281656-91-5

Upstream product

• 3612-18-8 N-ethyl-4-piperidone 
• 105-56-6 ethyl 2-cyanoacetate 

Downstream Products

• 934393-83-6 6-ethyl-2-[3-(4-methoxy-phenyl)-thioureido]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ethyl ester 
• 1383841-24-4 dimethyl 3'-(4-chlorophenyl)-1-ethyl-6'-methylidene-4'-oxo-3',4',5,6-tetrahydro-1H-spiro[pyridine-4,5'-thieno[2,3-d]pyrimidine]2,3-dicarboxylate 
• 1415734-82-5 dimethyl 3-(4-chlorophenyl)-7-ethyl-4-oxo-3,4,5,6,7,10-hexahydropyrimido[5',4':4,5]thieno[3,2-d]azocine-8,9-dicarboxylate 
• 1415734-62-1 methyl 3'-(4-chlorophenyl)-1-ethyl-6'-methylidene-4'-oxo-3',4',5,6-tetrahydro-1H-spiro[pyridine-4,5'-thieno[2,3-d]pyrimidine]-3-carboxylate 
• 1415734-85-8 methyl 3-(4-chlorophenyl)-7-ethyl-4-oxo-3,4,5,6,7,10-hexahydropyrimido[5',4':4,5]thieno[3,2-d]azocine-9-carboxylate 
• 1415734-64-3 3-acetyl-3'-(4-chlorophenyl)-1-ethyl-6'-methylidene-5,6-dihydro-1H-spiro[pyridine-4,5'-thieno[2,3-d]pyrimidin]-4'(3'H)-one 
• 1415734-88-1 9-acetyl-3-(4-chlorophenyl)-7-ethyl-5,6,7,10-tetrahydropyrimido[5',4':4,5]thieno[3,2-d]azocin-4(3H)-one 
• 1415734-66-5 dimethyl-1-ethyl-6'-methylidene-3'-(4-nitrophenyl)-4'-oxo-3',4',5,6-tetrahydro-1H-spiro[pyridine-4,5'-thieno[2,3-d]pyrimidine]-2,3-dicarboxylate 
• 1415734-91-6 dimethyl 7-ethyl-3-(4-nitrophenyl)-4-oxo-3,4,5,6,7,10-hexahydropyrimido[5',4':4,5]thieno[3,2-d]azocine-8,9-dicarboxylate 
• 1415734-68-7 methyl 1-ethyl-6'-methylidene-3'-(4-nitrophenyl)-4'-oxo-3',4',5,6-tetrahydro-1H-spiro[pyridine-4,5'-thieno[2,3-d]pyrimidine]-3-carboxylate 
• 1415734-94-9 methyl 7-ethyl-3-(4-nitrophenyl)-4-oxo-3,4,5,6,7,10-hexahydropyrimido[5',4':4,5]thieno[3,2-d]azocine-9-carboxylate 
• 1415734-70-1 3-acetyl-1-ethyl-6'-methylidene-3'-(4-nitrophenyl)-5,6-dihydro-1H-spiro[pyridine-4,5'-thieno[2,3-d]pyrimidin]-4'(3'H)-one 
• 1383841-25-5 dimethyl 1-ethyl-3'-(2-methoxyphenyl)-6'-methylidene-4'-oxo-3',4',5,6-tetrahydro-1H-spiro[pyridine-4,5'-thieno[2,3-d]pyrimidine]-2,3-dicarboxylate 
• 1415734-97-2 dimethyl 7-ethyl-3-(2-methoxyphenyl)-4-oxo-3,4,5,6,7,10-hexahydropyrimido[5',4':4,5]thieno[3,2-d]azocine-8,9-dicarboxylate 

Relevant academic research and scientific papers

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 Thieno[2,3- d]pyrimidine-Based Hydroxamic Acid Derivatives as Bromodomain-Containing Protein 4/Histone Deacetylase Dual Inhibitors Induce Autophagic Cell Death in Colorectal Carcinoma Cells

Bromodomain-containing protein 4 (BRD4) and histone deacetylases (HDAC) are both attractive epigenetic targets in cancer and other chronic diseases. Based on the integrated fragment-based drug design, synthesis, and in vitro and in vivo evaluations, a series of novel thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives are discovered as selective BRD4-HDAC dual inhibitors. Compound 17c is the most potent inhibitor for BRD4 and HDAC with IC50 values at nanomolar levels, as well as the expression level of c-Myc, and increases the acetylation of histone H3. Moreover, 17c presents inhibitory effects on the proliferation of colorectal carcinoma (CRC) cells via inducing autophagic cell death. It also has a good pharmacokinetic profile in rats and oral bioavailability of 40.5%. In the HCT-116 xenograft in vivo models, 17c displays potent inhibitory efficiency on tumor growth by inducing autophagic cell death and suppressing IL6-JAK-STAT signaling pathways. Our results suggest that the BRD4-HDAC dual inhibition might be an attractive therapeutic strategy for CRC.

ANTI-INFECTIVE 2-AMINOTHIOPHENES

2-Aminothiophene derivatives, uses of the same, and methods of making the same, are described.

Synthesis and evaluation of new 2-aminothiophenes against: Mycobacterium tuberculosis

Tuberculosis (TB) and its drug resistant forms kills more people than any other infectious disease. This fact emphasizes the need to identify new drugs to treat TB. 2-Aminothiophenes (2AT) have been reported to inhibit Pks13, a validated anti-TB drug target. We synthesized a library of 42 2AT compounds. Among these, compound 33 showed remarkable potency against Mycobacterium tuberculosis (Mtb) H37RV (MIC = 0.23 μM) and showed an impressive potency (MIC = 0.20-0.44 μM) against Mtb strains resistant to isoniazid, rifampicin and fluoroquinolones. The site of action for the compound 33 is presumed to be Pks13 or an earlier enzyme in the mycolic acid biosynthetic pathway. This inference is based on structural similarity of the compound 33 with known Pks13 inhibitors, which is corroborated by mycolic acid biosynthesis studies showing that the compound strongly inhibits the biosynthesis of all forms of mycolic acid in Mtb. In summary, these studies suggest 33 represents a promising anti-TB lead that exhibits activity well below toxicity to human monocytic cells.

COMPOUNDS FOR TREATING VIRAL INFECTIONS

The present invention relates to small molecule compounds and their use in the treatment of diseases, in particular viral diseases, in particular hepatitis C virus (HCV).

The first example of tetrahydrothieno[3,2-d]azocines synthesis

A novel and efficient one-pot synthesis of thieno[3,2-d]azocines based on tamden transformation of tetrahydropyridine ring was elaborated.

Synthesis and bioactivities of novel bicyclic thiophenes and 4,5,6,7-tetrahydrothieno[2,3-c]pyridines as inhibitors of tumor necrosis factor-alpha (TNF-alpha) production.

We synthesized bicyclic thiophenes and 4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives, and evaluated for their ability to inhibit LPS-stimulated production of TNF-alpha. Several compounds revealed excellent in vivo activity. Furthermore, an effective compound was found in adjuvant-induced arthritic model (AIA) of rat.