Identification of novel 2-((1-(Benzyl(2-hydroxy-2-phenylethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)benzoic acid analogues as BMP-2 stimulators

Balaramnavar, Vishal M., Khan, Imran A., Siddiqui, Jawed Akhtar, Khan, Mohd Parvez, Chakravarti, Bandana, Sharan, Kunal, Swarnkar, Gaurav, Rastogi, Namrata, Siddiqui, H. H., Mishra, Durga Prasad, Chattopadhyay, Naibedya and Saxena, Anil K. 2012. Identification of novel 2-((1-(Benzyl(2-hydroxy-2-phenylethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)benzoic acid analogues as BMP-2 stimulators. Journal of Medicinal Chemistry 55 (19) , 8248–8259. 10.1021/jm300985d

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Abstract

The synthesis and SAR studies of 10 new chemical entities (NCEs) that have shown BMP-2 stimulation and osteoblast differentiation are reported. Among these, 2-((1-(benzyl(2-hydroxy-2-phenylethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)benzoic acid (11) was the most effective while its analogue 13 also showed good activity in inducing osteoblast BMP-2 production. Compound 11 induced osteoblast differentiation in vitro, and this effect was abrogated by a physiological BMP-2 inhibitor, noggin. It also exhibited dose dependent increase in nascent bone formation (2.16- and 3.12-fold more than the control at 1 and 5 mg/kg dose, respectively) at the fracture site in rats. At the maximum osteogenic concentration, compound 11 significantly inhibited osteoblastic proteosomal activity. This compound was safe, as it had no effect on BMP synthesis in cardiovascular tissue.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	American Chemical Society
ISSN:	0022-2623
Last Modified:	19 Dec 2023 17:15
URI:	https://orca.cardiff.ac.uk/id/eprint/164611

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