The structures of the newly synthesized 4-methyl-N′-(3-alkyl-2r,6c-diarylpiperidin-4-ylidene)-1,2,3-thiadiazole-5-carbohydrazide (5a–5l) were confirmed by spectral and elemental analysis. The difference in the potency of activity against various free radicals, human cancer cells and microbial strains has been evaluated by SAR. Compounds with electron-donating methoxy (5i and 5c) and methyl (5h and 5b) substitutions at the para position of the phenyl showed excellent free radical scavenging effects. In the tested compounds, electron withdrawing fluoro (5k and 5e), chloro (5j and 5d), and bromo (5l and 5f) substitution at the para position of the phenyl ring attached to C-2 and C-6 carbons of the piperidine moiety outperformed cytotoxic and antimicrobial activities. Our findings suggest that the antioxidant, anti-tumor and anti-microbial activities of compounds 5a–5l create promising leads for the development of potent anti-tumor and anti-microbial agents.

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Key indicatorsSingle-crystal X-ray study T = 273 K Mean (C-C) = 0.002 Å R factor = 0.037 wR factor = 0.104 Data-to-parameter ratio = 14.5For details of how these key indicators were automatically derived from the article, see

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isopropyl esters has been synthesized by adopting a conventional method from cyclic -keto esters. 1 H, 13 C NMR, and IR spectra for all the compounds were investigated. HMBC, HSQC, COSY, and NOESY spectra of the representative compounds were studied. The stereochemistry of a six-membered ring of the fused indazoles resembled that of keto esters. From the HMBC correlations the indazole structure was confirmed as 1H-indazole.The universal requirements on heterocyclic compounds for their potential activities against microorganisms and significance in the pharmaceutical field prompted us to synthesize indazoles from cyclic keto esters. Several pathways have been described for the synthesis of indazoles [1][2][3][4][5].Recently we reported the synthesis and structural studies of r-2,c-4-bis(alkoxycarbonyl)-t-3-arylc-5-hydroxy-t-5-methylcyclohexanone by the condensation of acetoacetic esters with different aromatic aldehydes in the presence of methylamine [6][7][8]. The conformation of the two isopropyl groups of compound 1 was also studied with the help of X-ray crystallography of t-2-aryl-c-4-hydroxy-4-methyl-6-oxocyclohexane-r-1,c-3-dicarboxylic acid diisopropyl ester [9]. The present paper describes the use of the above compounds [8] assynthons for the preparation of 4,5,6,7-tetrahydro-1H-indazole. The synthesis of 4,5-trans-2-alkyl-4-hetaryl-5-ethoxycarbonyl(acetyl)-6-hydroxy-6-methyl-4,5,6,7-tetrahydro-2H-indazole has been reported [10]. Nevertheless, the published NMR spectral data apliesmoreto1H-indazolethan to 2H-indazole. N(2)-Substituted tetrahydroindazoles have been reported in [11].Synthesis of 4,5,6,7-1H-indazoles involves two steps. The first step, condensation of isopropyl acetoacetate with aromatic aldehydes in the presence of methylamine in ethanol, yielded cyclic -keto esters 1-7. They were treated with hydrazine hydrate in ethanol under reflux to give compounds 8-14 (Scheme). The mechanism of this second step was different from the expected one. Dehydration was faster than cyclization, and the cyclic intermediates formed in the reaction course were unstable and easily underwent amido-imidol tautomerism, yielding stable 1H-indazoles.