Title:
ISOPHTHALIC ACID DERIVATIVES AS MATRIX METALLOPROTEINASE INHIBITORS
Document Type and Number:
WIPO Patent Application WO2002064547
Kind Code:
A3
Abstract:
Selective MMP-13 inhibitors are isophthalic acid derivatives of the formula (I) wherein: R<1>, R<2>, and R<3> independently are hydrogen, halo, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, NO2, NR<4>R<5>, CN, or CF3; E is independently O or S; A and B independently are OR<4> or NR<4>R<5>; each R<4> and R<5> independently are H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (CH2)n aryl, (CH2)n cycloalkyl, (CH2)n heteroaryl, or R<4> and R<5> when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring, optionally containing heteroatom selected from O, S, or NH, and optionally substituted or unsubstituted; n is 0 to 6; or a pharmaceutically acceptable salt thereof. The compounds are useful for treating diseases in a mammal that are mediated by MMP enzymes.
Inventors:
BARVIAN NICOLE CHANTEL (US)
CONNOR DAVID THOMAS (US)
DYER RICHARD DENNIS (US)
JOHNSON ADAM RICHARD (US)
PATT WILLIAM CHESTER (US)
CONNOR DAVID THOMAS (US)
DYER RICHARD DENNIS (US)
JOHNSON ADAM RICHARD (US)
PATT WILLIAM CHESTER (US)
Application Number:
PCT/IB2002/000344
Publication Date:
December 05, 2002
Filing Date:
February 04, 2002
Export Citation:
Assignee:
WARNER LAMBERT CO (US)
BARVIAN NICOLE CHANTEL (US)
CONNOR DAVID THOMAS (US)
DYER RICHARD DENNIS (US)
JOHNSON ADAM RICHARD (US)
PATT WILLIAM CHESTER (US)
BARVIAN NICOLE CHANTEL (US)
CONNOR DAVID THOMAS (US)
DYER RICHARD DENNIS (US)
JOHNSON ADAM RICHARD (US)
PATT WILLIAM CHESTER (US)
International Classes:
A61K31/166; A61K31/192; A61K31/235; A61K31/36; A61K31/433; A61K31/4409; A61K31/444; A61P1/00; A61P9/00; A61P9/04; A61P9/10; A61P19/00; A61P19/02; A61P19/10; A61P25/00; A61P29/00; C12N9/99; A61P35/00; A61P43/00; C07C69/708; C07C69/732; C07C69/80; C07C69/90; C07C69/92; C07C205/57; C07C229/56; C07C229/60; C07C233/66; C07C233/67; C07C233/69; C07C233/73; C07C233/75; C07C233/78; C07C235/60; C07C235/64; C07D213/30; C07D285/14; C07D317/54; C07D317/58; (IPC1-7): C07C235/60; A61K31/166; A61K31/194; A61P19/00; A61P1/00; A61P9/00; C07D285/14; C07C69/92; C07C69/80; C07C69/90; C07D213/30; C07D317/54; A61K31/235; A61K31/36; A61K31/433; A61P35/00
Domestic Patent References:
| WO2001005389A2 | 2001-01-25 | |||
| WO1999005148A1 | 1999-02-04 |
Foreign References:
| JPH05193260A | 1993-08-03 |
Other References:
CHEN J M ET AL: "STRUCTURE-BASED DESIGN OF A NOVEL, POTENT, AND SELECTIVE INHIBITOR FOR MMP-13 UTILIZING NMR SPECTROSCOPY AND COMPUTER-AIDED MOLECULAR DESIGN", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, vol. 122, no. 40, - 11 October 2000 (2000-10-11), pages 9648 - 9654, XP001010185, ISSN: 0002-7863
BOGER, D.L. ET AL: "Identification of a novel class of small-molecule antiangiogenic agents through the screening of combinatorial libraries which function by inhibiting the binding and localization of proteinase MMP2 to integrin.alpha.V.beta.3", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2001), 123(7), 1280-1288, 2001 - 26 January 2001 (2001-01-26), XP002215423
SILLETTI, S. ET AL: "Disruption of matrix metalloproteinase 2 binding to integrin alpha.v.beta.3 by an organic molecule inhibits angiogenesis and tumor growth in vivo", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2001), 98(1), 119-124, - 2 January 2001 (2001-01-02), XP001115022
MILTON J ET AL: "Biaryl acids: novel non-nucleoside inhibitors of HIV reverse transcriptase types 1 and 2", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 8, no. 19, 6 October 1998 (1998-10-06), pages 2623 - 2628, XP004139590, ISSN: 0960-894X
BOGER, D.L. ET AL: "Identification of a novel class of small-molecule antiangiogenic agents through the screening of combinatorial libraries which function by inhibiting the binding and localization of proteinase MMP2 to integrin.alpha.V.beta.3", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2001), 123(7), 1280-1288, 2001 - 26 January 2001 (2001-01-26), XP002215423
SILLETTI, S. ET AL: "Disruption of matrix metalloproteinase 2 binding to integrin alpha.v.beta.3 by an organic molecule inhibits angiogenesis and tumor growth in vivo", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2001), 98(1), 119-124, - 2 January 2001 (2001-01-02), XP001115022
MILTON J ET AL: "Biaryl acids: novel non-nucleoside inhibitors of HIV reverse transcriptase types 1 and 2", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 8, no. 19, 6 October 1998 (1998-10-06), pages 2623 - 2628, XP004139590, ISSN: 0960-894X
Download PDF: