Details for Patent: 9,090,561

Title:	Acetylenic heteroaryl compounds
Abstract:	This invention relates to compounds of the general formula: ##STR00001## in which the variable groups are as defined herein, and to their preparation and use.
Inventor(s):	Wang; Yihan (Newton, MA), Zhu; Xiaotian (Newton, MA), Sundaramoorthi; Rajeswari (Watertown, MA), Huang; Wei-Sheng (Acton, MA), Zou; Dong (Concord, MA), Thomas; R. Mathew (Sharon, MA), Qi; Jiwei (West Roxbury, MA), Romero; Jan Antoinette C. (Somerville, MA), Dalgarno; David C. (Brookline, MA), Shakespeare; William C. (Southborough, MA), Sawyer; Tomi K. (Southborough, MA), Metcalf, III; Chester A. (Needham, MA)
Assignee:	ARIAD Pharmaceuticals, Inc. (Cambridge, MA)
Filing Date:	Sep 13, 2012
Application Number:	13/614,838
Claims:	1. A compound of Formula I, a tautomer thereof, or a pharmaceutically acceptable salt thereof: ##STR00105## wherein: Ring T represents a substituted or unsubstituted 6-membered heteroaryl ring, where the heteroaryl comprises 1 N; Ring A represents a 5- or 6-membered aryl or heteroaryl ring, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; Ring B represents a 5- or 6-membered aryl or heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; L.sup.1 is C(O)NR.sup.1; at each occurrence, R.sup.a and R.sup.b are independently selected from the group consisting of halo, --CN, --NO.sub.2, --R.sup.4, --OR.sup.2, --NR.sup.2R.sup.3, --C(O)YR.sup.2, --OC(O)YR.sup.2, --NR.sup.2C(O)YR.sup.2, --SC(O)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)YR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NR.sup.2SO.sub.2R.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3 and --NR.sup.2SO.sub.2NR.sup.2R.sup.3, wherein Y is independently a bond, --O--, --S-- or --NR.sup.3--; R.sup.1, R.sup.2 and R.sup.3 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S, and C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; wherein the NR.sup.2R.sup.3 moiety is optionally a 5- or 6-membered saturated, partially saturated or unsaturated ring, which is optionally substituted and which contains 0-2 additional heteroatoms selected from N, O and S(O).sub.r; each occurrence of R.sup.4 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S, and C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; (a) X.sup.1 is CH or CR.sup.t1 wherein R.sup.t1 is halo, OR.sup.5, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, carbon linked C.sub.5-14heteroaryl where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, or carbon linked C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S; wherein R.sup.5 is H, alkyl, alkenyl, or alkynyl; and X.sup.2 is CR.sup.t2 and X.sup.3 is CR.sup.t3 wherein R.sup.t2 and R.sup.t3 are independently selected from H or R.sup.a, with the proviso that when X.sup.1 is CH and R.sup.t3 is H, R.sup.t2 is not --C(O)OCH.sub.3, --C(O)OH or H; and where if X.sup.1 is CH, then at least one of R.sup.t2 and R.sup.t3 is R.sup.a; alternatively, R.sup.t2 and R.sup.t3 can form together with the atoms to which they are attached, a saturated, partially saturated or unsaturated 5- or 6-membered ring, comprising carbon atoms and 0-3 heteroatoms selected from O, N, S(O).sub.r and C(O) and the said ring is optionally substituted; with the proviso that when X.sup.1 is CH, R.sup.t2 and R.sup.t3 do not form an unsubstituted phenyl; or, (c) X.sup.1 is CR.sup.t, X.sup.2 is CR.sup.t2 and X.sup.3 is CR.sup.t3, wherein R.sup.t is selected from --CN, --NO.sub.2, --OR.sup.6, --NR.sup.2R.sup.3, --C(O)YR.sup.2, --OC(O)YR.sup.2, --NR.sup.2C(O)YR.sup.2, --SC(O)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)YR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NR.sup.2SO.sub.2R.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3 and --NR.sup.2SO.sub.2NR.sup.2R.sup.3, wherein R.sup.6 is cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, or C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S, and; (c)-1: at least one of R.sup.t, R.sup.t2, R.sup.t3, R.sup.a and R.sup.b is or contains a YP(.dbd.O)(YR.sup.4)(YR.sup.4), a Si(R.sup.4).sub.3 or --YC(.dbd.NR.sup.3)YR.sup.2 substituent; or (c)-2: at least one of R.sup.a and R.sup.t is or contains a --NR.sup.2C(.dbd.S)OR.sup.2, --OC(.dbd.S)YR.sup.2, or --C(.dbd.S)OR.sup.2 substituent; or (c)-3: at least one of R.sup.b, R.sup.t2 and R.sup.t3 is or contains a --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, or --C(.dbd.S)YR.sup.2 substituent; or (c)-4: R.sup.t2 and R.sup.t3 form together with the atoms to which they are attached, a saturated, partially saturated or unsaturated 5- or 6-membered ring, comprising carbon atoms and 0-3 heteroatoms selected from O, N, S(O).sub.r and C(O), wherein the ring is optionally substituted; and, alternatively R.sup.t and R.sup.t2 can form together with the atoms to which they are attached, a saturated, partially saturated or unsaturated 5- or 6-membered ring, comprising carbon atoms and 0-3 heteroatoms selected from O, N, S(O).sub.r and C(O), the ring being optionally substituted; each of the foregoing alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, or C.sub.5-14heterocyclyl, where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S, moieties are optionally substituted; each optional substituent on an unsaturated carbon atom of a C.sub.6-14aryl or C.sub.5-14heteroaryl group, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, is a halo, alkyl, alkenyl, alkynyl, --CN, --R.sup.4, --OR.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3, NR.sup.2R.sup.3, --(CO)YR.sup.2, --O(CO)YR.sup.2, --NR.sup.2(CO)YR.sup.2, --S(CO)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)Y'R.sup.2, --COCOR.sup.2, --COMCOR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NO.sub.2, --NR.sup.2SO.sub.2R.sup.2 or --NR.sup.2SO.sub.2NR.sup.2R.sup.3 moiety; each M is a 1-6 carbon alkyl group; each optional substituent on an alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl or non-aromatic C.sub.5-14heterocyclic moiety, where the heterocyclic comprises 1-4 heteroatoms selected from N, O, and S, is independently a halo, alkyl, alkenyl, alkynyl, --CN, --R.sup.4, --OR.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3, --NR.sup.2R.sup.3, --(CO)YR.sup.2, --O(CO)YR.sup.2, --NR.sup.2(CO)YR.sup.2, --S(CO)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)Y'R.sup.2, --COCOR.sup.2, --COMCOR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NO.sub.2, --NR.sup.2SO.sub.2R.sup.2 or --NR.sup.2SO.sub.2NR.sup.2R.sup.3 moiety; each optional substituent on a nitrogen is R.sup.4, --NR.sup.2R.sup.3, --C(.dbd.O)R.sup.2, --C(.dbd.O)OR.sup.2, --C(.dbd.O)SR.sup.2, --C(.dbd.O)NR.sup.2R.sup.3, --C(.dbd.NR.sup.2)NR.sup.2R.sup.3, --C(.dbd.NR.sup.2)OR.sup.2, --C(.dbd.NR.sup.2)R.sup.3, --COCOR.sup.2, --COMCOR.sup.2, --CN, --SO2R.sup.3, --S(O)R.sup.3, --P(.dbd.O)(YR.sup.2)(YR.sup.2), --NR.sup.2SO2R.sup.3 or --NR.sup.2SO2NR.sup.2R.sup.3; m is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3, 4 or 5; and r is 0, 1 or 2. 2. The compound of Formula I, a tautomer thereof, or a pharmaceutically acceptable salt thereof: ##STR00106## wherein: Ring T represents a substituted or unsubstituted 6-membered heteroaryl ring, comprising 1 nitrogen; Ring A represents a 5- or 6-membered aryl or heteroaryl ring, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; Ring B represents a 5- or 6-membered aryl or heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; L.sup.1 is C(O)NR.sup.1; at each occurrence, R.sup.a and R.sup.b are independently selected from the group consisting of halo, --CN, --NO.sub.2, --R.sup.4, --OR.sup.2, --NR.sup.2R.sup.3, --C(O)YR.sup.2, --OC(O)YR.sup.2, --NR.sup.2C(O)YR.sup.2, --SC(O)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)YR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NR.sup.2SO.sub.2R.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3 and --NR.sup.2SO.sub.2NR.sup.2R.sup.3, wherein Y is independently a bond, --O--, --S-- or --NR.sup.3--; R.sup.1, R.sup.2 and R.sup.3 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S, and C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; wherein the NR.sup.2R.sup.3 moiety is optionally a 5- or 6-membered saturated, partially saturated or unsaturated ring, which is optionally substituted and which contains 0-2 additional heteroatoms selected from N, O and S(O).sub.r; each occurrence of R.sup.4 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S, and C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; (a) X.sup.1 is CH or CR.sup.t1 wherein R.sup.t1 is halo, OR.sup.5, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, carbon linked C.sub.5-14heteroaryl where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, or carbon linked C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S; wherein R.sup.5 is H, alkyl, alkenyl, or alkynyl; and X.sup.2 is CR.sup.t2 and X.sup.3 is CR.sup.t3 wherein R.sup.t2 and R.sup.t3 are independently selected from H or R.sup.a; where if X.sup.1 is CH, then at least one of R.sup.t2 and R.sup.t3 is R.sup.a; and alternatively R.sup.t2 and R.sup.t3 can form together with the atoms to which they are attached, a saturated, partially saturated or unsaturated 5- or 6-membered ring, comprising carbon atoms and 0-3 heteroatoms selected from O, N, S(O).sub.r and C(O), and the said ring is optionally substituted, with the proviso that when X.sup.1 is CH, R.sup.t2 and R.sup.t3 do not form an unsubstituted phenyl; or, (c) X.sup.1 is CR.sup.t, X.sup.2 is CR.sup.t2 and X.sup.3 is CR.sup.t3, wherein R.sup.t is selected from --CN, --NO.sub.2, --OR.sup.6, --NR.sup.2R.sup.3, --C(O)YR.sup.2, --OC(O)YR.sup.2, --NR.sup.2C(O)YR.sup.2, --SC(O)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)YR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NR.sup.2SO.sub.2R.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3 and --NR.sup.2SO.sub.2NR.sup.2R.sup.3, wherein R.sup.6 is cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, or C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S, and; (c)-1: at least one of R.sup.t, R.sup.t2, R.sup.t3, R.sup.a and R.sup.b is or contains a YP(.dbd.O)(YR.sup.4)(YR.sup.4), a Si(R.sup.4).sub.3 or --YC(.dbd.NR.sup.3)YR.sup.2 substituent; or (c)-2: at least one of R.sup.a and R.sup.t is or contains a --NR.sup.2C(.dbd.S)OR.sup.2, --OC(.dbd.S)YR.sup.2, or --C(.dbd.S)OR.sup.2 substituent; or (c)-3: at least one of R.sup.b, R.sup.t2 and R.sup.t3 is or contains a --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, or --C(.dbd.S)YR.sup.2 substituent; or (c)-4: R.sup.t2 and R.sup.t3 form together with the atoms to which they are attached, a saturated, partially saturated or unsaturated 5- or 6-membered ring, comprising carbon atoms and 0-3 heteroatoms selected from O, N, S(O).sub.r and C(O), wherein the ring is optionally substituted; and, alternatively R.sup.t and R.sup.t2 can form together with the atoms to which they are attached, a saturated, partially saturated or unsaturated 5- or 6-membered ring, comprising carbon atoms and 0-3 heteroatoms selected from O, N, S(O), and C(O), the ring being optionally substituted; each of the foregoing alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, or C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S moieties are optionally substituted; each optional substituent on an unsaturated carbon atom of a C.sub.6-14aryl or C.sub.5-14heteroaryl group, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, is a halo, alkyl, alkenyl, alkynyl, --CN, --R.sup.4, --OR.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3, --NR.sup.2R.sup.3, --(CO)YR.sup.2, --O(CO)YR.sup.2, --NR.sup.2(CO)YR.sup.2, --S(CO)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)Y'R.sup.2, --COCOR.sup.2, --COMCOR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NO.sub.2, --NR.sup.2SO.sub.2R.sup.2 or --NR.sup.2SO.sub.2NR.sup.2R.sup.3 moiety; each M is a 1-6 carbon alkyl group; each optional substituent on an alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl or non-aromatic C.sub.5-14heterocyclic moiety, where the heterocyclic comprises 1-4 heteroatoms selected from N, O, and S, is independently a halo, alkyl, alkenyl, alkynyl, --CN, --R.sup.4, --OR.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3, --NR.sup.2R.sup.3, --(CO)YR.sup.2, --O(CO)YR.sup.2, --NR.sup.2(CO)YR.sup.2, --S(CO)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)Y'R.sup.2, --COCOR.sup.2, --COMCOR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NO.sub.2, --NR.sup.2SO.sub.2R.sup.2 or --NR.sup.2SO.sub.2NR.sup.2R.sup.3 moiety; each optional substituent on a nitrogen is R.sup.4, --NR.sup.2R.sup.3, --C(.dbd.O)R.sup.2, --C(.dbd.O)OR.sup.2, --C(.dbd.O)SR.sup.2, --C(.dbd.O)NR.sup.2R.sup.3, --C(.dbd.NR.sup.2)NR.sup.2R.sup.3, --C(.dbd.NR.sup.2)OR.sup.2, --C(.dbd.NR.sup.2)R.sup.3, --COCOR.sup.2, --COMCOR.sup.2, --CN, --SO2R.sup.3, --S(O)R.sup.3, --P(.dbd.O)(YR.sup.2)(YR.sup.2), --NR.sup.2SO2R.sup.3 or --NR.sup.2SO2NR.sup.2R.sup.3; m is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3, 4 or 5; r is 0, 1 or 2; and with the proviso that the compound is not: ##STR00107## ##STR00108## 3. The compound of claim 1 wherein: X.sup.1 is CH or CR.sup.t1; X.sup.2 is CR.sup.t2; and X.sup.3 is CR.sup.t3. 4. The compound of claim 2 having the formula II: ##STR00109## wherein: X.sup.1 is CR.sup.t, CR.sup.t1 or CH; E is a saturated, partially saturated or unsaturated 5- or 6-membered ring, comprising carbon atoms and 0-3 heteroatoms selected from O, N, S(O).sub.r2 C(O), and C(.dbd.S) and the said ring is optionally substituted with R.sup.e; each occurrence of R.sup.e is independently selected from the group consisting of halo, .dbd.O, .dbd.S, --CN, --NO.sub.2, --R.sup.4, --OR.sup.2, --NR.sup.2R.sup.3, --C(O)YR.sup.2, --OC(O)YR.sup.2, --NR.sup.2C(O)YR.sup.2, --SC(O)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)YR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NR.sup.2SO.sub.2R.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3 and --NR.sup.2SO.sub.2NR.sup.2R.sup.3, wherein Y is independently a bond, --O--, --S-- or --NR.sup.3--; R.sup.2 and R.sup.3 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S, and C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; wherein the NR.sup.2R.sup.3 moiety is optionally a 5- or 6-membered saturated, partially saturated or unsaturated ring, which is optionally substituted and which contains 0-2 additional heteroatoms selected from N, O and S(O).sub.r; each occurrence of R.sup.4 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S, and C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; each of the foregoing alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, or C.sub.5-14heterocyclyl where the heterocyclyl comprises 1-4 heteroatoms selected from N, O, and S moieties are optionally substituted; each optional substituent on an unsaturated carbon atom of a C.sub.6-14aryl or C.sub.5-14heteroaryl group, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, is a halo, alkyl, alkenyl, alkynyl, --CN, --R.sup.4, --OR.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3, --NR.sup.2R.sup.3, --(CO)YR.sup.2, --O(CO)YR.sup.2, --NR.sup.2(CO)YR.sup.2, --S(CO)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)Y'R.sup.2, --COCOR.sup.2, --COMCOR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NO.sub.2, --NR.sup.2SO.sub.2R.sup.2 or --NR.sup.2SO.sub.2NR.sup.2R.sup.3 moiety; each M is a 1-6 carbon alkyl group; each optional substituent on an alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl or non-aromatic C.sub.5-14heterocyclic moiety, where the heterocyclic comprises 1-4 heteroatoms selected from N, O, and S, is independently a halo, alkyl, alkenyl, alkynyl, --CN, --R.sup.4, --OR.sup.2, --S(O).sub.rR.sup.2, SO.sub.2NR.sup.2R.sup.3, --NR.sup.2R.sup.3, --(CO)YR.sup.2, --O(CO)YR.sup.2, --NR.sup.2(CO)YR.sup.2, --S(CO)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)Y'R.sup.2, --COCOR.sup.2, --COMCOR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NO.sub.2, --NR.sup.2SO.sub.2R.sup.2 or --NR.sup.2SO.sub.2NR.sup.2R.sup.3 moiety; each optional substituent on a nitrogen is R.sup.4, --NR.sup.2R.sup.3, --C(.dbd.O)R.sup.2, --C(.dbd.O)OR.sup.2, --C(.dbd.O)SR.sup.2, --C(.dbd.O)NR.sup.2R.sup.3, --C(.dbd.NR.sup.2)NR.sup.2R.sup.3, --C(.dbd.NR.sup.2)OR.sup.2, --C(.dbd.NR.sup.2)R.sup.3, --COCOR.sup.2, --COMCOR.sup.2, --CN, --SO2R.sup.3, --S(O)R.sup.3, --P(.dbd.O)(YR.sup.2)(YR.sup.2), --NR.sup.2SO2R.sup.3 or --NR.sup.2SO2NR.sup.2R.sup.3; s is 0, 1, 2, 3 or 4; and r is 0, 1, or 2. 5. The compound of claim 4 in which X.sup.1 is CH. 6. The compound of claim 4 in which X.sup.1 is CR.sup.t1. 7. The compound of claim 1 having Formula III: ##STR00110## wherein: Ring C represents a 5- or 6-membered heterocyclic or heteroaryl ring, comprising carbon atoms and 1-3 heteroatoms selected from O, N and S(O).sub.r; R.sup.c, at each occurrence, is independently selected from the group consisting of halo, .dbd.O, .dbd.S, --CN, --NO.sub.2, --R.sup.4, --OR.sup.2, --NR.sup.2R.sup.3, --C(O)YR.sup.2, --OC(O)YR.sup.2, --NR.sup.2C(O)YR.sup.2, --SC(O)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)YR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NR.sup.2SO.sub.2R.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3 and --NR.sup.2SO.sub.2NR.sup.2R.sup.3, wherein Y is independently a bond, --O--, --S-- or --NR.sup.3--; R.sup.2 and R.sup.3 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heterocyclic where the heterocyclic comprises 1-4 heteroatoms selected from N, O, and S, and C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; wherein the NR.sup.2R.sup.3 moiety is optionally a 5- or 6-membered saturated, partially saturated or unsaturated ring, which is optionally substituted and which contains 0-2 additional heteroatoms selected from N, O and S(O).sub.r; each occurrence of R.sup.4 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heterocyclic where the heterocyclic comprises 1-4 heteroatoms selected from N, O, and S, and C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; each of the foregoing alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, carbon linked C.sub.5-14heteroaryl where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, or carbon linked C.sub.5-14heterocycle where the heterocycle comprises 1-4 heteroatoms selected from N, O, and S, moieties is optionally substituted; each optional substituent on an unsaturated carbon atom of a C.sub.6-14aryl or C.sub.5-14heteroaryl group, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, is a halo, alkyl, alkenyl, alkynyl, --CN, --R.sup.4, --OR.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3, NR.sup.2R.sup.3, --(CO)YR.sup.2, --O(CO)YR.sup.2, --NR.sup.2(CO)YR.sup.2, --S(CO)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)Y'R.sup.2, --COCOR.sup.2, --COMCOR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NO.sub.2, --NR.sup.2SO.sub.2R.sup.2 or --NR.sup.2SO.sub.2NR.sup.2R.sup.3 moiety; each M is a 1-6 carbon alkyl group; each optional substituent on an alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl or non-aromatic C.sub.5-14heterocyclic moiety, where the heterocyclic comprises 1-4 heteroatoms selected from N, O, and S, is independently a halo, alkyl, alkenyl, alkynyl, --CN, --R.sup.4, --OR.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3, NR.sup.2R.sup.3, --(CO)YR.sup.2, --O(CO)YR.sup.2, --NR.sup.2(CO)YR.sup.2, --S(CO)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)Y'R.sup.2, --COCOR.sup.2, --COMCOR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NO.sub.2, --NR.sup.2SO.sub.2R.sup.2 or --NR.sup.2SO.sub.2NR.sup.2R.sup.3 moiety; each optional substituent on a nitrogen is R.sup.4, --NR.sup.2R.sup.3, --C(.dbd.O)R.sup.2, --C(.dbd.O)OR.sup.2, --C(.dbd.O)SR.sup.2, --C(.dbd.O)NR.sup.2R.sup.3, --C(.dbd.NR.sup.2)NR.sup.2R.sup.3, --C(.dbd.NR.sup.2)OR.sup.2, --C(.dbd.NR.sup.2)R.sup.3, --COCOR.sup.2, --COMCOR.sup.2, --CN, --SO2R.sup.3, --S(O)R.sup.3, --P(.dbd.O)(YR.sup.2)(YR.sup.2), --NR.sup.2SO2R.sup.3 or --NR.sup.2SO2NR.sup.2R.sup.3; v is 0, 1, 2, 3, 4 or 5 and t is 0, 1, 2, 3, or 4. 8. The compound of claim 7 wherein Ring C is a substituted or unsubstituted C.sub.5-14heteroaryl ring, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S. 9. The compound of claim 8 wherein Ring C is a substituted or unsubstituted imidazole ring. 10. The compound of claim 9 selected from the following formulae: ##STR00111## 11. The compound of claim 9 having Formula II-a: ##STR00112## wherein X.sup.1 is selected from CH, CR.sup.t1, and CR.sup.t. 12. The compound of claim 11 wherein X.sup.1 is selected from CH and CR.sup.t1. 13. The compound of claim 1 having Formula IV: ##STR00113## wherein: Ring D represents a 5- or 6-membered heterocyclic or heteroaryl ring, comprising carbon atoms and 1-3 heteroatoms independently selected from N, O, and S(O).sub.r; L.sup.2 is (CH.sub.2).sub.z, O(CH.sub.2).sub.x, NR.sup.3(CH.sub.2).sub.x, S(CH.sub.2).sub.x or (CH.sub.2).sub.xNR.sup.3C(O)(CH.sub.2).sub.x and the linkage unit can be used in either direction; R.sup.d, at each occurrence, is selected from the group consisting of halo, .dbd.O, .dbd.S, --CN, --NO.sub.2, --R.sup.4, --OR.sup.2, --NR.sup.2R.sup.3, --C(O)YR.sup.2, --OC(O)YR.sup.2, --NR.sup.2C(O)YR.sup.2, --SC(O)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)YR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NR.sup.2SO.sub.2R.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3 and --NR.sup.2SO.sub.2NR.sup.2R.sup.3, wherein Y is independently a bond, --O--, --S-- or --NR.sup.3--; R.sup.2 and R.sup.3 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heterocyclic where the heterocyclic comprises 1-4 heteroatoms selected from N, O, and S, and C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; wherein the NR.sup.2R.sup.3 moiety is a 5- or 6-membered saturated, partially saturated or unsaturated ring, which is optionally substituted and which contains 0-2 additional heteroatoms selected from N, O and S(O).sub.r; each occurrence of R.sup.4 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, C.sub.6-14aryl, C.sub.5-14heterocyclic where the heterocyclic comprises 1-4 heteroatoms selected from N, O, and S, and C.sub.5-14heteroaryl, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S; each of the foregoing alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle moieties is optionally substituted; each optional substituent on an unsaturated carbon atom of a C.sub.6-14aryl or C.sub.5-14heteroaryl group, where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S, is a halo, alkyl, alkenyl, alkynyl, --CN, --R.sup.4, --OR.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3, --NR.sup.2R.sup.3, --(CO)YR.sup.2, --O(CO)YR.sup.2, --NR.sup.2(CO)YR.sup.2, --S(CO)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)Y'R.sup.2, --COCOR.sup.2, --COMCOR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), Si(R.sup.4).sub.3, --NO.sub.2, --NR.sup.2SO.sub.2R.sup.2 or --NR.sup.2SO.sub.2NR.sup.2R.sup.3 moiety; each M is a 1-6 carbon alkyl group; each optional substituent on an alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl or non-aromatic C.sub.5-14heterocyclic moiety, where the heterocyclic comprises 1-4 heteroatoms selected from N, O, and S, is independently a halo, alkyl, alkenyl, alkynyl, --CN, --R.sup.4, --OR.sup.2, --S(O).sub.rR.sup.2, --SO.sub.2NR.sup.2R.sup.3, --NR.sup.2R.sup.3, --(CO)YR.sup.2, --O(CO)YR.sup.2, --NR.sup.2(CO)YR.sup.2, --S(CO)YR.sup.2, --NR.sup.2C(.dbd.S)YR.sup.2, --OC(.dbd.S)YR.sup.2, --C(.dbd.S)YR.sup.2, --YC(.dbd.NR.sup.3)Y'R.sup.2, --COCOR.sup.2, --COMCOR.sup.2, --YP(.dbd.O)(YR.sup.4)(YR.sup.4), --Si(R.sup.4).sub.3, --NO.sub.2, --NR.sup.2SO.sub.2R.sup.2 or --NR.sup.2SO.sub.2NR.sup.2R.sup.3 moiety; each optional substituent on a nitrogen is R.sup.4, --NR.sup.2R.sup.3, --C(.dbd.O)R.sup.2, --C(.dbd.O)OR.sup.2, --C(.dbd.O)SR.sup.2, --C(.dbd.O)NR.sup.2R.sup.3, --C(.dbd.NR.sup.2)NR.sup.2R.sup.3, --C(.dbd.NR.sup.2)OR.sup.2, --C(.dbd.NR.sup.2)R.sup.3, --COCOR.sup.2, --COMCOR.sup.2, --CN, --SO2R.sup.3, --S(O)R.sup.3, --P(.dbd.O)(YR.sup.2)(YR.sup.2), --NR.sup.2SO2R.sup.3 or --NR.sup.2SO2NR.sup.2R.sup.3; w is 0, 1, 2, 3, 4 or 5; x is 0, 1, 2 or 3; z is 1, 2, 3 or 4; and t is 0, 1, 2, 3, or 4. 14. The compound of claim 13 wherein Ring D is a substituted or unsubstituted C.sub.5-14heteroaryl where the heteroaryl comprises 1-4 heteroatoms selected from N, O, and S. 15. The compound of claim 13 wherein Ring D is a substituted or unsubstituted piperazine ring and L.sup.2 is CH.sub.2. 16. The compound of claim 15 having Formula IV-a: ##STR00114## 17. The compound of claim 15 having Formula II-b: ##STR00115## wherein X.sup.1 is selected from CH, CR.sup.t1, and CR.sup.t. 18. The compound of claim 17 wherein X.sup.1 is selected from CH and CR.sup.t1. 19. A method for treating leukemia in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of the compound of claim 1; or a pharmaceutically acceptable salt thereof. 20. A method for treating leukemia in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of the compound of claim 7; or a pharmaceutically acceptable salt, thereof. 21. A method for treating leukemia in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of the compound of claim 13; or a pharmaceutically acceptable salt thereof. 22. A composition comprising the compound of claim 1; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent or vehicle. 23. A composition comprising the compound of claim 7; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent or vehicle. 24. A composition comprising the compound of claim 13; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent or vehicle.