Heterocyclic inhibitors of ERK2 and uses thereof Number:6,743,791 from the United States Patent and Trademark Office (PTO) owispatent Described herein are compounds that are useful as protein kinase inhibitors having the formula: ##STR1##wherein Z.sup.1 and Z.sup.2 are each independently nitrogen or CH and Ring A, T.sub.m R.sup.1, QR.sup.2, U.sub.n R.sup.3, and Sp are as described in the specification. The compounds are especially useful as inhibitors of ERK2 and for treating diseases in mammals that are alleviated by a protein kinase inhibitor, particularly diseases such as cancer, inflammatory disorders, restenosis, diabetes, and cardiovascular disease.<H Heterocyclic, inhibitors, Heterocyclic, in, 6743791.html, Patent, pto, 6743791

Title: Heterocyclic inhibitors of ERK2 and uses thereof

Abstract: Described herein are compounds that are useful as protein kinase inhibitors having the formula: ##STR1##wherein Z.sup.1 and Z.sup.2 are each independently nitrogen or CH and Ring A, T.sub.m R.sup.1, QR.sup.2, U.sub.n R.sup.3, and Sp are as described in the specification. The compounds are especially useful as inhibitors of ERK2 and for treating diseases in mammals that are alleviated by a protein kinase inhibitor, particularly diseases such as cancer, inflammatory disorders, restenosis, diabetes, and cardiovascular disease.

Patent Number: 6,743,791 Issued on 06/01/2004 to Cao, et al.

Inventors: Cao; Jingrong (Newton, MA), Green; Jeremy (Burlington, MA), Hale; Michael (Bedford, MA), Maltais; Francois (Tewksbury, MA), Straub; Judy (Cambridge, MA), Tang; Qing (Cambridge, MA), Aronov; Alex (Watertown, MA)
Assignee: Vertex Pharmaceuticals Incorporated (Cambridge, MA)

Appl. No.: 10/071,699

Filed: February 8, 2002

Current U.S. Class: 514/235.8 ; 514/266.22; 514/275; 544/122; 544/284; 544/331

Current International Class: C07D 405/14 (20060101); C07D 405/00 (20060101); C07D 403/04 (20060101); C07D 413/14 (20060101); C07D 401/00 (20060101); C07D 403/00 (20060101); C07D 401/14 (20060101); C07D 403/14 (20060101); C07D 413/00 (20060101)

Field of Search: 544/122,284,331 514/235.8,266.22,275

References Cited [Referenced By]

U.S. Patent Documents


5792778	August 1998	de Laszlo et al.
6169086	January 2001	Ejima et al.
2003/0096816	May 2003	Cao et al.

Foreign Patent Documents


WO 95/13067	May., 1995	WO
WO 97/05878	Feb., 1997	WO
WO 97/16442	May., 1997	WO
WO 99/32121	Jul., 1999	WO
WO 99/58523	Nov., 1999	WO
WO 00/26209	May., 2000	WO

Other References

Damasio, Alzheimer's Disease and related dementias, Cecil Textbook of Medicine, 20th Edition, vol. 2, pp. 1992-1996, 1996.* .
Simone, Oncology: Introduction, Cecil Textbook of Medicine, 20th Edition, vol. 1, pp. 1004-1010, 1996.* .
Traxler, Review: Oncologic, Endocrine & Metabolic. Protein Tyrosine kinase inhibitors in cancer treatment, Exp. Opin. Ther. Patents, 7(6), pp. 571-588, 1997.* .
Layzer, Degenerative Diseases of the Nervous System, Cecil Textbook of Medicine, 20th Edition, vol. 2, pp. 2050-2057, 1996.* .
Impey et al., Making New Connections: Role of ERK/MAP Kinase Signaling in Neuronal Plasticity, Neuron, vol. 23, pp. 11-14, May 1999.* .
English et al., New Insights into the control of MAP Kinase pathways, Experimental Cell Research, 253, pp. 255-270, 1999..

Primary Examiner: Rao; Deepak
Attorney, Agent or Firm: Robidoux; Andrea L. C. Vertex Pharmaceuticals Incorporated

Parent Case Text

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent Application No. 60/267,818 filed Feb. 9, 2001 and U.S. Provisional Patent Application No. 60/328,768 filed Oct. 12, 2001, the contents of which are incorporated herein by reference.

Claims

We claim:

1. A compound of formula I': ##STR331##

or a pharmaceutically acceptable salt thereof, wherein: Sp is a spacer group comprising a 5-membered heteroaromatic ring, wherein Ring A and Q'R.sup.2' are attached to Sp at non-adjacent positions; and wherein Sp has up to two R.sup.6 substituents, provided that two substitutable carbon ring atoms in Sp are not simultaneously substituted by R.sup.6 ; Z.sup.1 is N and Z.sup.2 is CH; T is a linker group selected from --NH--, --CH.sub.2 --, --CO--, or a saturated or unsaturated C.sub.1-6 alkylidene chain which is optionally substituted, and wherein up to two saturated carbons of the chain are optionally replaced by --C(O)--, --C(O)C(O)--, --CONR.sup.7 --, --CONR.sup.7 NR.sup.7 --, --CO.sub.2 --, --OC(O)--, --NR.sup.7 CO.sub.2 --, --O--, --NR.sup.7 CONR.sup.7 --, --OC(O)NR.sup.7 --, --NR.sup.7 NR.sup.7 --, --NR.sup.7 CO--, --S--, --SO--, --SO.sub.2 --, --NR.sup.7 --, --SO.sub.2 NR.sup.7 --, or --NR.sup.7 SO.sub.2 --; Q' is selected from --CO.sub.2 --, --C(O)NR.sup.7 -- or SO.sub.2 NR.sup.7 --; U is selected from --NR.sup.7 --, --NR.sup.7 CO--, --NR.sup.7 CONR.sup.7 --, --NR.sup.7 CO.sub.2 --, --O--, --CONR.sup.7 --, --CO--, --CO.sub.2 --, --OC(O)--, --NR.sup.7 SO.sub.2 --, --SO.sub.2 NR.sup.7 --, --NR.sup.7 SO.sub.2 NR.sup.7 --, or --SO.sub.2 --; m and n are each independently selected from zero or one; R.sup.1 is selected from hydrogen, CN, halogen, R, N(R.sup.7).sub.2, OR, or OH; R.sup.2' is selected from --(CH.sub.2).sub.y CH(R.sup.5).sub.2 or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2 ; y is 0-6; R.sup.3 is selected from R.sup.7, R, --(CH.sub.2).sub.y CH(R.sup.8)R, CN, --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)N(R.sup.4).sub.2 ; each R is independently selected from an optionally substituted group selected from C.sub.1-6 aliphatic, C.sub.6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 3-10 ring atoms; each R.sup.4 is independently selected from R, R.sup.7, --COR.sup.7, --CO.sub.2 R, --CON(R.sup.7).sub.2, --SO.sub.2 R.sup.7, --(CH.sub.2).sub.y R.sup.5, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; each R.sup.5 is independently selected from R, OR, CO.sub.2 R, (CH.sub.2).sub.y N(R.sup.7).sub.2, N(R.sup.7).sub.2, OR.sup.7, SR.sup.7, NR.sup.7 COR.sup.7, NR.sup.7 CON(R.sup.7).sub.2, CON(R.sup.7).sub.2, SO.sub.2 R.sup.7, NR.sup.7 SO.sub.2 R.sup.7, COR.sup.7, CN, or SO.sub.2 N(R.sup.7).sub.2 ; each R.sup.6 is independently selected from R.sup.7, F, Cl, (CH.sub.2).sub.y N(R.sup.7).sub.2, N(R.sup.7).sub.2, OR.sup.7, SR.sup.7, NR.sup.7 COR.sup.7, NR.sup.7 CON(R.sup.7).sub.2, CON(R.sup.7).sub.2, SO.sub.2 R.sup.7 NR.sup.7 SO.sub.2 R.sup.7, COR.sup.7, CN, or SO.sub.2 N(R.sup.7).sub.2 ; each R.sup.7 is independently selected from hydrogen or an optionally substituted C.sub.1-6 aliphatic group, or two R.sup.7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; R.sup.8 is selected from R, (CH.sub.2).sub.w OR.sup.7, (CH.sub.2).sub.w N(R.sup.4).sub.2, or (CH.sub.2).sub.w SR.sup.7 ; and each w is independently selected from 0-4.

2. The compound according to claim 1, wherein Sp is selected from one of the following: ##STR332##

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 2, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, amino, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; and (c) R.sup.5 is R or OR.sup.7, wherein R is carbocyclic, or an optionally substituted 5 or 6-membered aryl or heteroaryl ring.

4. The compound according to claim 3, wherein: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, amino, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; and (c) R.sup.5 is R or OR.sup.7, wherein R is carbocyclic, or an optionally substituted 5 or 6-membered aryl or heteroaryl ring.

5. The compound according to claim 3, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is selected from hydrogen, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, isopropyl, --CH(CH.sub.2 OH)phenyl, --CH(CH.sub.2 OH)ethyl, --CH(CH.sub.2 OH).sub.2, --CH(CH.sub.2 OH)isopropyl, --CH(CH.sub.2 OH)CH.sub.2 cyclopropyl, or an optionally substituted phenyl, benzyl, or isoxazolyl group; (b) T.sub.m R.sup.1 is selected from optionally substituted phenyl, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, CH.sub.2 OCH.sub.3, CH.sub.2 OH, OH, NH.sub.2, NHCH.sub.3, NHAc, NHC(O)NHCH.sub.3, or CH.sub.2 NHCH.sub.3 ; and (c) R.sup.5 is OH, CH.sub.2 0H, carbocyclic, or an optionally substituted phenyl or pyridyl ring, and Q' is --C(O)NH--.

6. The compound according to claim 5, wherein: (a) R.sup.3 is selected from hydrogen, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, isopropyl, --CH(CH.sub.2 OH)phenyl, --CH(CH.sub.2 OH)ethyl, --CH(CH.sub.2 OH).sub.2, --CH(CH.sub.2 OH)isopropyl, --CH(CH.sub.2 OH)CH.sub.2 cyclopropyl, or an optionally substituted phenyl, benzyl, or isoxazolyl group; (b) T.sub.m R.sup.1 is selected from optionally substituted phenyl, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, CH.sub.2 OCH.sub.3, CH.sub.2 OH, OH, NH.sub.2, NHCH.sub.3, NHAc, NHC(O)NHCH.sub.3, or CH.sub.2 NHCH.sub.3 ; and (c) R.sup.5 is OH, CH.sub.2 OH, carbocyclic, or an optionally substituted phenyl or pyridyl ring, and Q' is --C(O)NH--.

7. The compound according to claim 2, wherein said compound is of formula I": ##STR333##

or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 7, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, N(R.sup.4).sub.2, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; and (c) R.sup.5 is an optionally substituted 6-membered aryl, heteroaryl, or carbocyclic ring.

9. The compound according to claim 8, wherein: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, N(R.sup.4).sub.2, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; and (c) R.sup.5 is an optionally substituted 6-membered aryl, heteroaryl, or carbocyclic ring.

10. The compound according to claim 2, wherein said compound is of formula I.degree.: ##STR334##

or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 10, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, amino, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; and (c) R.sup.5 is R or OR.sup.7, wherein R is carbocyclic, or an optionally substituted 5 or 6-membered aryl or heteroaryl ring.

12. The compound according to claim 11, wherein: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, amino, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; and (c) R.sup.5 is R or OR.sup.7, wherein R is carbocyclic, or an optionally substituted 5 or 6-membered aryl or heteroaryl ring.

13. A compound of formula III-a': ##STR335##

or a pharmaceutically acceptable salt thereof, wherein: T is a linker group selected from --NH--, --CH.sub.2 --, --CO--, or a a saturated or unsaturated C.sub.1-6 alkylidene chain which is optionally substituted, and wherein up to two saturated carbons of the chain are optionally replaced by --C(O)--, --C(O)C(O)--, --CONR.sup.7 --, --CONR.sup.7 NR.sup.7 --, --CO.sub.2 --, --OC(O)--, --NR.sup.7 CO.sub.2 --, --O--, --NR.sup.7 CONR.sup.7 --, --OC(O)NR.sup.7 --, --NR.sup.7 NR.sup.7 --, --NR.sup.7 CO--, --S--, --SO--, --SO.sub.2 --, --NR.sup.7 --, --SO.sub.2 NR.sup.7 --, or --NR.sup.7 SO.sub.2 --; U is selected from --NR.sup.7 --, --NR.sup.7 CO--, --NR.sup.7 CONR .sup.7 --, --NR.sup.7 CO.sub.2 --, --O--, --CONR.sup.7 --, --CO--, --CO.sub.2 --, --OC(O)--, --NR.sup.7 SO.sub.2 --, --SO.sub.2 NR.sup.7 --, --NR.sup.7 SO.sub.2 NR.sup.7 --, or --SO.sub.2 --; m and n are each independently selected from zero or one; R.sup.1 is selected from hydrogen, CN, halogen, R, N(R.sup.7).sub.2, OR, or OH; R.sup.3 is selected from R.sup.7, R, --(CH.sub.2).sub.y CH(R.sup.8)R, CN, --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)N(R.sup.4).sub.2 ; each R is independently selected from an optionally substituted group selected from C.sub.1-6 aliphatic, C.sub.6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 3-10 ring atoms; each R.sup.4 is independently selected from R, R.sup.7, --COR.sup.7, --CO.sub.2 R, --CON(R.sup.7).sub.2, --SO.sub.2 R.sup.7, --(CH.sub.2).sub.y R.sup.5, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; each R.sup.5 is independently selected from R, OR, CO.sub.2 R, (CH.sub.2).sub.y N(R.sup.7).sub.2, N(R.sup.7).sub.2, OR.sup.7, SR.sup.7, NR.sup.7 COR.sup.7, NR.sup.7 CON(R.sup.7).sub.2, CON(R.sup.7).sub.2, SO.sub.2 R.sup.7, NR.sup.7 SO.sub.2 R.sup.7, COR.sup.7, CN, or SO.sub.2 N(R.sup.7).sub.2 ; each R.sup.6 is independently selected from R.sup.7, F, Cl, (CH.sub.2).sub.y N(R.sup.7).sub.2, N(R.sup.7).sub.2, OR.sup.7, SR.sup.7, NR.sup.7 COR.sup.7, NR.sup.7 CON(R.sup.7).sub.2, CON(R.sup.7).sub.2, SO.sub.2 R.sup.7, NR.sup.7 SO.sub.2 R.sup.7, COR.sup.7, CN, or SO.sub.2 N(R.sup.7).sub.2 ; each R.sup.7 is independently selected from hydrogen or an optionally substituted C.sub.1-6 aliphatic group, or two R.sup.7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; R.sup.8 is selected from R, (CH.sub.2).sub.w OR.sup.7, (CH.sub.2).sub.w N(R.sup.4).sub.2, or (CH.sub.2).sub.w SR.sup.7 ; and each w is independently selected from 0-4.

14. The compound according to claim 13, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, N(R.sup.4).sub.2, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; and (c) R.sup.5 is an optionally substituted 6-membered aryl, heteroaryl, or carbocyclic ring.

15. The compound according to claim 14, wherein: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, N(R.sup.4).sub.2, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; and (c) R.sup.5 is an optionally substituted 6-membered aryl, heteroaryl, or carbocyclic ring.

16. The compound according to claim 14, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is selected from hydrogen, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, isopropyl, --CH(CH.sub.2 OH)phenyl, --CH(CH.sub.2 OH)ethyl, --CH(CH.sub.2 OH).sub.2, --CH(CH.sub.2 OH)isopropyl, --CH(CH.sub.2 OH)CH.sub.2 cyclopropyl, or an optionally substituted phenyl or benzyl group; (b) T.sub.m R.sup.1 is selected from optionally substituted phenyl, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, CH.sub.2 OCH.sub.3, CH.sub.2 OH, OH, NH.sub.2, NHCH.sub.3, NHAc, NHC(O)NHCH.sub.3, or CH.sub.2 NHCH.sub.3 ; and (c) R.sup.5 is cyclohexyl or an optionally substituted phenyl or pyridylring.

17. The compound according to claim 16, wherein: (a) R.sup.3 is selected from hydrogen, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, isopropyl, --CH(CH.sub.2 OH)phenyl, --CH(CH.sub.2 OH) ethyl, --CH(CH.sub.2 OH).sub.2, --CH(CH.sub.2 OH)isopropyl, --CH(CH.sub.2 OH)CH.sub.2 cyclopropyl, or an optionally substituted phenyl or benzyl group; (b) T.sub.m R.sup.1 is selected from optionally substituted phenyl, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, CH.sub.2 OCH.sub.3, CH.sub.2 OH, OH, NH.sub.2, NHCH.sub.3, NHAc, NHC(O)NHCH.sub.3, or CH.sub.2 NHCH.sub.3 ; and (c) R.sup.5 is cyclohexyl or an optionally substituted phenyl or pyridylring.

18. A compound of formula III-a.degree.: ##STR336##

or a pharmaceutically acceptable salt thereof, wherein: T is a linker group selected from --NH--, --CH.sub.2 --, --CO--, or a a saturated or unsaturated C.sub.1-6 alkylidene chain which is optionally substituted, and wherein up to two saturated carbons of the chain are optionally replaced by --C(O)--, --C(O)(CO)--, --CONR.sup.7 --, --CONR.sup.7 NR.sup.7 --, --CO.sub.2 --, --OC(O)--, --NR.sup.7 CO.sub.2 --, --O--, --NR.sup.7 CONR.sup.7 --, --OC(O)NR.sup.7 --, --NR.sup.7 NR.sup.7 --, --NR.sup.7 CO--, --S--, --SO--, --SO.sub.2 --, NR.sup.7, --SO.sub.2 NR.sup.7 --, or --NR.sup.7 SO.sub.2 --; U is selected from --NR.sup.7 --, --NR.sup.7 CO--, --NR.sup.7 CONR.sup.7 --, --NR.sup.7 CO.sub.2 --, --O--, --CONR.sup.7 --, --CO--, --CO.sub.2 --, --OC(O)--, --NR.sup.7 SO.sub.2 --, --SO.sub.2 NR.sup.7 --, --NR.sup.7 SO.sub.2 NR.sup.7 --, or --SO.sub.2 --; m and n are each independently selected from zero or one; R.sup.1 is selected from hydrogen, CN, halogen, R, N(R.sup.7).sub.2, OR, or OH; y is 0-6; R.sup.3 is selected from R.sup.7, R, --(CH.sub.2).sub.y CH(R.sup.8)R, CN, --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)N(R.sup.4).sub.2 ; each R is independently selected from an optionally substituted group selected from C.sub.1-6 aliphatic, C.sub.6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 3-10 ring atoms; each R.sup.4 is independently selected from R, R.sup.7, --COR.sup.7, --CO.sub.2 R, --CON(R.sup.7).sub.2, --SO.sub.2 R.sup.7, --(CH.sub.2).sub.y R.sup.5, or (CH.sub.2).sub.y CH(R.sup.5).sub.2 ; each R.sup.5 is independently selected from R, OR, C.sub.2 R, (CH.sub.2).sub.y N(R.sup.7).sub.2, N(R.sup.7).sub.2, OR.sup.7, SR.sup.7, NR.sup.7 COR.sup.7, NR.sup.7 CON(R.sup.7).sub.2, CON(R.sup.7).sub.2, SO.sub.2 R.sup.7, NR.sup.7 SO.sub.2 R.sup.7, COR.sup.7, CN, or SO.sub.2 N(R.sup.7).sub.2 ; each R.sup.6 is independently selected from R.sup.7, F, Cl, (CH.sub.2).sub.y N(R.sup.7).sub.2, N(R.sup.7).sub.2, OR.sup.7, SR.sup.7, NR.sup.7 COR.sup.7, NR.sup.7 CON(R.sup.7).sub.2, CON(R.sup.7).sub.2, SO.sub.2 R.sup.7, NR.sup.7 SO.sub.2 R.sup.7, COR.sup.7, CN, or SO.sub.2 N(R.sup.7).sub.2 ; each R.sup.7 is independently selected from hydrogen or an optionally substituted C.sub.1-6 aliphatic group, or two R.sup.7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; R.sup.8 is selected from R, (CH.sub.2).sub.w OR.sup.7, (CH.sub.2).sub.w N(R.sup.4).sub.2, or (CH.sub.2).sub.w SR.sup.7 ; and each w is independently selected from 0-4.

19. The compound according to claim 18, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, N(R.sup.4).sub.2, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; and (c) R.sup.5 is R or OR.sup.7, and R.sup.8 is R.sup.7 or OR.sup.7.

20. The compound according to claim 19, wherein: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, N(R.sup.4).sub.2, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; and (c) R.sup.5 is R or OR.sup.7, and R.sup.8 is R.sup.7 or OR.sup.7.

21. A compound selected from the group consisting of: 4-[2-Amino-5-(3-chloro-2-fluoro-phenyl)-pyrimidin-4-yl]-1H-pyrrole-2-carbox ylic acid (2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-amide; 4-(2-Amino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Amino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (3-hydroxy-1-phenyl-propyl)-amide; 4-(2-Amino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (3-hydroxy-1-phenyl-propyl)-amide; 4-[2-Amino-5-(3,5-dichloro-phenyl)-pyrimidin-4-yl]-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-Amino-5-(3,5-dichloro-phenyl)-pyrimidin-4-yl]-1H-pyrrole-2-carboxylic acid (2-dimethylamino-2-pyridin-3-yl-ethyl)-amide; 4-[5-(3,5-Dichloro-phenyl)-2-phenylamino-pyrimidin-4-yl]-1H-pyrrole-2-carbo xylic acid (2-morpholin-4-yl-2-pyridin-3-yl-ethyl)-amide; 4-[2-Amino-5-(3-fluoro-5-trifluoromethyl-phenyl)-pyrimidin-4-yl]-1H-pyrrole -2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(5-Methyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Amino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-amide; 4-(5-Methyl-2-methylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (1-hydroxymethyl-3-methyl-butyl)-amide; 4-(5-Methyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [1-hydroxymethyl-2-(1H-imidazol-4-yl)-ethyl]-amide; 4-(5-Methyl-2-methylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [1-(3-chloro-4-fluoro-phenyl)-2-hydroxy-ethyl]-amide; 4-(5-Methyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [1-(3-chloro-4-fluoro-phenyl)-2-hydroxy-ethyl]-amide; 4-[2-(3-Fluoro-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyli c acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(3-Methoxy-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyl ic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(3-Hydroxy-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyl ic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(Benzo[1,3]dioxol-5-ylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-car boxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[5-Methyl-2-(4-sulfamoyl-phenylamino)-pyrimidin-4-yl]-1H-pyrrole-2-carbox ylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(3-Benzyloxy-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carbox ylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(4-Hydroxy-cyclohexylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carb oxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(5-Cyclohexyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(5-Cyclopropyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(5-Methyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [1-(3-fluoro-4-methyl-phenyl)-2-hydroxy-ethyl]-amide; 4-(5-Methyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [2-hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-amide; 4-[2-(3-Fluoro-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyli c acid [1-(3-fluoro-4-methyl-phenyl)-2-hydroxy-ethyl]-amide; 4-[2-(3-Fluoro-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyli c acid [2-hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-amide; 4-[5-Methyl-2-(3-trifluoromethyl-phenylamino)-pyrimidin-4-yl]-1H-pyrrole-2- carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Benzylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(3,4-Dimethyl-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carbo xylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(4-Benzyloxy-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carbox ylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Isopropylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[5-Methyl-2-(2,2,2-trifluoro-ethylamino)-pyrimidin-4-yl]-1H-pyrrole-2-car boxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(2-Hydroxy-1-phenyl-ethylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2- carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(2-Methoxy-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyl ic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[5-Methyl-2-(4-trifluoromethoxy-phenylamino)-pyrimidin-4-yl]-1H-pyrrole-2 -carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Isobutylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(Cyclopropylmethyl-amino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carbox ylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(5-Methoxymethyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Amino-5-methoxymethyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Cyclopropylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(5-Methyl-2-propylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(2-Hydroxy-1-phenyl-ethylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2- carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Amino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-methyl-2-phenyl-ethyl)-amide; 4-(2-Amino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-methyl-2-phenyl-ethyl)-amide; 4-(2-Amino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-2-phenyl-ethyl)-methyl-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-methyl-2-phenyl-ethyl)-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-methyl-2-phenyl-ethyl)-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-2-phenyl-ethyl)-amide; 4-(2-Amino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-hydroxymethyl-2-phenyl-ethyl)-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-hydroxymethyl-2-phenyl-ethyl)-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (3-hydroxy-1-phenyl-propyl)-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (3-hydroxy-1-phenyl-propyl)-amide; 4-[2-(1-Hydroxymethyl-cyclopropylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole -2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(2-Hydroxy-ethylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyli c acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(2-Hydroxy-1-methyl-ethylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2- carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(2-Hydroxy-propylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyl ic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(2-Hydroxy-propylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyl ic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(2-Hydroxy-cyclohexylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carb oxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(5-Hydroxymethyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; {[4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carbonyl]-amino}-ph enyl-acetic acid methyl ester; 4-[2-(2-Hydroxy-1-methyl-ethylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2- carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(3-Dimethylamino-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-ca rboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Amino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-amide; 4-(2-Amino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-amide; 4-(2-Ethylamino-5-methoxymethyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-pyridin-3-yl-ethyl)-amide; 4-(2-Ethylamino-5-hydroxymethyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [1-(3-fluoro-5-trifluoromethyl-phenyl)-2-hydroxy-ethyl]-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [1-(3-fluoro-phenyl)-2-hydroxy-ethyl]-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [1-(2-fluoro-phenyl)-2-hydroxy-ethyl]-amide; 4-[2-(2-Cyclopropyl-1-hydroxymethyl-ethylamino)-5-methyl-pyrimidin-4-yl]-1H -pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(2,3-Dimethyl-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carbo xylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Ethoxyamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(1-Hydroxymethyl-2-methyl-propylamino)-5-methyl-pyrimidin-4-yl]-1H-pyr role-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-oxo-1-phenyl-propyl)-amide; 4-(2-Ethylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [2-hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-amide; 4-[2-(3-Fluoro-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyli c acid [2-hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-amide; 4-[2-(2-Chloro-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyli c acid [2-hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-amide; 4-[2-(2-Hydroxy-1-phenyl-ethylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2- carboxylic acid [2-hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-amide; 4-[2-(3-Dimethylamino-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-ca rboxylic acid [2-hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-amide; 4-(2-Cyclopropylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [2-hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-amide; 4-(2-Cyclopropylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [2-hydroxy-1-(2-methoxy-phenyl)-ethyl]-amide; 4-(2-Cyclopropylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amide; 4-(2-Cyclopropylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-m-tolyl-ethyl)-amide; 4-(2-Methoxyamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Isopropoxyamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(3-Dimethylamino-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-ca rboxylic acid (2-hydroxy-1-m-tolyl-ethyl)-amide; 4-[2-(2-Chloro-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyli c acid (2-hydroxy-1-m-tolyl-ethyl)-amide; 4-[2-(2-Hydroxy-1-phenyl-ethylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2- carboxylic acid (2-hydroxy-1-m-tolyl-ethyl)-amide; 4-[2-(2,3-Dimethyl-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carbo xylic acid (2-hydroxy-1-m-tolyl-ethyl)-amide; 4-[2-(3-Fluoro-phenylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyli c acid (2-hydroxy-1-m-tolyl-ethyl)-amide; 4-(2-Acetylamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(5-Methyl-2-o-tolylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[5-Methyl-2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-{5-Methyl-2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-pyrr ole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-{5-Methyl-2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-pyrr ole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; N'-{4-[5-(2-Hydroxy-1-phenyl-ethylcarbamoyl)-1H-pyrrol-3-yl]-5-methyl-pyrim idin-2-yl}-hydrazinecarboxylic acid ethyl ester; 4-{5-Methyl-2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-pyrrole-2-car boxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Cyclopropylmethoxyamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxyl ic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(Isoxazol-3-ylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(2-Cyanoamino-5-methyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(2-Hydroxy-1-methyl-ethylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2- carboxylic acid (2-hydroxy-1-m-tolyl-ethyl)-amide; 4-(5-Methyl-2-o-tolylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-m-tolyl-ethyl)-amide; 4-(5-Methyl-2-o-tolylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amide; 4-[2-(2-Hydroxy-ethoxyamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carboxyl ic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(N',N'-Dimethyl-hydrazino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-carbo xylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[5-Methyl-2-(2-trifluoromethyl-phenylamino)-pyrimidin-4-yl]-1H-pyrrole-2- carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[5-Methyl-2-(morpholin-4-ylamino)-pyrimidin-4-yl]-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[5-Methyl-2-(5-methyl-isoxazol-3-ylamino)-pyrimidin-4-yl]-1H-pyrrole-2-ca rboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-{2-[1-(3-Chloro-4-fluoro-phenyl)-2-hydroxy-ethylamino]-5-methyl-pyrimidin -4-yl}-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-(5-Methyl-2-phenylamino-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid [1-(3-fluoro-phenyl)-2-hydroxy-ethyl]-amide; 4-[2-(1-Hydroxymethyl-propylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-ca rboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amide; 4-[2-(2-Hydroxy-1-hydroxymethyl-ethylamino)-5-methyl-pyrimidin-4-yl]-1H-pyr role-2-carboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amide; 4-[2-(1-Hydroxymethyl-propylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-ca rboxylic acid (2-hydroxy-1-m-tolyl-ethyl)-amide; 4-[2-(2-Hydroxy-1-hydroxymethyl-ethylamino)-5-methyl-pyrimidin-4-yl]-1H-pyr role-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; 4-[2-(1-Hydroxymethyl-propylamino)-5-methyl-pyrimidin-4-yl]-1H-pyrrole-2-ca rboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide; and 4-[5-Methyl-2-(2-methyl-cyclopropylamino)-pyrimidin-4-yl]-1H-pyrrole-2-carb oxylic acid (2-hydroxy-1-phenyl-ethyl)-amide.

22. A composition comprising an effective amount of a compound according to any of claims 1-21 and a pharmaceutically acceptable carrier.

23. The composition according to claim 22, further comprising an additional therapeutic agent selected from a chemotherapeutic agent or anti-proliferative agent, or an agents for treating diabetes, an anti-inflammatory agent, an immunomodulatory or immunosuppressive agent, an agent for treating neurlogical disorders, an agent for treating cardiovascular disease, an agent for treating liver disease, cholestyramine, an interferon, an anti-viral agents, an agents for treating blood disorders, or an agent for treating immunodeficiency disorders.

24. A method of treating a disease in a patient, wherein the disease is transplant rejection, melanoma, or a cancer selected from colon, breast, lung, kidney, ovary, pancreas, CNS, or cancer of the gastric tract comprising the step of administering to said patient a composition according to claim 22.

25. A method of treating a disease in a patient, wherein the disease is cardiovascular disease, comprising the step of administering to said patient a composition according to claim 22.

26. The method according to claim 25, wherein the disease is a cardiovascular disease selected from restenosis, cardiomegaly, artherosclerosis, myocardial infarction, or congestive heart failure.

27. A method of treating a disease in a patient in need thereof, wherein said disease is diabetes, comprising the step of administering to said patient a composition according to claim 22.

28. A method of treating a disease in a patient in need thereof, wherein said disease is Alzheimer's disease, comprising the step of administering to said patient a composition according to claim 22.

29. A method of treating a disease in a patient in need thereof, wherein said disease is schizophrenia, comprising the step of administering to said patient a composition according to claim 22.

30. A method of enhancing glycogen synthesis in a patient in need thereof, which method comprises the step of administering to said patient a therapeutically effective amount of the composition according to claim 22.

31. A method of lowering blood levels of glucose in a patient in need thereof, which method comprises the step of administering to said patient a therapeutically effective amount of the composition according to claim 22.

32. A method of inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof, which method comprises the step of administering to said patient a therapeutically effective amount of the composition according to claim 22.

33. A method of inhibiting the phosphorylation of .beta.-catenin in a patient in need thereof, which method comprises the step of administering to said patient a therapeutically effective amount of the composition according to claim 22.

34. A method of treating a disease in a patient in need thereof, wherein said disease is selected from melanoma or a cancer selected from colon, breast, lung, kidney, ovary, pancreas, CNS, or cancer of the gastric tract, comprising the step of administering to said patient a composition according to claim 22.

35. A method of treating a disease in a patient in need thereof, wherein said disease is selected from an autoimmune disease or transplant rejection, comprising the step of administering to said patient a composition according to claim 22.

36. A method of inhibiting ERK2, Aurora-2, GSK-3, CDK-2, AKT3, or Lck activity in a biological sample comprising the step of contacting said biological sample with a compound according to any one of claims 1-21.

37. A method of treating a disease selected from transplant rejection, melanoma, or a cancer selected from colon, breast, lung, kidney, ovary, pancreas, CNS, or cancer of the gastric tract in a patient, which method comprises administering to said patient a compound of formula I: ##STR337##

or a pharmaceutically acceptable salt thereof, wherein: Sp is a spacer group having a 5-membered heteroaromatic ring, wherein Ring A and QR.sup.2 are attached to Sp at non-adjacent positions; and wherein Sp has up to two R.sup.6 substituents, provided that two substitutable carbon ring atoms in Sp are not simultaneously substituted by R.sup.6 ; Z.sup.1 is N and Z.sup.2 is CH; T is a linker group selected from --NH--, --CH.sub.2 --, --CO--, or a saturated or unsaturated C.sub.1-6 alkylidene chain which is optionally substituted, and wherein up to two saturated carbons of the chain are optionally replaced by --C(O)--, --C(O)C(O)--, --CONR.sup.7 --, --CONR.sup.7 NR.sup.7 --, --CO.sub.2 --, --OC(O)--, --NR.sup.7 CO.sub.2 --, --O--, --NR.sup.7 CONR.sup.7 --, --OC(O)NR.sup.7 --, --NR.sup.7 NR.sup.7 --, --NR.sup.7 CO--, --S--, --SO--, --SO.sub.2 --, --NR.sup.7 --, --SO.sub.2 NR.sup.7 --, or --NR.sup.7 SO.sub.2 --, Q is --CO.sub.2 --, --C(O)NR.sup.7 --, or --S(O).sub.2 NR.sup.7 --; U is selected from --NR.sup.7 --, --NR.sup.7 CO--, --NR.sup.7 CONR.sup.7 --, --NR.sup.7 CO.sub.2 --, --O--, --CONR.sup.7 --, --CO--, --CO.sub.2 --, --OC(O)--, --NR.sup.7 SO.sub.2 --, --SO.sub.2 NR.sup.7 --, --NR.sup.7 SO.sub.2 NR.sup.7 --, or --SO.sub.2 --; m and n are each independently selected from zero or one; R.sup.1 is selected from hydrogen, CN, halogen, R, N(R.sup.7).sub.2, OR, or OH; R.sup.2 is selected from --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, --N(R.sup.4).sub.2, or --NR.sup.4 (CH.sub.2).sub.y N(R.sup.4).sub.2 ; y is 0-6; R.sup.3 is selected from R.sup.7, R, --(CH.sub.2).sub.y CH(R.sup.8)R, CN, --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)N(R.sup.4).sub.2 ; each R is independently selected from an optionally substituted group selected from C.sub.1-6 aliphatic, C.sub.6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 3-10 ring atoms; each R.sup.4 is independently selected from R, R.sup.7, --COR.sup.7, --CO.sub.2 R, --CON(R.sup.7).sub.2, --SO.sub.2 R.sup.7, --(CH.sub.2).sub.y R.sup.5, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; each R.sup.5 is independently selected from R, OR, CO.sub.2 R, (CH.sub.2).sub.y N(R.sup.7).sub.2, N(R.sup.7).sub.2, OR.sup.7, SR.sup.7, NR.sup.7 COR.sup.7, NR.sup.7 CON(R.sup.7).sub.2, CON(R.sup.7).sub.2, SO.sub.2 R.sup.7, NR.sup.7 SO.sub.2 R.sup.7, COR.sup.7, CN, or SO.sub.2 N(R.sup.7).sub.2 ; each R.sup.6 is independently selected from R.sup.7, F, Cl, (CH.sub.2).sub.y N(.sup.7).sub.2, N(R.sup.7).sub.2, OR.sup.7, SR.sup.7, NR.sup.7 COR.sup.7, NR.sup.7 CON(R.sup.7).sub.2, CON(R.sup.7).sub.2, SO.sub.2 R.sup.7, SO.sub.2 R.sup.7, NR.sup.7 SO.sub.2 R.sup.7, COR.sup.7, CN, or SO.sub.2 N(R.sup.7).sub.2 ; each R.sup.7 is independently selected from hydrogen or an optionally substituted C.sub.1-6 aliphatic group, or two R.sup.7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; R.sup.8 is selected from R, (CH.sub.2).sub.w OR.sup.7, (CH.sub.2).sub.w N(R.sup.4).sub.2, or (CH.sub.2).sub.w SR.sup.7 ; and each w is independently selected from 0-4.

38. The method according to claim 37, wherein Sp is selected from one of the following: ##STR338##

or a pharmaceutically acceptable salt thereof.

39. The method according to claim 38, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, amino, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; (c) Q is --CO.sub.2 --, --CONH--, or --SO.sub.2 NH--; (d) R.sup.2 is --NR.sup.4 (CH.sub.2).sub.y N(R.sup.4).sub.2, --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2 ; (f) R.sup.4 is R, R.sup.7, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; and (g) R.sup.5 is an optionally substituted group selected from C.sub.1-6 aliphatic, phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocyclyl.

40. The method according to claim 39, wherein: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, amino, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; (c) Q is --CO.sub.2 --, --CONH--, or --SO.sub.2 NH--; (d) R.sup.2 is --NR.sup.4 (CH.sub.2).sub.y N(R.sup.4).sub.2, --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2 ; (f) R.sup.4 is R, R.sup.7, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; and (g) R.sup.5 is an optionally substituted group selected from C.sub.1-6 aliphatic, phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocyclyl.

41. The method according to claim 39, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is selected from hydrogen, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, isopropyl, --CH(CH.sub.2 OH)phenyl, --CH(CH.sub.2 OH)ethyl, --CH(CH.sub.2 OH).sub.2, --CH(CH.sub.2 OH)isopropyl, --CH(CH.sub.2 OH)CH.sub.2 cyclopropyl, or an optionally substituted phenyl, benzyl, or isoxazolyl group; (b) T.sub.m R.sup.1 is selected from optionally substituted phenyl, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, CH.sub.2 OCH.sub.3, CH.sub.2 OH, OH, NH.sub.2, NHCH.sub.3, NHAc, NHC(O)NHCH.sub.3, or CH.sub.2 NHCH.sub.3 ; (c) Q is --CONH--, or --SO.sub.2 NH--; (d) R.sup.2 is --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, wherein R.sup.8 is OH or CH.sub.2 OH; and (e) R.sup.5 is --CH.sub.2 OH, --(CH.sub.2).sub.2 OH, isopropyl, or an optionally substituted group selected from pyrrolidin-1-yl, morpholin-4-yl, piperidin-1-yl, piperazin-1-yl, 4-methyl[1,4]diazepan-1-yl, 4-phenyl-piperazine-1-yl, pyridin-3-yl, pyridin-4-yl, imidazolyl, furan-2-yl, 1,2,3,4-tetrahydroisoquinoline, tetrahydrofuran-2-yl, cyclohexyl, phenyl, or benzyl.

42. The method according to claim 41, wherein: (a) R.sup.3 is selected from hydrogen, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, isopropyl, --CH(CH.sub.2 OH)phenyl, --CH(CH.sub.2 OH)ethyl, --CH(CH.sub.2 OH).sub.2, --CH(CH.sub.2 OH)isopropyl, --CH(CH.sub.2 OH)CH.sub.2 cyclopropyl, or an optionally substituted phenyl, benzyl, or isoxazolyl group; (b) T.sub.m R.sup.1 is selected from optionally substituted phenyl, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, CH.sub.2 OCH.sub.3, CH.sub.2 OH, OH, NH.sub.2, NHCH.sub.3, NHAc, NHC(O)NHCH.sub.3, or CH.sub.2 NHCH.sub.3 ; (c) Q is --CONH--, or --SO.sub.2 NH--; (d) R.sup.2 is --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, wherein R.sup.8 is OH or CH.sub.2 OH; and (e) R.sup.5 is --CH.sub.2 OH, --(CH.sub.2).sub.2 OH, isopropyl, or an optionally substituted group selected from pyrrolidin-1-yl, morpholin-4-yl, piperidin-1-yl, piperazin-1-yl, 4-methyl[1,4]diazepan-1-yl, 4-phenyl-piperazine-1-yl, pyridin-3-yl, pyridin-4-yl, imidazolyl, furan-2-yl, 1,2,3,4-tetrahydroisoquinoline, tetrahydrofuran-2-yl, cyclohexyl, phenyl, or benzyl.

43. The method according to claim 38, wherein said compound is of formula III-a: ##STR339##

or a pharmaceutically acceptable salt thereof.

44. The method according to claim 43, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, N(R.sup.4).sub.2, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; (c) Q is --CO.sub.2 --, --CONH--, or --SO.sub.2 NH--; (d) R.sup.2 is --NR.sup.4 (CH.sub.2).sub.y N(R.sup.4).sub.2, --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2 ; (f) R.sup.4 is R, R.sup.7, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; and (g) R.sup.5 is an optionally substituted group selected from phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocyclyl.

45. The method according to claim 44, wherein: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, N(R.sup.4).sub.2, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; (c) Q is --CO.sub.2 --, --CONH--, or --SO.sub.2 NH--; (d) R.sup.2 is --NR.sup.4 (CH.sub.2).sub.y N(R.sup.4).sub.2, --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2 ; (f) R.sup.4 is R, R.sup.7, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; and (g) R.sup.5 is an optionally substituted group selected from phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocyclyl.

46. A method of inhibiting ERK-2, Aurora-2, GSK-3, CDK-2, AKT3, or Lck activity in a biological sample, which method comprises contacting said sample with a compound of formula I: ##STR340##

or a pharmaceutically acceptable salt thereof, wherein: Sp is a spacer group comprising a 5-membered heteroaromatic ring, wherein Ring A and QR.sup.2 are attached to Sp at non-adjacent positions; and wherein Sp has up to two R.sup.6 substituents, provided that two substitutable carbon ring atoms in Sp are not simultaneously substituted by R.sup.6 ; Z.sup.1 is N and Z.sup.2 is CH; T is a linker group selected from --NH--, --CH.sub.2 --, --CO--, or a a saturated or unsaturated C.sub.1-6 alkylidene chain which is optionally substituted, and wherein up to two saturated carbons of the chain are optionally replaced by --C(O)--, --C(O)C(O)--, --CONR.sup.7 --, --CONR.sup.7 NR.sup.7 --, --CO.sub.2 --, --OC(O)--, --NR.sup.7 CO.sub.2 --, --O--, --NR.sup.7 CONR.sup.7 --, --OC(O)NR.sup.7 --, --NR.sup.7 NR.sup.7 --, --NR.sup.7 CO--, --S--, --SO--, --SO.sub.2 --, --NR.sup.7 --, --SO.sub.2 NR.sup.7 --, or --NR.sup.7 SO.sub.2 --; Q is --CO.sub.2 --, --C(O)NR.sup.7 --, or --S(O)NR.sup.7 --; U is selected from --NR.sup.7 --, --NR.sup.7 CO--, --NR.sup.7 CONR.sup.7 --, --NR.sup.7 CO.sub.2 --, --O--, --CONR.sup.7 --, --CO--, --CO.sub.2 --, --OC(O)--, --NR.sup.7 SO.sub.2 --, --SO.sub.2 NR.sup.7 --, --NR.sup.7 SO.sub.2 NR.sup.7 --, or --SO.sub.2 --; m and n are each independently selected from zero or one; R.sup.1 is selected from hydrogen, CN, halogen, R, N(R.sup.7).sub.2, OR, or OH; R.sup.2 is selected from --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, --N(R.sup.4).sub.2, or --NR.sup.4 (CH.sub.2).sub.y N(R.sup.4).sub.2 ; y is 0-6; R.sup.3 is selected from R.sup.7, R, --(CH.sub.2).sub.y CH(R.sup.8)R, CN, --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)N(R.sup.4).sub.2 ; each R is independently selected from an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, a heteroaryl ring having 5-10 ring atoms, or a heterocyclyl ring having 3-10 ring atoms; each R.sup.4 is independently selected from R, R.sup.7, --COR.sup.7, --CO.sub.2 R, --CON(R.sup.7).sub.2, --SO.sub.2 R.sup.7, --(CH.sub.2).sub.y R.sup.5, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; each R.sup.5 is independently selected from R, OR, CO.sub.2 R, (CH.sub.2).sub.y N(R.sup.7).sub.2, N(R.sup.7).sub.2, OR.sup.7, SR.sup.7, NR.sup.7 COR.sup.7, NR.sup.7 CON(R.sup.7).sub.2, CON(R.sup.7).sub.2, SO.sub.2 R.sup.7, NR.sup.7 SO.sub.2 R.sup.7, COR.sup.7, CN, or SO.sub.2 N(R.sup.7).sub.2 ; each R.sup.6 is independently selected from R.sup.7, F, Cl, (CH.sub.2).sub.y N(R.sup.7).sub.2, N(R.sup.7).sub.2, OR.sup.7, SR.sup.7, NR.sup.7 COR.sup.7, NR.sup.7 CON(R.sup.7).sub.2, CON(R.sup.7).sub.2, SO.sub.2 R.sup.7, NR.sup.7 SO.sub.2 R.sup.7, COR.sup.7, CN, or SO.sub.2 N(R.sup.7).sub.2 ; each R.sup.7 is independently selected from hydrogen or an optionally substituted C.sub.1-6 aliphatic group, or two R.sup.7 on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring; R.sup.8 is selected from R, (CH.sub.2).sub.w OR.sup.7, (CH.sub.2).sub.w N(R.sup.4).sub.2, or (CH.sub.2).sub.w SR.sup.7 ; and each w is independently selected from 0-4.

47. The method according to claim 46, wherein Sp is selected from one of the following: ##STR341##

or a pharmaceutically acceptable salt thereof.

48. The method according to claim 47, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, amino, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; (c) Q is --CO.sub.2 --, --CONH--, --SO.sub.2 NH--; (d) R.sup.2 is --NR.sup.4 (CH.sub.2).sub.y N(R.sup.4).sub.2, --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2 ; (f) R.sup.4 is R, R.sup.7, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; and (g) R.sup.5 is an optionally substituted group selected from C.sub.1-6 aliphatic, phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocyclyl.

49. The method according to claim 48, wherein: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, amino, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; (c) Q is --CO.sub.2 --, --CONH--, or SO.sub.2 NH--; (d) R.sup.2 is --NR.sup.4 (CH.sub.2).sub.y N(R.sup.4).sub.2, --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2 ; (f) R.sup.4 is R, R.sup.7, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; and (g) R.sup.5 is an optionally substituted group selected from C.sub.1-6 aliphatic, phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocyclyl.

50. The method according to claim 48, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is selected from hydrogen, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, isopropyl, --CH(CH.sub.2 OH)phenyl, --CH(CH.sub.2 OH)ethyl, --CH(CH.sub.2 OH).sub.2, --CH(CH.sub.2 OH)isopropyl, --CH(CH.sub.2 OH)CH.sub.2 cyclopropyl, or an optionally substituted phenyl, benzyl, or isoxazolyl group; (b) T.sub.m R.sup.1 is selected from optionally substituted phenyl, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, CH.sub.2 OCH.sub.3, CH.sub.2 OH, OH, NH.sub.2, NHCH.sub.3, NHAc, NHC(O)NHCH.sub.3, or CH.sub.2 NHCH.sub.3 ; (c) Q is --CONH--, or --SO.sub.2 NH--; (d) R.sup.2 is --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, wherein R.sup.8 is OH or CH.sub.2 OH; and (e) R.sup.5 is --CH.sub.2 OH, --(CH.sub.2).sub.2 OH, isopropyl, or an optionally substituted group selected from pyrrolidin-1-yl, morpholin-4-yl, piperidin-1-yl, piperazin-1-yl, 4-methyl[1,4]diazepan-1-yl, 4-phenyl-piperazine-1-yl, pyridin-3-yl, pyridin-4-yl, imidazolyl, furan-2-yl, 1,2,3,4-tetrahydroisoquinoline, tetrahydrofuran-2-yl, cyclohexyl, phenyl, or benzyl.

51. The method according to claim 50, wherein: (a) R.sup.3 is selected from hydrogen, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, isopropyl, --CH(CH.sub.2 OH)phenyl, --CH(CH.sub.2 OH)ethyl, --CH(CH.sub.2 OH).sub.2, --CH(CH.sub.2 OH)isopropyl, --CH(CH.sub.2 OH)CH.sub.2 cyclopropyl, or an optionally substituted phenyl, benzyl, or isoxazolyl group; (b) T.sub.m R.sup.1 is selected from optionally substituted phenyl, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, CH.sub.2 OCH.sub.3, CH.sub.2 OH, OH, NH.sub.2, NHCH.sub.3, NHAc, NHC(O)NHCH.sub.3, or CH.sub.2 NHCH.sub.3 ; (c) Q is --CONH--, or --SO.sub.2 NH--; (d) R.sup.2 is --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2, wherein R.sup.8 is OH or CH.sub.2 OH; and (e) R.sup.5 is --CH.sub.2 OH, --(CH.sub.2).sub.2 OH, isopropyl, or an optionally substituted group selected from pyrrolidin-1-yl, morpholin-4-yl, piperidin-1-yl, piperazin-1-yl, 4-methyl[1,4]diazepan-1-yl, 4-phenyl-piperazine-1-yl, pyridin-3-yl, pyridin-4-yl, imidazolyl, furan-2-yl, 1,2,3,4-tetrahydroisoquinoline, tetrahydrofuran-2-yl, cyclohexyl, phenyl, or benzyl.

52. The method according to claim 47, wherein said compound is of formula III-a: ##STR342##

or a pharmaceutically acceptable salt thereof.

53. The method according to claim 52, wherein said compound has one or more features selected from the group consisting of: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, N(R.sup.4).sub.2, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; (c) Q is --CO.sub.2 --, --CONH--, or --SO.sub.2 NH--; (d) R.sup.2 is --NR.sup.4 (CH.sub.2).sub.y N(R.sup.4).sub.2, --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH(R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2 ; (f) R.sup.4 is R, R.sup.7, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; and (g) R.sup.5 is an optionally substituted group selected from phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocyclyl.

54. The method according to claim 53, wherein: (a) R.sup.3 is hydrogen, carbocyclyl, --CH(R.sup.8)R, or an optionally substituted group selected from C.sub.1-4 aliphatic, 3-6 membered heterocyclic, or a 5-6 membered aryl or heteroaryl ring; (b) T.sub.m R.sup.1 is hydrogen, N(R.sup.4).sub.2, OH, 3-6 membered carbocyclyl, or an optionally substituted group selected from C.sub.1-6 aliphatic or a 5-6 membered aryl or heteroaryl ring; (c) Q is --CO.sub.2 --, --CONH--, or --SO.sub.2 NH--; (d) R.sup.2 is --NR.sup.4 (CH.sub.2).sub.y N(R.sup.4).sub.2, --(CH.sub.2).sub.y R.sup.5, --(CH.sub.2).sub.y CH (R.sup.5).sub.2, or --(CH.sub.2).sub.y CH(R.sup.8)CH(R.sup.5).sub.2 ; (f) R.sup.4 is R, R.sup.7, or --(CH.sub.2).sub.y CH(R.sup.5).sub.2 ; and (g) R.sup.5 is an optionally substituted group selected from phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocyclyl.

55. A method of treating a disease selected from transplant rejection, melanoma, or a cancer selected from colon, breast, lung, kidney, ovary, pancreas, CNS, or cancer of the gastric tract in a patient, which method comprises administering to said patient a compound selected from the group consisting of: 4-(2-Amino-5-phenyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid dimethylamide; {4-[2-Amino-5-(3-chloro-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-pyrrolidin- 1-yl-methanone; {4-[2-Amino-5-(3-chloro-2-fluoro-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-py rrolidin-1-yl-methanone; 4-(2-Amino-5-phenyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-pyridin-3-yl-ethyl)-amide; [4-(2-Amino-5-phenyl-pyrimidin-4-yl)-1H-pyrrol-2-yl]-morpholin-4-yl-methano ne; [4-(2-Amino-5-phenyl-pyrimidin-4-yl)-1H-pyrrol-2-yl]-[1,4']bipiperidinyl-1' -yl-methanone; {4-[2-Amino-5-(3,4-dimethoxy-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-(3-hyd roxy-piperidin-1-yl)-methanone; {4-[2-Amino-5-(3,4-dimethoxy-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-[1,4'] bipiperidinyl-1'-yl-methanone; [4-(2-Amino-5-m-tolyl-pyrimidin-4-yl)-1H-pyrrol-2-yl]-[1,4']bipiperidinyl-1 '-yl-methanone; {4-[2-Amino-5-(3-chloro-2-fluoro-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-[1 ,4']bipiperidinyl-1'-yl-methanone; [4-(2-Amino-5-m-tolyl-pyrimidin-4-yl)-1H-pyrrol-2-yl]-(4-hydroxy-piperidin- 1-yl)-methanone; [4-(2-Amino-5-phenyl-pyrimidin-4-yl)-1H-pyrrol-2-yl]-[4-(2-fluoro-phenyl)-p iperazin-1-yl]-methanone; [4-(2-Amino-5-phenyl-pyrimidin-4-yl)-1H-pyrrol-2-yl]-(4-phenyl-piperazin-1- yl)-methanone; [4-(2-Amino-5-phenyl-pyrimidin-4-yl)-1H-pyrrol-2-yl]-[4-(4-fluoro-phenyl)-3 ,6-dihydro-2H-pyridin-1-yl]-methanone; [4-(2-Amino-5-phenyl-pyrimidin-4-yl)-1H-pyrrol-2-yl]-(4-pyridin-2-yl-pipera zin-1-yl)-methanone; {4-[2-Amino-5-(3,4-dimethoxy-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-morpho lin-4-yl-methanone; 4-[2-Amino-5-(3,4-dimethoxy-phenyl)-pyrimidin-4-yl]-1H-pyrrole-2-carboxylic acid (2-pyridin-3-yl-ethyl)-amide; [4-(2-Amino-5-m-tolyl-pyrimidin-4-yl)-1H-pyrrol-2-yl]-morpholin-4-yl-methan one; 4-(2-Amino-5-m-tolyl-pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (2-pyridin-3-yl-ethyl)-amide; 4-[2-Amino-5-(3-chloro-phenyl)-pyrimidin-4-yl]-1H-pyrrole-2-carboxylic acid (2-pyridin-3-yl-ethyl)-amide; {4-[2-Amino-5-(3-chloro-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-[4-(2-fluor o-phenyl)-piperazin-1-yl]-methanone; {4-[2-Amino-5-(3-chloro-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-(4-phenyl-p iperazin-1-yl)-methanone; {4-[2-Amino-5-(3-chloro-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-[4-(4-fluor o-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-methanone; {4-[2-Amino-5-(3-chloro-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-(3,4-dihydr o-1H-isoquinolin-2-yl)-methanone; {4-[2-Amino-5-(3-chloro-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-(4-pyridin- 2-yl-piperazin-1-yl)-methanone; {4-[2-Amino-5-(3-chloro-2-fluoro-phenyl)-pyrimidin-4-yl]-1H-pyrrol-2-yl}-mo rpho