4,5-Diphenyltriazol-3-ones:  Openers of Large-Conductance Ca²⁺-Activated Potassium (Maxi-K) Channels

Abstract

A series of diphenyl-substituted heterocycles were synthesized and evaluated by electrophysiological techniques as openers of the cloned mammalian large-conductance, Ca(2+)-activated potassium (maxi-K) channel. The series was designed from deannulation of known benzimidazolone maxi-K opener NS-004 (2) thereby providing an effective template for obtaining structure-activity-related information. The triazolone ring system was the most studied wherein 4,5-diphenyltriazol-3-one 6d (maxi-K = 158%) was identified as the optimal maxi-K channel opener.

One pot cascade synthesis of substituted 1,2,4-triazol-3-ones

“…The electron-deficient aldehydes ( Table 2, entries 5-11) and the electron-rich hydrazines ( Table 2, entries 9-13) gave higher yields than the electron-rich aldehydes ( Table 2, entries 14-16) and the electron-deficient hydrazines ( Table 2, entries 4 and 5). The strongly electron-deficient hydrazine did not work ( The product structures were characterized by 1 H NMR, 13 C NMR, IR and HRMS spectra. The structure of compound 4b was confirmed by X-ray analysis (Figure 1).…”

“…There have been numerous reports concerning the development of synthetic methods for construction of triazolinones, the majority of which involve intramolecular cyclocondensation of formyl semicarbazides [8,9], condensation of an amidrazone with phosgene or a phosgene surrogate [10][11][12][13], the Mitsunobu reaction of isocyanates and diisopropyl azodicarboxylate [14], cyclization of semicarbazide [15][16][17] and intramolecular cyclocondensation of hydrazidehydrazones [18]. This work describes a one pot synthesis of substituted triazolinones via a three-component reaction of aldehydes, hydrazines and azodicarboxylates using trifluoroacetic acid (TFA) as catalyst.…”

Dimethylformamide dimethyl acetal as a building block in heterocyclic synthesis

“…Hydrazides (265a-e) were converted to 3-aminopyrimido [5,4-c]cinnolines (266a-e) by refluxing with DMFDMA in diethylene glycol dimethyl ether [161,162]. (267) with DMFDMA to give triazole ring followed by hydrolysis [163].…”

Synthesis and Antimicrobial Studies of Some 4-(Substituted)-Ethanoylamino-3-Mercapto-5- (4-Substituted) Phenyl-1,2,4-Triazoles

“…It is evident that antimicrobial resistance is associated with an increase in mortality. 1 7-18, 2012 (June) antibacterial, antifungal, [2][3][4][5][6][7][8] antitubercular, 9,10 anticancer, 11 anti-tumor, 12 anti-inflammatory [13][14][15] , anticonvulsant, [16][17] urease inhibitor, 18 openers of Caactivated potassium (Maxi-K) channel, 19 tubulin polymerization inhibitors, 20 ghrelin receptor antagonist 21 and antiviral activities. 22 These findings prompted us to synthesize 4-(substituted) ethanoylamino-3-mercapto-5-(4-substituted) phenyl-1,2,4-triazoles 6-14a,b having substitution on aromatic ring and different secondary amino groups were attached on ethanoyl moiety and these compounds were evaluated for antimicrobial activity.…”