874801-60-2

Upstream product

• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 3473-63-0 formamidine acetic acid 
• 463-52-5 formamidine 
• 193537-14-3 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert-butyl ester 3-ethyl ester 

Downstream Products

• 946198-89-6 tert-butyl 4-chloro-5,6-dihydropyrido(4’,3’:4,5)thieno(2,3-d)pyrimidine-7(8H)-carboxylate 
• 1226548-17-9 tert-butyl (S)-4-((2-hydroxy-1-phenylethyl)amino)-5,8-dihydropyrido[4’,3’:4,5]thieno[2, 3-d]pyrimidine-7(6H)carboxylate 
• 1226548-19-1 (S)-2-phenyl-2-((5,6,7,8-tetrahydropyrido[4’,3’:4,5]thieno[2,3-d]pyrimidin-4-yl)amino)ethan-1-ol 

Relevant academic research and scientific papers

Structure based design, synthesis and evaluation of new thienopyrimidine derivatives as anti-bacterial agents

TrmD, tRNA-(N1G37) methyltransferase, a member of SpoU-TrmD (SPOUT) RNA methyltransferase family, is one of the key enzymes responsible for the growth of Staphylococcus aureus, Pseudomonas aeruginosa, Mycobacterium tuberculosis (Mtb) and Mycobacterium abscessus (Mab). A number of TrmD inhibitors including thienopyrimidines and fused thienopyrimidines are reported as potent anti-bacterial and anti-mycobacterial agents. In the current study, a library of ~200 structurally diverse thienopyrimidines were designed and subjected to preliminary in silico studies. 22 of the compounds were selected, synthesized and were evaluated for their inhibitory activities against a panel of pathogens consisting E. coli, S. aureus, K. pneuminiae, A. baumannii and P. aeruginosa and M. tuberculosis (ATCC 27294). Among the tested compounds, 13b, 18a-e were found to inhibit M. tuberculosis (ATCC 27294) with the MIC of 16-32 μg/mL. The compound 18f was found to be selective against S. aureus with the MIC of 4 μg/mL and moderate activity against M. tuberculosis. The selected compounds were further subjected to docking, 3D-QSAR and ADME/T studies to understand the mechanism of action and also their physico chemical profile.

Discovery of novel TNNI3K inhibitor suppresses pyroptosis and apoptosis in murine myocardial infarction injury

Myocardial infarction (MI) injury is a highly lethal syndrome that has, until recently, suffered from a lack of clinically efficient targeted therapeutics. The cardiac troponin I interacting kinase (TNNI3K) exacerbates ischemia-reperfusion (IR) injury via oxidative stress, thereby promoting cardiomyocyte death. In this current study, we designed and synthesized 35 novel TNNI3K inhibitors with a pyrido[4,5]thieno[2,3-d] pyrimidine scaffold. In vitro results indicated that some of the inhibitors exhibited sub-micromolar TNNI3K inhibitory capacity and good kinase selectivity, as well as cytoprotective activity, in an oxygen-glucose deprivation (OGD) injury cardiomyocyte model. Furthermore, investigation of the mechanism of the representative derivative compound 6o suggested it suppresses pyroptosis and apoptosis in cardiomyocytes by interfering with p38MAPK activation, which was further confirmed in a murine myocardial infarction injury model. In vivo results indicate that compound 6o can markedly reduce myocardial infarction size and alleviate cardiac tissue damage in rats. In brief, our results provide the basis for further development of novel TNNI3K inhibitors for targeted MI therapy.

Discovery of novel akt1 inhibitor induces autophagy associated death in hepatocellular carcinoma cells

In this study, a series of thieno [2,3-d]pyrimidine derivatives were designed, synthesized and evaluated as novel AKT1 inhibitors. In vitro antitumor assay results showed that compounds 9d-g and 9i potently suppressed the enzymatic activities of AKT1 and

Design, synthesis and molecular mechanisms of novel dual inhibitors of heat shock protein 90/phosphoinositide 3-kinase alpha (Hsp90/PI3Kα) against cutaneous melanoma

Overexpression of heat shock protein 90 (Hsp90) is common in various types of cancer. In cutaneous melanoma, a cancer with one of the high levels of Hsp90 overexpression, such expression was correlated with a panel of protein kinases, thus offering an opportunity to identify Hsp90-based multi-kinase inhibitors for novel cancer therapies. Towards this goal, we utilized a 2,4-dihydroxy-5-isopropylbenzate-based Hsp90 inhibitor scaffold and thieno[2,3-d]pyrimidine-based kinase inhibitor scaffold to develop a Hsp90-inhibiting compound library. Our inhibitory compound named 8m inhibited Hsp90 and PI3Kα with an IC50 value of 38.6 nM and 48.4 nM, respectively; it displayed improved cellular activity which could effectively induce cell cycle arrest and apoptosis in melanoma cells and lead to the inhibition of cell proliferation, colony formation, migration and invasion. Our results demonstrated 8m to be a promising lead compound for further therapeutic potential assessment of Hsp90/PI3Kα dual inhibitors in melanoma targeted therapy.

Design, synthesis and biological evaluation of 4-aniline-thieno[2,3-d]pyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma

MAP Kinase Interacting Serine/Threonine Kinase 1 (MNK1)play important roles in the signaling transduction of MAPK pathways. It is significantly overexpressed in renal clear cell carcinoma and head-neck squamous cell carcinoma tissues in both mRNA and prot

PET probe detecting non-small cell lung cancer susceptible to epidermal growth factor receptor tyrosine kinase inhibitor therapy

Tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR-TKIs) are used as molecular targeted therapy for non-small cell lung cancer (NSCLC) patients. The therapy is applied to the patients having EGFR-primary L858R mutation, but drug toleran

Nuclear Medicine Diagnostic Imaging Agent

Provided is a radioactive labeled compound capable of detecting a secondary mutation of an epidermal growth factor receptor, where the compound is represented by Formula (1) or a pharmaceutically acceptable salt thereof, where R1, R2

Discovery of potent c-MET inhibitors with new scaffold having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine headgroups

Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N1-(3-fluoro-4-methoxyphenyl)-N3-(4-fluorophenyl) malonamide derivatives were designed and synthesized, some of them were identified as c-MET inhibitors. Among these compounds with new scaffolds having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine head groups, compound 11c, 11i, 13b, 13h exhibited both potent inhibitory activities against c-MET and high anticancer activity against tested cancer cell lines in vitro. In addition, kinase selectivity assay further demonstrated that both 13b and 13h are potent and selective c-MET inhibitors. Molecular docking supported that they bound well to c-MET and VEGFR2, which demonstrates that they are potential c-MET RTK inhibitors for cancer therapy.

Quinazoline and tetrahydropyridothieno[2,3-d]pyrimidine derivatives as irreversible EGFR tyrosine kinase inhibitors: Influence of the position 4 substituent

Herein, we describe new quinazoline and tetrahydropyridothieno[2,3-d] pyrimidine derivatives with an acrylamido group at positions 6 and 7 respectively, and with variable anilino, sulfonamido and cycloalkylamino substituents at position 4. The lipophilic and steric properties of the position 4 substituent seem crucial for activity. Several compounds were more active than gefitinib in inhibiting the wild type EGFR enzyme, the autophosphorylation of the mutant EGFR expressing cell line (H1975), and the growth of cell lines with wild type and mutant EGFR tyrosine kinase. Moreover, a novel synthesis of the quinazoline nucleus from a formimidate derivative is described.

Fused Bicyclic and Tricyclic Pyrimidine Compounds as Tyrosine Kinase Inhibitors

Fused bicyclic or tricyclic compounds of formula (I): wherein A, B, C, X, Y, m, and n are defined herein. Also disclosed are a method for inhibiting EGFR kinase activity and a method for treating cancer with these compounds.