Synthesis of 2,4-Disubstituted Thiazoles and Selenazoles as Potential Antitumor and Antifilarial Agents: 1. Methyl 4-(Isothiocyanatomethyl)thiazole-2-carbamates, -selenazole-2-carbamates, and Related Derivatives

Yatendra Kumar, Rachel Green, Katherine Z. Borysko, Dean S. Wise, Linda L. Wotring, Leroy B. Townsend

Research output: Contribution to journalArticlepeer-review

Abstract

Methyl 4-(isothiocyanatomethyl)thiazole-2-carbamate and methyl 4-(isothiocyanatomethyl)selenazole-2-carbamate have been prepared via chemical transformations involving 2-amino-4-(chloromethyl)thiazole (1) and 2-amino-4-(chloromethyl)selenazole (2), respectively, as starting materials. The homoanalog, methyl 4-(2-isothiocyanatoethyl)thiazole-2-carbamate, was prepared from (2-aminothiazol-4-yl)acetic acid. All compounds prepared were evaluated for their ability to inhibit leukemia L1210 cell proliferation. Methyl 4-(isothiocyanatomethyl)thiazole-2-carbamate (7) was the most active compound in this screen, inhibiting the growth of L1210 leukemic cells with an IC50 = 3.2 µM. Mitotic blocking appears to be its primary mechanism of cytotoxic activity. Compound 7 also was the only compound which demonstrated significant in vivo antifilarial activity against the adult worms of Acanthocheilonema viteae in experimentally infected jirds. This compound was inactive against Brugia pahangi at a dosage of 100 mg/kg × 5 days.

Original languageEnglish (US)
Pages (from-to)3843-3848
Number of pages6
JournalJournal of medicinal chemistry
Volume36
Issue number24
DOIs
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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