Docking Studies, Synthesis, and Evaluation of Antioxidant Activities of N-Alkylated, 1,2,4-Triazole, 1,3,4-Oxa-, and Thiadiazole Containing the Aminopyrazolopyridine Derivatives

Synthesis of some 1,3,4-thia-, oxa-diazol and 1,2,4 triazole incorporated the biologically active and the pyrazolopyri-dine derivative. Molecular modeling and docking of the active compounds into AKR1C3 complexed with its bound inhibitor indomethacin using Molsoft ICM 3.4-8C program were performed in order to predict the affinity and orientation of the synthesized compounds at the active site.

Synthesis and Crystal Structure of 1-Phenyl-3-methyl-4-（4-bromophenyl）-6-（2-chlorophenyl）pyrazolo[3,4-b] Pyridine under Microwave Irradiation

The title compound (C25H17BrClN3) has been synthesized by the reaction of 1-(2- chlorophenyl)-3-(4-bromophenyl)-2-propylene-1-one with 5-amino-3-methyl-1-phenyl pyrazole under microwave irradiation and its structure was determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P1 with a = 9.3798(11), b = 10.6200(13), c = 11.7433(15) ?, α = 72.932(9), β = 78.877(10), γ = 72.045(9)o, V = 1057.0(2) ?3, Z = 2, Dc = 1.492 g/cm3, μ = 2.088 mm -1 , F(000) = 480, Mr = 474.78, the final R = 0.0428 and wR = 0.0879. X-ray analysis revealed that the dihedral angle between the pyrazol and pyridine planes is 6.45o.

Synthesis and Crystal Structure of 4-(2- Chlorophenyl)-5-cyano-3-methyl-6-oxo-1- phenyl-4,5,6,7-tetrahydropyrazolo[3,4-b] Pyridine under Microwave Irradiation

The title compound (C20H15ClN4O, Mr = 362.81) was synthesized by the reaction of ethyl 2-cyano-3-(2-chlorophenyl)-1-acylate with 5-amino-3-methyl-1-phenylpyrazole under microwave irradiation and its structure was determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 8.8192(19), b = 15.976(3), c = 13.094(3) ? = 103.074(4), V = 1797.1(7) ?, Z = 4, Dc = 1.341 g/cm3, = 0.229 mm-1, F(000) = 752, R = 0.0632 and wR = 0.1278. X-ray analysis reveals that the pyridine ring adopts an envelope conformation. The dihedral angle between the pyrazole and pyridine planes is 2.19, and inter- molecular hydrogen bonds are also observed in the molecule.

Design, Synthesis and Cancer Cell Line Activities of Pyrazolo[3,4-<i>b</i>]pyridine Derivatives

Starting from 4,6-dimethyl-2-oxo-(1H)-3-pyridinecarbonitrile 1 and 3-aminopyrazolopyridine 4, a series of cyanopyri- dine derivatives 3a-i, Schiff bases 5a-f, urea and thiourea derivatives 6a-b, amide derivatives 7a-h, pyridopyra- zolopy-rimidine 8a-b and pyridopyrazolotriazine 10a-b were synthesized. Activities of eleven representative compounds were evaluated against A-549 (lung), HEPG2 (liver) and HCT-116 (colon) cancer cell lines. The findings revealed that some of the synthesized compounds showed remarkable anticancer activities, especially 8b which displayed the highest activity among the tested compounds with IC50 equal to 2.9, 2.6 and 2.3 μmol. In addition to synthesis and biological activities, we present discussion about the rationale of the design and activity of the potent compound 8b using struc- ture-based modeling tools.

Novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives: Synthesis, crystal structure, fluorescence properties and cytotoxicity evaluation against human breast cancer cells

A series of novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives （II） have been designed and synthesized. The target com- pounds have been identified by elemental analysis and spectral （1H NMR, IR, and MS） data and the absolute configuration of compound （IIl） was confirmed by single crystal X-ray diffraction. The cytotoxicity of the target compounds have been evalu- ated in vitro against two human breast cancer cell lines MCF-7 and MDA-MB-231 by MTT assay. Most compounds exhibited good inhibition, and compounds II21 （IC50 = 4.7 μM for MCF-7 and IC50 = 9.3 μM for MDA-MB-231）, 1133 （IC50 = 2.4 μM for MCF-7 and IC50 = 4.2 gM for MDA-MB-231） and 114o （IC50 = 3.3 μM for MCF-7 and IC5o =8.6 μM for MDA-MB-231） dis- played better inhibitory activity than 5-fluorouracil （IC50 = 4.8 μM for MCF-7 and IC50 = 9.6 I, tM for MDA-MB-231, respec- tively）. Flow cytometric analysis and DNA fragmentation suggest that II33 is cytotoxic and able to induce the apoptosis of MCF-7 cells. The fluorescence properties of compounds IIl, II6, II11,II16, II23, Il2s, and II3s were also studied and compound Ilzs afforded the highest photoluminescence quantum yield （38%）.