Synthesis, Characterization, and Docking Evaluations of New Derivatives of Pyrimido[4,5‐c]pyridazine as Potential Human AKT1 Inhibitors

Abstract

A number of new derivatives of pyrimido[4,5‐c]pyridazine have been synthesized from the treatment of 6‐acetyl‐3‐amino‐2,5‐diphenyl‐2,5‐dihydropyridazine‐4‐carbonitrile (1) as precursor with various reactants obtained quantitatively the desired products (2), (5), (7), and (9a, 9b, 9c, 9d, 9e). The structures of all the synthesized products have been elucidated thoroughly. The potential AKT1 inhibitory activities of these new synthesized compounds have also been studied by docking calculations, which have been performed in Gold 5.2 software using Genetic algorithm.

Organic Base-Promoted C–N- and C–O-Coupled Domino Cyclization Strategy: Syntheses of Oxazine-6-ones and 4-Pyrimidinols

“…Subsequently, a [1, 3]-H-abstraction occurs in the intermediate I to produce the intermediate II . In the next step, thiourea reacts with one cyano group of intermediate II , leading to the formation of intermediate III . Then, the lone pair of the O atom attacks the imine bond, and the weak C–S bond breaks and cyclizes to produce the intermediate IV .…”

Synthesis and Density Functional Theory Study of [1,2,3]Triazolo[4,5-d][1,2,4] Triazolo[4,3-a]Pyrimidine Derivatives: A Novel Heterocyclic System

“…[17][18][19] Some recently published protocols for assembling this bicyclic system have been accomplished through a one-pot multicomponent reaction using substituted aromatic aldehydes, malononitrile and 3-amino-1,2,4-triazole catalysed by boric acid in aqueous micellar conditions, 20 oxidative cyclisation of 4-amino-6-arylidene(heteroarylmethylidene) hydrazinyl-1,3,5-triazin-2-ones with Pb(OAc) 4 via a Dimroth-type rearrangement, 21 treatment of chloro-5,6diaminopyrimidines with NaNO 2 /HCl 22 and cyclisation of diethyl 2,4,6-trifluorophenylmalonate with 3-amino-1,2,4triazole. 11 Regarding these points, and due to our interest in the synthesis of various fused heterocyclic derivatives with a pyrimidine core, [23][24][25][26][27][28] herein we wish to report a convenient method for…”