Studies of chirality effect of 4-(phenylamino)-pyrrolo[2, 1-f][1, 2, 4]triazine on p38alpha by molecular dynamics simulations and free energy calculations

4-(Phenylamino)-pyrrolo[2,1-f][1,2,4]triazines have been discovered as inhibitors of p38alpha. Experimental assays have proven that the configuration of alpha-Me-benzyl connected with amide at C6 is essential for the binding affinity. The S-configured inhibitor (11j) displays 80 times more potency than the R-configured one (11k). Here we investigated the… CONTINUE READING