A new group of potential antituberculotics: hydrochlorides of piperidinylalkyl esters of alkoxy-substituted phenylcarbamic acids.
A group of 31 of alkoxy-substituted phenylcarbamic acids with the alkoxy group in ortho, meta or para position, and methyl or ethoxymethyl attached to the ethylene moiety in position 1, including both basic ethyl esters and derivatives branched on ethylene, were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, and M. avium. To describe the structure-antimycobacterial activity relationships (QSARs), an approach based on a combination of the Free-Wilson analysis was used to express the influence of the substituents on the ethylene group as well as the position of the alkoxy groups on the phenyl ring and of the hydrophobicity of alkyls. In vitro antimycobacterial activity becomes higher with increasing hydrophobic properties of the alkoxy groups. The para- and meta-substituted derivatives were more active than the ortho-substituted ones. Substitution of ethylene in position 1 by methyl increased the activity against M. tuberculosis, a similar substitution by ethoxymethyl increased the activity against M. kansasii. The most active compounds were piperidinyl-1-(ethoxymethyl)ethylesters of heptoxyphenylcarbamic acids.
Waisser
K
K
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czechia.
Drazková
K
K
Cizmárik
J
J
Kaustová
J
J
D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009162:Mycobacterium avium / Q000187:drug effects; D019909:Mycobacterium kansasii / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents; D002219:Carbamates; C059692:phenylcarbamic acid