Synthesis of NO-donor bisphosphonates and their in-vitro action on bone resorption

被引：24

作者：

Lazzarato, L

Rolando, B

Lolli, ML

Tron, GC

Fruttero, R

Gasco, A

Deleide, G

Guenther, HL

机构：

[1] Univ Turin, Dipartimento Sci & Tecnol Farm, I-10125 Turin, Italy

[2] Univ Piemonte, Dipartimento Sci Chim Alimentari Farmaceut & Farm, I-28100 Novara, Italy

[3] Nycomed Amersham Sorin Srl, I-13040 Saluggia, VC, Italy

[4] Univ Bern, Dept Clin Res, CH-3010 Bern, Switzerland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 05期

关键词：

D O I：

10.1021/jm040830d

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of bisphosphonates containing nitrooxy NO-donor functions has been developed. The products proved to display affinity for hydroxyapatite. Injection of Tc-99m-labeled derivatives 11 and 18 into male rats showed a preferential accumulation of the compounds in bone as compared to blood and muscles. The products were found to inhibit the differentiation of preosteoclasts to functional osteoclasts induced by receptor activator of NF-kappaB ligand (RANKL), through a prevalent NO-dependent mechanism.

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页码：1322 / 1329

页数：8

相关论文

共 48 条

[11] Bisphosphonates and novel related structural classes for bone resorption disorders [J].

Esswein, A ;

Bauss, F ;

Muehlbauer, R ;

Guenther, H ;

Bosies, E .

PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS, 1999, 144 :13-16

[12] Alendronate mechanism of action:: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro [J].

Fisher, JE ;

Rogers, MJ ;

Halasy, JM ;

Luckman, SP ;

Hughes, DE ;

Masarachia, PJ ;

Wesolowski, G ;

Russell, RGG ;

Rodan, GA ;

Reszka, AA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (01) :133-138

[13] Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training [J].

Fukai, T ;

Siegfried, MR ;

Ushio-Fukai, M ;

Cheng, Y ;

Kojda, G ;

Harrison, DG .

JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (11) :1631-1639

[14]

Gunther H., 1995, NMR SPECTROSCOPY BAS, P199

[15] Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis [J].

Halasy-Nagy, JM ;

Rodan, GA ;

Reszka, AA .

BONE, 2001, 29 (06) :553-559

[16] Direct action of nitric oxide on osteoblastic differentiation [J].

Hikiji, H ;

Shin, WS ;

Oida, S ;

Takato, T ;

Koizumi, T ;

Toyooka, T .

FEBS LETTERS, 1997, 410 (2-3) :238-242

[17] Androgens suppress osteoclast formation induced by RANKL and macrophage-colony stimulating factor [J].

Huber, DM ;

Bendixen, AC ;

Pathrose, P ;

Srivastava, S ;

Dienger, KM ;

Shevde, NK ;

Pike, JW .

ENDOCRINOLOGY, 2001, 142 (09) :3800-3808

[18] INHIBITION OF OSTEOCLAST-LIKE CELL-FORMATION BY BISPHOSPHONATES IN LONG-TERM CULTURES OF HUMAN-BONE MARROW [J].

HUGHES, DE ;

MACDONALD, BR ;

RUSSELL, RGG ;

GOWEN, M .

JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (06) :1930-1935

[19] SYNTHESIS OF ALKYLATED METHYLENE BISPHOSPHONATES VIA ORGANOTHALLIUM INTERMEDIATES [J].

HUTCHINSON, DW ;

SEMPLE, G .

JOURNAL OF ORGANOMETALLIC CHEMISTRY, 1985, 291 (02) :145-151

[20]

JORK H, 1990, THIN LAYER CHROMATOG, V1, P170

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