Sulfonimidamide Analogs of Oncolytic Sulfonylureas^,1

Abstract

A series of sulfonimidamide analogs of the oncolytic diarylsulfonylureas was synthesized and evaluated for (1) in vitro cytotoxicity against CEM cells, (2) in vivo antitumor activity against subaxillary implanted 6C3HED lymphosarcoma, and (3) metabolic breakdown to the o-sulfate of p-chloroaniline. The separated enantiomers of one sulfonimidamide analog displayed very different activities in the in vivo screening model. In general, several analogs demonstrated excellent growth inhibitory activity in the 6C3HED model when dosed orally or intraperitoneally. A correlative structure-activity relationship to the oncolytic sulfonylureas was not apparent.

Glutathione and Mercapturic Acid Conjugates of Sulofenur and Their Activity against a Human Colon Cancer Cell Line

“…Diarylsulfonylureas, including sulofenur, have been developed as a novel class of anticancer agents with a broad spectrum of activity in several solid tumor models but as yet an unidentified mechanism of action (Toth et al, 1997). Sulofenur has undergone extensive clinical trials based on its impressive preclinical activity.…”

Synthesis, characterization and in vitro biological evaluation of some new diarylsulfonylurea-chalcone hybrids as potential 5-lipoxygenase inhibitors

“…Diarylsulfonylureas became widely available since 1955 as popular antidiabetic drugs in clinical practice for the treatment of type 2 diabetes, by virtue of their insulin secretagogue properties. The synthesis of compounds containing diarylsulfonylurea moiety has been a subject of extensive research in the recent past because of their enormous biological activities such as hypoglycemics [4], Vibrio fischeri quorum sensing regulators [5], CXCR2 receptor antagonists [6], antimalarials [7], antibacterials [8], human thromboxane A2 receptor isoforms TPα and TPβ antagonists [9], reversible inhibitors of human steroid sulfatase [10], KATP-channel openers [11], ANG II (AT1) receptor antagonists [12], oncolytics [13], acyl-CoA inhibitors [14], vasodilators [15], aldehyde dehydrogenase inhibitors [16], cancer chemotherapeutics [17], diuretic [18], β3 adrenergic receptor agonists [19], non competitive inhibitors of acetohydroxyacid synthase from Mycobacterium tuberculosis [20], and as peroxisome proliferator activated receptor gamma (PPARγ) agonists [21].…”

URD12: A urea derivative with marked antitumor activities

“…Its derivatives have been studied for their biological activities including anti-atherosclerotic, antibiotic (1) and hypoglycemic effects (2) and antitumor activities (3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”