Abstract:
:A series of analogues of 4,5-bis(((N-methylcarbamoyl)oxy)methyl)-1-methyl-2-(methylthio)-im idazole (1, carmethizole) were synthesized. The chemical reactivities of the analogues (as electrophiles) were evaluated and related to the antitumor activity (in vivo and in vitro). Changes in the alkylthio moiety had a significant effect upon the chemical reactivity. Electron-withdrawing groups on the sulfur decreased chemical reactivity and, in parallel, decreased antitumor activity. Carmethizole sulfoxide (11a) was unreactive as an electrophile and exhibited no antitumor activity either in vivo or in vitro; this led to the conclusion that carmethizole sulfoxide was not acting as a "carrier form" of carmethizole. The disulfides 17 and 18 were unreactive as electrophiles but did exhibit antitumor activity. The activity of 17 and 18 was attributed to the thiol 10 that would be generated upon cleavage of the disulfide bond.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Jarosinski MA,Reddy PS,Anderson WKdoi
10.1021/jm00075a017subject
Has Abstractpub_date
1993-11-12 00:00:00pages
3618-27issue
23eissn
0022-2623issn
1520-4804journal_volume
36pub_type
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