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Discovery of coumarin-dihydropyridine hybrids as bone anabolic agents.

Abstract：

:The concept of molecular hybridization led us to discover a novel series of coumarin-dihydropyridine hybrids that have potent osteoblastic bone formation in vitro and that prevent ovariectomy-induced bone loss in vivo. In this context, among all the compounds screened for alkaline phosphatase activity, four compounds 10, 14, 18, and 22 showed significant activity at picomolar concentrations. A series of other in vitro data strongly suggested compound 18 as the most promising bone anabolic agent, which was further evaluated for in vivo studies. From these studies compound 18 proved to be useful, which at low oral dose of 1 (mg/kg)/day body weight increased bone mass density and volume, expression of osteogenic genes (RUNX2, BMP-2, and ColI), bone formation rate (BFR), and mineral apposition rate (MAR), improved the trabecular microarchitecture, and decreased bone turn over markers in an ovariectomized rodent model for postmenopausal osteoporosis.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Sashidhara KV,Kumar M,Khedgikar V,Kushwaha P,Modukuri RK,Kumar A,Gautam J,Singh D,Sridhar B,Trivedi R

doi

10.1021/jm301281e

subject

Has Abstract

pub_date

2013-01-10 00:00:00

pages

109-22

issue

1

eissn

0022-2623

issn

1520-4804

journal_volume

56

pub_type

杂志文章

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