87165-08-0

Upstream product

• 578-54-1 ortho-ethylaniline 
• 105-56-6 ethyl 2-cyanoacetate 
• 372-09-8 cyanoacetic acid 

Downstream Products

• 304887-45-4 3-[N-(2-ethylphenyl)carboxamido]chromene-2-one 
• 129014-33-1 (Z)-N-(2-Ethyl-phenyl)-3-furan-2-yl-2-(4-oxo-4,5-dihydro-thiazol-2-yl)-acrylamide 
• 129014-32-0 (Z)-N-(2-Ethyl-phenyl)-2-(4-oxo-4,5-dihydro-thiazol-2-yl)-3-thiophen-2-yl-acrylamide 
• 129014-29-5 N-(2-Ethyl-phenyl)-2-[2-oxo-1,2-dihydro-indol-(3Z)-ylidene]-2-(4-oxo-4,5-dihydro-thiazol-2-yl)-acetamide 
• 129014-31-9 4-Amino-1-(2-ethyl-phenyl)-3-[1-furan-2-yl-meth-(E)-ylidene]-5-(4-oxo-4,5-dihydro-thiazol-2-yl)-3H-pyridine-2,6-dione 
• 129014-30-8 4-Amino-1-(2-ethyl-phenyl)-5-(4-oxo-4,5-dihydro-thiazol-2-yl)-3-[1-thiophen-2-yl-meth-(E)-ylidene]-3H-pyridine-2,6-dione 
• 129014-26-2 5-Amino-6-cyano-3-oxo-7-thiophen-2-yl-2-[1-thiophen-2-yl-meth-(E)-ylidene]-2,3-dihydro-7H-thiazolo[3,2-a]pyridine-8-carboxylic acid (2-ethyl-phenyl)-amide 
• 129014-27-3 5-Amino-6-cyano-7-furan-2-yl-2-[1-furan-2-yl-meth-(E)-ylidene]-3-oxo-2,3-dihydro-7H-thiazolo[3,2-a]pyridine-8-carboxylic acid (2-ethyl-phenyl)-amide 
• 129014-28-4 5-Amino-6-cyano-7-naphthalen-1-yl-2-[1-naphthalen-1-yl-meth-(Z)-ylidene]-3-oxo-2,3-dihydro-7H-thiazolo[3,2-a]pyridine-8-carboxylic acid (2-ethyl-phenyl)-amide 
• 1254944-97-2 2-amino-5-cyano-N,1-di-(2-ethylphenyl)-6-oxo-1,6-dihydropyridine-3-carboxamide 
• 1394964-68-1 6-amino-1-(2-ethylphenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile 
• 1394964-74-9 ethyl 2-amino-5-cyano-1-(2-ethylphenyl)-6-oxo-1,6-dihydropyridine-3-carboxylate 
• 1094362-41-0 3-amino-3-(hydroxyimino)-N-[2-(ethyl)phenyl]propanamide 

Relevant academic research and scientific papers

Synthesis, antibacterial and cytotoxic activities of cyanoenonebenzenesulfonamide, acetamide and pyridine-3-Carbonitrile derivatives

A series of sulfonamides having biologically active acrylamides moieties (2, 3, 5), penta-2,4-dienamide (4), chromene-2-carboxamide (6), acetamide derivatives (7, 8) and pyridone derivative (9) were prepared. The structure of the synthesized compounds was

Identification of Novel Fused Heteroaromatics-Based MALT1 Inhibitors by High-Throughput Screening to Treat B Cell Lymphoma

Development of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitors is of great value and significance in the treatment of neoplastic disorders and inflammatory and autoimmune diseases. However, there is a lack of effective MALT1 inhibitors in clinic. Herein, a novel class of potent 5-oxo-1-thioxo-4,5-dihydro-1H-thiazolo[3,4-a]quinazoline-based MALT1 inhibitors and their covalent derivatives were first identified and designed through high-throughput screening. We demonstrated that compounds 15c, 15e, and 20c effectively inhibited the MALT1 protease and displayed selective cytotoxicity to activated B cell-like diffuse large B cell lymphoma with low single-digit micromolar potency. Furthermore, compound 20c specifically repressed NF-κB signaling and induced cell apoptosis in MALT1-dependent TMD8 cells in a dose-dependent manner. More importantly, 20c showed good pharmacokinetic properties and antitumor efficacy with no significant toxicity in the TMD8 xenograft tumor model. Collectively, this study provides valuable lead compounds of MALT1 inhibitors for further structural optimization and antitumor mechanism study.

Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer

Aldo-keto reductase (AKR) 1C3 catalyzes the synthesis of active androgens that promote the progression of prostate cancer. AKR1C3 also contributes to androgen-independent cell proliferation and survival through the metabolism of prostaglandins and reactive aldehydes. Because of its elevation in castration-resistant prostate cancer (CRPC) tissues, AKR1C3 is a promising therapeutic target for CRPC. In this study, we found a novel potent AKR1C3 inhibitor, N-(4-fluorophenyl)-8-hydroxy-2-imino-2H-chromene-3-carboxamide (2d), and synthesized its derivatives with IC50 values of 25-56 nM and >220-fold selectivity over other AKRs (1C1, 1C2, and 1C4). The structural factors for the inhibitory potency were elucidated by crystallographic study of AKR1C3 complexes with 2j and 2l. The inhibitors suppressed proliferation of prostate cancer 22Rv1 and PC3 cells through both androgen-dependent and androgen-independent mechanisms. Additionally, 2j and 2l prevented prostate tumor growth in a xenograft mouse model. Furthermore, the inhibitors significantly augmented apoptotic cell death induced by anti-CRPC drugs (abiraterone or enzalutamide).

Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A)

Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium-activated chloride channel expressed widely mammalian cells, including epithelia, vascular smooth muscle tissue, electrically excitable cells, and some tumors. TMEM16A inhibitors have been proposed for treatment of disorders of epithelial fluid and mucus secretion, hypertension, asthma, and possibly cancer. Herein we report, by screening, the discovery of 2-acylaminocycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A and analysis of 48 synthesized analogs (10ab-10bw) of the original AACT compound (10aa). Structure-activity studies indicated the importance of benzene substituted as 2- or 4-methyl, or 4-fluoro, and defined the significance of thiophene substituents and size of the cycloalkylthiophene core. The most potent compound (10bm), which contains an unusual bromodifluoroacetamide at the thiophene 2-position, had IC50 of ～30 nM, ～3.6-fold more potent than the most potent previously reported TMEM16A inhibitor 4 (Ani9), and >10-fold improved metabolic stability. Direct and reversible inhibition of TMEM16A by 10bm was demonstrated by patch-clamp analysis. AACTs may be useful as pharmacological tools to study TMEM16A function and as potential drug development candidates.

Low molecular weight amidoximes that act as potent inhibitors of lysine-specific demethylase 1

The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 dysregulation is thought to contribute to the development of cancer. We reported that (bis)guanidines, (bis)biguanides, and their urea- and thiourea isosteres are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of small molecule amidoximes that are moderate inhibitors of recombinant LSD1 but that produce dramatic changes in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2, H-cadherin (HCAD), and the transcription factor GATA4. These compounds represent leads for an important new series of drug-like epigenetic modulators with the potential for use as antitumor agents.

Novel pirfenidone analogs as antifibrotic agents: Synthesis and antifibrotic evaluation of 2-pyridones and fused pyridones

A new series of substituted 1-(2-ethylphenyl)-2-oxo-1,2-dihydropyridine-3- carbonitriles have been synthesized. Moreover, substituted bicyclic derivatives e.g. thieno[3,4-c]pyridone, pyrido[3,4-c]pyridone, benzo[c]pyridone and tricyclic derivatives, chrom

HETEROCYCLES SYNTHESIS THROUGH REACTIONS OF NUCLEOPHILES WITH ACRYLONITRILES, PART 5, SYNTHESIS OF SEVERAL NEW THIAZOLE AND THIAZOLOPYRIDINE DERIVATIVES

Several new thiazole and thiazolopyridine derivatives were prepared by reaction of the thiazolin-4-one derivatives 2 (synthesised from α-cyano-2-ethylacetanilide and thioglycollic acid) with acrylonitriles 1a-h.