A convenient synthesis and molecular modeling study of novel pyrazolo[3,4-d]pyrimidine and pyrazole derivatives as anti-tumor agents.

An efficient method to obtain ethyl 5-amino-1-tosyl-1H-pyrazole-4-carboxylate (3) was outlined using condensation reactions of 4-methylbenzenesulfonylhydrazide with (E)-ethyl 2-cyano-3-ethoxyacrylate. The cyclocondensation reaction of this substrate and its hydrazide derivative with urea, thiourea, formamide, formic acid, d-glucose, o-phenylenediamine, 4-dimethylaminobenzaldehyde, anthracene-9-carbaldehyde, thioglycolic acid and carbon disulphide then with hydrazine hydrate analogues furnished a series of pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-d]oxazin-4-one, pyrazole-4-glucoside, 4-benzo[d]imidazole, 1,3-thiazolidinone, 1,3,4-oxadiazol-2(3H)-thione and 1,2,4-triazol-5(4H)-thione derivatives respectively. The structure of the compound 3 was supported by X-Ray crystallographic data. Orally administrated, one of each of the series of pyrazoles showed significant effects in mouse tumor model cancer cell lines (EAC) and two human cancer cell lines of Colon cancer (HCT-29) and Breast cancer (MCF-7) with docking studies.

A second polymorph of (Z)-3-amino-4-(2-phenyl-hydrazinyl-idene)-1H-pyrazol-5(4H)-one.

The mol-ecule of the title compound, C9H9N5O, is approximately planar (the r.m.s. deviation of all non-H atoms is 0.08 Å). The amine substituent is pyramidal at the N atom. An intra-molecular N-Hhydrazine⋯O=C hydrogen bond is present. In the crystal, mol-ecules are connected via N-H⋯N and N-H⋯O hydrogen bonds, forming infinite layers parallel to (010). This polymorph is triclinic, space group P-1, whereas the previously reported form was monoclinic, space group P21/c [Elgemeie et al. (2013 ▶). Acta Cryst. E69, o187], with stepped layers and a significantly lower density.

Ethyl 5-amino-1-[(4-methyl-phen-yl)sulfon-yl]-1H-pyrazole-4-carboxyl-ate.

In the title mol-ecule, C13H15N3O4S, the benzene and pyrazole rings are inclined to each other at 77.48 (3)°. Two amino H atoms are involved in bifurcated hydrogen bonds, viz. intra-molecular N-H⋯O and inter-molecular N-H⋯O(N). The inter-molecular hydrogen bonds link the mol-ecules related by translation in [100] into chains. A short distance of 3.680 (3) Šbetween the centroids of benzene and pyrazole rings from neighbouring mol-ecules shows the presence of π-π inter-actions, which link the hydrogen-bonded chains into layers parallel to the ab plane.

Molecular modeling study bioactive natural product of khellin analogues as a novel potential pharmacophore of EGFR inhibitors.

Khelline is naturally occurring furochromone exhibited significant Epidermal Growth Factor Receptor (EGFR) inhibitory activity. The newly synthesized compounds 2-5 displayed the most potent EGFR inhibitory activity on MCF-7 and HeLa. In vitro study against 59 different human tumour cell lines derived from nine cancer type in NCI (USA), which was presented and documented. Molecular docking simulation was performed to position compounds 1-5 into the EGFR active site to determine the probable binding mode.

A convenient synthesis and molecular modeling study of novel purine and pyrimidine derivatives as CDK2/cyclin A3 inhibitors.

A series of novel purine and pyrimidine derivatives were prepared and biologically evaluated for their in vitro anti-CDK2/cyclin A3 and antitumor activities in Ehrlich ascites carcinoma (EAC) cell based assay. The novel purine derivatives 13a,b demonstrated potent inhibitor activities with IC(50) values of 14±9 and 13±9 µM, respectively. Additionally, compound 15a showed the highest potency (IC(50)=10±6 µM) in EAC cell based assay. Molecular modeling study, including fitting to a 3D-pharmacophore model and their docking into cyclin dependant kinase2 (CDK2) active site showed high fit values and docking scores.