2,2,2-trifluo- roethyl)acetamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-cyclohexylacetam- ide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-neopentylace- tamide, 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-(prop-2-y- nyl)acetamide, N-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenyl)-4-methylpiperazine-- 1-carboxamide, 3-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenyl)-1,1-dimethylurea, N-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenyl)-2-methoxyacetamide, methyl 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenylamino)-2-oxoac- etate, 1-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenyl)-3-(2-(dimethy- lamino)ethyl)urea, N-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenyl)-2-morpholinoacetami- de, N-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenyl)-3-(4-isopropylpi- perazin-1-yl)propanamide, N-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenyl)piperidine-4-carboxa- mide, and N-(3-(4-(1H-indazol-5-ylamino)-6-(2-methoxyethoxy)quinazolin-2-y- l)phenyl)butyramide. 24. The compound of claim 1, having the formula: ##STR00322## 25. The compound of claim 1, having the formula: ##STR00323## 26. The compound of claim 1, having the formula: ##STR00324## 27. The compound of claim 1, having the formula: ##STR00325## 28. The compound of claim 1, having the formula: ##STR00326## 29. The compound of claim 1, having the formula: ##STR00327## 30. The compound of claim 1, having the formula: ##STR00328## 31. A pharmaceutical composition comprising a compound according to any one of claims 1 to 23 or 24 to 30 or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier. 32. A method of inhibiting the activity of a Rho kinase comprising contacting the Rho kinase with a compound according to any one of claims 1 to 23 or 24 to 30 or a pharmaceutically acceptable salt thereof.