The Johns Hopkins University

James D Dick

Francis P Kuhajda

Gary R Pasternack

Craig Arthur Townsend

Nicole M Parrish

Craig A Townsend

This invention provides compounds and methods for treating, with said compound, a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R&#x2014;SO-Z-CO&#x2014;Y, where R is an alkyl groups having 6-20 carbon atoms, unsaturated hydrocarbon groups having 6-20 carbon atoms, or alkyl groups having 6-20 carbon atoms interrupted by at least one aromatic ring; Z is &#x2014;CH&#x2014;, &#x2014;CHCH&#x2014;, &#x2014;NH&#x2014;NH&#x2014;, &#x2014;O&#x2014;, &#x2014;&#x2014;NH&#x2014;, &#x2014;O&#x2014;NH&#x2014;, &#x2014;CH&#x2014;NH&#x2014;, &#x2014;CH&#x2014;O&#x2014;, &#x2014;NH&#x2014;O&#x2014;, &#x2014;NH&#x2014;CH&#x2014;, &#x2014;O&#x2014;CH&#x2014;, and &#x2014;CH&#x2550;CH&#x2014;; Y is &#x2014;NH, &#x2014;O&#x2014;CH&#x2014;CH, &#x2014;CO&#x2014;CO&#x2014;O&#x2014;CH, and &#x2014;O&#x2014;CH; and n is 1 or 2. It has been discovered that these compounds treat microbially-based infections caused by corynebacteria, nocardiae, rhodococcus, and mycobacteria. These compounds may be used to treat mycobacterial cells, such as, drug resistant, and pathogenicsp.

Antimicrobial compounds

This invention provides methods for treating a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R&mdash;SO &mdash;Z&mdash;CO&mdash;Y, where R is an alkyl group having 6-20 carbons; Z is a radical selected from &mdash;CH &mdash;, &mdash;O&mdash;, and &mdash;NH&mdash;, two of these radicals coupled together, or &mdash;CH &boxH;CH &mdash;; Y is &mdash;NH , O&mdash;CH &mdash;C H , &mdash;CO&mdash;CO&mdash;O&mdash;CH , or O&mdash;CH ; and n is 1 or 2. It has been discovered that these compounds inhibit growth of microbial cells which synthesize &agr;-substitued, &bgr;-hydroxy fatty acids, particularly corynemycolic acid, nocardic acid, and mycolic acid. These compounds may be used to inhibit growth of mycobacterial cells, such as drug-resistant and

Fatty acid synthase (FAS) is overexpressed by certain infectious organisms that are resistant to most currently available antibiotics. Contrarywise, little FAS expression is identified in patient tissues. Inhibition of fatty acid synthesis is thus selectively toxic to invasive cells, while patient cells with low FAS activity are resistant. This invention provides a method of treating septic patients where fatty acid synthesis by invading cells is inhibited with resultant interruption of the disease process.

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Upperco, MD, United States of America

James D Dick