Inhibitors of prenyl-protein transferase

The compound of having Formula D

• wherein:
• R1b is selected from:
• 1) hydrogen,
• 2) aryl,
• 3) heterocyclyl,
• 4) C3-C10 cycloalkyl,
• 5) C2-C6 alkenyl,
• 6) C2-C6 alkynyl,
• 7) OR10,
• 8) R11S(O)m—,
• 9) R10C(O)NR10—,
• 10) (R10)2N—C(O)—,
• 11) CN,
• 12) NO2,
• 13) (R10)2N—C(NR10)—,
• 14) R10C(O)—,
• 15) R10OC(O)—,
• 16) N3,
• 17) —N(R10)2,
• 18) R11OC(O)NR10—, and
• 19) C1-C6 alkyl, said alkyl optionally substituted with one or more substituents selected from the following:
• a) aryl,
• b) heterocyclyl,
• c) C3-C10 cycloalkyl,
• d) C2-C6 alkenyl,
• e) C2-C6 alkynyl,
• f) R10O—,
• g) R11S(O)m—,
• h) R10C(O)NR10—,
• i) (R10)2N—C(O)—,
• j) CN,
• k) (R10)2N—C(NR10)—,
• l) R10C(O)—,
• m) R10OC(O)—,
• n) N3,
• o) N(R10)2, or
• p) R11OC(O)—NR10—;
• R2 is selected from:
• 1) oxo,
• 2) C1-8 alkyl,
• 3) C2-8 alkenyl,
• 4) C2-8 alkynyl,
• 5) aryl,
• 6) heterocyclyl,
• 7) (CO)NR6R7, and
• 8) (CO)OR6,
• wherein said alkyl, alkenyl, alkynyl, aryl and heterocyclyl is optionally substituted with one or more of the following:
• 1) aryl or heterocyclyl, optionally substituted with:
• a) C1-4 alkyl,
• b) (CH2)pOR6,
• c) (CH2)pNR6R7,
• d) halogen, or
• e) CN,
• 2) C3-6 cycloalkyl,
• 3) OR6,
• 4) S(O)mR4,
• 5) NR6R7,
• 6) NR6(CO)R7,
• 7) NR6(CO)NR5R7,
• 8) O(CO)NR6R7,
• 9) O(CO)OR6,
• 10) (CO)NR6R7,
• 11) SO2NR6R7,
• 12) NR6SO2R4,
• 13) (CO)R6,
• 14) (CO)OR6,
• 15) N3, and
• 16) F, or
• two R2's are attached to the same C atom and are combined to form —(CH2)u— wherein one of the carbon atoms is optionally replaced by a moiety selected from:
• O, S(O)m, —NC(O)—, and —N(COR10)—;
• R3 is selected from:
• a) C1-4 alkyl, unsubstituted or substituted with:
• aa) C1-4 alkoxy,
• bb) NR6R7,
• cc) C3-6 cycloalkyl,
• dd) aryl,
• ee) heterocyclyl,
• ff) OH,
• gg) —S(O)mR4, or
• hh) —C(O)NR6R7,
• b) aryl,
• c) heterocyclyl,
• d) halogen,
• e) OR6,
• f) NR6R7,
• g) CN,
• h) NO2,
• i) CF3,
• j) —S(O)mR4,
• k) —C(O)NR6R7, or
• l) C3-C6 cycloalkyl;
• R4 is selected from:
• 1) C1-6 alkyl,
• 2) C3-6 cycloalkyl,
• 3) heterocyclyl, and
• 4) aryl,
• said alklyl, cycloalkyl, and heterocyclyl optionally substituted with one or more of the following:
• a) C1-4 alkoxy,
• b) aryl,
• c) heterocyclyl,
• d) halogen,
• e) OH,
• f) (CO)R11,
• g) SO2R11, or
• h) N(R10)2;
• R5, R6 and R7 are independently selected from:
• 1) H,
• 2) C1-6 alkyl,
• 3) C3-6 cycloalkyl,
• 4) heterocyclyl,
• 5) aryl,
• 6) aroyl,
• 7) heteroaroyl,
• 8) arylsulfonyl, and
• 9) heteroarylsulfonyl,
• said alkyl, cycloalkyl, heterocyclyl, aryl, aroyl, heteroaroyl, arylsulfonyl, and heteroarylsulfonyl is optionally substituted with one or more of the following:
• a) C1-4 alkoxy,
• b) aryl,
• c) heterocyclyl,
• d) halogen,
• e) OH,
• f) (CO)R11,
• g) SO2R11, or
• h) N(R10)2,
• R6 and R7 may be joined in a ring, and independently,
• R5 and R7 may be joined in a ring;
• R8 is selected from:
• 1) aryl,
• 2) heterocyclyl,
• 3) C3-C10 cycloalkyl,
• 4) C2-C6 alkenyl,
• 5) C2-C6 alkynyl,
• 6) perfluoroalkyl,
• 7) halogen,
• 8) R10O—,
• 9) R11S(O)m—,
• 10) R10C(O)NR10—,
• 11) (R10)2NC(O)—,
• 12) R102N—C(NR10)—,
• 13) CN,
• 14) NO2,
• 15) R10C(O)—,
• 16) R10OC(O)—,
• 17) N3,
• 18) N(R10)2,
• 19) R11OC(O)NR10—, and
• 20) C1-C6 alkyl, said alkyl optionally substituted with the following:
• a) aryl,
• b) heterocyclyl,
• c) C3-C10 cycloalkyl,
• d) C2-C6 alkenyl,
• e) C2-C6 alkynyl,
• f) perfluoroalkyl,
• g) halogen,
• h) R10O—,
• i) R11S(O)m—,
• j) R10C(O)NR10—,
• k) (R10)2NC(O)—,
• l) R102N—C(NR10)—,
• m) CN,
• n) R10C(O)—,
• o) R10OC(O)—,
• p) N3,
• q) —N(R10)2, and
• r) R11OC(O)NR10—;
• R9 is selected from:
• 1) C2-C6 alkenyl,
• 2) C2-C6 alkynyl,
• 3) perfluoroalkyl,
• 4) halogen,
• 5) R10O,
• 6) R11S(O)m—,
• 7) R10C(O)NR10—,
• 8) (R10)2NC(O)—,
• 9) R102N—C(NR10)—,
• 10) CN,
• 11) NO2,
• 12) R10C(O)—,
• 13) R10OC(O)—,
• 14) N3,
• 15) —N(R10)2,
• 16) R11OC(O)NR10—, or
• 17) C1-C6 alkyl, said alkyl optionally substituted with one or more of the following:
• a) perfluoroalkyl,
• b) halogen,
• c) R10O—,
• d) R11S(O)m—,
• e) R10C(O)NR10—,
• f) (R10)2NC(O)—,
• g) R102N—C(NR10)—,
• h) CN,
• i) R10C(O)—,
• j) R10OC(O)—,
• k) N3,
• l) —N(R10)2, or
• m) R11OC(O)NR10—;
• R10 is selected from:
• 1) hydrogen,
• 2) C1-C6 alkyl,
• 3) benzyl,
• 4) aryl, and
• 5) heterocyclyl;
• R11 is selected from:
• 1) C1-C6 alkyl,
• 2) aryl, and
• 3) heterocyclyl;
• V is selected from:
• phenyl or naphthyl;
• Z1 is selected from:
• phenyl or naphthyl;
• heteroaryl is:
• any stable monocyclic or bicyclic carbon ring of up to 7 members in each ring, wherein at least one ring is aromatic and wherein from one to four carbon atoms are replaced by heteroatoms selected from the group consisting of N, O, and S;
• heterocyclyl is:
• a stable 5- to 7-membered monocyclic or stable 8- to 11-membered bicyclic heterocyclic ring which is either saturated or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O, and S;
• m is 0, 1 or 2;
• n is 0, 1, 2, 3 or 4;
• p is 1, 2, or 3;
• q is 0, 1 or 2;
• r is 0 to 5;
• s is 0, 1, 2 or 3;
• t is 0, 1, 2, or 3;
• and u is 4 or 5;
• or a pharmaceutically acceptable salt or stereoisomer thereof.