182127-92-0

Basic information

• Product Name: 2-MERCAPTO-6-METHYL-4-(TRIFLUOROMETHYL)NICOTINONITRILE
• Synonyms: 2-MERCAPTO-6-METHYL-4-(TRIFLUOROMETHYL)NICOTINONITRILE;AKOS BBS-00000377;3-Pyridinecarbonitrile,1,2-dihydro-6-Methyl-2-thioxo-4-(trifluoroMethyl)-;1,2-dihydro-6-methyl-2-thioxo-4-((trifluoromethyl))-pyridin-3-carbonitrile
• CAS NO: 182127-92-0
• Molecular Formula: C₈H₅F₃N₂S
• Molecular Weight: 218.2
• Mol File: 182127-92-0.mol

Chemical Properties

• Melting Point: 200 °C
• Boiling Point: 204.4°Cat760mmHg
• Flash Point: 77.4°C
• Appearance: /
• Density: 1.44g/cm³
• Vapor Pressure: 0.263mmHg at 25°C
• Refractive Index: 1.536
• CAS DataBase Reference: 2-MERCAPTO-6-METHYL-4-(TRIFLUOROMETHYL)NICOTINONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-MERCAPTO-6-METHYL-4-(TRIFLUOROMETHYL)NICOTINONITRILE(182127-92-0)
• EPA Substance Registry System: 2-MERCAPTO-6-METHYL-4-(TRIFLUOROMETHYL)NICOTINONITRILE(182127-92-0)

Safety Data

• Hazard Codes: T
• Statements: 36/37/38-25
• Safety Statements: 26-36/37/39-45
• Hazardous Substances Data: 182127-92-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research:
2-Mercapto-6-methyl-4-(trifluoromethyl)nicotinonitrile is used as a key intermediate in the synthesis of various pharmaceutical compounds. Its unique functional groups allow for the development of new drugs with improved efficacy and selectivity.
Used in Organic Synthesis:
In the field of organic synthesis, 2-Mercapto-6-methyl-4-(trifluoromethyl)nicotinonitrile is used as a versatile building block for the creation of a wide range of chemical compounds. Its reactivity and functional groups enable the formation of diverse molecular structures with potential applications in various industries.
Used in Medicinal Chemistry:
2-Mercapto-6-methyl-4-(trifluoromethyl)nicotinonitrile is employed as a valuable tool in medicinal chemistry for the design and optimization of drug candidates. Its unique structure allows for the exploration of novel chemical space and the identification of new therapeutic agents with improved pharmacological properties.
Used in Drug Discovery:
In drug discovery efforts, 2-Mercapto-6-methyl-4-(trifluoromethyl)nicotinonitrile serves as a promising starting point for the development of new therapeutic agents. Its unique chemical properties and reactivity enable the generation of novel compounds with potential applications in the treatment of various diseases and conditions.

InChI:InChI=1/C8H5F3N2S/c1-4-2-6(8(9,10)11)5(3-12)7(14)13-4/h2H,1H3,(H,13,14)

Upstream product

• 7357-70-2 Cyanothioacetamide 
• 144864-94-8 5,5,5-trifluoro-4-hydroxy-pent-3-en-2-one 
• 234112-44-8 4-methoxy-1,1,1-trifluoropent-3-en-2-one 
• 367-57-7 1,1,1-Trifluoro-2,4-pentanedione 
• 135351-20-1 1,1,1-trifluoro-4-methoxypent-3-en-2-one 

Downstream Products

• 182127-95-3 6-Methyl-2-(2-oxo-2-phenyl-ethylsulfanyl)-4-trifluoromethyl-nicotinonitrile 
• 206280-70-8 N-(3-Butoxy-phenyl)-2-(3-cyano-6-methyl-4-trifluoromethyl-pyridin-2-ylsulfanyl)-acetamide 
• 206280-68-4 2-(3-Cyano-6-methyl-4-trifluoromethyl-pyridin-2-ylsulfanyl)-N-phenyl-acetamide 
• 206280-69-5 2-(3-Cyano-6-methyl-4-trifluoromethyl-pyridin-2-ylsulfanyl)-N-p-tolyl-acetamide 
• 610259-30-8 3-amino-6-methyl-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-carboxylic acid 
• 313379-68-9 methyl 3-amino-6-methyl-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-carboxylate 
• 299198-61-1 ethyl 3-amino-6-methyl-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-carboxylate 

Relevant articles and documents

CARBOXAMIDES AS UBIQUITIN-SPECIFIC PROTEASE INHIBITORS

The present disclosure relates to modulators, such as inhibitors, of at least one pathway chosen from USP28 and USP25, pharmaceutical compositions comprising the inhibitors, and methods of using the inhibitors. The modulators, such as inhibitors, of at least one pathway chosen from USP28 and USP25 can be useful in the treatment of cancers, among other ailments.

Discovery and optimization of thienopyridine derivatives as novel urea transporter inhibitors

Urea transporters (UTs) play an important role in the urine concentrating mechanism and are recognized as novel targets for developing small molecule inhibitors with salt-sparing diuretic activity. Thienoquinoline derivatives, a class of novel UT-B inhibitors identified by our group, play a significant diuresis in animal model. However, the poor solubility and low bioavailability limited its further development. To overcome these shortcomings, the structure modification of thienoquinoline was carried out in this study, which led to the discovery of novel thienopyridine derivatives as specific urea transporter inhibitors. Further optimization obtained the promising preclinical candidate 8n with not only excellent inhibition effect on urea transporters and diuretic activity on rat model, but also suitable water solubility and Log P value.

Discovery and structure-activity relationships study of thieno[2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors

Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC50 = 33.8 μM) characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC50 = 16.8 μM) and 9d (IC50 = 12.3 μM) with potent inhibition of hepatic glucose production and good drug-like properties. Furthermore, the mechanism of 8e for the inhibition of hepatic glucose production was also identified, which could be effective through the reductive expression of the mRNA transcription level of gluconeogenic genes, including glucose-6-phosphatase (G6Pase) and hepatic phosphoenolpyruvate carboxykinase (PEPCK). Additionally, 8e could also reduce the fasting blood glucose and improve the oral glucose tolerance and pyruvate tolerance in db/db mice. The optimization of this class of derivatives had provided us a start point to develop new anti-hepatic gluconeogenesis agents.

NEW COMPOUNDS

The present invention relates to new compounds of formula (I) wherein R1 to R9, X, p and n are defined as in claim 1, or salts, solvates or solvated salts thereof, processes for their preparation and to new intermediates used in the preparation thereof, pharmaceutical compositions containing said compounds and to the use of said compounds in therapy.

Regioselective synthesis and properties of 3-cyano-6-methyl-4-trifluoromethylpyridine-2(1H)-thione. Molecular and crystal structure of 3-cyano-2-ethylthio-6-methyl-4-trifluoromethylpyridine

The reaction of trifluoroacetylacetone with cyanothioacetamide proceeded regioselectively to form 3-cyano-6-methyl-4-trifluoromethylpyridine-2(1H)-thione from which the corresponding 2-alkylthiopyridines and 3-aminothieno[2,3-b]pyridines were obtained. The crystal and molecular structure of 3-cyano-2-ethylthio-6-methyl-4-trifluoromethylpyridine was established by X-ray diffraction analysis.

Regioselective synthesis and S-derivatization reactions of 4- and 6-trifluoromethyl-3-cyano-2(1H)-pyridinethiones

The regioselective synthesis of the title compounds was developed on the basis of condensation reactions of trifluoroacetylacetone and its methyl enacetal with cyanothioacetamide in the presence of bases. Thus, the condensation of trifluoroacetylacetone with cyanothioacetamide yields predominantly 4-trifluoromethyl-6-methyl-3-cyano-2(1H)-pyridinethiones, whereas the methyl enacetal of trifluoroacetylacetone gives exclusively the 6-trifluoromethyl-4-methyl isomer. S-Alkylation of the trifluoromethylpyridinethione salts can be achieved using methyl iodide or bromoacetophenone in DMF-water. Bromoacetophenone derivatives can be further transformed into 3-aminothieno[2,3-b]pyridines in the presence of excess KOH.