Synthesis of 2,4-disubstituted thiazoles and selenazoles as potential antifilarial and antitumor agents. 2. 2-Arylamido and 2-alkylamido derivatives of 2-amino-4-(isothiocyanatomethyl)thiazole and 2-amino-4-(isothiocyanatomethyl)selenazole.
The synthesis of a series of 2-arylamido and 2-alkylamido derivatives of 2-amino-4-(isothiocyanatomethyl)thiazole and 2-amino-4-(isothiocyanatomethyl)selenazole is described. In vitro antiproliferative evaluations were carried out using L1210 cells. The 2-(alkylamido)thiazole derivatives were moderately antiproliferative, with IC50's of 4-8 microM. A significant increase in activity was obtained for the arylamido derivatives, with IC50's of 0.2-1 microM. The results obtained for the selenazoles were similar to those for the thiazoles. 2-Benzamido-4-(isothiocyanatomethyl)-thiazole (19) was found to be a potent inhibitor of GMP synthetase. None of the compounds prepared in this study demonstrated antifilarial activity.
Kumar
Y
Y
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Green
R
R
Wise
D S
DS
Wotring
L L
LL
Townsend
L B
LB
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019731:Carbon-Nitrogen Ligases; D002455:Cell Division / Q000187:drug effects; D005369:Filaricides / Q000138:chemical synthesis* / Q000494:pharmacology; D017879:Isothiocyanates / Q000138:chemical synthesis* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000473:pathology; D008025:Ligases / Q000037:antagonists & inhibitors; D008938:Mitosis / Q000187:drug effects; D008940:Mitotic Index; D015394:Molecular Structure; D018036:Selenium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D005369:Filaricides; D017879:Isothiocyanates; D018036:Selenium Compounds; D013844:Thiazoles; C084673:2-benzamido-4-(isothiocyanatomethyl)thiazole; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C020828:GMP synthase (glutamine-hydrolyzing)