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Titolo:
Synthesis and biological evaluation of prostaglandin-F alkylphosphinic acid derivatives as bone anabolic agents for the treatment of osteoporosis
Autore:
Soper, DL; Milbank, JBJ; Mieling, GE; Dirr, MJ; Kende, AS; Cooper, R; Jee, WSS; Yao, W; Chen, JL; Bodman, M; Lundy, MW; De, B; Stella, ME; Ebetino, FH; Wang, YL; deLong, MA; Wos, JA;
Indirizzi:
Procter & Gamble Pharmaceut, Mason, OH 45040 USA Procter & Gamble Pharmaceut Mason OH USA 45040 aceut, Mason, OH 45040 USA Univ Rochester, Dept Chem, Rochester, NY 14627 USA Univ Rochester Rochester NY USA 14627 Dept Chem, Rochester, NY 14627 USA Univ Utah, Dept Radiobiol, Salt Lake City, UT 84112 USA Univ Utah Salt Lake City UT USA 84112 obiol, Salt Lake City, UT 84112 USA
Titolo Testata:
JOURNAL OF MEDICINAL CHEMISTRY
fascicolo: 24, volume: 44, anno: 2001,
pagine: 4157 - 4169
SICI:
0022-2623(20011122)44:24<4157:SABEOP>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
GRB2-SH2 DOMAIN INHIBITORS; F2-ALPHA ISOPROPYL ESTER; STRUCTURE-BASED DESIGN; PHOSPHINATE ISOSTERES; OVARIECTOMIZED RATS; ANTIGLAUCOMA AGENTS; RECEPTOR; F1-ALPHA; ANALOGS; PHOSPHOTYROSINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Wos, JA Procter & Gamble Pharmaceut, 8700 Mason Montgomery Rd, Mason, OH 45040 USA Procter & Gamble Pharmaceut 8700 Mason Montgomery Rd Mason OH USA 45040
Citazione:
D.L. Soper et al., "Synthesis and biological evaluation of prostaglandin-F alkylphosphinic acid derivatives as bone anabolic agents for the treatment of osteoporosis", J MED CHEM, 44(24), 2001, pp. 4157-4169

Abstract

A series of novel C-1 alkylphosphinic acid analogues of the prostaglandin-F family have been evaluated at the eight human prostaglandin receptors forpotential use in the treatment of osteoporosis. Using molecular modeling as a tool for structure-based drug design, we have discovered that the phosphinic acid moiety (P(O)(OH)R) behaves as an isostere for the C-1. carboxylic acid in the human prostaglandin FP binding assay in vitro and possesses enhanced hFP receptor selectivity when compared to the parent carboxylic acid. When evaluated in vivo, the methyl phosphinic acid analogue (4b) produced a bone anabolic response in rats, returning bone mineral density (BMD) tointact levels in the distal femur in the ovariectomized rat (OVX) model. These results suggest that prostaglandins of this class may be useful agentsin the treatment of diseases associated with bone loss.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 00:52:38