Identification of Diarylsulfone Sulfonamides as Secreted Frizzled Related Protein-1 (sFRP-1) Inhibitors

被引：47

作者：

Gopalsamy, Ariamala ^{[1
]}

Shi, Mengxiao ^{[1
]}

Stauffer, Barbara ^{[3
]}

Bahat, Ramesh ^{[3
]}

Billiard, Julia ^{[3
]}

Ponce-de-Leon, Helga ^{[3
]}

Seestaller-Wehr, Laura ^{[3
]}

Fukayama, Shoichi ^{[2
]}

Mangine, Annamarie ^{[3
]}

Moran, Robert ^{[3
]}

Krishnamurthy, Girija ^{[1
]}

Bodine, Peter ^{[3
]}

机构：

[1] Wyeth Res, Chem & Screening Sci, Pearl River, NY 10965 USA

[2] Wyeth Res, Womens Hlth & Musculoskeletal Biol, Cambridge, MA 02140 USA

[3] Wyeth Res, Womens Hlth & Musculoskeletal Biol, Collegeville, PA 19426 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 24期

关键词：

D O I：

10.1021/jm801069w

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inhibitor of secreted frizzled related protein-1 (sFRP-1) would be a novel potential osteogenic agent, since loss of sFRP-1 affects osteoblast proliferation, differentiation, and activity, resulting in improved bone mineral density, quality, and strength. We have identified small molecule diarylsulfone sulfonamide derivatives as sFRP-1 inhibitors. Struture-activity relationship generated for various regions of the scaffold was utilized to improve the biochemical profile, resulting in the identification of potent selective analogues, such as 16 with desirable pharmaceutical profile.

引用

页码：7670 / 7672

页数：3

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