67808-64-4

Usage

InChI:InChI=1/C7H6O3S/c1-10-7(9)6-3-2-5(4-8)11-6/h2-4H,1H3

Upstream product

• 4565-31-5 5-formyl-2-thiophencarboxylic acid 
• 74-88-4 methyl iodide 
• 1001200-44-7 5,5-dibromomethylthiophene-2-carboxylic acid methyl ester 
• 7732-18-5 water 
• 154935-51-0 2-Carboxy-5-formylthiophene dimethyl acetal 
• 98-03-3 thiophene-2-carbaldehyde 
• 58268-08-9 2-(2-thienyl)-1,3-dioxolane 
• 1918-79-2 2-methylthiophene-5-carboxylic acid 
• 19432-69-0 methyl 5-methylthiophene-2-carboxylate 
• 67-56-1 methanol 
• 52157-62-7 2-(5-bromothiophen-2-yl)-1,3-dioxolane 
• 79-22-1 methyl chloroformate 
• 5380-42-7 thiophene-2-carboxylic acid methyl ester 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 50340-79-9 thiophene-2,5-dicarboxylic acid monomethyl ester 
• 133380-55-9 2-phenyl-3-methyl-5-(5-methoxycarbonyl-2-thenoyl)oxazole N-oxide hydrochloride 
• 4565-31-5 5-formyl-2-thiophencarboxylic acid 
• 189330-23-2 5-(difluoromethyl)thiophene-2-carboxylic acid 
• 2495-15-0 N-(5-methoxycarbonyl-2-thenoyl)-N'-benzoylhydrazide 
• 133380-75-3 O-(2-methoxycarbonyl-5-thenoyl)benzamide oxime 
• 133380-49-1 methyl 5--2-thiophenecarboxylate 
• 133380-43-5 N-(5-methoxycarbonyl-2-thenoyl)-α-aminoacetophenone 
• 133380-57-1 methyl 5-(2-phenyl-3-methyloxazol-5-yl)-2-thiophenecarboxylate 
• 133380-93-5 methyl 5-(5-phenyl-1,2,4-oxadiazol-3-yl)-2-thiophenecarboxylate 
• 133380-51-5 methyl 5-(2-phenyloxazol-5-yl)-2-thiophenecarboxylate 
• 133380-45-7 methyl 5-(5-phenoxazol-2-yl)-2-thiophenecarboxylate 

Relevant academic research and scientific papers

Chemical switching in reaction behavior of azine: Synthesis of a novel thienodiazepine derivative

We previously have reported that an acid-promoted condensation of a hydrazonoester derived from phenylalanine afforded an azine which was converted to a pyrrole through 3 steps: isomerization to dienamine, [3,3]-sigmatropic rearrangement, and cyclization.

Discovery of Novel and Potent N-Methyl- d -aspartate Receptor Positive Allosteric Modulators with Antidepressant-like Activity in Rodent Models

N-Methyl-d-aspartate receptors (NMDARs) are glutamate-gated Na+ and Ca2+-permeable ion channels involved in excitatory synaptic transmission and synaptic plasticity. NMDAR hypofunction has long been implicated in the pathophysiology including major depressive disorders (MDDs). Herein, we report a series of furan-2-carboxamide analogues as novel NMDAR-positive allosteric modulators (PAMs). Through structure-based virtual screen and electrophysiological tests, FS2921 was identified as a novel NMDAR PAM with potential antidepressant effects. Further structure-activity relationship studies led to the discovery of novel analogues with increased potentiation. Compound 32h caused a significant increase in NMDAR excitability in vitro and impressive activity in the forced swimming test. Moreover, compound 32h showed no significant inhibition of hERG or cell viability and possessed a favorable PK/PD profile. Our study presented a series of novel NMDAR PAMs and provided potential opportunities for discovering of new antidepressants.

Harnessing the Role of HDAC6 in Idiopathic Pulmonary Fibrosis: Design, Synthesis, Structural Analysis, and Biological Evaluation of Potent Inhibitors

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive-fibrosing phenotype. IPF has been associated with aberrant HDAC activities confirmed by our immunohistochemistry studies on HDAC6 overexpression in IPF lung tissues. We herein developed a series of novelhHDAC6 inhibitors, having low inhibitory potency overhHDAC1 andhHDAC8, as potential pharmacological tools for IPF treatment. Their inhibitory potency was combined with lowin vitroandin vivotoxicity. Structural analysis of 6h and structure-activity relationship studies contributed to the optimization of the binding mode of the new molecules. The best-performing analogues were tested for their efficacy in inhibiting fibrotic sphere formation and cell viability, proving their capability in reverting the IPF phenotype. The efficacy of analogue 6h was also determined in a validated human lung model of TGF-β1-dependent fibrogenesis. The results highlighted in this manuscript may pave the way for the identification of first-in-class molecules for the treatment of IPF.

Spiroindoline-Capped Selective HDAC6 Inhibitors: Design, Synthesis, Structural Analysis, and Biological Evaluation

Histone deacetylase inhibitors (HDACi) have emerged as promising therapeutics for the treatment of neurodegeneration, cancer, and rare disorders. Herein, we report the development of a series of spiroindoline-based HDAC6 isoform-selective inhibitors based on the X-ray crystal studies of the hit 6a. We identified compound 6j as the most potent and selective hHDAC6 inhibitor of the series. Biological investigation of compounds 6b, 6h, and 6j demonstrated their antiproliferative activity against several cancer cell lines. Western blotting studies indicated that they were able to increase tubulin acetylation, without significant variation in histone acetylation state, and induced PARP cleavage indicating their apoptotic potential at the molecular level. 6j induced HDAC6-dependent pSTAT3 inhibition.

Novel spiroindoline HDAC inhibitors: Synthesis, molecular modelling and biological studies

This paper describes the rational development of a series of novel spiroindoline derivatives endowed with selective inhibitory activity on the HDAC6 isoform. A convenient multicomponent one-pot protocol was applied for the assembly of the desired N1-substituted spiroindoline core which allowed a straightforward analoging. Computational studies and in vitro determination of inhibitory potency for the developed compounds against HDAC6 and HDAC1 isoforms were flanked by cell-based studies on histone H3 and α-tubulin acetylation. The effects on cancer cell cycle and apoptosis of the best performing derivatives were assessed on cancer cell lines highlighting a promising antitumor potential. In view of cell-based data and calculated drug-like properties, the selective HDAC6 inhibitor 5b, with a spiroindoline-based hydroxamate bearing a tert-butyl carbamate functionality, was selected to be further investigated for its potential in inhibiting tumor cells migration. It was able to potently inhibit cell migration in SH-SY5Y neuroblastoma cells and did not display toxicity in NIH3T3 mouse fibroblasts. Taken together, these data foster further investigation and optimization for this class of compounds as novel anticancer agents.

ORGANIC DYE COMPLEX AND MANUFACTURING METHOD THEREFOR

PROBLEM TO BE SOLVED: To provide an organic dye complex having a wider area of absorption wavelengths, especially a wider area of absorption wavelengths in a near-infrared region. SOLUTION: There is provided a composite of a specific phthalocyanine derivative and a porphyrin derivative having a structure of the formula (2). In the formula (2), A, B, C and D represent each independently a hydrogen atom, a halogen atom or a monovalent organic group, at least two of the A to D are substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, M2 represents at least one atom or atom group that may bind with porphyrin. COPYRIGHT: (C)2015,JPO&INPIT

Selective nitrile inhibitors to modulate the proteolytic synergism of cathepsins S and F

A series of dipeptide nitriles with different P3 substituents was designed to explore the S3 binding pocket of cathepsin S. Racemic 7-16 and the enantiopure derivative (R)-22 proved to be potent inhibitors of human cathepsin S and exhibited notable selectivity over human cathepsins L, K, and B. Inhibition of cathepsin F, the functional synergist of cathepsin S, was not observed. The azadipeptide analogue of 22, compound 26, was highly potent but nonselective.

CONDENSED PYRIDINE COMPOUND

The present invention provides a compound having excellent JAK3 inhibitory activity and being useful as an active ingredient of an agent for treating and/or preventing various immune diseases including autoimmune diseases, inflammatory diseases, and allergic diseases. As a result of investigations with respect to novel condensed heterocyclic derivatives, the inventors have verified that a condensed pyridine compound has excellent JAK3 inhibitory activity, thereby completing the present invention. More specifically, it has been verified that since the compound according to the present invention has inhibitory activity against JAK3, the compound is useful as an active ingredient of an agent for treating or preventing diseases caused by undesirable cytokine signal transduction (e.g., rejection during live organ/tissue transplantation, autoimmune diseases, asthma, atopic dermatitis, rheumatism, psoriasis and atherosclerotic disease), or diseases caused by abnormal cytokine signal transduction (e.g., cancer and leukemia).

Design of chimeric histone deacetylase- and tyrosine kinase-inhibitors: A series of Imatinib hybrides as potent Inhibitors of wild-type and mutant BCR-ABL, PDGF-Rβ, and histone deacetylases

Inhibitors of histone deacetylases are a new class of cancer therapeutics with possibly broad applicability. Combinations of HDAC inhibitors with the kinase inhibitor 1 (Imatinib) in recent studies showed additive and synergistic effects. Here we present a new concept by combining inhibition of protein kinases and HDACs, two independent pharmacological activities, in one synthetic small molecule. In general, the HDAC inhibition profile, the potencies, and the probable binding modes to HDAC1 and HDAC6 were similar as for 6 (SAHA). Inhibition of Abl kinase in biochemical assays was maintained for most compounds, but in general the kinase selectivity profile differed from that of 1 with nearly equipotent inhibition of the wildtype and the Imatinib resistant Abl T315I mutant. A potent cellular inhibition of PDGFR and cytotoxicity toward EOL-1 cells, a model for idiopathic hypereosinophilic syndrome (HES), are restored or enhanced for selected analogues (12b, 14b, and 18b). Cytotoxicity was evaluated by using a broad panel of tumor cell lines, with selected analogues displaying mean IC50 values between 3.6 and 7.1 μM.