Anti-human immunodeficiency activity of novel 2-arylpyrrolidine analogs

作者：Martirosyan Ashot H; Gasparyan Sahak P^*; Alexanyan Marina V; Harutyunyan Gohar K; Panosyan Henry A; Schinazi Raymond F

来源：Medicinal Chemistry Research, 2017, 26(1): 101-108.

DOI：10.1007/s00044-016-1731-7

• Pyrrolidinecarbonitriles
• Aminomethylpyrrolidines
• Anti-HIV-1
• Cytotoxicity activity

A series of 26 new compounds were synthesized and screened for their anti-human immunodeficiency virus-1 and cytotoxicity activity. Of these, 14 were found to be inhibitors of human immunodeficiency virus replications in primary human lymphocytes with 50 % effective concentration values < 20 A mu M. Moreover, most of the compounds were cytotoxic to human lymphocytes, CEM, and Vero cells. Our structure activity relationship study identified different patterns. Compounds 2g-j and 4 (whose structure is closer to the loviride structure) were very potent. Comparing the activity of the compounds containing the 2-aryl substituents, we observed that compounds with benzyloxyphenyl groups were more potent. Compounds in which the 1-aryl moiety contained methyl group in 4- or 3,5-positions also showed high activity. In the series of compounds containing the nitrile, amine, and amide groups, we observed a decrease in activity with CN > NH2 > C(O)NH2. The difference of activity between the 5-membered and 4-membered rings compounds was not significant. This initial information could be used to design improved anti-human immunodeficiency virus compounds in this class.