The acid-catalysed synthesis of 7-azaindoles from 3-alkynyl-2-aminopyridines and their antimicrobial activity

Abstract

The synthesis of 7-azaindoles from 3-alkynyl-2-aminopyridines using acidic conditions, namely, a mixture of trifluoroacetic acid (TFA) and trifluoroacetic anhydride (TFAA), is described. This methodology resulted in the synthesis of fifteen 7-azaindoles, with most containing substituents at the 2- and 5-positions. The majority of these were tested for antimicrobial activity against a range of bacteria and yeasts. The 7-azaindoles displayed the best activity against the yeasts, particularly against Cryptococcus neoformans, where activities as low as 3.9 μg ml(-1) were observed.

Double Sonogashira reactions on dihalogenated aminopyridines for the assembly of an array of 7-azaindoles bearing triazole and quinoxaline substituents at C-5: Inhibitory bioactivity against Giardia duodenalis trophozoites

“…7 During the course of this work we were able to show that through the use of the Sonogashira coupling reaction using dihalogenated aminopyridines we were able to introduce two acetylenes onto a 2-aminopyridine nucleus (Fig. 2).…”

“…For this purpose we found that the use of potassium t-butoxide in a mixture of DMF and THF was the best method to afford the desired azaindoles 15a-e, rather than the acid-mediated methodology we had developed. 7 We were now in a position to apply another Sonogashira coupling reaction to the bromoazaindoles 15a-e. Conducting the reaction on 15a-e at reflux led to the formation of 16a-e, which was subjected to conditions (TBAF) for the removal of the TMS substituent to furnish 17a-e (Scheme 2).…”

Synthesis and evaluation of biological activities of new sulfonamide and carbamate derivatives of 1H-pyrrolo[2,3-b]pyridine (7-azaindole)

“…They have attracted considerable interest from the chemical community because of their potential applications in natural product synthesis and pharmaceuticals due to their hydrogen bonding properties and excellent water solubility. The 1H-pyrrolo [2,3-b]pyridine moiety exhibits a broad spectrum of biological activities, including anticancer [2], antitumor [3][4][5], anti-angiogenic [6], antimicrobial [7], as inhibitor of HIV-1 [8,9] and cell division cycle of 7-kinase [10], antifungal [11], analgesic [12], antimalarial [13], antiproliferative [14,15], antibacterial [16], reducing chronic pain [17], as cisplatin and transplatin derivatives [18], antimycobacterial [19], as Topoisomerase I inhibitors [20] and protein kinase inhibition [21], etc. Azaindole and its core containing compounds which include neocryptolepine (1), variolin-B (VAR-B) (2) and grossularines (3) are natural products, while 7-aza-rebeccamycin (4) and 5-azaellipticine (5) are of synthetic origin, whose activity is related to DNA, i.e.…”

The Fischer Reaction in the Synthesis of 2,3-Disubstituted 7-Azaindoles*

“…Currently the most common routes for the synthesis of 7-azaindoles and their derivatives are, first of all, various modifications of Madelung and Reissert syntheses [2], as well as palladium-catalyzed processes based on 2-aminopyridine [10], and, secondly, the annelation of pyridine ring to pyrrole ring [2,11]. _______ *Dedicated to Academician of the Russian Academy of Sciences Yu.…”