Patent ID: 6545054
Filing Date: 2003-04-08
Classification: A61P,C07C,C07D

Abstract:
A compound of formula IIa or IIb: wherein:D is where R14 and R16 are independently selected from the group consisting of H, â€”(CH2)0-12â€”SH, â€”(CH2)1-12â€”OH, â€”(CH2)0-12â€”NH2, â€”(CH2)0-12â€”12â€”C0-6â€”(CH2)0-12â€”F, â€”(CH2)0-12â€”Br, â€”(CH2)0-12â€”I, â€”(CF2)1-5â€”(CF3), â€”(CH2)0-12â€”(CF3), â€”(CH2)0-12â€”CN, â€”(CH2)0-12â€”NO2, â€”(CH2)0-12â€”CHO, â€”C1-12alkyl, â€”C0-12alkylâ€”N(Raâ€²)(R3â€²)0-1â€”C0-12alkyl, â€”(CH2)0-12â€”CH=(CH)0-1â€”(CH2)1-12(CH3)0-1, â€”Oâ€”C1-12alkylâ€”N(Raâ€²)(R bâ€²)0-1â€”C0-12alkYl, â€”C1-12alkylâ€”Oâ€”C1-12alkyl, â€”C0-12alkylâ€”Oâ€”C2-12alkenyl, â€”C2-12alkenylâ€”Oâ€”C1-12alkyl, â€”C2-12alkinyl, â€”C0-12alkylâ€”Oâ€”C1-6alkinyl, â€”C0-12alkinylâ€”Oâ€”C0-12alkylâ€”, â€”C6-10aryl, â€”C0-12alkylâ€”Oâ€”C6-10aryl, â€”S(=O)10-12â€”C1-12alkylâ€”N(Raâ€²)(Rbâ€²)0-1â€”C1-12alkyl, â€”C0-12alkylâ€”S(=O)0-2â€”C1-12alkyl, â€”C0-12alkylâ€”S(=O)0-2â€”C2-12alkenyl, â€”C2-12alkenylâ€”S(=O)0-2â€”C1-12alkyl, â€”C0-12alkylâ€”S(=O)0-2â€”C1-6alkinyl, â€”C0-12alkinylâ€”S(=O)0-2â€”C0-12alkylâ€”, â€”C0-12alkylâ€”S(=O)0-2â€”C6-10aryl, â€”C0-12alkylC6-10aryl, â€”C2-12alkenylC6-10aryl, â€”C2-12alkinylC6aryl, â€”COOH, â€”C0-12alkylâ€”COOâ€”C1-12alkyl, â€”C0-12alkylâ€”COOâ€”C2-12alkenyl, â€”C1-12alkylâ€”COOâ€”C2-12alkinyl, â€”C2-12alkenylâ€”COOâ€”C1-12alkyl, â€”C2-12alkinylâ€”COOâ€”C1-12alkyl, â€”C2-6 12alkenylâ€”COOâ€”C1-12alkyl, â€”C2-12alkinylâ€”COOâ€”C1-12alkyl, â€”C6-10aryl monocyclic or bicyclic ring structure, and a three to ten membered heterocyclic monocyclic or bicyclic heterocyclic ring structure containing 1-4 heteroatoms selected from N, O and S;Raâ€² and Rbâ€² are each independently selected from the group consisting of H, â€”CN, â€”C0-6alkylâ€”SH, â€”C0-6alkylâ€”OH, â€”C0-6alkylâ€”CHO, â€”C0-6alkylâ€”COOH, â€”C0-6alkylâ€”N Rcâ€²Rdâ€², â€”C0-6alkenylâ€”SH, â€”C0-6alkenylâ€”OH, â€”C0-6alkenylâ€”CHO, â€”C0-6alkenylâ€”COOH, â€”C0-6alkenylâ€”N Rcâ€²Rdâ€², â€”C0-6alkinylâ€”SH, â€”C0-6alkinylâ€”OH, â€”C0-6alkinylâ€”CHO, â€”C0-6alkinylâ€”COOH, â€”C0-6alkinylâ€”N Rcâ€²Rdâ€², â€”C1-6alkyl, â€”(CH2)1-6â€”C0-6â€”(CH2)1-6â€”F, â€”(CH2)1-6â€”Br, â€”(CH2)1-6â€”I, â€”(CF2)1-3â€”(CF3), â€”(CH2)1-6â€”(CF3), â€”(CH2)1-6â€”CN, â€”(CH2)0-6â€”NO2, â€”C1-6alkyl, â€”(CH2)0-4â€”CH=(CH)0-1â€”(CH2)0-4(CH3)0-1, â€”CO0-5alkylâ€”Oâ€”C1-6alkyl, â€”C0-5alkylâ€”Oâ€”C2-6alkenyl, â€”C2-6alkenylâ€”Oâ€”C1-6alkyl, â€”C2-6alkinyl, â€”C0-5alkylâ€”Oâ€”C2-6alkinyl, â€”C2-6alkinylâ€”Oâ€”C1-6alkylâ€”, â€”C6-10aryl, â€”C0-6alkylâ€”Oâ€”C6-10aryl, â€”C0-6alkylâ€”S(=O)0-2â€”C1-6alkyl, â€”C0-6alkylâ€”S(=O)0-2â€”C2-6alkenyl, â€”C2-6alkenylâ€”S(=O)0-2â€”C16alkyl, â€”C0-6alkylâ€”S(=O)0-2â€”C1-6alkinyl, â€”C2-6alkinylâ€”S(=O)0-2â€”C1-6alkylâ€”, â€”C0-6alkylâ€”S(=O)0-2â€”C6-10aryl, â€”C0-6alkylC6-10aryl, â€”C2-6alkenylC6-10aryl, â€”C2-6alkinylC6-10aryl, â€”C0-6alkylâ€”COOâ€”C1-6alkyl, â€”C0-6alkylâ€”COOâ€”C2-6alkenyl, â€”C0-1alkylâ€”COOâ€”C2-6alkinyl, â€”C2-6alkenylâ€”COOâ€”C1-6alkyl, â€”C2-6alkinylâ€”COOâ€”C1-6alkyl, â€”C2-6alkenylâ€”COOâ€”C1-6alkyl, â€”C2-6alkinylâ€”COOâ€”C1-6alkyl, a three to ten membered monocyclic or bicyclic heterocyclic ring structure containing 14 heteroatoms selected from N, O and S, and Ra, and Rb, taken together or with a carbon atom having a free hydrogen to form an intracyclic bond resulting in a three to ten membered heterocyclic ring having from 1-4 heteroatoms selected from N, O and S, where the alkyl, alkenyl, and alkinyl portions of said Raâ€² and Rbâ€², may be linear or branched and substituted with from 0-6 members independently selected from the group consisting of â€”I, â€”F, â€”Br, â€”OH, â€”NO2, â€”CF3, â€”CHO, â€”NH2 and â€”COOH; Rcâ€² and Rdâ€² are independently selected from the group consisting of H, C1-6alkylâ€”CHO, C0-6alkylâ€”COOH, C0-6alkylâ€”COCl, C0-6alkylâ€”COI, C0-6alkylâ€”COF,C0-6alkylâ€”COBr, C0-6alkylâ€”COOâ€”C1-6alkyl, C1-6alkylâ€”COOâ€”C2-6alkenyl, C1-6alkylâ€”COOâ€”C2-6alkinyl, C0-6alkylâ€”COOâ€”C0-6alkylâ€”CF3, C1-6alkylâ€”COOâ€”C6-10aryl â€”COOH, C0-6alkylâ€”CN, C2-6alkylâ€”NO2, C1-6alkylâ€”C0-6C1-6alkylâ€”Br, C1-6alkylâ€”I, C1-6alkylâ€”F, C1-6alkylâ€”CF3, C1-6alkylâ€”CF2â€”CF3, C1-6alkylâ€”SH, C1-6alkyl, C1-6alkenyl, C1-6alkynyl, C1-6alkyloxy, C1-6alkenyloxy, C1-6alkylthio, C1-6alkenylthio, C3-8cycloalkyl, C6-10aryl, C1-6alkylC6-10aryl, a three to ten membered heterocyclic monocyclic or bicyclic ring system containing 1-4 heteroatoms selected from N, O and S; and C1-4alkylheterocyclic monocyclic or bicyclic ring system having in the ring system 3 to 10 atoms with 1-14 4 of such atoms being selected from N, O and S; R18 is a member selected from the group consisting H, â€”(CH2)0-12â€”SH, â€”(CH2)0-12â€”OH, â€”(CH2)0-12â€”NH2, â€”(CH2)0-12â€”Cl, â€”(CH2)0-12â€”F, â€”(CH2)0-12â€”Br, â€”(CH2)0-12â€”I, â€”(CF2)1-5â€”(CF3), â€”(CH2)0-12â€”(CF3), â€”(CH2)1-12â€”CN, â€”(CH2)0-12â€”NO2, â€”(CH2)0-12â€”CHO, â€”C0-12alkyl, â€”C0-12alkylâ€”N(R3â€²)(Rbâ€²)0-1â€”C0-12alkyl, â€”(CH2)0-12â€”CH=(CH)0-1â€”â€”(CH2)0-12(CH3)0-1, â€”Oâ€”C1-12alkylâ€”N(R3â€²)(Rbâ€²)0-1â€”C0-12alkyl, â€”C1-12alkylâ€”Oâ€”C1-12alkyl, â€”C0-12alkylâ€”Oâ€”C2-12alkenyl, â€”C2-12alkenylâ€”Oâ€”C1-12alkyl, â€”C2-12alkinyl, â€”C0-12alkylâ€”Oâ€”C1-6alkinyl, â€”C0-12alkinylâ€”Oâ€”C0-12alkylâ€”, â€”C6-10aryl, â€”C0-12alkylâ€”Oâ€”C6-10aryl, â€”S(=O)0-2â€”C1-12alkylâ€”N(Raâ€²)(Rbâ€²)01-â€”C1-12alkyl, â€”C0-12alkylâ€”S(=O)0-2â€”C1-12alkyl, â€”C1-12alkylâ€”S(=O)0-2â€”C2-12alkenyl, â€”C2-12alkenylâ€”S(=O)0-2â€”C1-12alkyl, â€”CO 2alkylâ€”S(=O)0-2â€”C1-6alkinyl, â€”C0-12alkinylâ€”S(=O)0-2â€”C0-12alkylâ€”, â€”C-12alkylâ€”S(=O)0-2â€”C6-10aryl, â€”C0-12alkylC6-10aryl, â€”C2-12alkenylC60-10aryl, â€”C2-12alkinylC6-10aryl, â€”COOH, â€”C0-12alkylâ€”COOâ€”C1-12alkyl, â€”C0-12alkylâ€”COOâ€”C2-12alkenyl, â€”C0-12alkylâ€”COOâ€”C2-12alkinyl, â€”C2-12alkenylâ€”COOâ€”C1-12alkyl, â€”C2-12alkinylâ€”COOâ€”C1-12alkyl, â€”C2-12alkenylâ€”COOâ€”C1-12alkyl, â€”C2-12alkinylâ€”COOâ€”C1-12alkyl, â€”C6-10aryl monocyclic or bicyclic ring structure, and a three to ten membered heterocyclic monocyclic or bicyclic heterocyclic ring structure containing 1-4 heteroatoms selected from N, O and S, wherein Rat and Rbâ€² are each as defined above; E is a C3-16 carbocyclic ring structure or a three to ten membered heterocyclic monocyclic or bicyclic ring structure system containing 14 heteroatoms selected from N, O and S, substituted with 0 to 4 R groups independently selected from the group consisting of H, â€”SH, â€”OH, â€”C0-6â€”F, â€”Br, â€”I, â€”CN, â€”NO2, â€”CHO, â€”COOH, â€”NRâ€²Râ€³ and a substituent member, wherein said substituent member is selected from the group consisting of a linear or branched C1-12alkyl group, a linear or branched C2-12alkenyl group, a linear or branched C2-12alkinyl group and a C3-12cycloalkyl group containing linear or branched chained portions, and wherein said substituent member contains 0 to 4 chain bridging groups independently selected from the group consisting of â€”NHâ€”, â€”Oâ€”, â€”Sâ€”, â€”S(=O)â€”, and â€”S(=O)2â€”, and wherein for each of said substituent member: (a) two hydrogens on the same carbon atom of said alkyl, alkenyl, alkinyl or cycloalkyl substituent member are replaced with =O or =N(Râ€²â€³); (b) one or more hydrogens, independently, on said alkyl, alkenyl, alkinyl or cycloalkyl substituent member or on the â€”NHâ€”chain bridging groups are replaced by Riv; or (c) one or more hydrogens, independently, on carbon atom(s) of said alkyl, alkenyl, alkinyl or cycloalkyl substituent member, on said â€”NHâ€”chain bridging group or on R1 , Râ€œ, R1 â€³or Riv are replaced to form an intracyclic bond resulting in a C3-12carbocyclic ring structure or a three to seven membered heterocyclic ring containing 1-4 heteroatoms selected from N, O and S; Râ€²,Râ€³, Râ€²â€³ and Riv are independently selected from the group consisting of H, â€”(CH2)0-12â€”SH, â€”(CH2)0-12â€”OH, â€”(CH2)0-12â€”NH2, â€”(CH2)0-12â€”Cl, (CH2)0-12â€”F, â€”(CH2)0-12â€”Br, â€”(CH2)0-12â€”I, â€”(CF2)1-5â€”(CF3), â€”(CH2)0-12â€”(CF3), â€”(CH2)0-12â€”CN, â€”(CH2)0-12â€”NO2, â€”(CH2)0-12â€”CHO, â€”C1-12alkyl, â€”C0-12alkylâ€”N(Ra)(Rb)0-1C0-12alkyl, â€”(CH2)0-12â€”CH=(CH) 0-1â€”(CH2)0-12(CH3)0-1, â€”Oâ€”C1-12alkylâ€”N(Ra )(Rb)0-1â€”C0-12alkyl, â€”C0-12alkylâ€”Oâ€”C1-12alkyl, â€”C0-12alkylâ€”Oâ€”C2-12alkenyl, â€”C2-12alkenylâ€”Oâ€”C1-12alkyl, â€”C2-12alkinyl, â€”C0-12alkylâ€”Oâ€”C1-6alkinyL, â€”C0-12alkinylâ€”Oâ€”C0-12alkylâ€”, â€”C6-10aryl, â€”C0-12alkylâ€”Oâ€”C6-10aryl, â€”S(=O)0-2â€”C1-12alkylâ€”N(Ra)(R Raâ€² and Rbâ€² are each independently selected from the group consisting of H, -CN,