TY - JOUR
KW - Amides
KW - Antitubercular Agents
KW - Microbial Sensitivity Tests
KW - Mycobacterium tuberculosis
KW - Structure-Activity Relationship
KW - Sulfones
AU - Jones P B
AU - Parrish N M
AU - Houston T A
AU - Stapon A
AU - Bansal N P
AU - Dick J D
AU - Townsend C A
AB - <p>Long-chain lipid envelopes are characteristic of mycobacteria such as those that cause tuberculosis and leprosy. Inhibition of fatty acid synthesis or elongation is a strategy demonstrated to be clinically effective against M. tuberculosis. A new class of compounds designed to inhibit the beta-ketoacyl synthase reaction of fatty acid synthesis has been developed. Of >30 compounds described, the most active were acetamides containing alkylsulfonyl substituents. Inhibitory activities were acutely sensitive to net charge, chain length, and degree of unsaturation. The most active compound 5 (alkyl = C(10)) contained a single methylene spacer between the sulfone and carboxamide and exhibited an MIC of 0.75-1.5 microg/mL, comparable to first-line antituberculosis drugs. These compounds are species-specific, exhibiting no significant activity against bacterial species other than M. tuberculosis and closely related strains. The synthesis, biological activity, and specificity of these compounds are described.</p>
BT - Journal of medicinal chemistry
C1 - http://www.ncbi.nlm.nih.gov/pubmed/10966749?dopt=Abstract
DA - 2000 Aug 24
DO - 10.1021/jm000149l
IS - 17
J2 - J. Med. Chem.
LA - eng
N2 - <p>Long-chain lipid envelopes are characteristic of mycobacteria such as those that cause tuberculosis and leprosy. Inhibition of fatty acid synthesis or elongation is a strategy demonstrated to be clinically effective against M. tuberculosis. A new class of compounds designed to inhibit the beta-ketoacyl synthase reaction of fatty acid synthesis has been developed. Of >30 compounds described, the most active were acetamides containing alkylsulfonyl substituents. Inhibitory activities were acutely sensitive to net charge, chain length, and degree of unsaturation. The most active compound 5 (alkyl = C(10)) contained a single methylene spacer between the sulfone and carboxamide and exhibited an MIC of 0.75-1.5 microg/mL, comparable to first-line antituberculosis drugs. These compounds are species-specific, exhibiting no significant activity against bacterial species other than M. tuberculosis and closely related strains. The synthesis, biological activity, and specificity of these compounds are described.</p>
PY - 2000
SP - 3304
EP - 14
T2 - Journal of medicinal chemistry
TI - A new class of antituberculosis agents.
VL - 43
SN - 0022-2623
ER -