87362-28-5

Upstream product

• 42839-08-7 pyrimidine-2-carboxylic acid ethyl ester 
• 14080-23-0 2-cyanopyrimidine 
• 31519-62-7 pyrimidine-2-carboxylic acid 
• 34253-03-7 pyrimidine-2-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Synthesis, biological activity, and mechanism of action of new 2-pyrimidinyl hydrazone and N-acylhydrazone derivatives, a potent and new classes of antileishmanial agents

In this work, we report the antileishmanial activity of 15 compounds based on 2-pyrimidinyl hydrazone and N-acylhydrazone derivatives, being 13 new compounds. All compounds were tested against promastigotes and Leishmania amazonensis-GFP amastigotes, as well as murine macrophages. Besides, studies about the mechanism of action of the best antileishmanial compounds and in silico physicochemical and pharmacokinetic properties were performed. Studies about the mechanism of action of representative compounds of each class showed slight differences in mode of action and both are able to cause mitochondrial depolarization and increase of intracellular ROS levels. Through computational tool and further analysis of the physicochemical and pharmacokinetic parameters, the results indicating good oral bioavailability. These results confirm the potential of 2-pyrimidinyl derivatives as lead compounds in antileishmanial drug discovery.

Solvent Polarity Predictably Tunes Spin Crossover T1/2 in Isomeric Iron(II) Pyrimidine Triazoles

Two isomeric pyrimidine-based Rdpt-type triazole ligands were made: 4-(4-methylphenyl)-3-(2-pyrimidyl)-5-phenyl-4H-1,2,4-triazole (L2pyrimidine) and 4-(4-methylphenyl)-3-(4-pyrimidyl)-5-phenyl-4H-1,2,4-triazole (L4pyrimidine). When reacted with [FeII(pyridine)4(NCE)2], where E = S, Se, or BH3, two families of mononuclear iron(II) complexes are obtained, including six solvatomorphs, giving a total of 12 compounds: [FeII(L2pyrimidine)2(NCS)2] (1), [FeII(L2pyrimidine)2(NCSe)2] (2), 2·1.5H2O, [FeII(L2pyrimidine)2(NCBH3)2]·2CHCl3 (3·2CHCl3), 3 and 3·2H2O, [FeII(L4pyrimidine)2(NCS)2] (4), 4·H2O, [FeII(L4pyrimidine)2(NCSe)2] (5), 5·2CH3OH, 5·1.5H2O, and [FeII(L4pyrimidine)2(NCBH3)2]·2.5H2O (6·2.5H2O). Single-crystal X-ray diffraction reveals that the N6-coordinated iron(II) centers in 1, 2, 3·2CHCl3, 4, 5, and 5·2CH3OH have two bidentate triazole ligands equatorially bound and two axial NCE co-ligands trans-coordinated. All structures are high spin (HS) at 100 K, except 3·2CHCl3, which is low spin (LS). Solid-state magnetic measurements show that only 3·2CHCl3 (T1/2 above 400 K) and 5·1.5H2O (T1/2 = 110 K) undergo spin crossover (SCO); the others remain HS at 300-50 K. When 3·2CHCl3 is heated at 400 K it desorbs CHCl3 becoming 3, which remains HS at 400-50 K. UV-Vis studies in CH2Cl2, CHCl3, (CH3)2CO, CH3CN, and CH3NO2 solutions for the BH3 analogues 3 and 6 led to a 6:1 ratio of Lnpyrimidine/Fe(II) being employed for the solution studies. These revealed SCO activity in all five solvents, with T1/2 values for the 2-pyrimidine complex (247-396 K) that were consistently higher than for the 4-pyrimidine complex (216-367 K), regardless of solvent choice, consistent with the 2-pyrimidine ring providing a stronger ligand field than the 4-pyrimidine ring. Strong correlations of solvent polarity index with the T1/2 values in those solvents are observed for each complex, enabling predictable T1/2 tuning by up to 150 K. While this correlation is tantalizing, here it may also be reflecting solvent-dependent speciation - so future tests of this concept should employ more stable complexes. Differences between solid-state (ligand field; crystal packing; solvent content) and solution (ligand field; solvation; speciation) effects on SCO are highlighted.

HETEROARYL-SUBSTITUTED TRIAZOLES AS APJ RECEPTOR AGONISTS

Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

Approaches to design non-covalent inhibitors for human granzyme B (hGrB)

A structure-based design campaign for non-covalent small molecule inhibitors of human granzyme B was carried out by means of a virtual screening strategy employing three constraints and probe site-mapping with FTMAP to identify ligand "hot spots". In addition, new scaffolds of diverse structures were subsequently explored with ROCS shape-based superposition methods, following by Glide SP docking, induced fit docking and analysis of QikProp molecular properties. Novel classes of moderately active small molecule blockers (≥25 μM IC50 values) from commercially available libraries were identified, and three novel scaffolds have been synthesized by multi-step procedures. Furthermore, we provide an example of a comprehensive structure-based drug discovery approach to non-covalent inhibitors that relies on the X-ray structure of a covalently bound ligand and suggest that the design path may be compromised by alternative and unknown binding poses. This journal is

P2X7 MODULATORS

The present invention is directed to a compound of Formula (I): The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invent

P2X7 MODULATORS

The present invention is directed to a compound of Formula (I) and to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

A general and efficient entry to asymmetric tetrazines for click chemistry applications

The importance of click chemistry is widely recognized. Among all the known click reactions, those involving tetrazines represent the fastest click reactions reported and are generating a great deal of interest. However, there is no efficient entry to asymmetric tetrazines and those with strong electron withdrawing groups, which limits the development of this field. Herein, we report a general and efficient entry to asymmetric tetrazines with strongly electron withdrawing groups.

HERBICIDAL TRIAZINES

The present invention relates to triazines the general formula I, wherein the variables are defined according to the description, including their agriculturally acceptable salts or, provided that the triazines of formula I have a carboxyl group, their agriculturally acceptable derivatives, in particular to processes for the preparation of said triazines. The invention further relates to compositions comprising compound of formula I and processes for the preparation of these compositions. Further it relates to use of the triazines of formula I as an herbicide as well as to a method of controlling undesired vegetation.

Ketolide Compounds Having Antimicrobial Activity

The invention relates to ketolide compound of Formula-I and the pharmaceutically acceptable salts thereof having antimicrobial activity. The invention also provides pharmaceutical compositions containing the compounds of invention and methods of treating or preventing microbial infections with the compound of invention.

KETOLIDE COMPOUNDS HAVING ANTIMICROBIAL ACTIVITY

The invention relates to ketolide compound of Formula (I) and the pharmaceutically acceptable salts thereof having antimicrobial activity. The invention also provides pharmaceutical compositions containing the compounds of invention and methods of treating or preventing microbial infections with the compound of invention.