Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives

Abstract

The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described. The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using [3H]oxotremorine and [3H]quinuclidinyl benzilate. Potency and efficacy were found in compounds in which the azole moiety was attached to the azabicyclic ring either through a carbon atom or a nitrogen atom. Electrostatic potential maps of both the C-linked and the novel N-linked series of compounds were calculated. A relationship between position and depth of the electrostatic minima relative to the azabicyclic ring and the potency and efficacy of the compounds was determined.

Design and Synthesis of New Bioactive 1,2,4-Triazoles, Potential Antitubercular and Antimicrobial Agents

“…The 1,2,4-triazole, as well found to exhibit antiasthmatic [14] , antiviral (ribavirin) [15] , antifungal (fluconazole) [16] , antimicrobial [17,18] , antibacterial [19][20][21] , insecticidal [22] , hypnotic [23] , cytotoxic [24] , antitubercular [25] and hypotensive [26,27] activities. This moiety was also found in potent agonist and antagonist receptor ligands [28,29] in HIV-1 protease inhibitors [30] and in thrombin inhibitors [31] .…”

Pharmacological significance of triazole scaffold

“…The GH releasing mechanism was found to be mediated through a G-protein coupled receptor named growth hormone secretagogue receptor type 1 a (GHS-R1a) [73]. Presence of 1,2,4-triazole moiety was found in a series of potent agonist or antagonist G-protein coupled receptor ligands [74][75][76][77].…”

Chemoselective synthesis of novel thiatriazolophanes

“…6 Various 1,2,4-triazoles are found to be associated with diverse pharmacological activities such as antiasthmatic, 7 antiviral (ribavirin), 8 antifungal (fluconazole), 9 antimicrobial, 10 antibacterial, 11 insecticidal, 11,12 amoebicidal, 13 hypnotic, 14 cytotoxic, 15 and hypotensive 16 activities. This moiety was also found in potent agonist and antagonist receptor ligands, 17 in HIV-1 protease inhibitors 18 and in thrombin inhibitors. 19 Along with these significant pharmaceutical uses, 1,2,4-triazole derivatives are effectively used in polymers, dyestuff, photographic chemicals and agricultural chemicals.…”