Synthesis of Indolecarboxamides and Their Docking Studies with H1,5HT and CCR2 Antagonist Receptors

A simple and straightforward novel method to synthesis indolecarboxamides by amidation of indole carboxylic acid and amines in the presence of TCT was developed. The newly synthesized  indolecarboxamide ligands 3a-m were subjected to in silico docking studies against H1,5HT and CCR2 antagonist receptor. Good to excellent yield of 3a-m was obtained when we use 0.25 equivalent of TCT to couple indole carboxylic acid and amine in THF solvents.  This methods was convenient both for aliphatic and aromatic amines. Further this method tolerates different functionality such as hydroxyl, chloro, fluoro and trifluoromethyl as well. In silicostudy reveals that the ligands 3a-m were exhibited good to excellent binding interactions with H1 protein receptor. In particular 3b, 3c & 3i have shown strong 3 hydrogen bonding interaction each with H1 protein receptor whose binding energy is -19.1501, -14.8505, -17.1749 Kcal/mol and inhibitory constant of is 91.6718, 100.49, 85.0736 µM respectively. At the same time the ligands 3a-m have shown moderate inhibition and hydrogen bond interaction with 5HT and CCR2 protein receptors. Here the ligands 3b, 3c & 3i  shows single hydrogen bonding interaction with 5HT protein receptor whose binding energies are -10.9311, -9.2191 -11.1749 Kcal/mol respectively is a moderate interaction and thus drawing the attention  in terms of high degree of selectivity of the ligands with protein receptors.