Evaluation of 1,2,3-triazoles as amide bioisosteres in cystic fibrosis transmembrane conductance regulator modulators VX-770 and VX-809 was written by Doiron, Jake E.;Le, Christina A.;Ody, Britton K.;Brace, Jonathon B.;Post, Savannah J.;Thacker, Nathan L.;Hill, Harrison M.;Breton, Gary W.;Mulder, Matthew J.;Chang, Sichen;Bridges, Thomas M.;Tang, Liping;Wang, Wei;Rowe, Steven M.;Aller, Stephen G.;Turlington, Mark. And the article was included in Chemistry – A European Journal in 2019.Safety of 6-Nitro-1H-indole This article mentions the following:
The 1,2,3-triazole has been successfully utilized as an amide bioisostere in multiple therapeutic contexts. Based on this precedent, triazole analogs derived from VX-809 and VX-770, prominent amide-containing modulators of the cystic fibrosis transmembrane conductance regulator (CFTR), were synthesized and evaluated for CFTR modulation. Triazole 11, derived from VX-809, displayed markedly reduced efficacy in F508del-CFTR correction in cellular TECC assays in comparison to VX-809. Surprisingly, triazole analogs derived from potentiator VX-770 displayed no potentiation of F508del, G551D, or WT-CFTR in cellular Ussing chamber assays. However, patch clamp anal. revealed that triazole 60 potentiates WT-CFTR similarly to VX-770. The efficacy of 60 in the cell-free patch clamp experiment suggests that the loss of activity in the cellular assay could be due to the inability of VX-770 triazole derivatives to reach the CFTR binding site. Moreover, in addition to the neg. impact on biol. activity, triazoles in both structural classes displayed decreased metabolic stability in human microsomes relative to the analogous amides. In contrast to the many studies that demonstrate the advantages of using the 1,2,3-triazole, these findings highlight the neg. impacts that can arise from replacement of the amide with the triazole and suggest that caution is warranted when considering use of the 1,2,3-triazole as an amide bioisostere. In the experiment, the researchers used many compounds, for example, 6-Nitro-1H-indole (cas: 4769-96-4Safety of 6-Nitro-1H-indole).
6-Nitro-1H-indole (cas: 4769-96-4) belongs to indole derivatives. In addition to tryptophan, indigo, and indoleacetic acid, numerous compounds obtainable from plant or animal sources contain the indole molecular structure. Moreover, it is known that it controls biofilm formation. However, the role of indole in the cell has not been fully elucidated.Safety of 6-Nitro-1H-indole
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles