856973-81-4

Upstream product

• 322691-38-3 4-chloro-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylamine 
• 109-01-3 1-methyl-piperazine 
• 3993-78-0 2-amino-4-chloropyrimidine 

Relevant academic research and scientific papers

Optimization of Physicochemical Properties for 4-Anilinoquinoline Inhibitors of Plasmodium falciparum Proliferation

We recently reported the medicinal chemistry reoptimization of a known human tyrosine kinase inhibitor, lapatinib, against a variety of parasites responsible for numerous tropical diseases, including human African trypanosomiasis (Trypanosoma brucei), Chagas disease (T. cruzi), Leishmaniasis (Leishmania spp.), and malaria (Plasmodium falciparum). Herein, we report our continuing efforts to optimize this series against P. falciparum. Through the design of a library of compounds focused on reducing the lipophilicity and molecular weight, followed by an SAR exploration, we have identified NEU-1953 (40). This compound is a potent inhibitor of P. falciparum with an improved ADME profile over the previously reported compound, NEU-961 (3).

SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS

Provided herein are novel substituted bridged urea and related analogs and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Ligand based design of novel histamine H4 receptor antagonists; Fragment optimization and analysis of binding kinetics

The histamine H4 receptor is a G protein-coupled receptor that has attracted much interest for its role in inflammatory and immunomodulatory functions. In our search for new H4R ligands, a low affinity isoquinoline fragment was optimized to 7-(furan-2-yl)-4-(piperazin-1-yl) quinazolin-2-amine (VUF11489), as a new H4R antagonist. Analysis of its binding kinetics at the human H4R showed this compound to have a very different dissociative half-life in comparison with reference antagonist JNJ7777120.

4-SUBSTITUTED-2-AMINO-PYRIMIDINE DERIVATIVES

Compounds of the formula wherein R1 and R2 are as disclosed herein, are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor full or partial agonists. Also disclosed are pharmaceutical compositions, methods for using such compounds and compositions, and processes for preparing the compounds

Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands

A series of 2-aminopyrimidines was synthesized as ligands of the histamine H4 receptor (H4R). Working in part from a pyrimidine hit that was identified in an HTS campaign, SAR studies were carried out to optimize the potency, which led to compound 3,4-tert-butyl-6-(4-methylpiperazin-1-yl) pyrimidin-2-ylamine. We further studied this compound by systematically modifying the core pyrimidine moiety, the methylpiperazine at position 4, the NH2 at position 2, and positions 5 and 6 of the pyrimidine ring. The pyrimidine 6 position benefited the most from this optimization, especially in analogs in which the 6-tert-butyl was replaced with aromatic and secondary amine moieties. The highlight of the optimization campaign was compound 4,4-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]benzonitrile, which was potent in vitro and was active as an anti-inflammatory agent in an animal model and had antinociceptive activity in a pain model, which supports the potential of H4R antagonists in pain.