Antimicrobial activity of gemfibrozil and related compounds and derivatives and metabolites thereof
AssigneesThe Trustees of Columbia University in the City of New York, Albert Einstein College of Medicine of Yeshiva University
InventorsChristina Kabbash, Samuel C. Silverstein, Howard A. Shuman, John S. Blanchard
Life of this patent
Estimating the term…
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 entoy 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.
Claims7
A method of selecting a compound which inhibits the enzymatic activity of enoyl reductase which comprises:
- (A) contacting enoyl reductase with the compound;
- (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 or ester thereof, wherein
- (i) each of R1, R2, R3, R4, R5 and R6 is independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —OH, —OR7, —CN, —COR7, —SR7, —N(R7)2, —NR7—COR8, —NO2, —(CH2)p—OR7, —COSR7, —C(═O)—OH, —CONH2, —NH2, a straight chain or branched, substituted or unsubstituted C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, thioalkyl, methylene thioalkyl, acyl, phenyl, substituted phenyl and heteroaryl;
- (ii) the compound is in the form of an acyl carrier protein metabolite;
- (iii) L is —N—, —S—, —O—, —C≡C— or —CH2—;
- (iv) R7 is independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —OH, —CN, —COH, —SH, —NH2, —NHCOH, —(CH2)pOH, a straight chain or branched, substituted or unsubstituted C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, thioalkyl, methylene thioalkyl, acyl, phenyl, substituted phenyl and heteroaryl;
- (v) A is selected from the group consisting of —N2—, —NH—, —CH═C≡CH—, —C≡C—CH(OH)—, —C≡C—CH2—, —CH2—CH2—O—, —CH2—CH2—CH2—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 (C1-C10)-alkyl chain, (C1-C10)-alkenyl chain or (C1-C10) -alkynyl chain which is branched or unbranched, substituted or unsubstituted and is optionally interrupted 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(CH3)2—, —C(CH3)2—C (═O)—NH— or —C(CH3)2—C (═O)—O—.
A method of selecting a compound which inhibits the enzymatic activity of enoyl reductase which comprises:
- (A) contacting enoyl reductase with the compound;
- (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:
- in the form of an acyl carrier protein metabolite.
Dependencies are inferred from the claim text.