Synthesis and cytotoxic activity of pyridylthio, pyridylsulfinyl, and pyridylsulfonyl methyl acrylates.
Nineteen 2-pyridylthio (2), 2-pyridylsulfinyl (3) or 2-pyridylsulfonyl (4) derivatives of (Z)-methyl acrylate were synthesized in order to investigate the effect of the oxidation state of the sulfur atom, and the position and nature of pyridyl substituents on cytotoxic activity. Analogous sulfinyl and sulphonyl derivatives were equipotent, and more potent than analogous thio derivatives, in an vitro L1210 screen. In most cases, incorporation of nuclear trifluoromethyl and chloro substituents at various positions of the pyridyl ring of the sulfinyl derivatives (compounds 3b-3h) decreased activity relative to the unsubstituted sulfinyl 3a (ED50 0.43 micrograms/ml). Compounds 3b, 3d and 3i exhibited weak antineoplastic activity in an in vivo P388 screen at a dose of 5 mg/kg.
Phillips
O A
OA
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Nelson
L A
LA
Knaus
E E
EE
Allen
T M
TM
Fathi-Afshar
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents