Substituted tetrahydrofuroyl-1-phenylalanine derivatives as potent and specific VLA-4 antagonists

被引：20

作者：

Doherty, GA ^{[1
]}

Yang, GX

Borges, E

Chang, LL

MacCoss, M

Tong, S

Kidambi, U

Egger, LA

McCauley, E

Van Riper, G

Mumford, RA

Schmidt, JA

Hagmann, WK

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Immunol & Rheumatol Res, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(02)00211-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of substituted tetra hydrofuroyl-1-phenylalanine derivatives was prepared and evaluated as VLA-4 antagonists. Substitution of the a carbon of the tetrahydrofuran with aryl groups increased the specificity for VLA-4 versus alpha(4)beta(7) while amide substitution increased the potency of the series without increasing the specificity. Substitution of the P carbon of the tetrahydrofuran with keto or amino groups slightly improved the specificity for VLA-4 versus alpha(4)beta(7) but with a significant loss in binding affinity for VLA-4. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1501 / 1505

页数：5

共 50 条

[41] Discovery and evaluation of N-(triazin-1,3,5-yl) phenylalanine derivatives as VLA-4 integrin antagonists [J].

Porter, JR ;

Archibald, SC ;

Brown, JA ;

Childs, K ;

Critchley, D ;

Head, JC ;

Hutchinson, B ;

Parton, TAH ;

Robinson, MK ;

Shock, A ;

Warrellow, GJ ;

Zomaya, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (12) :1591-1594

[42] Highly constrained bicyclic VLA-4 antagonists [J].

Chang, Linda L. ;

Truong, Quang ;

Doss, George A. ;

MacCoss, Malcolm ;

Lyons, Kathryn ;

McCauley, Ermengilda ;

Mumford, Richard ;

Forrest, Gail ;

Vincent, Stella ;

Schmidt, John A. ;

Hagmann, William K. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (03) :597-601

[43] N-(pyrimidin-4-yl) and N-(pyridin-2-yl) phenylalanine derivatives as VLA-4 integrin antagonists [J].

Porter, JR ;

Archibald, SC ;

Brown, JA ;

Childs, K ;

Critchley, D ;

Head, JC ;

Hutchinson, B ;

Parton, TAH ;

Robinson, MK ;

Shock, A ;

Warrellow, GJ ;

Zomaya, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (12) :1595-1598

[44] A novel and potent VLA-4 antagonist based on trans-4-substituted cyclohexanecarboxylic acid [J].

Muro, Fumihito ;

Iimura, Shin ;

Yoneda, Yoshiyuki ;

Chiba, Jun ;

Watanabe, Toshiyuki ;

Setoguchi, Masaki ;

Takayama, Gensuke ;

Yokoyama, Mika ;

Takashi, Tohru ;

Nakayama, Atsushi ;

Machinaga, Nobuo .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (03) :1232-1243

[45] N-Acylphenylalanines as antagonists of VLA-4/VCAM-1 [J].

不详 .

EXPERT OPINION ON THERAPEUTIC PATENTS, 1999, 9 (10) :1443-1446

[46] Quantitative Structure Activity Relationship Studies of Piperazinyl Phenylalanine Derivatives as VLA-4/VCAM-1 Inhibitors [J].

Bhargava, Dinesh ;

Karthikeyan, C. ;

Moorthy, N. S. H. N. ;

Trivedi, Piyush .

MEDICINAL CHEMISTRY, 2009, 5 (05) :446-454

[47] Identification of potent, selective VLA-4 antagonists as chemical tools to answer biological questions. [J].

Huryn, DM ;

Ashwell, S ;

Baudy, RB ;

Dressen, DB ;

Freedman, SB ;

Grant, FS ;

Kennedy, J ;

Konradi, AW ;

Kreft, A ;

Lombardo, LJ ;

Pleiss, MA ;

Sarantakis, D ;

Yednock, T .

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2004, 228 :U936-U936

[48] 3D QSAR (COMFA) of a series of potent and highly selective VLA-4 antagonists [J].

Singh, J ;

van Vlijmen, H ;

Lee, WC ;

Liao, Y ;

Lin, KC ;

Ateeq, H ;

Cuervo, J ;

Zimmerman, C ;

Hammond, C ;

Karpusas, M ;

Palmer, R ;

Chattopadhyay, T ;

Adams, SP .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2002, 16 (03) :201-211

[49] Amidines as amide bond replacements in VLA-4 antagonists [J].

Kamenecka, TM ;

Park, YJ ;

Lin, LS ;

de Laszlo, S ;

McCauley, ED ;

Van Riper, G ;

Egger, L ;

Kidambi, U ;

Mumford, RA ;

Tong, S ;

Tang, W ;

Colletti, A ;

Teffera, Y ;

Stearns, R ;

MacCross, M ;

Schmidt, JA ;

Hagmann, WK .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (09) :2323-2326

[50] Design and synthesis of VLA-4/VCAM antagonists. [J].

Huryn, DM .

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2001, 221 :U34-U34

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