Synthesis and SAR of bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors

被引：33

作者：

Zask, A

Gu, Y

Albright, JD

Du, X

Hogan, M

Levin, JI

Chen, JM

Killar, LM

Sung, A

DiJoseph, JF

Sharr, MA

Roth, CE

Skala, S

Jin, G

Cowling, R

Mohler, KM

Barone, D

Black, R

March, C

Skotnicki, JS

机构：

[1] Wyeth Ayerst Res, Pearl River, NY 10965 USA

[2] Wyeth Ayerst Res, Princeton, NJ 08543 USA

[3] Immunex Corp, Seattle, WA 98101 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 08期

关键词：

D O I：

10.1016/S0960-894X(03)00127-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Potent and selective bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors were synthesized by a novel convergent route. Selectivity and efficacy versus MMPs and TACE could be controlled by appropriate substitution on the scaffolds and by variation of the P1' group. Select compounds were found to be effective in in vivo models of arthritis. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：1487 / 1490

页数：4

共 23 条

[1] (E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2′-isobutyl-2′-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), a selective and orally active inhibitor of tumor necrosis factor-α convertase [J].

Beck, G ;

Bottomley, G ;

Bradshaw, D ;

Brewster, M ;

Broadhurst, M ;

Devos, R ;

Hill, C ;

Johnson, W ;

Kim, HJ ;

Kirtland, S ;

Kneer, J ;

Lad, N ;

Mackenzie, R ;

Martin, R ;

Nixon, J ;

Price, G ;

Rodwell, A ;

Rose, F ;

Tang, JP ;

Walter, DS ;

Wilson, K ;

Worth, E .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 302 (01) :390-396

[2] A NOVEL IN-VIVO MODEL FOR THE STUDY OF CARTILAGE DEGRADATION [J].

BISHOP, J ;

GREENHAM, AK ;

LEWIS, EJ .

JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 1993, 30 (01) :19-25

[3] Structural properties of matrix metalloproteinases [J].

Bode, W ;

Fernandez-Catalan, C ;

Tschesche, H ;

Grams, F ;

Nagase, H ;

Maskos, K .

CELLULAR AND MOLECULAR LIFE SCIENCES, 1999, 55 (04) :639-652

[4] Anthranilate sulfonamide hydroxamate TACE inhibitors.: Part 1:: Structure-based design of novel acetylenic P1′ groups [J].

Chen, JM ;

Jin, GX ;

Sung, A ;

Levin, JI .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (08) :1195-1198

[5]

DiJoseph JF, 1998, DRUG DEVELOP RES, V43, P200, DOI 10.1002/(SICI)1098-2299(199804)43:4<200::AID-DDR3>3.0.CO

[6]

2-M

[7] A continuous fluorimetric assay for tumor necrosis factor-α converting enzyme [J].

Jin, GX ;

Huang, XY ;

Black, R ;

Wolfson, M ;

Rauch, C ;

McGregor, H ;

Ellestad, G ;

Cowling, R .

ANALYTICAL BIOCHEMISTRY, 2002, 302 (02) :269-275

[8] Anthranilate sulfonamide hydroxamate TACE inhibitors.: Part 2:: SAR of the acetylenic P1′ group [J].

Levin, JI ;

Chen, JM ;

Du, MT ;

Nelson, FC ;

Killar, LM ;

Skala, S ;

Sung, A ;

Jin, G ;

Cowling, R ;

Barone, D ;

March, CJ ;

Mohler, KM ;

Black, RA ;

Skotnicki, JS .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (08) :1199-1202

[9] The discovery of anthranilic acid-based MMP inhibitors. Part 3: Incorporation of basic amines [J].

Levin, JI ;

Chen, JM ;

Du, MT ;

Nelson, FC ;

Wehr, T ;

DiJoseph, JF ;

Killar, LM ;

Skala, S ;

Sung, A ;

Sharr, MA ;

Roth, CE ;

Jin, G ;

Cowling, R ;

Di, L ;

Sherman, M ;

Xu, ZB ;

March, CJ ;

Mohler, KM ;

Black, RA ;

Skotnicki, JS .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (22) :2975-2978

[10] The discovery of anthranilic acid-based MMP inhibitors.: Part 2:: SAR of the 5-position and P11 groups [J].

Levin, JI ;

Chen, J ;

Du, M ;

Hogan, M ;

Kincaid, S ;

Nelson, FC ;

Venkatesan, AM ;

Wehr, T ;

Zask, A ;

DiJoseph, J ;

Killar, LM ;

Skala, S ;

Sung, A ;

Sharr, M ;

Roth, C ;

Jin, G ;

Cowling, R ;

Mohler, KM ;

Black, RA ;

March, CJ ;

Skotnicki, JS .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (16) :2189-2192

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