16285-69-1

Upstream product

• 22288-78-4 Methyl 3-aminothiophene-2-carboxylate 
• 298-12-4 Glyoxilic acid 
• 64-18-6 formic acid 

Downstream Products

• 552295-33-7 6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)thieno[3,2-d]pyrimidin-4-amine 

Relevant academic research and scientific papers

Copper-Catalyzed Cascade N-Dealkylation/N-Methyl Oxidation of Aromatic Amines by Using TEMPO and Oxygen as Oxidants

A novel tandem N-dealkylation and N-methyl aerobic oxidation of tertiary aromatic amines to N-arylformamides using copper and TEMPO has been developed. This methodology suggested an alternative synthetic route from N-methylarylamines to N-arylformamides.

4-phenoxythiophene[3,2-d]pyrimido-alpha-amido thioamide compound as well as preparation method and application thereof

The invention relates to a 4-phenoxythiophene[3,2-d]pyrimido-alpha-amido thioamide compound I. The 4-phenoxythiophene[3,2-d]pyrimido-alpha-amido thioamide compound I is used as a tyrosine kinase inhibitor, especially a c-Met inhibitor. The invention also

Design, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction

In our continuing efforts to develop novel c-Met inhibitors as potential anticancer candidates, a series of new N-sulfonylamidine derivatives were designed, synthesized via Cu-catalyzed multicomponent reaction (MCR) as the key step, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (A549, HT-29, MKN-45 and MDA-MB-231). Most of the target compounds showed moderate to significant potency at both the enzyme-based and cell-based assay and possessed selectivity for A549 and HT-29 cancer cell lines. The preliminary SAR studies demonstrated that compound 26af (c-Met IC50 = 2.89 nM) was the most promising compound compared with the positive foretinib, which exhibited the remarkable antiproliferative activities, with IC50 values ranging from 0.28 to 0.72 μM. Mechanistic studies of 26af showed the anticancer activity was closely related to the blocking phosphorylation of c-Met, leading to cell cycle arresting at G2/M phase and apoptosis of A549 cells by a concentration-dependent manner. The promising compound 26af was further identified as a relatively selective inhibitor of c-Met kinase, which also possessed an acceptable safety profile and favorable pharmacokinetic properties in BALB/c mouse. The favorable drug-likeness of 26af suggested that N-sulfonylamidines may be used as a promising scaffold for antitumor drug development. Additionally, the docking study and molecular dynamics simulations of 26af revealed a common mode of interaction with the binding site of c-Met. These positive results indicated that compound 26af is a potential anti-cancer candidate for clinical trials, and deserves further development as a selective c-Met inhibitor.

Electrochemical N -Formylation of Amines via Decarboxylation of Glyoxylic Acid

A new method for the synthesis of formamides has been developed through electrochemical decarboxylative N-formylation of amines with glyoxylic acid. This protocol provides an efficient approach to formamides with a broad range of functional group tolerance under ambient conditions.

Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery

Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases. Building on the previous identification of NEU-617 (1) as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, we describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors' biological activities against these parasites. In doing this, we have identified several potent proliferation inhibitors for each pathogen, such as 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile (NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.

Evaluation of aromatic 6-substituted thienopyrimidines as scaffolds against parasites that cause trypanosomiasis, leishmaniasis, and malaria

Target repurposing is a proven method for finding new lead compounds that target Trypanosoma brucei, the causative agent of human African trypanosomiasis. Due to the recent discovery of a lapatinib-derived analog 2 with excellent potency against T. brucei (EC50 = 42 nM) and selectivity over human host cells, we have explored other classes of human tyrosine kinase inhibitor scaffolds in order to expand the range of chemotypes for pursuit. Following library expansion, we found compound 11e to have an EC50 of 84 nM against T. brucei cells while maintaining selectivity over human hepatocytes. In addition, the library was tested against causative agents of Chagas' disease, leishmaniasis, and malaria. Two analogs with sub-micromolar potencies for T. cruzi (4j) and Plasmodium falciparum (11j) were discovered, along with an analog with considerable potency against Leishmania major amastigotes (4e). Besides identifying new and potent protozoan growth inhibitors, these data highlight the value of concurrent screening of a chemical library against different protozoan parasites. This journal is

Irreversible inhibitors of the epidermal growth factor receptor: Thienopyrimidine core with α,β-unsaturated amide side chain

Overexpression of epidermal growth factor receptor (EGFR) tyrosine kinases has been found in a variety of cancers such as breast, ovarian, colon, and non-small-cell lung cancers, which is associated with poor prognosis in patients. In an effort to find effective irreversible inhibitors of the EGFR tyrosine kinase family (mainly HER2), two series of HER2 tyrosine kinase inhibitors with thieno[3,2-d]pyridine and thieno[2,3-d]pyridine as central part and with a basic α,β-unsaturated amide side chain were developed. The α,β-unsaturated amide side chain (the Michael acceptor) at the 6-position, which forms a covalent bond to Cys773 located in the ATP binding pocket of the EGFR enzyme, is a major factor in the generation of irreversible inhibition. In our study, thienopyrimidine instead of quinazoline was used as the central structure, and different substituents were introduced at the 4-position to investigate the structure-activity relationships. The thieno[2,3-d]pyrimidine derivatives 16a-d showed potent HER2 enzyme inhibition and anti-proliferative activity against SK-BR-3 cells. Especially, (E)-N-(4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)thieno[2,3-d] pyrimidin-6-yl)-4-(dimethylamino)but-2-enamide 16d was identified as a potential irreversible HER2 inhibitor. Both its catalytic enzyme activity profile and its cellular efficacy were found to be superior to those of the marketed drug lapatinib.

ANTI-INFLAMMATORY COMPOUND HAVING INHIBITORY ACTIVITY AGAINST MULTIPLE TYROSINE KINASES AND PHARMACEUTICAL COMPOSITION CONTAINING SAME

The present invention is for the anti-inflammatory compounds that have an inhibitory activity against protein tyrosine kinases and their pharmaceutical composition(s) containing the compound as the active ingredient. Since the compounds of the present invention can inhibit multiple protein kinases associated with inflammatory diseases and immune disorders, they are useful for their prevention or treatment.

Small molecule thienopyrimidine-based protein tyrosine kinase inhibitors

Various thienopyrimidine-based analog compounds are able to selectively inhibit the Src family of tyrosine kinases. These compounds are useful in the treatment of various diseases including hyperproliferative diseases, hematologic diseases, osteoporosis, neurological diseases, autoimmune diseases, allergic/immunological diseases, or viral infections.

AKT PROTEIN KINASE INHIBITORS

The present invention provides compounds, including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, comprising the Formula: A-L-CR where CR is a cyclical core group, L is a linking group and A is as defined herein. Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.