Unsaturated Phosphonates as Hauser Acceptors for the Synthesis of Phosphonylated Dihydroxynaphthalenes and Naphthoquinones

The unsaturated phosphonates were utilized as Hauser acceptors successfully for the first time. The products phosphonylated 1,4-dihydroxynaphthalenes were isolated in good yields in short reaction time and were further oxidized to the corresponding 1,4-naphthoquinones in quantitative yields. The reaction provides an efficient and straightforward approach for the synthesis of pharmacologically privileged disubstituted naphthalene-1,4-diols and naphtha-1,4-diones bearing a phosphonate group at the 2-position and various (het)­aryl groups at the 3-position

Access to the Phosphorylindenopyrazole Scaffold via a Metal-Free Domino Reaction of Diazoalkylphosphonates with 3‑Bromophthalides

A novel strategy is reported here for the synthesis of an indenopyrazole scaffold bearing a phosphonate group. The entire sequence includes nucleophilic addition–elimination, Seyferth–Gilbert homologation, transphosphorylation, and a 1,3-dipolar cycloaddition reaction of diazoalkylphosphonates in a perfect “domino” manner

Access to the Phosphorylindenopyrazole Scaffold via a Metal-Free Domino Reaction of Diazoalkylphosphonates with 3‑Bromophthalides

A novel strategy is reported here for the synthesis of an indenopyrazole scaffold bearing a phosphonate group. The entire sequence includes nucleophilic addition–elimination, Seyferth–Gilbert homologation, transphosphorylation, and a 1,3-dipolar cycloaddition reaction of diazoalkylphosphonates in a perfect “domino” manner

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-(benzyl­(2-hydroxy-2-phenylethyl)­amino)-1-oxo-3-phenylpropan-2-yl)­carbamoyl)­benzoic 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