Multicomponent Approach for the Sustainable Syntheses of Pyrido[2,3-d]pyrimidine Scaffold

: Pyrido[2,3-d]pyrimidine is an N-fused heterocyclic compound formed by the ortho fusion of pyridine and pyrimidine ring. Pyrido[2,3-d]pyrimidines hold a prominent position in medicinal chemistry owing to their wide spectrum of biological activities like antiviral, antihistaminic, antibacterial, diuretic, anti-inflammatory, analgesic, anticonvulsive, antipyretic, etc. The extraordinary features of pyrido[2,3-d]pyrimidines make their synthesis a perpetual field of research. Moreover, the construction of elaborate biologically relevant moieties via a multicomponent approach has become a promising area of research, owing to the burgeoning ‘green chemistry drive’. Advances in the exploitation of proficient synthetic routes involving a multicomponent approach for the assembly of this scaffold are reported in this review.

Design, Synthesis and Anticancer Profile of New 4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine-Linked Sulfonamide Derivatives with V600EBRAF Inhibitory Effect

A new series of 4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine linked sulfonamide derivatives 12a–n was designed and synthesized according to the structure of well-established V600EBRAF inhibitors. The terminal sulfonamide moiety was linked to the pyrimidine ring via either ethylamine or propylamine bridge. The designed series was tested at fixed concentration (1 µM) against V600EBRAF, finding that 12e, 12i and 12l exhibited the strongest inhibitory activity among all target compounds and 12l had the lowest IC50 of 0.49 µM. They were further screened on NCI 60 cancer cell lines to reveal that 12e showed the most significant growth inhibition against multiple cancer cell lines. Therefore, cell cycle analysis of 12e was conducted to investigate the effect on cell cycle progression. Finally, virtual docking studies was performed to gain insights for the plausible binding modes of vemurafenib, 12i, 12e and 12l.

Synthetic Strategies of Pyrimidine-Based Scaffolds as Aurora Kinase and Polo-like Kinase Inhibitors

The past few decades have witnessed significant progress in anticancer drug discovery. Small molecules containing heterocyclic moieties have attracted considerable interest for designing new antitumor agents. Of these, the pyrimidine ring system is found in multitude of drug structures, and being the building unit of DNA and RNA makes it an attractive scaffold for the design and development of anticancer drugs. Currently, 22 pyrimidine-containing entities are approved for clinical use as anticancer drugs by the FDA. An exhaustive literature search indicates several publications and more than 59 patents from the year 2009 onwards on pyrimidine derivatives exhibiting potent antiproliferative activity. These pyrimidine derivatives exert their activity via diverse mechanisms, one of them being inhibition of protein kinases. Aurora kinase (AURK) and polo-like kinase (PLK) are protein kinases involved in the regulation of the cell cycle. Within the numerous pyrimidine-based small molecules developed as anticancer agents, this review focuses on the pyrimidine fused heterocyclic compounds modulating the AURK and PLK proteins in different phases of clinical trials as anticancer agents. This article aims to provide a comprehensive overview of synthetic strategies for the preparation of pyrimidine derivatives and their associated biological activity on AURK/PLK. It will also present an overview of the synthesis of the heterocyclic-2-aminopyrimidine, 4-aminopyrimidine and 2,4-diaminopyrimidine scaffolds, and one of the pharmacophores in AURK/PLK inhibitors is described systematically.

Synthesis, Single Crystal Structural Investigation, Hirshfeld Surface Analysis, Thermoanalysis and Spectroscopic Study of Two New Cu(II) and Co(II) Transition-Metal Complexes

Two new complexes, [Cu(dimpyr)2(H2O)2](NO3)2.2H2O (1) and (Hamdimpy)2[CoCl4].H2O (2), with the monodentate ligand 2-amino-6-methylpyrimidin-4-(1H)-one (dimpyr) and the countercation 4-amino-2,6-dimetylpyrimidium (Hamdimpy), respectively, were prepared and characterized by single crystal X-ray diffraction, elemental analysis and IR spectroscopy. In (1), the Cu(II) cation is tetracoordinated, in a square plan fashion, by two nitrogen atoms from the pyrimidine ring of the organic ligand and two oxygen atoms of two coordinated water molecules. In the atomic arrangement, the CuO2N2 square planes are interconnected via the formation of O-H…O hydrogen bonds involving both coordinated and free water molecules and NO3− nitrate anions to form inorganic layers parallel to the (a, b) plane at z = (2n + 1)/4. In (2), the central atom Co(II) is four-coordinated in a distorted tetrahedral fashion by four Cl− ions. The [CoCl4]2− tetrahedra are arranged parallel to the plane (110) at x = (2n + 1)/2 and the organic cations are grafted between them by establishing with them hydrogen bonds of CH…Cl and NH…Cl types. The vibrational absorption bands were identified by infrared and Raman spectroscopy. Intermolecular interactions were investigated via Hirshfeld surfaces and electronic properties such as HOMO and LUMO energies were derived. The two compounds were characterized by thermal analysis to determine their thermal behavior with respect to temperature.

Crystal structure of palbociclib isethionate Form B, (C24H30N7O2)(C2H5O4S)

The crystal structure of palbociclib isethionate has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory techniques. Palbociclib isethionate crystallizes in space group P-1 (#2) with a = 8.71334(4), b = 9.32119(6), c = 17.73725(18) Å, α = 80.0260(5), β = 82.3579(3), γ = 76.1561(1)°, V = 1371.282(4) Å3, and Z = 2. The crystal structure is dominated by cation⋯anion and cation⋯cation hydrogen bonds, which result in layers roughly parallel to the (104) plane. Both hydrogen atoms on the protonated nitrogen atom of the pyrimidine ring participate in strong hydrogen bonds to the anions. One proton binds to the sulfonate group, while the other bonds to the hydroxyl group of the isethionate anion. The hydroxyl group of the anion acts as a donor to a ketone oxygen atom in the cation. There are also strong N–H⋯N hydrogen bonds, which occur in pairs linking the cations into dimers with rings having a graph set R2,2(8). The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™.

Therapeutic Potential, Synthesis, Patent evaluation and SAR studies of thieno[3,2-d]pyrimidine derivatives: Recent updates.

: Thieno[3,2-d]pyrimidine ring framework comprises a significant class of heterocyclics that serve as a promising platform showing different pharmacological activities. The interest in thieno[3,2-d]pyrimidine cores for pharmaceutical products makes this scaffold an exceptionally helpful building block for organic chemistry. This review presents current research on thieno[3,2-d]pyrimidines and elucidates their biological importance in anti-cancer, anti-infectious, anti-convulsant, anti-diabetic, CNS, and osteoporosis drug discoveries. Patents on the thieno[3,2-d]pyrimidines are also elaborated as a piece of useful information. Here we additionally focus on the synthesis of this vital ring and the discovery of new thieno[3,2-d]pyrimidines.

Hardly Flammable Polyurethane Foams with 1,3-Pyrimidine Ring and Boron Atoms

This work presents the results of research related to the determination of application possibilities of new oligoetherols with 1,3-pyrimidine rings and boron atoms in rigid polyurethane foam production. Oligoetherols were obtained from 1,3-bis(2-hydroxyethyl)uracil, boric acid, and ethylene carbonate. Their structure was determined by instrumental methods (IR, 1H-NMR and MALDI-ToF spectra) and the physicochemical and thermal properties were examined. Obtained oligoetherols were used for synthesis of polyurethane foams. Some properties of the foams, such as apparent density, water uptake, dimensions stability, thermal stability, compression strength, thermal conductivity, oxygen index, and horizontal burning were investigated. The introduction of boron atoms into the foam structure reduced their flammability, but unfortunately it had a negative effect on the water absorption of the obtained materials—the water absorption was higher compared to the boron-free foams. The obtained foams showed good thermal stability compared to classic, rigid polyurethane foams.