Chemistry of Heterocyclic Compounds, Vol. 45, No. 6, 2009 4-HYDROXY-2-QUINOLONES 165*. 1-R-4-HYDROXY-2-OXO-1,2-DIHYDRO- QUINOLINE-3-CARBALDEHYDES AND THEIR THIOSEMICARBAZONES. SYNTHESIS, STRUCTURE, AND BIOLOGICAL PROPERTIES I. V. Ukrainets 1 **, Liu Yangyang 1 , A. A. Tkach 1 , O. V. Gorokhova 1 , and A. V. Turov 2 Two variants are discussed of the synthesis of 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid β-N-tosylhydrazides which undergo a McFayden-Stevens reaction to give 1-R-4-hydroxy-2-oxo- 1,2-dihydroquinoline-3-carbaldehydes in high yields. It was shown that the thiosemicarbazones prepared from them exist in the solid state exclusively in the syn-form while in solution a hydrazone ↔ enhydrazine tautomerism is observed. The results of a study of the antitubercular activity of the synthesized compounds are reported. Keywords: 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbaldehydes, thiosemicarbazones, isomeri- zation, antitubercular activity, X-ray structural analysis. Thiosemicarbazones have a broad spectrum of pharmacological activities. Amongst this class of substances there are found compounds with antiproliferative [2] and antiamebal [3] activity. They are effective in the fight against malaria [4], the herpes simplex virus [5], carcinoma of the prostate gland [6], hormone dependent breast cancer [7], and other types of malignant neoplasms [8, 9]. However, the widest use of thiosemicarbazones is actually found in the treatment of various microbial infections [10-16]. There is special interest in their ability to inhibit the growth of the tubercular mycobacterium. Conditions of continuing pandemic and the appearance of multiresistant strains of pathogen in this insidious illness serve as a reason for the search for novel antimycobacterial agents in this series of compounds. The first antitubercular preparation in the group discussed (p-acetamidobenzaldehyde thiosemicarbazone) has been used in medical practice for more than 50 years under the trade name of thiacetazone (tibon) [17]. It shows clear bacteriostatic activity towards the tubercular mycobacterium but, in view of its relatively high toxicity, it has limited use and is usually prescribed in combination with other preparations for improving their therapeutic effect and to avoid the _______ * For Communication 164 see [1]. ** To whom correspondence should be addressed, e-mail: uiv@kharkov.ua. 1 National University of Pharmacy, Kharkiv 61002, Ukraine. 2 Taras Shevchenko National University, Kiev 01033, Ukraine; e-mail: nmrlab@univ.kiev.ua. __________________________________________________________________________________________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 883-894, June, 2009. Original article submitted June 16, 2008. 0009-3122/09/4506-0705©2009 Springer Science+Business Media, Inc. 705