Claims for Patent: 8,648,087

Summary for Patent: 8,648,087

Title:	N4-phenyl-quinazoline-4-amine derivatives and related compounds as ErbB type I receptor tyrosine kinase inhibitors for the treatment of hyperproliferative diseases
Abstract:	This invention provides compounds of Formula I ##STR00001## wherein B, G, A, E, R.sup.1, R.sup.2, R.sup.3, m and n are as defined herein, which are useful as type I receptor tyrosine kinase inhibitors, and methods of use thereof in the treatment of hyperproliferative disorders in mammals.
Inventor(s):	Lyssikatos; Joseph P. (Piedmont, CA), Greschuk; Julie Marie (Erie, CO), Marmsater; Fredrik P. (Boulder, CO), Zhao; Qian (Superior, CO), Hennings; D. David (Loveland, CO), Liu; Weidong (Superior, CO)
Assignee:	Array Biopharma, Inc. (Boulder, CO)
Application Number:	12/085,048
Patent Claims:	1. A compound of Formula I ##STR00353## or a pharmaceutically acceptable salt thereof, wherein: A is O, C(.dbd.O), S, SO or SO.sub.2; G is N; B represents a fused 6-membered aryl ring; E is ##STR00354## X is N or CH; D.sup.1, D.sup.2 and D.sup.3 are independently N or CR.sup.19; D.sup.4 and D.sup.5 are independently N or CR.sup.19 and D.sup.6 is O, S, or NR.sup.20, wherein at least one of D.sup.4 and D.sup.5 is not CR.sup.19; D.sup.7, D.sup.8, D.sup.9 and D.sup.10 are independently N or CR.sup.19, wherein at least one of D.sup.7, D.sup.8, D.sup.9 and D.sup.10 is N; R.sup.1 is H or alkyl; each R.sup.2 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.15C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.qheterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; each R.sup.3 is independently Q, Z, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy, trifluoromethyl, difluoromethyl, fluoromethyl, OR.sup.15, NR.sup.15R.sup.16, NR.sup.15OR.sup.16, NR.sup.15C(.dbd.O)OR.sup.18, NR.sup.15C(.dbd.O)R.sup.16, SO.sub.2NR.sup.15R.sup.16, SR.sup.15, SOR.sup.15, SO.sub.2R.sup.15, C(.dbd.O)R.sup.15, C(.dbd.O)OR.sup.15, OC(.dbd.O)R.sup.15, C(.dbd.O)NR.sup.15R.sup.16, NR.sup.15C(O)NR.sup.16R.sup.17, NR.sup.15C(.dbd.NCN)NR.sup.16R.sup.17, or NR.sup.15C(.dbd.NCN)R.sup.16, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl are optionally substituted with one or more groups independently selected from halogen, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy, trifluoromethyl, difluoromethyl, fluoromethyl, OR.sup.15, NR.sup.15R.sup.16, NR.sup.15OR.sup.16, NR.sup.15C(.dbd.O)OR.sup.18, NR.sup.15C(.dbd.O)R.sup.16, SO.sub.2NR.sup.15R.sup.16, SR.sup.15, SOR.sup.15, SO.sub.2R.sup.15, C(.dbd.O)R.sup.15, C(.dbd.O)OR.sup.15, OC(.dbd.O)R.sup.15, C(.dbd.O)NR.sup.15R.sup.16, NR.sup.15C(.dbd.O)NR.sup.16R.sup.17, NR.sup.15C(.dbd.NCN)NR.sup.16R.sup.17, NR.sup.15C(.dbd.NCN)R.sup.16, (C.sub.1-C.sub.4 alkyl)NR.sup.aR.sup.b and NR.sup.15C(O)CH.sub.2OR.sup.a; or R.sup.3 is a 5-6 membered heterocyclic ring containing from 1 to 4 heteroatoms selected from N, O, S, SO and SO.sub.2 and substituted with -M.sup.1-M.sup.2-M.sup.3-M.sup.4 or -M.sup.1-M.sup.5, wherein M.sup.1 is C.sub.1-C.sub.4 alkyl, wherein optionally a CH.sub.2 is replaced by a C(.dbd.O) group; M.sup.2 is NR.sup.e or CR.sup.eR.sup.f; M.sup.3 is C.sub.1-C.sub.4 alkyl; M.sup.4 is CN, NR.sup.eS(O).sub.0-2R.sup.f, S(O).sub.0-2NR.sup.gR.sup.h, COR.sup.gR.sup.h, S(O).sub.0-2R.sup.f, or CO.sub.2R.sup.f, and M.sup.5 is NR.sup.gR.sup.h, wherein R.sup.e, R.sup.f, R.sup.g and R.sup.h are independently H or C.sub.1-C.sub.4 alkyl, or R.sup.g and R.sup.h together with the nitrogen atom to which they are attached form a 5- or 6-membered ring optionally containing 1 or 2 additional heteroatoms selected from N, O, S, SO and SO.sub.2 in which any ring nitrogen atom present is optionally substituted with a C.sub.1-C.sub.4 alkyl group and which ring may optionally have one or two oxo or thiooxo substituents; Q is ##STR00355## Z is selected from ##STR00356## and tautomers thereof; W and V are independently O, NR.sup.6, S, SO, SO.sub.2, CR.sup.7R.sup.8, CR.sup.8R.sup.9 or C.dbd.O; W.sup.2 is O or S; Y is S, SO, SO.sub.2, CR.sup.7CR.sup.8, or CR.sup.8R.sup.9, provided that when W is O, NR.sup.6, S, SO, or SO.sub.2, then V is CR.sup.8R.sup.9, and when V is O, NR.sup.6, S, SO, or SO.sub.2, then W and Y are each CR.sup.8R.sup.9; R.sup.8b is H or C.sub.1-C.sub.6 alkyl; each R.sup.6, R.sup.8, R.sup.8a and R.sup.9 are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, S(.dbd.O)R.sup.15, SO.sub.2R.sup.15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl, or R.sup.8 and R.sup.8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring; R.sup.7 is hydrogen, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclylalkyl, --NR.sup.15SO.sub.2R.sup.16, --SO.sub.2NR.sup.15R.sup.16, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.15C(O)OR.sup.18, --NR.sup.15C(O)R.sup.16, --C(O)NR.sup.15R.sup.16, --NR.sup.15R.sup.16, --NR.sup.15C(O)NR.sup.16R.sup.17, --OR.sup.15, --S(O)R.sup.15, --SO.sub.2R.sup.15, or SR.sup.15, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.15SO.sub.2R.sup.16, SO.sub.2NR.sup.15R.sup.16, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.15C(O)OR.sup.18, --NR.sup.15C(O)R.sup.16, --C(O)NR.sup.15R.sup.16, --NR.sup.15R.sup.16, --NR.sup.15C(O)NR.sup.16R.sup.17, --OR.sup.15, --S(O)R.sup.15, --SO.sub.2R.sup.15, SR.sup.15, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl; R.sup.10 is hydrogen, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclylalkyl, --NR.sup.15C(O)OR.sup.18, --NR.sup.15C(O)R.sup.16, --NR.sup.15R.sup.16, or --OR.sup.15, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.15SO.sub.2R.sup.16, --SO.sub.2NR.sup.15R.sup.16, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.15C(O)OR.sup.18, --NR.sup.15C(O)R.sup.16, --C(O)NR.sup.15R.sup.16, --NR.sup.15R.sup.16, --NR.sup.15C(O)NR.sup.16R.sup.17, --OR.sup.15, --S(O)R.sup.15, --SO.sub.2R.sup.15, SR.sup.15, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl; or R.sup.6 and R.sup.8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; or R.sup.7 and R.sup.8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated cycloalkyl or heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; or R.sup.8 and R.sup.9 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated cycloalkyl or heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; or R.sup.6 and R.sup.10 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; or R.sup.8 and R.sup.10 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; each R.sup.12 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sup.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.13C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; R.sup.13 and R.sup.14 are independently hydrogen or alkyl, or R.sup.13 and R.sup.14 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl, or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl portions are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; R.sup.15, R.sup.16 and R.sup.17 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, NR.sup.aC(.dbd.O)NR.sup.bR.sup.c, OC(.dbd.O)NR.sup.aR.sup.b, and C(.dbd.O)CH.sub.2OR.sup.a; or any two of R.sup.15, R.sup.16 and R.sup.17 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.a, NR.sup.aR.sup.b, SR.sup.a, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl, or R.sup.13 and R.sup.15 together with the atom to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; R.sup.18 is CF.sub.3, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c, or R.sup.15 and R.sup.18 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; each R.sup.19 is independently H, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.13C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14 alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; each R.sup.20 is independently C.sub.1-C.sub.4 alkyl, saturated or partially unsaturated cycloalkyl, trifluoromethyl, difluoromethyl, or fluoromethyl; R.sup.a, R.sup.b and R.sup.c are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl, or NR.sup.aR.sup.b forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C.sub.1-C.sub.3 alkyl), or NR.sup.bR.sup.c forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms; j is 0, 1, 2 or 3; m is 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; q is 0, 1, 2, 3, 4, or 5; and p is 0, 1 or 2; wherein when said compound of Formula I is represented by the formula ##STR00357## and R.sup.3 is other than Q or Z, then E is not a benzofuranyl, indolyl, quinazolinyl, quinolinyl, or isoquinolinyl ring. 2. The compound of claim 1, wherein: each R.sup.3 is independently Q, Z, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy, trifluoromethyl, difluoromethyl, fluoromethyl, OR.sup.15, NR.sup.15R.sup.16, NR.sup.15OR.sup.16, NR.sup.15C(.dbd.O)OR.sup.18, NR.sup.15C(.dbd.O)R.sup.16, SO.sub.2NR.sup.15R.sup.16, SR.sup.15, SOR.sup.15, SO.sub.2R.sup.15, C(.dbd.O)R.sup.15, C(.dbd.O)OR.sup.15, OC(.dbd.O)R.sup.15, C(.dbd.O)NR.sup.15R.sup.16, NR.sup.15C(.dbd.O)NR.sup.16R.sup.17, NR.sup.15C(.dbd.NCN)NR.sup.16R.sup.17, or NR.sup.15C(.dbd.NCN)R.sup.16, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl are optionally substituted with one or more groups independently selected from halogen, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy, trifluoromethyl, difluoromethyl, fluoromethyl, OR.sup.15, NR.sup.15R.sup.16, NR.sup.15OR.sup.16, NR.sup.15C(.dbd.O)OR.sup.18, NR.sup.15C(.dbd.O)R.sup.16, SO.sub.2NR.sup.15R.sup.16, SR.sup.15, SOR.sup.15, SO.sub.2R.sup.15, C(.dbd.O)R.sup.15, C(.dbd.O)OR.sup.15, OC(.dbd.O)R.sup.15, C(.dbd.O)NR.sup.15R.sup.16, NR.sup.15C(.dbd.O)NR.sup.16R.sup.17, NR.sup.15C(.dbd.NCN)NR.sup.16R.sup.17, and NR.sup.15C(.dbd.NCN)R.sup.16; Z is selected from ##STR00358## each R.sup.6, R.sup.8, R.sup.8a and R.sup.9 are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15S(.dbd.O)R.sup.15, SO.sub.2R.sup.15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; R.sup.15, R.sup.16 and R.sup.17 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; and R.sup.a, R.sup.b and R.sup.c are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl. 3. A compound of claim 1, wherein G is N and A is O or S. 4. A compound according to claim 1 having the formula ##STR00359## 5. A compound according to claim 1, wherein E is selected from ##STR00360## 6. The compound of claim 5, wherein E is selected from the structures: ##STR00361## wherein k is 0, 1, 2, or 3. 7. The compound of claim 6, wherein E is selected from the structures: ##STR00362## 8. A compound according to claim 1, wherein E is selected from ##STR00363## 9. The compound of claim 8, wherein E is selected from the structures: ##STR00364## wherein each R.sup.12 group and each R.sup.19 group is independent of the other. 10. The compound of claim 9, wherein E is selected from: ##STR00365## 11. A compound according to claim 1, wherein m is 1 and R.sup.3 is Z. 12. The compound of claim 11, wherein Z is selected from ##STR00366## in which W is O or S; W.sup.2 is O or S; and V is CR.sup.8R.sup.9. 13. The compound of claim 12, wherein: Z is selected from the structures: ##STR00367## R.sup.6 is H or C.sub.1-C.sub.6 alkyl; and R.sup.8 and R.sup.8a are independently H or C.sub.1-C.sub.6 alkyl optionally substituted with OR.sup.a in which R.sup.a is H or C.sub.1-C.sub.6 alkyl, or R.sup.8 and R.sup.8a together with the atom to which they are attached form a C.sub.3-C.sub.6 cycloalkyl ring. 14. The compound of claim 13, wherein m is 1 and R.sup.3 is selected from the structures: ##STR00368## 15. A compound according to claim 1, wherein m is 1 and R.sup.3 is OR.sup.15. 16. The compound of claim 15, wherein R.sup.15 is (i) H; (ii) C.sub.3-C.sub.6 cycloalkyl optionally substituted with OR.sup.a; (iii) cycloalkylalkyl; (iv) C.sub.1-C.sub.6 alkyl optionally substituted with one or two groups independently selected from --OR.sup.a, --OC(O)R.sup.a, --CO.sub.2R.sup.a, --SO.sub.2R.sup.a, --SR.sup.a, --C(O)NR.sup.aR.sup.b, --NR.sup.aR.sup.b, --NR.sup.aC(O)R.sup.b, --OC(O)NR.sup.aR.sup.b, and NR.sup.aC(O)NR.sup.bR.sup.c; (v) a 5-6 membered heterocyclic ring having a ring heteroatom selected from N and O and optionally substituted with --C(O)R.sup.a, C.sub.1-C.sub.6 alkyl, --C(O)NR.sup.aR.sup.b, --SO.sub.2R.sup.a, or C(O)CH.sub.2OR.sup.a; (vi) heterocyclylalkyl, wherein said heterocyclic portion is a 5-6 membered ring having 1 or 2 ring heteroatoms independently selected from N and O and is optionally substituted with C.sub.1-C.sub.6 alkyl, halogen, OR.sup.a or oxo; (vii) a 5-6 membered heteroaryl ring having from 1 to three ring nitrogen atoms and optionally substituted with C.sub.1-C.sub.6 alkyl or halogen; or (viii) heteroarylalkyl, wherein said heteroaryl portion is a 5-6 membered ring having 1-2 ring nitrogen atoms and is optionally substituted with C.sub.1-C.sub.6 alkyl. 17. The compound of claim 16, wherein R.sup.3 is: (i) OH; (ii) cyclopentanoxy, 2-hydroxycyclopentoxy, or cyclohexanoxy; (iii) 1-cyclopropylmethoxy; (iv) CH.sub.3O--, CH.sub.3CH.sub.2O--, CH.sub.3O(CH.sub.2).sub.2O--, CH.sub.3CH.sub.2O(CH.sub.2).sub.2O--, HO(CH.sub.2).sub.2O--, HOCH.sub.2CH(OH)CH.sub.2O--, CH.sub.3CH(OH)CH.sub.2O--, HOC(CH.sub.3).sub.2CH.sub.2O--, (PhCH.sub.2O)CH.sub.2CH.sub.2O--, (PhCH.sub.2)OCH.sub.2CH(OH)CH.sub.2O--, --O--(CH.sub.2).sub.2OC(O)CH.sub.3, --O--(CH.sub.2)CO.sub.2CH.sub.3, --O(CH.sub.2).sub.3SO.sub.2CH.sub.3, --O(CH.sub.2).sub.3SCH.sub.3, --OCH.sub.2C(O)N(CH.sub.3).sub.2, --OCH.sub.2C(O)NH(CH.sub.3), --OCH.sub.2C(O)NH.sub.2, ##STR00369## --O(CH.sub.2).sub.3N(CH.sub.3).sub.2, --O(CH.sub.2).sub.2N(CH.sub.3).sub.2, --O(CH.sub.2).sub.2NHC(O)CH.sub.3, --O(CH.sub.2).sub.2NHC(O)CH.sub.2CH.sub.3, --O(CH.sub.2).sub.2OC(O)N(CH.sub.3).sub.2, ##STR00370## ##STR00371## (vii) 2-methylpyridin-4-yloxy, 2-chloropyridin-4-yloxy, or 2-methylpyridin-4-yloxy; or ##STR00372## 18. A compound according to claim 17, wherein m is 1 and R.sup.3 is: (i) a 5 membered heterocyclic ring having a ring nitrogen atom and optionally having a second ring heteroatom selected from N and O, wherein said heterocyclic ring is optionally substituted with one or two groups independently selected from C.sub.1-C.sub.6 alkyl, oxo and (CH.sub.2).sub.1-2NR.sup.aR.sup.b; (ii) a 5-6 membered heteroaryl ring having 1-3 nitrogen atoms, wherein said heteroaryl is linked to the B ring by a ring nitrogen atom; (iii) --NR.sup.15C(O)R.sup.16 wherein R.sup.15is H or methyl and R.sup.16 is selected from: (a) C.sub.2-C.sub.6 alkenyl optionally substituted with NR.sup.aR.sup.b; (b) a 5-6 membered heterocyclic ring optionally substituted with C.sub.1-C.sub.6 alkyl; and (c) C.sub.1-C.sub.6 alkyl optionally substituted with one or more groups independently selected from C.sub.1-C.sub.6 alkyl or OR.sup.a; (iv) --C(.dbd.O)NR.sup.15R.sup.16 wherein R.sup.15 and R.sup.16 independently are H or C.sub.1-C.sub.6 alkyl, or R.sup.15 and R.sup.16 together with the atom to which they are attached form a 6 membered heterocyclic ring optionally having a second heteroatom selected from N and O and optionally substituted with C.sub.1-C.sub.6 alkyl; (v) SO.sub.2R.sup.15 wherein R.sup.15 is C.sub.1-C.sub.6 alkyl or a phenyl group optionally substituted with C.sub.1-C.sub.6 alkyl; (vi) SOR.sup.15 wherein R.sup.15 is C.sub.1-C.sub.6 alkyl; (vii) SR.sup.15 wherein R.sup.15 is C.sub.1-C.sub.6 alkyl; (viii) halogen; (ix) R.sup.3 is --CO.sub.2R.sup.15, wherein R.sup.15 is a 6 membered heterocyclic ring having one or two ring nitrogen atoms and optionally substituted with C.sub.1-C.sub.6 alkyl; (x) C.sub.1-C.sub.6 alkyl optionally substituted with OR.sup.15 wherein R.sup.15 is H or C.sub.1-C.sub.6 alkyl; (xi) C.sub.3-C.sub.6 alkynyl optionally substituted with OR.sup.15, NR.sup.15C(O)CH.sub.2OR.sup.a or a 6 membered heterocyclic ring having one or two ring heteroatoms independently selected from N, O, and SO.sub.2, wherein R.sup.15 and R.sup.17 are independently H or C.sub.1-C.sub.6 alkyl, and R.sup.a is C.sub.1-C.sub.6 alkyl; (xii) --NR.sup.15C(O)NR.sup.16R.sup.17, wherein R.sup.15, R.sup.16 and R.sup.17 are independently H or C.sub.1-C.sub.6 alkyl, or R.sup.16 and R.sup.17 together with the nitrogen atom to which they are attached form a 5-6 membered heterocyclic ring optionally having a second heteroatom selected from N and O and which is optionally substituted with C.sub.1-C.sub.6 alkyl; or (xiii) heterocyclylalkyl wherein said heterocyclyl portion is a 6 membered ring having a ring nitrogen atom and optionally having a second ring heteroatom selected from N and SO.sub.2. 19. The compound of claim 18, wherein R.sup.3 is: ##STR00373## (ii) 1H-pyrazol-1-yl; (iii) (CH.sub.2.dbd.CH)--C(O)NH--, (CH.sub.3).sub.2NCH.sub.2(CH.dbd.CH)C(O)NH--, ##STR00374## CH.sub.3C(O)NH--, (CH.sub.3).sub.2C(O)NH--, CH.sub.3CH.sub.2C(O)N(CH.sub.3)--, CH.sub.3OCH.sub.2C(O)NH--, CH.sub.3OCH.sub.2C(O)N(CH.sub.3)--, CH.sub.3CH(OCH.sub.3)C(O)NH--, CH.sub.3OCH.sub.2CH.sub.2C(O)NH--, CH.sub.3OCH(CH.sub.3)C(O)NH--, CH.sub.3OCH.sub.2CH(CH.sub.3)C(O)NH--; (iv) (CH.sub.3).sub.2NC(O)--, (4-morpholinyl)C(O)--, or (1-methylpiperazin-4-yl)C(O)--; (v) 4-methylbenzenesulfonate, ethanesulfonate; (vi) ethysulfinyl; (vii) EtS--; (viii) Br; (ix) (1-methylpiperazin-4-yl)CO.sub.2--; (x) HO(CH.sub.2).sub.3-- or CH.sub.3O(CH.sub.2).sub.3--; ##STR00375## ##STR00376## or ##STR00377## 20. A compound according to claim 1 wherein: E is selected from ##STR00378## R.sup.12 is halogen; j is 0 or 1; R.sup.19 is H, C.sub.1-C.sub.6 alkyl, or halogen; and R.sup.20 is H; provided that R.sup.3 of Formula I is not NR.sup.15C(.dbd.O)(CH.dbd.CH)R.sup.16a wherein R.sup.16a is H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, NR.sup.aC(.dbd.O)NR.sup.bR.sup.c, OC(.dbd.O)NR.sup.aR.sup.b, and C(.dbd.O)CH.sub.2OR.sup.a. 21. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. 22. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable diluent or carrier. 23. A method of preparing a compound of Formula I according to claim 1, comprising: (a) reacting a compound of formula (F1) ##STR00379## with a compound of formula (F2) ##STR00380## in which Z represents a leaving atom or group; or (b) for a compound of Formula I in which G is N, reacting a compound of formula (F3) ##STR00381## in which R represents a tertiary amino group, for example di(1-6C)alkylamino, such as dimethylamino, with a compound of formula (F1); followed if necessary, by converting the compound of Formula I into another compound of Formula I having a different R.sup.3 group. 24. A compound of Formula I as defined in claim 1 and selected from the structures: ##STR00382## ##STR00383## ##STR00384## ##STR00385## ##STR00386## ##STR00387## ##STR00388## ##STR00389## ##STR00390## ##STR00391## ##STR00392## ##STR00393## ##STR00394## ##STR00395## ##STR00396## ##STR00397## ##STR00398## ##STR00399## ##STR00400## ##STR00401## ##STR00402## ##STR00403## ##STR00404## ##STR00405## ##STR00406## ##STR00407## ##STR00408## ##STR00409## ##STR00410## ##STR00411## ##STR00412## ##STR00413## ##STR00414## ##STR00415## ##STR00416## ##STR00417## ##STR00418## ##STR00419## ##STR00420## ##STR00421## ##STR00422## ##STR00423## ##STR00424## ##STR00425## ##STR00426## ##STR00427## ##STR00428## or a pharmaceutically acceptable salt thereof. 25. A compound according to claim 24, having the structure: ##STR00429## 26. A compound according to claim 24, having the structure: ##STR00430## 27. A compound according to claim 24, having the structure: ##STR00431## 28. A compound according to claim 24, having the structure: ##STR00432## 29. A compound according to claim 24, having the structure: ##STR00433## 30. A compound according to claim 24, having the structure: ##STR00434## 31. A compound of Formula 8: ##STR00435## wherein each R.sup.6, R.sup.8, and R.sup.8a are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, S(.dbd.O)R.sup.15, SO.sub.2R.sup.15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl, or R.sup.8 and R.sup.8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring; or R.sup.6 and R.sup.8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; R.sup.15 and R.sup.16 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, NR.sup.aC(.dbd.O)NR.sup.bR.sup.c, OC(.dbd.O)NR.sup.aR.sup.b, and C(.dbd.O)CH.sub.2OR.sup.a; or R.sup.15 and R.sup.16 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.a, NR.sup.aR.sup.b, SR.sup.a, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; and R.sup.a, R.sup.b and R.sup.c are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl, or NR.sup.aR.sup.b forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C.sub.1-C.sub.3 alkyl), or NR.sup.bR.sup.c forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms. 32. A compound of Formula 9: ##STR00436## wherein A is O, C(.dbd.O), S, SO or SO.sub.2; E is: ##STR00437## X is N or CH; D.sup.1, D.sup.2 and D.sup.3 are independently N or CR.sup.19; D.sup.4 and D.sup.5 are independently N or CR.sup.19 and D.sup.6 is O, S, or NR.sup.20, wherein at least one of D.sup.4 and D.sup.5 is not CR.sup.19; D.sup.7, D.sup.8, D.sup.9 and D.sup.10 are independently N or CR.sup.19, wherein at least one of D.sup.7, D.sup.8, D.sup.9 and D.sup.10 is N; R.sup.1 is H or alkyl; each R.sup.2 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.15C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; each R.sup.6, R.sup.8, and R.sup.8a are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, S(.dbd.O)R.sup.15, SO.sub.2R.sup.15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl, or R.sup.8 and R.sup.8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring; or R.sup.6 and R.sup.8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.15, Nee, SR.sup.15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; each R.sup.12 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.13C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; R.sup.13 and R.sup.14 are independently hydrogen or alkyl, or R.sup.13 and R.sup.14 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl, or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl portions are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; R.sup.15 and R.sup.16 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, NR.sup.aC(.dbd.O)NR.sup.bR.sup.c, OC(.dbd.O)NR.sup.aR.sup.b, and C(.dbd.O)CH.sub.2OR.sup.a; or R.sup.15 and R.sup.16 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.a, NR.sup.aR.sup.b, SR.sup.a, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl, or R.sup.13 and R.sup.15 together with the atom to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; R.sup.18 is CF.sub.3, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c, or R.sup.15 and R.sup.18 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; each R.sup.19 is independently H, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.13C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; each R.sup.2.degree. is independently C.sub.1-C.sub.4 alkyl, saturated or partially unsaturated cycloalkyl, trifluoromethyl, difluoromethyl, or fluoromethyl; R.sup.a, R.sup.b and R.sup.c are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl, or NR.sup.aR.sup.b forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C.sub.1-C.sub.3 alkyl), or NR.sup.bR.sup.c forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms; j is 0, 1, 2 or 3; n is 0, 1, 2, 3, or 4; q is 0, 1, 2, 3, 4, or 5; and p is 0, 1 or 2. 33. A process for preparing a compound of Formula 9: ##STR00438## comprising condensing a compound of Formula 8: ##STR00439## with a compound of Formula 2: ##STR00440## in the presence of an acid in a suitable solvent to provide a compound of Formula 9; wherein A is O, C(.dbd.O), S, SO or SO.sub.2; E is: ##STR00441## X is N or CH; D.sup.1, D.sup.2 and D.sup.3 are independently N or CR.sup.19; D.sup.4 and D.sup.5 are independently N or CR.sup.19 and D.sup.6 is O, S, or NR.sup.20, wherein at least one of D.sup.4 and D.sup.5 is not CR.sup.19; D.sup.7, D.sup.8, D.sup.9 and D.sup.10 are independently N or CR.sup.19, wherein at least one of D.sup.7, D.sup.8, D.sup.9 and D.sup.10 is N; R.sup.1 is H or alkyl; each R.sup.2 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.15C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; each R.sup.6, R.sup.8, and R.sup.8a are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, S(.dbd.O)R.sup.15, SO.sub.2R.sup.15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl, or R.sup.8 and R.sup.8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring; or R.sup.6 and R.sup.8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; each R.sup.12 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.13C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; R.sup.13 and R.sup.14 are independently hydrogen or alkyl, or R.sup.13 and R.sup.14 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl, or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl portions are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; R.sup.15 and R.sup.16 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, NR.sup.aC(.dbd.O)NR.sup.bR.sup.c, OC(.dbd.O)NR.sup.aR.sup.b, and C(.dbd.O)CH.sub.2OR.sup.a; or R.sup.15 and R.sup.16 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.a, NR.sup.aR.sup.b, SR.sup.a, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl, or R.sup.13 and R.sup.15 together with the atom to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; R.sup.18 is CF.sub.3, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c, or R.sup.15 and R.sup.18 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; each R.sup.19 is independently H, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.13C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O).sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; each R.sup.20is independently C.sub.1-C.sub.4 alkyl, saturated or partially unsaturated cycloalkyl, trifluoromethyl, difluoromethyl, or fluoromethyl; R.sup.a, R.sup.b and R.sup.c are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl, or NR.sup.aR.sup.b forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C.sub.1-C.sub.3 alkyl), or NR.sup.bR.sup.c forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms; j is 0, 1, 2 or 3; n is 0, 1, 2, 3, or 4; q is 0, 1, 2, 3, 4, or 5; and p is 0, 1 or 2. 34. The process of claim 33, wherein the acid is HOAc and the solvent is isopropyl acetate. 35. A process for preparing a compound of Formula 10: ##STR00442## comprising: (a) condensing a compound of Formula 8: ##STR00443## with a compound of Formula 2: ##STR00444## in the presence of an acid in a suitable solvent to provide a compound of Formula 9: ##STR00445## and (b) cyclizing the thiourea of Formula 9 to provide a compound of Formula 10; wherein A is O, C(.dbd.O), S, SO or SO.sub.2; E is: ##STR00446## X is N or CH; D.sup.1, D.sup.2 and D.sup.3 are independently N or CR.sup.19; D.sup.4 and D.sup.5 are independently N or CR.sup.19 and D.sup.6 is O, S, or NR.sup.20, wherein at least one of D.sup.4 and D.sup.5 is not CR.sup.19; D.sup.7, D.sup.8, D.sup.9 and D.sup.10 are independently N or CR.sup.19, wherein at least one of D.sup.7, D.sup.8, D.sup.9 and D.sup.10 is N; R.sup.1 is H or alkyl; each R.sup.2 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.15C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; each R.sup.6, R.sup.8, and R.sup.8a are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, S(.dbd.O)R.sup.15, SO.sub.2R.sup.15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl, or R.sup.8 and R.sup.8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring; or R.sup.6 and R.sup.8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.15, NR.sup.15R.sup.16, SR.sup.15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl; each R.sup.12 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.13C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; R.sup.13 and R.sup.14 are independently hydrogen or alkyl, or R.sup.13 and R.sup.14 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl, or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl portions are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; R.sup.15 and R.sup.16 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, NR.sup.aC(.dbd.O)NR.sup.bR.sup.c, OC(.dbd.O)NR.sup.aR.sup.b, and C(.dbd.O)CH.sub.2OR.sup.a; or R.sup.15 and R.sup.16 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO.sub.2 and NR.sup.6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR.sup.a, NR.sup.aR.sup.b, SR.sup.a, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl, or R.sup.13 and R.sup.15 together with the atom to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; R.sup.18 is CF.sub.3, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c, or R.sup.15 and R.sup.18 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, OR.sup.a, NR.sup.aR.sup.b, NR.sup.aOR.sup.b, NR.sup.aCO.sub.2R.sup.b, NR.sup.aCOR.sup.b, SO.sub.2NR.sup.aR.sup.b, SR.sup.a, SOR.sup.a, SO.sub.2R.sup.a, S--S--R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, OC(.dbd.O)R.sup.a, C(.dbd.O)NR.sup.aR.sup.b, NR.sup.aC(.dbd.O)R.sup.b, and NR.sup.aC(.dbd.O)NR.sup.bR.sup.c; each R.sup.19 is independently H, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, --SR.sup.18, --OR.sup.15, --C(O)R.sup.15, --C(O)OR.sup.15, --NR.sup.14C(O)OR.sup.18, --OC(O)R.sup.15, --NR.sup.14SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.14, --NR.sup.14C(O)R.sup.15, --C(O)NR.sup.15R.sup.14, --NR.sup.13C(O)NR.sup.15R.sup.14, --NR.sup.13C(NCN)NR.sup.15R.sup.14, --NR.sup.15R.sup.14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, --S(O).sub.p(alkyl), --S(O).sub.p(CR.sup.13R.sup.14).sub.q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, --O(CR.sup.13R.sup.14).sub.q-aryl, --NR.sup.15(CR.sup.13R.sup.14).sub.q-aryl, --O(CR.sup.13R.sup.14).sub.q-heteroaryl, --NR.sup.13(CR.sup.13R.sup.14).sub.q-heteroaryl, --O(CR.sup.13R.sup.14).sub.q-heterocyclyl or --NR.sup.15(CR.sup.13R.sup.14).sub.q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, --NR.sup.13SO.sub.2R.sup.18, --SO.sub.2NR.sup.15R.sup.13, --C(O)R.sup.15, --C(O)OR.sup.15, --OC(O)R.sup.15, --NR.sup.13C(O)OR.sup.18, --NR.sup.13C(O)R.sup.15, --C(O)NR.sup.15R.sup.13, --NR.sup.15R.sup.13, --NR.sup.14C(O)NR.sup.15R.sup.13, --NR.sup.14C(NCN)NR.sup.15R.sup.13, --OR.sup.15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR.sup.15R.sup.13 and OR.sup.15; each R.sup.20 is independently C.sub.1-C.sub.4 alkyl, saturated or partially unsaturated cycloalkyl, trifluoromethyl, difluoromethyl, or fluoromethyl; R.sup.a, R.sup.b and R.sup.c are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl, or NR.sup.aR.sup.b forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C.sub.1-C.sub.3 alkyl), or NR.sup.bR.sup.c forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms; j is 0, 1, 2 or 3; n is 0, 1, 2, 3, or 4; q is 0, 1, 2, 3, 4, or 5; and p is 0, 1 or 2. 36. The process of claim 35, wherein the acid is HOAc and the solvent is isopropyl acetate. 37. The process of claim 35, wherein the thiourea is cyclized by treating the compound of Formula 9 with TsCl and aqueous NaOH in THF.