2-巯基-6-甲基-4-(三氟甲基)烟腈 | 182127-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2-巯基-6-甲基-4-(三氟甲基)烟腈
• 英文名称: 6-methyl-2-thioxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile
• 英文别名: 2-Mercapto-6-methyl-4-(trifluoromethyl)nicotinonitrile；6-methyl-2-sulfanylidene-4-(trifluoromethyl)-1H-pyridine-3-carbonitrile
• CAS: 182127-92-0
• 化学式: C₈H₅F₃N₂S
• mdl: MFCD01313795
• 分子量: 218.202
• InChiKey: SNXNHTJMLREHDW-UHFFFAOYSA-N

物化性质

• 熔点：
  200 °C
• 沸点：
  204.4±50.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R20/21/22,R
• 海关编码：
  2933399090
• 安全说明：
  S36/37

SDS

Name:	2-Mercapto-6-methyl-4-(trifluoromethyl)nicotinonitrile 97% Material Safety Data Sheet
Synonym:
CAS:	182127-92-0

Section 1 - Chemical Product MSDS Name:2-Mercapto-6-methyl-4-(trifluoromethyl)nicotinonitrile 97% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
182127-92-0	2-Mercapto-6-methyl-4-(trifluoromethyl	97%	unlisted

Hazard Symbols: XN
Risk Phrases: 20/21/22

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Harmful by inhalation, in contact with skin and if swallowed.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. Harmful if absorbed through the skin.
Ingestion:
Harmful if swallowed. May cause irritation of the digestive tract.
Inhalation:
Harmful if inhaled. May cause respiratory tract irritation.
Chronic:
Not available.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container.

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Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 182127-92-0: Personal Protective Equipment Eyes: Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: Not available.
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 214 - 217 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C8H5F3N2S
Molecular Weight: 218.2

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Hydrogen cyanide, nitrogen oxides, carbon monoxide, oxides of sulfur, carbon dioxide, fluorine, hydrogen fluoride gas.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 182127-92-0 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
2-Mercapto-6-methyl-4-(trifluoromethyl)nicotinonitrile - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Shipping Name: NITRILES, SOLID, TOXIC, N.O.S.*
Hazard Class: 6.1
UN Number: 3276
Packing Group: III
IMO
Shipping Name: NITRILES, TOXIC, N.O.S.
Hazard Class: 6.1
UN Number: 3276
Packing Group: III
RID/ADR
Shipping Name: NITRILES, TOXIC, N.O.S.
Hazard Class: 6.1
UN Number: 3276
Packing group: III

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XN
Risk Phrases:
R 20/21/22 Harmful by inhalation, in contact with
skin and if swallowed.
Safety Phrases:
S 36/37 Wear suitable protective clothing and
gloves.
WGK (Water Danger/Protection)
CAS# 182127-92-0: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 182127-92-0 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 182127-92-0 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  2-巯基-6-甲基-4-(三氟甲基)烟腈 在 溶剂黄146 、 potassium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(2,4-dimethoxy-3-methylphenyl)-7-methyl-9-(trifluoromethyl)-2,3-dihydropyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4(1H)-one
  参考文献：
  名称：

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

  摘要：

  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 mu M) 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 mu M) and 9d (IC50 = 12.3 mu M) 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. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.04.028
• 作为产物：
  描述：

  2-氰基硫代乙酰胺 、 5,5,5-三氟-4-羟基-戊-3-烯-2-酮 在 三乙胺 作用下， 以 乙醇 为溶剂， 以88%的产率得到2-巯基-6-甲基-4-(三氟甲基)烟腈
  参考文献：
  名称：

  4-和6-三氟甲基-3-氰基-2（1H）-吡啶硫酮的区域选择性合成和S-衍生化反应

  摘要：

  在三氟乙酰丙酮及其甲基烯醇缩醛与氰基硫代乙酰胺在碱存在下的缩合反应的基础上，开发了标题化合物的区域选择性合成方法。因此，三氟乙酰丙酮与氰基硫代乙酰胺的缩合主要产生4-三氟甲基-6-甲基-3-氰基-2（1H）-吡啶硫酮，而三氟乙酰丙酮的甲基乙缩醛仅产生6-三氟甲基-4-甲基异构体。三氟甲基-吡啶硫酮盐的S-烷基化可通过在DMF水中使用甲基碘或溴苯乙酮来实现。在过量的KOH存在下，可以将溴苯乙酮衍生物进一步转化为3-氨基噻吩-[2,3-b]吡啶。

  DOI：

  10.1016/0040-4020(96)00632-1

文献信息

• [EN] THIENOPYRIDINE CARBOXAMIDES AS UBIQUITIN-SPECIFIC PROTEASE INHIBITORS<br/>[FR] THIÉNOPYRIDINE CARBOXAMIDES UTILISÉS COMME INHIBITEURS DE PROTÉASE SPÉCIFIQUE DE L'UBIQUITINE
  申请人：FORMA THERAPEUTICS INC

  公开号：WO2017139778A1

  公开（公告）日：2017-08-17

  The disclosure relates to inhibitors of USP28 and/or USP25 useful in the treatment of cancers, inflammation, autoimmune diseases, and infectious diseases, having the Formula (I), where R1, R2, R3, R4, R5, R5', R6, R7, X, m, and n are described herein.

  该披露涉及抑制剂USP28和/或USP25，用于治疗癌症、炎症、自身免疫疾病和传染病，具有式(I)，其中R1、R2、R3、R4、R5、R5'、R6、R7、X、m和n如本文所述。
• [EN] CARBOXAMIDES AS UBIQUITIN-SPECIFIC PROTEASE INHIBITORS<br/>[FR] CARBOXAMIDES UTILISÉES EN TANT QU'INHIBITEURS DE PROTÉASE SPÉCIFIQUE DE L'UBIQUITINE
  申请人：FORMA THERAPEUTICS INC

  公开号：WO2019032863A1

  公开（公告）日：2019-02-14

  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.

  本公开涉及调节剂，如抑制剂，至少选择自USP28和USP25中的一条途径的药物组合物包括这些抑制剂，以及使用这些抑制剂的方法。这些调节剂，如抑制剂，至少选择自USP28和USP25中的一条途径，可用于治疗癌症等疾病。
• Discovery and optimization of thienopyridine derivatives as novel urea transporter inhibitors
  作者：Yan Zhao、Min Li、Bowen Li、Shun Zhang、Aoze Su、Yongning Xing、Zemei Ge、Runtao Li、Baoxue Yang

  DOI：10.1016/j.ejmech.2019.03.060

  日期：2019.6

  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

  尿素转运蛋白（UTs）在尿液浓缩机制中起着重要作用，被公认为是开发具有保盐利尿活性的小分子抑制剂的新型靶标。硫喹啉衍生物是我们小组确定的一类新型UT-B抑制剂，在动物模型中起着重要的利尿作用。然而，差的溶解度和低的生物利用度限制了它的进一步发展。为了克服这些缺点，本研究对噻吩并喹啉进行了结构修饰，从而发现了新型噻吩并吡啶衍生物作为特定的尿素转运蛋白抑制剂。进一步的优化获得了有希望的临床前候选药物8n 对大鼠模型的尿素转运蛋白和利尿活性均具有优异的抑制作用，还具有一定的水溶性和Log P值。
• 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
  作者：K. G. Nikishin、V. P. Kislyi、V. N. Nesterov、A. M. Shestopalov、Yu. T. Struchkov、V. V. Semenov

  DOI：10.1007/bf02495655

  日期：1998.3

  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.

  三氟乙酰丙酮与氰硫基乙酰胺的反应区域选择性地进行，形成 3-氰基-6-甲基-4-三氟甲基吡啶-2(1H)-硫酮，从中获得相应的 2-烷基硫代吡啶和 3-氨基噻吩并 [2,3-b] 吡啶。通过X射线衍射分析确定了3-氰基-2-乙硫基-6-甲基-4-三氟甲基吡啶的晶体和分子结构。
• Compounds
  申请人：Griffin Andrew

  公开号：US20080306107A1

  公开（公告）日：2008-12-11

  The present invention relates to new compounds of formula (I) wherein R 1 to R 9 , 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.

  本发明涉及公式（I）的新化合物，其中R1到R9、X、p和n如权利要求1中所定义，或其盐、溶剂合物或溶剂化盐，其制备方法以及用于制备中的新中间体，含有该化合物的制药组合物以及在治疗中使用该化合物的用途。

表征谱图