Document Report Card

ID: ALA1138791

Journal: J Med Chem

Title: Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.

Authors: Lobb KL, Hipskind PA, Aikins JA, Alvarez E, Cheung YY, Considine EL, De Dios A, Durst GL, Ferritto R, Grossman CS, Giera DD, Hollister BA, Huang Z, Iversen PW, Law KL, Li T, Lin HS, Lopez B, Lopez JE, Cabrejas LM, McCann DJ, Molero V, Reilly JE, Richett ME, Shih C, Teicher B, Wikel JH, White WT, Mader MM.

Abstract: Two closely related diaryl acylsulfonamides were recently reported as potent antitumor agents against a broad spectrum of human tumor xenografts (colon, lung, breast, ovary, and prostate) in nude mice. Especially intriguing was their activity against colorectal cancer xenografts. In this paper, rapid parallel synthesis along with traditional medicinal chemistry techniques were used to quickly delineate the structure-activity relationships of the substitution patterns in both phenyl rings of the acylsufonamide anti-proliferative scaffold. Although the molecular target of the compounds remains unclear, we determined that the vascular endothelial growth factor-dependent human umbilical vein endothelial cells assay in combination with a soft agar disk diffusion assay allowed for optimization of potency in the series. The pharmacokinetic properties and in vivo activity in an HCT116 xenograft model are reported for representative compounds.

CiteXplore: 15481975

DOI: 10.1021/jm030594r