193537-14-3

Usage

Uses

Used in Medicinal Chemistry:
2-Amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert butyl ester 3-ethyl ester is used as a chemical intermediate for the synthesis of various pharmaceutical compounds. Its unique structure and functional groups make it a promising candidate for the development of new drugs with potential therapeutic applications.
Used in Drug Discovery:
In the field of drug discovery, 2-Amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert butyl ester 3-ethyl ester serves as a key building block for the design and synthesis of novel drug molecules. Its presence in the molecular structure can influence the pharmacokinetic and pharmacodynamic properties of the resulting compounds, potentially leading to improved efficacy and safety profiles.
Used in Material Science:
2-Amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert butyl ester 3-ethyl ester is used as a component in the development of advanced materials with specific properties. Its incorporation into polymers or other materials can impart unique characteristics, such as improved stability, enhanced reactivity, or tailored electronic properties, depending on the application.

InChI:InChI=1/C15H22N2O4S/c1-5-20-13(18)11-9-6-7-17(8-10(9)22-12(11)16)14(19)21-15(2,3)4/h5-8,16H2,1-4H3

Upstream product

• 98977-36-7 3-oxo-piperidine-1-carboxylic acid tert-butyl ester 
• 105-56-6 ethyl 2-cyanoacetate 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 

Downstream Products

• 851852-78-3 3-(3-fluorophenyl)-2-mercapto-4-oxo-3,5,6,8-tetrahydro-4H-9-thia-1,3,7-triazafluorene-7-carboxylic acid tert-butyl ester 
• 851852-76-1 [3-(3-fluorophenyl)-7-methyl-4-oxo-3,4,5,6,7,8-hexahydro-9-thia-1,3,7-triazafluoren-2-ylsuIfanyl]acetic acid ethyl ester 
• 851852-75-0 [3-(3-fluorophenyl)-4-oxo-3,4,5,6,7,8-hexahydro-9-thia-1,3,7-triazafluoren-2-ylsulfanyl]acetic acid ethyl ester 
• 851852-77-2 [3-(3-fluorophenyl)-4-oxo-7-propyl-3,4,5,6,7,8-hexahydro-9-thia-1,3,7-triazafluoren-2-ylsulfanyl]acetic acid ethyl ester 
• 851852-74-9 2-ethoxycarbonylmethylsulfanyl-3-(3-fluorophenyl)-4-oxo-3,5,6,8-tetrahydro-4H-9-thia-1,3,7-triazafluorene-7-carboxylic acid tert-butyl ester 
• 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 
• 874801-60-2 tert-butytert-butyl-4-oxo-3,4,5,6,7,8-hexahydropyrido[4′,3′:4,5]thieno-[2,3-d]pyrimidine-7-carboxylatel-4-oxo-3,4,5,6,7,8-hexahydropyrido[4′,3′:4,5]thieno-[2,3-d]pyrimidine-7-carboxylate 

Relevant academic research and scientific papers

Synthesis and Evaluation of 2-Aminothiophene Derivatives as Staphylococcus aureus Efflux Pump Inhibitors

2-aminothiophene derivatives (2AT) in which the thiophene ring is fused with a cycloalkyl or a N-acylated piperidine ring by positions 5 and 6 and carrying a 3-carbethoxy group were synthesized and their bacterial growth and enzyme inhibitory effects against efflux proteins of Staphylococcus aureus leading to resistance to fluoroquinolones and erythromycin (ERY) were investigated. Compounds that most effectively decreases the minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) were assayed for their dose and time effects on the accumulation and efflux of ethidium bromide (EtBr) in the SA-1 strain. None of the compounds displayed antibacterial activity however, three derivatives carrying 2-amino, 2-aminoacetyl and 2-aminotrifluoroacetyl group enhanced the activity of CIP and ERY by 8- and 16-fold, respectively, and were able to restore the sensitivity of resistant strains, acting as typical efflux pump inhibitors (EPIs). The 2-aminoacetyl and 2-aminotrifluoroacetyl derivatives and two other piperidinyl 2-aminotrifluoroacetyl derivatives increased EtBr accumulation in a dose- and time-dependent manner, and one of them was also able to inhibit the EtBr efflux. Taken together, these results represent an important advance in the development of new EPIs, and demonstrate that 2AT represent a good scaffold for developing new antibiotic adjuvants.

SYNTHESIS, CHARACTERIZATION, THERMAL, X-RAY, AND DFT ANALYSES OF 6-TERT-BUTYL?3-ETHYL 2-[(3-METHOXY/5-BROMO)-2-HYDROXY AND (3-NITRO/3-METHOXY)BENZYLIDENEAMINO]- 4,5-DIHYDROTHIENO[2,3-C]PYRIDINE-3,6(7H)-DICARBOXYLATE

Abstract: In this work, 6-tert-butyl 3-ethyl 2-amino-4,5-dihydrothieno[2,3-c]pyridine-3,6(7H)-dicarboxylate is synthesized from starting tert-butyl 4-oxopiperidine-1-carboxylate, ethyl cyanomalonate, and sulfur, and then, coupled with same aromatic aldehyde affords the corresponding Schiff base compounds. These compounds (2a–d) are characterized using FTIR, 1H and 13C NMR spectroscopic methods. The crystal and molecular structure of (E)-6-tert-butyl 3-ethyl 2-((2-hydroxy-3-methoxybenzylidene)amino)-4,5-dihydrothieno[2,3-c]pyridine-3,6(7H)-dicarboxylate (2a) is characterized by the X-ray crystallographic analysis. Compound 2a crystallizes in the monoclinic space group P21/c. The molecular and crystal structure is stabilized by two O–H?N and O–H?O intramolecular hydrogen bonds (O?N and O?O are 2.598(5)?? and 2.990(5)??, respectively; O–H?N?=?147° and O–H?O?=?134°). According to DFT, compound 2d also shows the intramolecular hydrogen bonding, while there is no this type of interaction in compound 2b and 2c.

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.

PYRIDINESULFONAMIDE DERIVATIVES AS TRAP1 MODULATORS AND USES THEREOF

The present disclosure provides compounds of Formula (I): and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof. The provided compounds may be tumor necrosis factor ("TNF") receptor associated protein 1 ("TRAP1") modulators (e.g., TRAP1 activators). The provided compounds may also rescue the activity in PTEN-induced kinase 1 ("PINK1") loss of function contexts. The provided compounds may also improve mitochondrial health, function, quality, quantity, and/or activity, and/or reduce the production of reactive oxygen species. The provided compounds may also refold or solubilize aggregated or misfolded proteins such as a-synuclein. The present disclosure also provides pharmaceutical compositions comprising the provided compounds; kits comprising the provided compounds or pharmaceutical compositions; and methods of using the provided compounds and pharmaceutical compositions (e.g., for treating a disease in a subject in need thereof).

2-Substituted thienotetrahydropyridine derivatives: Allosteric ectonucleotidase inhibitors

The antithrombotic prodrugs ticlopidine and clopidogrel are thienotetrahydro-pyridine derivatives that are metabolized in the liver to produce thiols that irreversibly block adenosine diphosphate (ADP)-activated P2Y12 receptors on thrombocytes. In their native, nonmetabolized form, both drugs were reported to act as inhibitors of ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1, CD39). CD39 catalyzes the extracellular hydrolysis of nucleoside tri- and diphosphates, mainly adenosine 5?-triphosphate (ATP) and ADP, yielding adenosine monophosphate, which is further hydrolyzed by ecto-5?-nucleotidase (CD73) to produce adenosine. While ATP has proinflammatory effects, adenosine is a potent anti-inflammatory, immunosuppressive agent. Inhibitors of CD39 and CD73 have potential as novel checkpoint inhibitors for the immunotherapy of cancer and infection. In the present study, we investigated 2-substituted thienotetrahydropyridine derivatives, structurally related to ticlopidine, as CD39 inhibitors. Due to their substituent on the 2-position, they will not be metabolically transformed into reactive thiols and can, therefore, be expected to be devoid of P2Y12 receptor-antagonistic activity in vivo. Several of the investigated 2-substituted thienotetrahydropyridine derivatives showed concentration-dependent inhibition of CD39. The most potent derivative, 32, showed similar CD39-inhibitory potency to ticlopidine, both acting as allosteric inhibitors. Compound 32 showed an improved selectivity profile: While ticlopidine blocked several NTPDase isoenzymes, 32 was characterized as a novel dual inhibitor of CD39 and CD73.

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.

PENTACYCLIC HETEROCYCLES

The present invention provides compounds represented by formulas (I) to (XVII) or pharmaceutically acceptable salts thereof:

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

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.

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