Facile Synthesis, Single‐Crystal Structure, and Biological Evaluation of Novel Pyrazolo[5,1‐d][1,2,5]triazepin‐4‐ones

Abstract

A facile ring-enlargement reaction of 2,6-diphenyl-4H-pyrazolo [5,1-c] C-NMR, and HR-MS data. Moreover, the molecular structure was confirmed by the X-ray crystal-structure analysis of one compound that was prone to crystallization. Preliminary biological evaluation showed that the compounds 2e -2h promote the viability and inhibit the apoptosis of vascular endothelial cells at low concentration.Introduction. -Small-and medium-sized N-containing heterocyclic skeletons, such as fused triazepines with a bridgehead N-atom in the molecule exhibit remarkable biological properties [1]. Although several methods for constructing 1,3,5-triazepine can be found in the literature [2], the 1,2,5-triazepin skeleton has only received scant attention [3].It has been reported that the class of pyrazoles represents structurally diverse molecules with widespread and diverse pharmacological properties such as anticancer We previously reported our efforts to identify novel potential agents, which inhibited human umbilical vein endothelial cell (HUVEC) apoptosis, based on pyrazole heterocycles [15]. More recently, we became interested in exploring pyrazolefused heterocycles that contain more heteroatoms, ultimately discovering novel antithrombotic and anticancer agents [16]. In continuation of our search for biologically potent molecules, we hereby report the synthesis and structure characterization of pyrazolo [5,1-d][1,2,5]triazepin-4-one derivatives, which could inhibit endothelial cell apoptosis.