35978-39-3

Usage

Uses

Used in Pharmaceutical Industry:
7-Phenyl-9-thia-2,4-diazabicyclo[4.3.0]nona-2,7,10-trien-5-one is used as a reagent for the preparation of c-Met kinase inhibitors bearing thieno-pyrimidine or furo-pyrimidine scaffolds. These inhibitors have potential antitumor properties, making them valuable in the development of new cancer treatments.
Used in Chemical Research:
Due to its unique structure and reactivity, 7-phenyl-9-thia-2,4-diazabicyclo[4.3.0]nona-2,7,10-trien-5-one can be utilized in chemical research to explore new reactions and synthesize novel compounds with potential applications in various industries, such as pharmaceuticals, materials science, and agrochemicals.
Used in Drug Design:
7-phenyl-9-thia-2,4-diazabicyclo[4.3.0]nona-2,7,10-trien-5-one's structural features make it a promising candidate for drug design, particularly in the development of targeted therapies for cancer and other diseases. Its ability to form specific interactions with biological targets can be exploited to create more effective and selective drugs.

InChI:InChI=1/C12H8N2OS/c15-11-10-9(8-4-2-1-3-5-8)6-16-12(10)14-7-13-11/h1-7H,(H,13,14,15)

Upstream product

• 4815-36-5 ethyl 2-amino-4-phenyl-thiophene-3-carboxylate 
• 16712-16-6 ammonium formate 
• 77287-34-4 formamide 
• 3473-63-0 formamidine acetic acid 
• 100-52-7 benzaldehyde 
• 14533-92-7 ethyl 2-cyano-3-phenylbut-2-enoate 
• 98-86-2 acetophenone 
• 5447-87-0 2-(1-phenylethylidene)propanedinitrile 
• 64-18-6 formic acid 

Downstream Products

• 108311-85-9 3-(4-Oxo-5-phenyl-4H-thieno[2,3-d]pyrimidin-3-yl)-propionic acid ethyl ester 
• 182198-35-2 4-chloro-5-phenyl-thieno[2,3-d]pyrimidine 
• 1321618-70-5 3-fluoro-4-({5-phenylthieno[2,3-d]pyrimidin-4-yl}oxy)aniline 
• 896423-27-1 N-{3-[3-(4-oxo-5-phenylthieno[2,3-d]pyrimidin-1(4H)-yl)propoxy]phenyl}-acetamide 
• 1459230-13-7 5-phenyl-3-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4(3H)-one 
• 1459229-98-1 6-(4-((1r,3r)-1-amino-3-hydroxycyclobutyl)phenyl)-5-phenyl-3-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4(3H)-one 
• 1459230-23-9 tert-butyl ((1s,3s)-3-hydroxy-1-(4-(4-oxo-5-phenyl-3-(2,2,2-trifluoroethyl)-3,4-dihydrothieno[2,3-d]pyrimidin-6-yl)phenyl)cyclobutyl)carbamate 

Relevant academic research and scientific papers

Identification of the first small-molecule inhibitor of the REV7 DNA repair protein interaction

DNA interstrand crosslink (ICL) repair (ICLR) has been implicated in the resistance of cancer cells to ICL-inducing chemotherapeutic agents. Despite the clinical significance of ICL-inducing chemotherapy, few studies have focused on developing small-molec

Design, molecular docking and biological evaluation of fused thienopyrimidines and quinazoline

The anticancer activity of the condensed pyrimidine and quinazoline moieties are pronounced with a different pathway. Thienopyrimidine is considered as ring equivalent bioisosteres of quinazolines and present in other heterocyclic compounds including thienopyrimidine. The present investigation focused on the synthesis of thienopyrimidine and quinazoline derivatives for their anticancer activity against the human oral squamous carcinoma-3 (HSC-3) cell line. The synthesized compound confirmed for their structural characteristics from spectral analysis and tested for anti-proliferative activity from MTT assay. The electron-withdrawing group in 4-chloro thienopyrimidines and amino ester derivate/facilitate the inhibition of cancer cells. Further probing by docking studies revealed that the compounds exhibit possible interactions with VEGF, FGFR and c-Met proteins, which are known to have a role in the pathogenesis of oral squamous cell carcinoma. Among the derivatives a moderate activity demonstrated by substituted 4-chloro-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]-pyrimidine (4a) and ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1a) derivatives. Lack of chirality and the presence of bulky substituents in few of the compounds were found to be the cause for lower potency.

ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) MODULATORS AND USES THEREOF

Provided herein are small molecule modulators of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor

We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like NAMs that retain robust negative cooperativity, such as 3. Herein, we report the synthesis and functional profiling of analogues of 3, placing specific emphasis on examining secondary and tertiary amino substituents at the 4-position, combined with a range of substituents at the 5/6-positions (e.g. aromatic/aliphatic carbocycles). We identify analogues with diverse pharmacology at the D2R including NAMs with sub-μM affinity (9h) and, surprisingly, low efficacy partial agonists (9d and 9i).

Design, Synthesis, and Biological Evaluation of 6-Substituted Thieno[3,2- d]pyrimidine Analogues as Dual Epidermal Growth Factor Receptor Kinase and Microtubule Inhibitors

The clinical evidence for the success of tyrosine kinase inhibitors in combination with microtubule-targeting agents prompted us to design and develop single agents that possess both epidermal growth factor receptor (EGFR) kinase and tubulin polymerization inhibitory properties. A series of 6-aryl/heteroaryl-4-(3′,4′,5′-trimethoxyanilino)thieno[3,2-d]pyrimidine derivatives were discovered as novel dual tubulin polymerization and EGFR kinase inhibitors. The 4-(3′,4′,5′-trimethoxyanilino)-6-(p-tolyl)thieno[3,2-d]pyrimidine derivative 6g was the most potent compound of the series as an antiproliferative agent, with half-maximal inhibitory concentration (IC50) values in the single- or double-digit nanomolar range. Compound 6g bound to tubulin in the colchicine site and inhibited tubulin assembly with an IC50 value of 0.71 μM, and 6g inhibited EGFR activity with an IC50 value of 30 nM. Our data suggested that the excellent in vitro and in vivo profile of 6g may be derived from its dual inhibition of tubulin polymerization and EGFR kinase.

Identification of 4-methoxythieno[2,3-d]pyrimidines as FGFR1 inhibitors

Aim. To identify novel FGFR1 inhibitors using virtual screening approach. Methods. We used methods of organic synthesis, molecular docking via the Autodock 4.2.6 program package and in vitro biochemical tests with γ-32P. Results. In vitro experiments showed that 9 of 23 tested compounds possess inhibitory activity against FGFR1 with IC50 values in the range from 0.9 to 5.6 μM. Conclusions. Nine FGFR1 inhibitors were developed. The mode of compounds binding with the ATP-acceptor site was determined using molecular docking methods and the dependence of the compounds’ activity on the substituents R1, R4 and R5 was evaluated.

Polysubstituted quinolone compounds, and preparation method and use thereof

The invention provides polysubstituted quinolone compounds, and a preparation method and a use thereof, and concretely provides a polysubstituted quinolone compound represented by formula I, and optical isomers, pharmaceutically acceptable salts or solvates thereof. All groups in the formula I are defined in the description. The quinolone compound has excellent c-Met inhibition activity, and can be used for treating c-Met activity or expression level corrected diseases.

4-Substituted thieno[2,3-d]pyrimidines as potent antibacterial agents: Rational design, microwave-assisted synthesis, biological evaluation and molecular docking studies

In an attempt to discover a new class of antibacterial agents with improved efficacy and to overcome the drug-resistant problems, some novel 4-substituted thieno[2,3-d]pyrimidines have been synthesized via microwave-assisted methodology and evaluated for their in vitro antibacterial activity against various pathogenic bacterial strains. Compounds 12b and 13c showed the promising inhibitory potencies against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli with MICs ranging from 2 to 10?μg/ml. Compound 13c was also found to be highly potent against methicillin-resistant S. aureus (MRSA) with MIC value of 4?μg/ml. Docking simulation studies have been performed to unravel the mode of action and association study indicate the binding of potent compounds with DHPS enzyme. In silico ADME studies suggest the drug-like characteristics of the potent compounds.

Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines

An extension of our previous research work has resulted in a number of new ATP-competitive CK2 inhibitors that have been identified among 4-aminothieno[2,3-d]pyrimidine derivatives. The most active compounds obtained in the course of the research are 3-(5-p-tolyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5e (NHTP23, IC50 = 0.01 μM), 3-(5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5g (NHTP25, IC50 = 0.065 μM) and 3-(6-methyl-5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5n (NHTP33, IC50 = 0.008 μM). Structure-activity relationships of the tested 4-aminothieno[2,3-d]pyrimidine derivatives have been studied and their binding mode with ATP-acceptor site of CK2 has been proposed. A negative effect of intramolecular hydrogen bonding in the compounds' structure is discussed.

Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin- 4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2

A novel series of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids has been synthesized and tested in vitro towards human protein kinase CK2. It was revealed that the most active compounds inhibiting CK2 are 3-{[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid and 3-{[5-(4-ethoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid (IC 50 values are 0.1 μM and 0.125 μM, respectively). Structure-activity relationships of 28 tested thienopyrimidine derivatives have been studied and binding mode of this chemical class has been predicted. Evaluation of the inhibitors on seven protein kinases revealed considerable selectivity towards CK2.