Patent ID: 8314114

Claim:
A method of inhibiting receptor tyrosine kinase(s), dihydrofolate reductase, thymidylate synthase and/or dihydroorotate dehydrogenase activity in an animal or human in need thereof, comprising administering to said animal or human a therapeutically effective amount in unit dosage form of a compound of formula I: wherein both B and C rings may be completely or partially saturated or unsaturated with respect to bond 4b-8a, 5-6 and 7-8; X and/or Y=N, NH, O, S, CH 2 ; P=CR 4 R 5 wherein R 4 and R 5 =lower alkyl, alkene, alkyne, and all of R 1 and R 2 ; R 1 =an alkyl having C 2 to C 6 , a cycloalkyl having 6 or less carbons, alkene, alkyne, aryl, heteroaryl, substituted aryl, substituted heteroaryl, alkylaryl, alkylheteroaryl, substituted alkylaryl or alkylheteroaryl, and R 1 may be H when said C ring is partially or completely saturated or partially unsaturated; and R 2 =H, an alkyl, a cycloalkyl having 6 or less carbons, alkene, alkyne, aryl, heteroaryl, substituted aryl, substituted heteroaryl, alkylaryl, alkylheteroaryl, substituted alkylaryl or alkylheteroaryl; Z=S, O, NR 6 , S—CH 2 , CH 2 —S, O—CHR 6 , CHR 6 —O, NR 6 —CH 2 , CH 2 —NR 6 , CHR 6 —NR 7 or CR 6 R 7 , wherein R 6 and/or R 7 =H or a lower alkyl, alkene or alkyne having 6 or less C atoms; wherein Z may be attached to the C ring at positions 5, 6, 7, or 8 and may be attached to more than one of said positions 5, 6, 7, or 8 on the ring, wherein Z may be the same or different; wherein Z may be zero and R 3 may be directly attached to the C-ring at positions 5, 6, 7, and/or 8; wherein when the C-ring is saturated or partially saturated the substituted Z or R 3 creates chirality when P=C and R 6 and R 7 are different, then all stereoisomers thereof both separately and as racemic and/or diastereoisomeric mixtures are included; R 3 =H, alkyl, cycloalkyl, aryl, heteroaryl, substituted aryl, substituted heteroaryl, alkylaryl, alkylheteroaryl and substituted saturated or unsaturated alkylheteroaryl and alkylheterocyclic, alkylaryl, p-, m-, o-benzoyl-L-glutamate or 2,5-, 2,4-thienoyl-L-glutamate when the benzene and thiophene ring may or may not have additional substitutions including F, mono-, bi- and tricyclic aryl, heteroaryl or combinations thereof, ring substitutions including biphenyl, bipyridyl or a phenyl-pyridyl or a fused moiety including a quinoline or naphthyl including substituted systems including a 2-chloro,4-biphenyl and tricyclic and substituted tricyclic systems.