ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

A new group of potential antituberculotics: N-(2-pyridylmethyl)salicylamides and N-(3-pyridylmethyl)salicylamides

Eva Petrlíková, Karel Waisser, Karel Palát, Jiří Kuneš, and Jarmila Kaustová

Department of Inorganic and Organic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, CZ-50003 Hradec Králové, Czech Republic

E-mail: eva.petrlikova@faf.cuni.cz

Abstract: As a part of our systematic study of antimycobacterially active derivatives of salicylamides, a series of nineteen derivatives of N-(2-pyridylmethyl)salicylamides and N-(3-pyridylmethyl)salicylamides was synthesised. The compounds exhibited in vitro activity against Mycobacterium tuberculosis and M. avium. Their lipophilicity, R _M, was measured by thin layer chromatography on silica gel impregnated with trioctadecylsilane and the logarithm of the partition coefficient (octanol-water), logP, was calculated. Both the parameters of lipophilicity correlated. The quantitative relationship between the structure and antimycobacterial activity was calculated. Antimycobacterial activity increased with an increase in lipophilicity. The N-(2-pyridylmethyl)salicylamide derivatives were more active than the derivatives of isomeric N-(3-pyridylmethyl)salicylamides. The geometry of compounds was calculated and the calculation was verified by measuring the length of the hydrogen bond between hydroxyl and carbonyl groups on the salicylic moiety.

Keywords: salicylamide – picoline – lipophilicity – TLC – QSAR – antimycobacterial activity

Full paper is available at www.springerlink.com.

DOI: 10.2478/s11696-010-0084-9

Chemical Papers 65 (1) 52–59 (2011)