Acyl Sulfonamide Anti-Proliferatives: Benzene Substituent Structure−Activity Relationships for a Novel Class of Antitumor Agents
摘要:
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.
Rearrangement Amination of o-Chloro- and o-Bromophenyl Methyl Sulfides and o-Bromophenyl Methyl Sulfone in Liquid Ammonia
作者:Henry Gilman、George A. Martin
DOI:10.1021/ja01141a027
日期:1952.11
MALONAMIDE DERIVATIVES WITH ANTITHROMBOTIC ACTIVITY
申请人:SANOFI
公开号:EP2176223B1
公开(公告)日:2013-01-23
US4146496A
申请人:——
公开号:US4146496A
公开(公告)日:1979-03-27
Dialysis-resistant pulmonary oedema
作者:S.-C. Hung、S.-H. Hung、W.-C. Yang、D.-C. Tarng
DOI:10.1093/ndt/gfg136
日期:2003.7.1
Acyl Sulfonamide Anti-Proliferatives: Benzene Substituent Structure−Activity Relationships for a Novel Class of Antitumor Agents
作者:Karen L. Lobb、Philip A. Hipskind、James A. Aikins、Enrique Alvarez、Yiu-Yin Cheung、Eileen L. Considine、Alfonso De Dios、Gregory L. Durst、Rafael Ferritto、Cora Sue Grossman、Deborah D. Giera、Beth A. Hollister、Zhongping Huang、Philip W. Iversen、Kevin L. Law、Tiechao Li、Ho-Shen Lin、Beatriz Lopez、Jose E. Lopez、Luisa M. Martin Cabrejas、Denis J. McCann、Victoriano Molero、John E. Reilly、Michael E. Richett、Chuan Shih、Beverly Teicher、James H. Wikel、Wesley T. White、Mary M. Mader
DOI:10.1021/jm030594r
日期:2004.10.1
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.