Nonpeptide αvβ3 antagonists.: Part 2:: Constrained glycyl amides derived from the RGD tripeptide

被引：45

作者：

Meissner, RS ^{[1
]}

Perkins, JJ

Duong, LT

Hartman, GD

Hoffman, WF

Huff, JR

Ihle, NC

Leu, CT

Nagy, RM

Naylor-Olsen, A

Rodan, GA

Rodan, SB

Whitman, DB

Wesolowski, GA

Duggan, ME

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Bone Biol & Osteoporosis Res, West Point, PA 19486 USA

[3] Merck Res Labs, Dept Mol Design & Divers, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 01期

关键词：

D O I：

10.1016/S0960-894X(01)00687-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Mimetics of the RGD tripeptide are described that are potent, selective antagonists of the integrin receptor, alpha (v)beta (3). The use of the 5,6,7,8-tetrahydro[1,8]naphthyridine group as a potency-enhancing N-terminus is demonstrated. Two 3-substituted-3-amino-propionic acids previously contained in alpha (IIb)beta (3) antagonists were utilized to enhance binding affinity and functional activity for the targeted receptor. Further affinity increases were then achieved through the use of cyclic glycyl amide bond constraints. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：25 / 29

页数：5

共 28 条

[1] Nonpeptide glycoprotein IIb/IIIa inhibitors .13. Design and synthesis of an orally active pyrazolopiperazinone nonpeptide fibrinogen receptor antagonist. [J].

Askew, BC ;

McIntyre, CJ ;

Hunt, CA ;

Claremon, DA ;

Baldwin, JJ ;

Anderson, PS ;

Gould, RJ ;

Lynch, RJ ;

Chang, CCT ;

Cook, JJ ;

Lynch, JJ ;

Holahan, MA ;

Sitko, GR ;

Stranieri, MT .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (12) :1531-1536

[2]

CHAMBERS TJ, 1986, BONE MINER, V1, P127

[3]

CLOVER J, 1992, J CELL SCI, V103, P267

[4] Antibody to beta(3) integrin inhibits osteoclast-mediated bone resorption in the thyroparathyroidectomized rat [J].

Crippes, BA ;

Engleman, VW ;

Settle, SL ;

Delarco, J ;

Ornberg, RL ;

Helfrich, MH ;

Horton, MA ;

Nickols, GA .

ENDOCRINOLOGY, 1996, 137 (03) :918-924

[5] Nonpeptide αvβ3 antagonists.: 1.: Transformation of a potent, integrin-selective αIIbβ3 antagonist into a potent αvβ3 antagonist [J].

Duggan, ME ;

Duong, LT ;

Fisher, JE ;

Hamill, TG ;

Hoffman, WF ;

Huff, JR ;

Ihle, NC ;

Leu, CT ;

Nagy, RM ;

Perkins, JJ ;

Rodan, SB ;

Wesolowski, G ;

Whitman, DB ;

Zartman, AE ;

Rodan, GA ;

Hartman, GD .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (20) :3736-3745

[6] A peptidomimetic antagonist of the alpha(v)beta(3) integrin inhibits bone resorption in vitro and prevents osteoporosis in vivo [J].

Engelman, VW ;

Nickols, GA ;

Ross, FP ;

Horton, MA ;

Griggs, DW ;

Settle, SL ;

Ruminski, PG ;

Teitelbaum, SL .

JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (09) :2284-2292

[7] INHIBITION OF OSTEOCLASTIC BONE-RESORPTION INVIVO BY ECHISTATIN, AN ARGINYL-GLYCYL-ASPARTYL (RGD)-CONTAINING PROTEIN [J].

FISHER, JE ;

CAULFIELD, MP ;

SATO, M ;

QUARTUCCIO, HA ;

GOULD, RJ ;

GARSKY, VM ;

RODAN, GA ;

ROSENBLATT, M .

ENDOCRINOLOGY, 1993, 132 (03) :1411-1413

[8] STRUCTURAL-ANALYSIS OF INTEGRIN RECOGNITION AND THE INHIBITION OF INTEGRIN-MEDIATED CELL FUNCTIONS BY NOVEL NONPEPTIDIC SURROGATES OF THE ARG-GLY-ASP SEQUENCE [J].

GREENSPOON, N ;

HERSHKOVIZ, R ;

ALON, R ;

VARON, D ;

SHENKMAN, B ;

MARX, G ;

FEDERMAN, S ;

KAPUSTINA, G ;

LIDER, O .

BIOCHEMISTRY, 1993, 32 (04) :1001-1008

[9] Non-peptide glycoprotein IIb/IIIa antagonists .2. Design and in vivo evaluation of 3,4-dihydro-1(1H)-isoquinolinone-based antagonists and ethyl ester prodrugs [J].

Hutchinson, JH ;

Cook, JJ ;

Brashear, KM ;

Breslin, MJ ;

Glass, JD ;

Gould, RJ ;

Halczenko, W ;

Holahan, MA ;

Lynch, RJ ;

Sitko, GR ;

Stranieri, MT ;

Hartman, GD .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (23) :4583-4591

[10] Antagonism of the osteoclast vitronectin receptor with an orally active nonpeptide inhibitor prevents cancellous bone loss in the ovariectomized rat [J].

Lark, MW ;

Stroup, GB ;

Dodds, RA ;

Kapadia, R ;

Hoffman, SJ ;

Hwang, SM ;

James, IE ;

Lechowska, B ;

Liang, XG ;

Rieman, DJ ;

Salyers, KL ;

Ward, K ;

Smith, BR ;

Miller, WH ;

Huffman, WF ;

Gowen, M .

JOURNAL OF BONE AND MINERAL RESEARCH, 2001, 16 (02) :319-327

← 1 2 3 →