N-aroyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists

被引：20

作者：

Sidduri, A ^{[1
]}

Tilley, JW ^{[1
]}

Lou, JP ^{[1
]}

Chen, L ^{[1
]}

Kaplan, G ^{[1
]}

Mennona, F ^{[1
]}

Campbell, R ^{[1
]}

Guthrie, R ^{[1
]}

Huang, TN ^{[1
]}

Rowan, K ^{[1
]}

Schwinge, V ^{[1
]}

Renzetti, LM ^{[1
]}

机构：

[1] Hoffmann La Roche Inc, Roche Res Ctr, Nutley, NJ 07110 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 17期

关键词：

D O I：

10.1016/S0960-894X(02)00387-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-benzoyl-4-[(2,6-dichlorobenzoyl)amino]-L-phenylalanine derivatives was prepared in order to optimize the substitution on the N-benzoyl moiety for VCAM/VLA-4 antagonist activity. Disubstitution in the 2- and 6-positions is favored and a range of small alkyl and halogen are tolerated. A model of the bioactive conformation of these compounds is proposed. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：2479 / 2482

页数：4

共 13 条

[1]

Adams SP, 2001, PROG R RES, V31, P302

[2] Design and synthesis of potent and selective α4β7 integrin antagonists [J].

Boer, J ;

Gottschling, D ;

Schuster, A ;

Semmrich, M ;

Holzmann, B ;

Kessler, H .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (16) :2586-2592

[3] N-benzylpyroglutamyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists [J].

Chen, L ;

Tilley, JW ;

Guthrie, RW ;

Mennona, F ;

Huang, TN ;

Kaplan, G ;

Trilles, R ;

Miklowski, D ;

Huby, N ;

Schwinge, V ;

Wolitzky, B ;

Rowan, K .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (08) :729-733

[4] Focused library approach for identification of new N-acylphenylalanines as VCAM/VLA-4 antagonists [J].

Chen, L ;

Trilles, R ;

Miklowski, D ;

Huang, TN ;

Fry, D ;

Campbell, R ;

Rowan, K ;

Schwinge, V ;

Tilley, JW .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (12) :1679-1682

[5] N-acyl-L-phenylalanine derivatives as potent VLA-4 antagonists that mimic a cyclic peptide conformation [J].

Chen, L ;

Tilley, J ;

Trilles, RV ;

Yun, WY ;

Fry, D ;

Cook, C ;

Rowan, K ;

Schwinge, V ;

Campbell, R .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (02) :137-140

[6]

CHEN L, Patent No. 9910312

[7]

Elices M. J., 1999, CELL ADHES MOL MATRI, P133

[8] The design and synthesis of potent cyclic peptide VCAM-VLA-4 antagonists incorporating an achiral Asp-Pro mimetic [J].

Fotouhi, N ;

Joshi, P ;

Fry, D ;

Cook, C ;

Tilley, JW ;

Kaplan, G ;

Hanglow, A ;

Rowan, K ;

Schwinge, V ;

Wolitzky, B .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (11) :1171-1173

[9] Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory epitope to a small molecule [J].

Gadek, TR ;

Burdick, DJ ;

McDowell, RS ;

Stanley, MS ;

Marsters, JC ;

Paris, KJ ;

Oare, DA ;

Reynolds, ME ;

Ladner, C ;

Zioncheck, KA ;

Lee, WP ;

Gribling, P ;

Dennis, MS ;

Skelton, NJ ;

Tumas, DB ;

Clark, KR ;

Keating, SM ;

Beresini, MH ;

Tilley, JW ;

Presta, LG ;

Bodary, SC .

SCIENCE, 2002, 295 (5557) :1086-1089

[10] NUCLEOPHILIC AROMATIC-SUBSTITUTION ON ORTHO-(METHOXY)ARYLOXAZOLINES - CONVENIENT SYNTHESIS OF ORTHO-ALKYLIDENE ACIDS AND ORTHO-ALKYLDENE AND ORTHO-ARYLBENZOIC ACIDS [J].

MEYERS, AI ;

GABEL, R ;

MIHELICH, ED .

JOURNAL OF ORGANIC CHEMISTRY, 1978, 43 (07) :1372-1379

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