TY - JOUR
T1 - 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
AU - Balaramnavar, Vishal M.
AU - Khan, Imran A.
AU - Siddiqui, Jawed Akhtar
AU - Khan, Mohd Parvez
AU - Chakravarti, Bandana
AU - Sharan, Kunal
AU - Swarnkar, Gaurav
AU - Rastogi, Namrata
AU - Siddiqui, H. H.
AU - Mishra, Durga Prasad
AU - Chattopadhyay, Naibedya
AU - Saxena, Anil K.
PY - 2012/10/11
Y1 - 2012/10/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84867350005&partnerID=8YFLogxK
U2 - 10.1021/jm300985d
DO - 10.1021/jm300985d
M3 - Article
C2 - 22978808
AN - SCOPUS:84867350005
SN - 0022-2623
VL - 55
SP - 8248
EP - 8259
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 19
ER -