Non-peptide αvβ3 antagonists.: Part 6:: Design and synthesis of αvβ3 antagonists containing a pyridone or pyrazinone central scaffold

被引：15

作者：

Breslin, MJ

Duggan, ME

Halczenko, W

Fernandez-Metzler, C

Hunt, CA

Leu, CT

Merkle, KM

Naylor-Olsen, AM

Prueksaritanont, T

Stump, G

Wallace, A

Rodan, SB

Hutchinson, JH

机构：

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

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

[3] Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA

[4] Merck Res Labs, Dept Pharmacol, W Point, PA 19486 USA

[5] Merck Res Labs, Dept Mol Design & Divers, W Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 10期

关键词：

D O I：

10.1016/S0960-894X(03)00254-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two novel series of small-molecule RGD mimetics containing either a substituted pyridone or pyrazinone central constraint were prepared. Modification of the P-alanine 3-substituent produced compounds that are potent and selective alpha(v)beta(3) antagonists and exhibit a range of physicochemical properties. (C) 2003 Elsevier Science Ltd. All rights reserved.

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页码：1809 / 1812

页数：4

相关论文

共 17 条

[1] Non-peptide αvβ3 antagonists.: Part 4:: Potent and orally bioavailable chain-shortened RGD mimetics [J].

Coleman, PJ ;

Askew, BC ;

Hutchinson, JH ;

Whitman, DB ;

Perkins, JJ ;

Hartman, GD ;

Rodan, GA ;

Leu, CT ;

Prueksaritanont, T ;

Fernandez-Metzler, C ;

Merkle, KM ;

Lynch, R ;

Lynch, JJ ;

Rodan, SB ;

Duggan, ME .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (17) :2463-2465

[2] Non-peptide αvβ3 antagonists.: Part 3:: Identification of potent RGD mimetics incorporating novel β-amino acids as aspartic acid replacements [J].

Coleman, PJ ;

Brashear, KM ;

Hunt, CA ;

Hoffman, WF ;

Hutchinson, JH ;

Breslin, MJ ;

McVean, CA ;

Askew, BC ;

Hartman, GD ;

Rodan, SB ;

Rodan, GA ;

Leu, CT ;

Prueksaritanont, T ;

Fernandez-Metzler, C ;

Ma, B ;

Libby, LA ;

Merkle, KM ;

Stump, GL ;

Wallace, AA ;

Lynch, JJ ;

Lynch, R ;

Duggan, ME .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (01) :31-34

[3] 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

[4] Ligands to the integrin receptor αvβ3 [J].

Duggan, ME ;

Hutchinson, JH .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2000, 10 (09) :1367-1383

[5]

Duong Le T., 1998, Frontiers in Bioscience, V3, pD757

[6] The synthesis of the αvβ3 integrin receptor ligand [125I]L-775,219. [J].

Hamill, TG ;

Duggan, ME ;

Perkins, JJ .

JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2001, 44 (01) :55-59

[7] αvβ3 integrin antagonists as inhibitors of bone resorption [J].

Hartman, GD ;

Duggan, ME .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2000, 9 (06) :1281-1291

[8] Rapid inhibition of thyroxine-induced bone resorption in the rat by an orally active vitronectin receptor antagonist [J].

Hoffman, SJ ;

Vasko-Moser, J ;

Miller, WH ;

Lark, MW ;

Gowen, M ;

Stroup, G .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 302 (01) :205-211

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

Meissner, RS ;

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 .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (01) :25-29