1 research outputs found
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
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-(benzylÂ(2-hydroxy-2-phenylethyl)Âamino)-1-oxo-3-phenylpropan-2-yl)Âcarbamoyl)Âbenzoic
acid (<b>11</b>) was the most effective while its analogue <b>13</b> also showed good activity in inducing osteoblast BMP-2
production. Compound <b>11</b> 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 <b>11</b> significantly inhibited osteoblastic
proteosomal activity. This compound was safe, as it had no effect
on BMP synthesis in cardiovascular tissue