Inhibitors of HIV-1 attachment. Part 7: Indole-7-carboxamides as potent and orally bioavailable antiviral agents

Homology models of the HIV‐1 attachment inhibitor BMS‐626529 bound to gp120 suggest a unique mechanism of action

“…Figure shows structural motifs that were widely used in earlier AIs in the series that led to the identification of BMS‐626529. The putative binding sites identified within the hydrophobic cleft in the outer domain of gp120 and the gp120 water channel/CD4:F43 binding pocket were compared against the full range of SARs for the AI series in order to determine their feasibility.…”

Synthesis and MRSA PK inhibitory activity of thiazole containing deoxytopsentin analogues

“…Failure to exclude water would lead to hydrolysis of the acid chloride to afford indole-3-carboxylic acid which is an unsuitable electrophile for nucleophilic cyanide attack. Application of our optimized method to the halogenated indoles (32-34) yielded the desired carbonylnitriles 28, 29 and 30 in lower yields (40%, 38% and 33% respectively) as predicted by Janosik et al 32 Interestingly, although Yeung et al 43 reported the substitution of the C-7 bromine substituent on an indole ring by cyanide following the addition of CuCN in DMF, we found no evidence of this substitution in our synthesis. The widely used method 19,44,45,46 for conversion of nitriles into thioamides originally introduced by Taylor and Zoltewicz, 47 was deemed suitable for our purposes to synthesize 11-14.…”

A new synthesis of versatile indolyl-3-carbonylnitriles

“…Interestingly, 7-chloroindole (entry 5) significantly impeded the formation of 15, reducing the overall yield of carbonyl nitrile 7. However, this result was still pleasing since it had been demonstrated by Yeung et al 24 that C-7 halogen displacement was possible in the presence of a nucleophilic cyanide species, which is commonly utilised in the previously described methods for carbonyl nitrile formation.…”