A novel and efficient synthesis of pyrazolo[3,4-d]pyrimidine derivatives and the study of their anti-bacterial activity

In this work 4-amino-6-aryl-2-phenyl pyrimidine-5-carbonitrile derivatives were synthesized through a one-pot, three-component reaction of an aldehyde, malononitrile and benzamidine hydrochloride, in the presence of magnetic nano Fe304 particles as a catalyst under solvent-free conditions. 3-Amino-6-aryl- 2-phenylpyrazolo[3,4-d]pyrimidine derivatives were prepared through an efficient and environmentally friendly reaction between 4-amino-6-aryl-2-phenylpyrimidine-5-carbonitrile derivatives and hydra- zine hvdrate and their antibacterial activity has been evaluated

Multicomponent Strategy for the Preparation of Pyrrolo[1,2-a]- pyrimidine Derivatives under Catalyst-Free and Microwave Irradiation Conditions

A simple and efficient one-pot procedure has been developed for the construction of pyrrolo[ 1,2-a]pyrimidines via the three-component domino reaction of 5-aminopyrazoles, acetylenedicarboxylates and malononitrile under catalyst-free, microwave irradiation conditions. The key step in this transformation is the N--N bond cleavage reac- tion of the 5-aminopyrazole substrate, which has been reported in this context for the first time in this study. The advantages of this protocol include readily available starting materials, short reaction times and good regioselectivity.

Use of 3-(2'-formyl-l'-chlorovinyl)coumarin in the syntheses of pyrazol, salicylaldazine and pyrimidine derivatives

3-(Pyrazol-5'-yl)coumarin (3) was prepared from condensation of 3-(2'-formyl-1'-chlorovinyl)-coumarin (1) with hydrazine hydrate at room temperature, followed by cyclization with base. Salicylaldazine was prepared from methoxylation of 1 to give acetal 7, followed by condensation of 7 with hydrazine hydrate at 80℃. Treatment of acetal 7 with thiourea yielded the corresponding 4-substituted-2-thioxo-2H-pyrimidine [ 3, 4-b]-coumarin (12).

Spectroscopic analysis on the binding interaction of biologically active pyrimidine derivative with bovine serum albumin

A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-（4-N, N-dimethylaminophenyl）-pyr- imidine-5-carbonitrile （AHDMAPPC）, was synthesized. It was employed to investigate the binding in- teraction with the bovine serum albumin （BSA） in detail using different spectroscopic methods. It ex- hibited antibacterial activity against Escherichia cali and Staphylococcus aureus which are common food poisoning bacteria. The experimental results showed that the fluorescence quenching of model carrier protein BSA by AHDMAPPC was due to static quenching. The site binding constants and number of binding sites （n ≈ 1） were determined at three different temperatures based on fluorescence quenching results. The thermodynamic parameters, enthalpy change （AH）, free energy （AG） and entropy change （AS） for the reaction were calculated to be 15.15 kJ/mol, -36.11 kJ/mol and 51.26J/mol K according to van＇t Hoff equation, respectively. The results indicated that the reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in the binding between drug and BSA. The distance between donor and acceptor is 2.79 nm according to Forster＇s theory. The alterations of the BSA secondary structure in the presence of AHDMAPPC were confirmed by UV-visible, synchronous fluorescence, circular dichroism （CD） and three-dimensional fluorescence spectra. All these results in- dicated that AHDMAPPC can bind to BSA and be effectively transported and eliminated in the body. It can be a useful guideline for further drug design.

Hydrothermal Syntheses, Crystal Structures and Fluorescence of a Copper(I) Polymer and a Salt with H_2SO_4 Based on a Pyrimidine Building Block

Based on the building block of 2-phenyl-4,6-di（pyridin-2-yl）pyrimidine （L = C20H14N4）, a Cu（I） polymer [（CuC20H14N4）（CuCl2）]∞ and a salt with H2SO4 [（C20H16N4）（HSO4）2] have been synthesized by hydrothermal method and characterized by X-ray single-crystal diffraction. In the Cu（Ⅰ） polymer, although the central metal ions of Cu（Ⅰ） directly coordinate with the building block L, they still do not assembly expected grid-type complexes and there exists a one-dimensional chain constructed through coordinate bonds. In the salt, hydrogen bonds along with two kinds of π…π supramoleuclar interactions fabricate two-dimensional （2D） networks which further generate a 3D supramolecular architecture via interlayer π…π interactions. Fluorescent spectra show that the L emits blue fluorescence and its Cu（Ⅰ） polymer and salt decrease the fluorescent intensity.

Discovery and synthesis of N^2,N^4-substitued-cycloalkyl[d]pyrimidine-2,4-diamine analogs: The first examples of small-molecular FGFR-1 activator

A series of novel, cycloalkyl-modified pazopanib analogs 2 and 3 were designed and synthesized. Their kinase modulatory effects on FGFR-1, VEGFR-2, PDGFR-β and c-KIT were evaluated by the caliper mobility shift assay. Introduction of cycloalkyl into the pyrimidine linker of pazopanib almost abolished the four kinases inhibitory potency of compounds 2 and 3, but surprisingly, resulted in good activation effects on FGFR-1. Compounds 3d and 3g showed double-digit, nanomolar, selective activation effects on FGFR-1, and could be classified as first-generation small molecular activators of FGFR-1 kinase.