3359-24-8Relevant articles and documents
Human β3-adrenergic receptor agonists containing 1,2,3-triazole-substituted benzenesulfonamides
Brockunier, Linda L.,Parmee, Emma R.,Ok, Hyun O.,Candelore, Mari R.,Cascieri, Margaret A.,Colwell Jr., Lawrence F.,Deng, Liping,Feeney, William P.,Forrest, Michael J.,Hom, Gary J.,MacIntyre, D. Euan,Tota, Laurie,Wyvratt, Matthew J.,Fisher, Michael H.,Weber, Ann E.
, p. 2111 - 2114 (2000)
Compounds containing a 1,2,3-triazole-substituted benzenesulfonamide were prepared and found to be potent and selective human β3-adrenergic receptor agonists. The most interesting compound, trifluoromethylbenzyl analogue 12e (β3 ECs
1-Aryl-1H- and 2-aryl-2H-1,2,3-triazole derivatives blockade P2X7 receptor in?vitro and inflammatory response in?vivo
Gonzaga, Daniel Tadeu Gomes,Ferreira, Leonardo Braga Gomes,Moreira Maramaldo Costa, Thadeu Estevam,von Ranke, Natalia Lidmar,Anastácio Furtado Pacheco, Paulo,Sposito Sim?es, Ana Paula,Arruda, Juliana Carvalho,Dantas, Luiza Pereira,de Freitas, Hércules Rezende,de Melo Reis, Ricardo Augusto,Penido, Carmen,Bello, Murilo Lamim,Castro, Helena Carla,Rodrigues, Carlos Rangel,Ferreira, Vitor Francisco,Faria, Robson Xavier,da Silva, Fernando de Carvalho
, p. 698 - 717 (2017/09/01)
Fifty-one 1,2,3-triazole derivatives were synthesized and evaluated with respect to P2X7 receptor (P2X7R) activity and its associated pore. These triazoles were screened in vitro for dye uptake assay and its cytotoxicity against mammalian cell types. Seven 1,2,3-triazole derivatives (5e, 6e, 8h, 9d, 9i, 11, and 12) potently blocked P2X7 receptor pore formation in vitro (J774.G8 cells and peritoneal macrophages). All blockers displayed IC50 value inferior to 500 nM, and they have low toxicity in either cell types. These seven selected triazoles inhibited P2X7R mediated interleukin-1 (IL-1β) release. In particular, compound 9d was the most potent P2X7R blocker. Additionally, in mouse acute models of inflammatory responses induced by ATP or carrageenan administration in the paw, compound 9d promoted a potent blocking response. Similarly, 9d also reduced mouse LPS-induced pleurisy cellularity. In silico predictions indicate this molecule appropriate to develop an anti-inflammatory agent when it was compared to commercial analogs. Electrophysiological studies suggest a competitive mechanism of action of 9d to block P2X7 receptor. Molecular docking was performed on the ATP binding site in order to observe the preferential interaction pose, indicating that binding mode of the 9d is by interacting its 1,2,3-triazole and ether moiety with positively charged residues and with its chlorobenzene moiety orientated toward the apolar end of the ATP binding site which are mainly composed by the Ile170, Trp167 and Leu309 residues from α subunit. These results highlight 9d derivative as a drug candidate with potential therapeutic application based on P2X7 receptor blockade.
Activation of Exocyclic α-Positions of Azole N-Oxides by O-Silylation
Begtrup, Mikael,Vedso, Per
, p. 2555 - 2564 (2007/10/02)
Exocyclic α-positions at immonium ring carbon atoms of pyrazole and 1,2,3-triazole 1-oxides are selectively attacked in a one-pot sequence comprising silylation with iodotrimethylsilane, deprotonation with 1,2,2,6,6-pentamethylpiperidine and allylic substitution of the trimethylsilyloxy group with the iodide ions liberated by the silylation.In this way 3- and 5-iodomethylpyrazoles as well as 4-iodomethyl-1,2,3-triazoles are obtained in good yields.These may be useful for the preparation of heteroarylmethyl derivatives since the iodine atom can be displaced by even weak nucleophiles such as acetate ions.The side chain iodination is complementary to O-alkylation of the N-oxides followed by nucleophilic attack which preferentially takes place at ring carbon atoms.
