IP Library Granted Patent US 6,881,553
Granted Patent B2
US 6,881,553 · App. 10/366,686 · Granted Apr 19, 2005

Antimicrobial activity of gemfibrozil and related compounds and derivatives and metabolites thereof

Assignees: The Trustees of Columbia University in the City of New York; Albert Einstein College of Medicine of Yeshiva University
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Quick Facts
Patent No.
US 6,881,553
App. No.
10/366,686
Granted
Apr 19, 2005
Kind
B2
Abstract

The present invention provides a method of selecting a compound which inhibits the enzymatic activity of enoyl reductase which comprises: (A) contacting enoyl reductase with the compound linked to an acyl carrier protein; (B) measuring the enzymatic activity of the enoyl reductase of step (A) compared with the enzymatic activity of enoyl reductase in the absence of the compound and selecting the compound which inhibits the enzymatic activity of enoyl reductase.

Claims (13)

1. A method of selecting a compound which inhibits the enzymatic activity of enoyl reductase which comprises;

(A) contacting enoyl reductase with the compound; and

(B) measuring the enzymatic activity of the enoyl reductase of step (A) compared with the enzymatic activity of enoyl reductase in the absence of the compound, and selecting the compound which inhibits the enzymatic activity of enoyl reductase,

wherein the compound has the structure:

or a pharmaceutically acceptable salt ester thereof, wherein

(i) each of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —OH, —OR 7 , —CN, —COR 7 , —SR 7 , —N(R 7 ) 2 , —NO 2 , —(CH 2 )—OR 7 , —COSR 7 , —C(═O)—OH, —CONH 2 , —NH 2 , a straight chain or branched, substituted or unsubstituted C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 10 cycloalkyl, C 3 -C 10 cycloalkenyl, thicalkyl, methylene thioalkyl, acyl, phenyl, substituted phenyl and heteroaryl;

(ii) the compound is in the form of acyl carrier protein metabolite;

(iii) L is —N—, —S—, —O—, —C≡C— or —CH 2 —;

(iv) R 7 is independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —OH, —CN, —COH, —SH, —NH 2 , —NHCOH, —(CH 2 )OH, a straight chain or branched, substituted or unsubstituted C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 10 cycloalkyl, C 3 -C 10 cycloalkenyl, thioalkyl, methylene thioalkyl, acyl, phenyl, substituted phenyl and heteroaryl;

(v) A is selected from the group consisting of —N 2 —, —NH—, —CH═C═CH—, —C≡C—CH(OH)—, C≡C—CH 2 —, —CH 2 —CH 2 —O—, —CH 2 —CH 2 —CH 2 —O—, —S—, —S(═O) 2 —, —C(═O)—, —C(═O)—O—, —NH—C(═O)— and —C(═O)—NH—;

(vi) Q is independently an integer from 1 to 10, and if Q is 1, A may be a (C 1 -C 10 )-alkyl chain, (C 2 -C 10 )-alkenyl chain or (C 2 -C 10 )-alkynyl chain which is branched or unbranched, substituted or unsubstituted and is optionally inturrupted 1 to 3 times by —O— or —S— or —N—; and

(vii) X is —C(═O)O—, —CH═CH—, phenyl, substituted phenyl, heteroaryl, —O-phenyl (CH 3 ) 2 —, C(CH 3 ) 2 —C(═O)—NH— or —C(CH 3 ) 2 —C(═O)—O—.

2. The method of claim 1 , wherein the compound contacts enoyl reductase at the site at which gemfibrozil contacts enoyl reductase.

Assignments (2)
CONFIRMATORY LICENSE Recorded Jun 21, 2017
From: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
To: NATIONAL INSTITUTES OF HEALTH - DIRECTOR DEITR
Reel/Frame 042765/0696 →
CONFIRMATORY LICENSE Recorded Mar 30, 2009
From: COLUMBIA UNIV NEW MORNINGSIDE
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 022466/0475 →
Continuity (2)
Continuation 0943814400 · Nov 10, 1999
Related Publication 20030191146A1 · Oct 9, 2003