490038-74-9

Upstream product

• 886498-84-6 1-(2,6-difluoro-4-methoxyphenyl)ethan-1-one 
• 93343-10-3 3,5-difluoroanisol 
• 598-21-0 2-Bromoacetyl bromide 

Downstream Products

• 1183239-44-2 4-(2,6-difluoro-4-methoxyphenyl)thiazol-2-amine 
• 1334920-73-8 N-[4-(2,6-difluoro-4-methoxyphenyl)thiazol-2-yl]pyridine-4-carboxamide 

Relevant academic research and scientific papers

NEGATIVE ALLOSTERIC MODULATION OF GLUN3-CONTAINING N-METHYL-D-ASPARTATE RECEPTORS

Disclosed are negative allosteric modulators of GluN3-containing NMDA receptors. In general, these compounds are highly selective for GluN3 (such as GluN3A and/or GluN3B) over GluN1 and/or GluN2. They can function as non-competitive antagonists with activity that is independent of membrane potential, glycine concentration, and extracellular pH. Also disclosed are pharmaceutical formulations of the negative allosteric modulators. These compounds can be used to enhance synaptic function and/or treating a neurological condition or disorder. Exemplary neurological conditions or disorders include, but are not limited to, major mental disorders, conditions that involve basal ganglia or altered dopamine, substance abuse/addiction or predisposition to substance abuse/addiction, pain disorders, developmental delay or situations with impaired learning, memory, and/or cognition, acute neuronal or glial injuries, and circuit disorders.

Synthesis and biological evaluation of N-(4-phenylthiazol-2-yl)cinnamamide derivatives as novel potential anti-tumor agents

In this study, a series of novel N-(4-phenylthiazol-2-yl)cinnamamide derivatives (7a-8n) were synthesized and evaluated for their anti-proliferative activities in vitro by MTT assay and a possible antitumor mechanism was also explored. SAR analysis showed that steric effects played an important role on the anti-tumor activity. The most potent analogue 8f showed excellent inhibitions on the K562, Bel7402, A549 and Jurkat cells ranging from sub-micromolar to nanomolar concentration. Compound 8f inhibited Jurkat cells with an IC50 value of 0.035 μM with no apparent toxicity in different non-cancerous cells. Furthermore, it was suggested that the possible mechanism of 8f might be associated with inducing cancer cell apoptosis following flow cytometer analysis and Hoechst 33358 staining assays.

Discovery of 4-aryl-N-arylcarbonyl-2-aminothiazoles as Hec1/Nek2 inhibitors. Part I: Optimization of in vitro potencies and pharmacokinetic properties

A series of 4-aryl-N-arylcarbonyl-2-aminothiazoles of scaffold 4 was designed and synthesized as Hec1/Nek2 inhibitors. Structural optimization of 4 led to compound 32 bearing C-4′ 4-methoxyphenoxy and 4-(o-fluoropyridyl) carbonyl groups that showed low nanomolar in vitro antiproliferative activity (IC50: 16.3-42.7 nM), high intravenous AUC (64.9 μM·h, 2.0 mg/kg) in SD rats, and significant in vivo antitumor activity (T/C = 32%, 20 mg/kg, IV) in mice bearing human MDA-MB-231 xenografts. Cell responses resulting from Hec1/Nek2 inhibition were observed in cells treated with 32, including a reduced level of Hec1 coimmunoprecipitated with Nek2, degradation of Nek2, mitotic abnormalities, and apoptosis. Compound 32 showed selectivity toward cancer cells over normal phenotype cells and was inactive in a [ 3H]astemizole competitive binding assay for hERG liability screening. Therefore, 32 is as a good lead toward the discovery of a preclinical candidate targeting Hec1/Nek2 interaction.

IMPROVED MODULATORS OF HEC1 ACTIVITY AND METHODS THEREFOR

Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Such compounds disrupt Nek2/Hec1 binding and may be useful as chemotherapeutic agents for neoplastic diseases

Modulators Of HEC1 Activity And Methods Therefor

Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Especially preferred compounds disrupt Nek2/Hec1 binding and are therefore useful as chemotherapeutic agent for neoplastic diseases.

A new approach to the synthesis of 2-aminoimidazo[1,2-a]pyridine derivatives through rapid parallel synthesis

Different substituted 6-(2,6-difluorobenzoyl)-imidazopyridines 3 have been prepared using rapid parallel synthesis. Key cyanamide intermediate 4 was prepared from chloropyridine 1, and alkylated at the endocyclic nitrogen with different bromoacetophenones (prepared also in rapid parallel synthesis fashion). Subsequent cyclization was performed in situ with EtOAc/H2O to give target molecules.