Lead identification of a potent benzopyranone selective estrogen receptor modulator

doi:10.1016/j.bmcl.2004.04.081

Bioorganic & Medicinal Chemistry Letters

Volume 14, Issue 13, 5 July 2004, Pages 3407-3410

https://doi.org/10.1016/j.bmcl.2004.04.081 Get rights and content

Abstract

Starting from a phenol screening hit (6), three series of benzopyranone selective estrogen receptor modulators (SERMs) have been designed, synthesized, and analyzed for both estrogen receptor alpha binding affinity and in vitro activity in two cell assays. The lead compound identified, SP500263 (13), was more potent than raloxifene and tamoxifen in a cell-based assay measuring inhibition of interleukin-6 release.

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Citation Excerpt :
In contrast, the coumarin–PBD conjugate bearing a propylene linker (X = CH2) was the most potent compound (IC50 values ≤ 3.2 μM). The biological assessments revealed that the linker structure within these coumarin–PBD conjugates had significant influence on the extent and time course of DNA binding, in vitro cytotoxic potency and cellular distribution [54]. Mohareb et al. have synthesized a series of hydrazide–hydrazone derivatives including coumarin 22 (Fig. 5).
Cancer is one of the leading health hazards and the prominent cause of death in the world. A number of anticancer agents are currently in clinical practice and used for treatment of various kinds of cancers. There is no doubt that the existing arsenal of anticancer agents is insufficient due to the high incidence of side effects and multidrug resistance. In the efforts to develop suitable anticancer drugs, medicinal chemists have focused on coumarin derivatives. Coumarin is a naturally occurring compound and a versatile synthetic scaffold possessing wide spectrum of biological effects including potential anticancer activity. This review article covers the current developments of coumarin-based anticancer agents and also discusses the structure–activity relationship of the most potent compounds.

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Lead identification of a potent benzopyranone selective estrogen receptor modulator

Abstract

Nature

Proc. Natl. Acad. Sci.

Endocrinology

J. Clin. Endocrinol. Metab.

Ann. Int. Med.

JAMA

Maturitas

Endocrinology