Carbazole and carboline kinase inhibitors

A compound of formula I

• stereoisomers or pharmaceutically acceptable salts, thereof, wherein:
• the compound of formula (I) is selected from
• R1 is —CONH2;
• D is N or CR5;
• E is N, N(+)—O(−) or CR6;
• Z is a bond, NR, CRR, —CH═CH—, O, or S;
• R2 is C3-8 cycloalkyl optionally substituted with 0-3 Ra, C3-8 carbocycle optionally substituted with 0-3 Ra, C6-10 aryl substituted with 0-3 Ra, or a 5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 Ra;
• R4 is independently hydrogen, halo, C1-6 alkyl substituted with 0-3 Ra, —CO—NR7—R8, —CO—NR7—SO2—R8, —(CH2)rO—R10, —(CH2)rSR10, —(CH2)rOC(O)—R10, —NR7R8, —NR—CO—R10, —NR—CO—O—R9, NR—CO—NR7—R8, —CO—O—R, SO2R10, a 5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 Ra;
• R5 and R6 are independently H, halo, or C1-4 alkyl;
• R is independently H, or C1-4 alkyl;
• R7 and R8 are independently hydrogen, C1-6 alkyl substituted with 0-2 R7a, C3-6 cycloalkyl substituted with 0-2 R7a, a 5-7 membered heterocyclic system containing 1-2 heteroatoms selected from N, O, and S, substituted with 0-2 R7a;
• a 5-6 membered heteroaryl containing 1-2 heteroatoms selected from N, O, and S, substituted with 0-2 R7a;
• alternatively R7 and R8, along with nitrogen atom to which they are attached, join to form a 5-10 membered heterocyclic ring containing 0-1 additional heteroatoms selected from N, O or S, substituted with 0-2 R7a;
• R7a is hydrogen, ═O, F, Cl, Br, OCF3, CF3, CHF2, CN, NO2, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rC(O)ORb, —(CH2)rOC(O)Rb, —(CH2)rNR11R12, —(CH2)rC(O)NR11R12, —(CH2)rNRbC(O)Rc, —(CH2)rNRbC(O)ORc, —NRbC(O)NR11R12, —S(O)pNR11R12, —NRbS(O)pRc, —S(O)Rc, —S(O)2Rc, C1-6 alkyl substituted with 0-2 Ra, C1-6 haloalkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-1 Ra, or —(CH2)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-2 Ra, alternatively two R7a on adjacent or the same carbon atom form a cyclic acetal of the formula —O—(CH2)n—O—, wherein n is selected from 1 or 2;
• R9 is C1-6 alkyl optionally substituted with 0-1Ra, C3-6 cycloalkyl optionally substituted with Ra, C6-10 aryl substituted with 0-3 Ra, or a 5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 Ra;
• R10 is hydrogen, C1-6 alkyl optionally substituted with 0-1 Ra, C3-6 cycloalkyl optionally substituted with 0-1 Ra, C6-10 aryl substituted with 0-3 Ra, or a 5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 Ra;
• or
• R11 and R12 are independently hydrogen, C1-6 alkyl substituted with 0-1 Rd, C3-6 cycloalkyl substituted with 0-1 Rd, or (CH2)r-phenyl substituted with 0-1 Rd;
• alternatively R11 and R12, along with nitrogen atom to which they are attached, join to form a 5-10 membered heterocyclic ring containing 1-4 heteroatoms selected from N, O, and S;
• Ra is hydrogen, F, Cl, Br, OCF3, CF3, CHF2, CN, NO2, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rC(O)ORb, —(CH2)rOC(O)Rb, —(CH2)rNR11R12, —(CH2)rC(O)NR11R12, —(CH2)rNRbC(O)Rc, —(CH2)rNRbC(O)ORc, —NRbC(O)NR11R12, —S(O)pNR11R12, —NRbS(O)pRc, —S(O)Rc, —S(O)2Rc, C1-6 alkyl, C1-6 haloalkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-2 Rb, or —(CH2)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-2 Rb, alternatively two Ra on adjacent or the same carbon atom form a cyclic acetal of the formula —O—(CH2)n—O—, or —O—CF2—O—, wherein n is selected from 1 or 2;
• Rb is hydrogen, C1-6 alkyl substituted with 0-2 Rd, C1-6 haloalkyl, C3-6 cycloalkyl substituted with 0-2 Rd, or (CH2)r-phenyl substituted with 0-2 Rd;
• Rc is C1-6 alkyl, C3-6 cycloalkyl, or (CH2)r-phenyl;
• Rd is hydrogen, F, Cl, Br, OCF3, CF3, CN, NO2, —ORe, —(CH2)rC(O)Rb, —NReRe, —NReC(O)ORc, C1-6 alkyl, or (CH2)r-phenyl, pyrrolidinyl, imidazolyl, morpholinyl, pyrrazolyl, 1,4-diazepanyl, piperidinyl substituted with 0-1 Rf, 1,4-oxazepanyl, piperazinyl, 1,1-dioxothiomorpholinyl;
• Re is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, or (CH2)r-phenyl;
• Rf is hydrogen, C1-6 alkyl, —COCH3, —CH2CH2-COCH3, —CH2CH2—OCH3, or morpholinyl;
• r is 0, 1, 2, 3,or 4.