2-苯基-1,3-噻唑-4-甲酸 | 7113-10-2

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-苯基-1,3-噻唑-4-甲酸
• 中文别名: 2-苯基噻唑-4-羧酸；2-苯基-1,3-噻唑-4-羧酸
• 英文名称: 2-phenyl-1,3-thiazole-4-carboxylic acid
• 英文别名: 2-phenylthiazole-4-carboxylic acid
• CAS: 7113-10-2
• 化学式: C₁₀H₇NO₂S
• mdl: MFCD00141954
• 分子量: 205.237
• InChiKey: IBUSLNJQKLZPNR-UHFFFAOYSA-N

物化性质

• 熔点：
  175-177°C
• 沸点：
  420.5±37.0 °C(Predicted)
• 密度：
  1.368
• 溶解度：
  28.2 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 安全说明：
  S26,S36/37/39
• 海关编码：
  2934100090
• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温

SDS

Name:	2-Phenyl-1 3-thiazole-4-carboxylic acid 97% Material Safety Data Sheet
Synonym:
CAS:	7113-10-2

Section 1 - Chemical Product MSDS Name:2-Phenyl-1 3-thiazole-4-carboxylic acid 97% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
7113-10-2	2-Phenyl-1,3-thiazole-4-carboxylic aci	97%	unlisted

Hazard Symbols: XI
Risk Phrases: 36/37/38

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
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:
Treat symptomatically and supportively.

---

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:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 7113-10-2: 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: cream
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 173 - 177 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: C10H7NO2S
Molecular Weight: 205

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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:
Nitrogen oxides, carbon monoxide, oxides of sulfur, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 7113-10-2 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
2-Phenyl-1,3-thiazole-4-carboxylic acid - 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
No information available.
IMO
No information available.
RID/ADR
No information available.

---

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 37/39 Wear suitable gloves and eye/face
protection.
WGK (Water Danger/Protection)
CAS# 7113-10-2: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 7113-10-2 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 7113-10-2 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

制备方法与用途

用途

2-苯基-1,3-噻唑-4-甲酸作为一种噻唑-4-甲酸衍生物，广泛应用于医药化工领域。噻唑-4-甲酸是合成噻苯咪唑的关键中间体，而噻苯咪唑是最早研制的苯并咪唑类药物之一，于1968年由美国默沙东公司开发成功。噻苯咪唑的应用非常广泛，主要作为抗寄生虫药物、杀菌剂和保鲜剂被广泛应用。

制备

以苯甲醛为原料，与3-(二甲氨基)-2-异氰基丙烯酸甲酯在温和的反应条件下，通过一锅法反应合成了2-苯基-1,3-噻唑-4-甲酸。该方法操作简便、纯度高且无需催化剂即可将多种官能团组装到分子内。

合成过程：

1. 2-苯基-1,3-噻唑-4-甲酸甲酯的合成

   • 在反应瓶中依次加入苯甲醛、3-(二甲氨基)-2-异氰基丙烯酸甲酯和无水甲醇。
   • 搅拌下加入无水硫酸镁，置于冰水浴冷却至0℃，反应2小时后升温至30℃继续反应16小时。
   • 真空旋干溶剂得2-苯基-1,3-噻唑-4-甲酸甲酯。

2. 2-苯基-1,3-噻唑-4-甲酸的合成

   • 在反应瓶中依次加入2-苯基-1,3-噻唑-4-甲酸甲酯、氢氧化锂溶液和甲醇。
   • 搅拌下于30℃反应6小时后，真空旋除溶剂。
   • 用稀盐酸调至pH 3~5，用二氯甲烷(2×50 mL)萃取并浓缩，经硅胶柱层析[洗脱剂：V（二氯甲烷): V(甲醇)=15:1]纯化得2-苯基-1,3-噻唑-4-甲酸。

反应信息

• 作为反应物：
  描述：

  2-苯基-1,3-噻唑-4-甲酸 在 甲醇 、 sodium tetrahydroborate 、 草酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 二丁醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.78h， 生成 1-(2-phenylthiazol-4-yl)ethanol
  参考文献：
  名称：

  [EN] IMIDAZOTHIADIAZOLE AND IMIDAZOPYRAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION
  [FR] DÉRIVÉS D'IMIDAZOTHIADIAZOLE ET D'IMIDAZOPYRAZINE UTILISÉS COMME INHIBITEURS DU RÉCEPTEUR 4 ACTIVÉ PAR UNE PROTÉASE (PAR4) POUR LE TRAITEMENT DE L'AGRÉGATION PLAQUETTAIRE

  摘要：

  本发明提供了式I的噻唑化合物，其中W、Y、R0、R2、R4、R5、R6、R7、X1、X2、X3和X4如本文所定义，或其立体异构体、互变异构体、药学上可接受的盐、前药酯或溶剂化合物形式，其中所有变量均如本文所定义。这些化合物是血小板聚集抑制剂，因此可用作治疗或预防血栓栓塞性疾病的药物。

  公开号：

  WO2013163279A1
• 作为产物：
  描述：

  硫代苯甲酰胺 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 8.0h， 生成 2-苯基-1,3-噻唑-4-甲酸
  参考文献：
  名称：

  发现了2-苯基噻唑-4-羧酸，一种新型有效的黄嘌呤氧化酶抑制剂。

  摘要：

  黄嘌呤氧化酶（XO）在产生尿酸中起着重要作用，因此XO抑制剂被认为是高尿酸血症和痛风的有前途的疗法之一。我们先前已经报道了一系列带有吡唑骨架的XO抑制剂，以扩展当前XO抑制剂的化学空间。在这里，我们描述了进一步的结构优化，以通过用该领域未开发的5个杂环骨架取代非布索坦的噻唑环来探索最佳杂环。所有这些努力导致了化合物8的鉴定，该化合物是一种具有新型2-苯基噻唑-4-羧酸支架的有效XO抑制剂（IC50 = 48.6 nM）。此外，铅化合物8在草酸钾-次黄嘌呤诱导的高尿酸血症小鼠中表现出低尿酸作用。

  DOI：

  10.1016/j.bmcl.2019.01.005

文献信息

• Inhibitors of cathepsin S
  申请人：IRM LLC

  公开号：US20040198780A1

  公开（公告）日：2004-10-07

  The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme (e.g., cathespin K). The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.

  本发明提供了用于选择性抑制蛋白酶S的化合物、组合物和方法。在一个优选方面，当至少存在另一种蛋白酶同工酶（例如，蛋白酶K）时，选择性地抑制蛋白酶S。本发明还提供了通过选择性抑制蛋白酶S来治疗受试者疾病状态的方法。
• Inhibitors of histone deacetylase
  申请人：——

  公开号：US20020177594A1

  公开（公告）日：2002-11-28

  Compounds having the formula 1 or therapeutically acceptable salts thereof, are histone deacetylase (HDAC) inhibitors. Preparation of the compounds, compositions containing the compounds, and treatment of diseases using the compounds are disclosed.

  具有以下化学式的化合物或其治疗上可接受的盐是组蛋白去乙酰化酶（HDAC）抑制剂。本文揭示了该化合物的制备、含有该化合物的组合物以及使用该化合物治疗疾病的方法。
• [EN] SUBSTITUTED BENZAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE BENZAMIDE SUBSTITUÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011076678A1

  公开（公告）日：2011-06-30

  The invention relates to compounds of formula I wherein R is hydrogen or lower alkyl; R1 is -(CH2)n-(O)o-heterocycloalkyl or -C(O)-heterocycloalkyl, wherein the heterocycloalkyl group is optionally substituted by lower alkyl, hydroxy, halogen or by -(CH2)p-aryl; n is 0, 1 or 2; o is 0 or 1; p is 0, 1 or 2; R2 is CF3, cycloalkyl, optionally substituted by lower alkoxy or halogen, or is indan-2-yl, or is heterocycloalkyl, optionally substituted by heteroaryl, or is aryl or heteroaryl, wherein the aromatic rings are optionally substituted by one or two substituents, selected from lower alkyl, halogen, heteroaryl, hydroxy, CF3, OCF3, OCH2CF3, OCH2-cycloalkyl, OCH2C(CH2OH)(CH2C1)(CH3), S-lower alkyl, lower alkoxy, CH2-lower alkoxy, lower alkinyl or cyano, or by-C(O)-phenyl, -O-phenyl, -O- CH2-phenyl, phenyl or -CH2-phenyl, and wherein the phenyl rings may optionally be substituted by halogen, -C(O)-lower alkyl, -C(O)OH or -C(O)O-lower alkyl, or the aromatic rings are optionally substituted by heterocycloalkyl, OCH2-oxetan-3-yl or O-tetrahydropyran-4-yl, optionally substituted by lower alkyl; X is a bond, -NR'-, -CH2NH-, -CHR''-, -(CHR'')q-O-, -O-(CHR'')q- or -(CH2)2-; Y is a bond or -CH2- R' is hydrogen or lower alkyl, R'' is hydrogen, lower alkyl, CF3, lower alkoxy, q is 0, 1, 2 or 3; or to a pharmaceutically suitable acid addition salt thereof. It has now been found that the compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinsons disease, neurodegenerative disorders such as Alzheimers disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  该发明涉及以下式I的化合物，其中R是氢或较低的烷基；R1是-(CH2)n-(O)o-杂环烷基或-C(O)-杂环烷基，其中杂环烷基基团可选择地被较低的烷基，羟基，卤素或-(CH2)p-芳基取代；n为0、1或2；o为0或1；p为0、1或2；R2为CF3，环烷基，可选择地被较低的烷氧基或卤素取代，或为茚-2-基，或为杂环烷基，可选择地被杂芳基取代，或为芳基或杂芳基，其中芳香环可选择地被来自较低的烷基，卤素，杂芳基，羟基，CF3，OCF3，OCH2CF3，OCH2-环烷基，OCH2C(CH2OH)(CH2C1)(CH3)，S-较低的烷基，较低的烷氧基，CH2-较低的烷氧基，较低的炔基或氰基，或-C(O)-苯基，-O-苯基，-O-CH2-苯基，苯基或-CH2-苯基选择的一个或两个取代基取代，其中苯环可选择地被卤素，-C(O)-较低的烷基，-C(O)OH或-C(O)O-较低的烷基取代，或芳香环可选择地被杂环烷基，OCH2-氧杂环戊烷-3-基或O-四氢吡喃-4-基，可选择地被较低的烷基取代；X为键，-NR'-，-CH2NH-，-CHR''-，-(CHR'')q-O-，-O-(CHR'')q-或-(CH2)2-；Y为键或-CH2-；R'为氢或较低的烷基，R''为氢，较低的烷基，CF3，较低的烷氧基，q为0、1、2或3；或其药学上适宜的酸盐。现已发现，该式I的化合物对痕量胺相关受体（TAARs）具有良好的亲和力，特别是对于TAAR1。这些化合物可用于治疗抑郁症，焦虑症，躁郁症，注意力缺陷多动障碍（ADHD），与压力有关的疾病，如精神分裂症，帕金森病等神经疾病，阿尔茨海默病等神经退行性疾病，癫痫，偏头痛，高血压，物质滥用和代谢性疾病，如进食障碍，糖尿病，糖尿病并发症，肥胖症，血脂异常，能量消耗和吸收异常，体温稳态异常，睡眠和昼夜节律异常，以及心血管疾病。
• Discovery of a Potent, Selective, and Orally Active Proteasome Inhibitor for the Treatment of Cancer
  作者：Bruce D. Dorsey、Mohamed Iqbal、Sankar Chatterjee、Ernesto Menta、Raffaella Bernardini、Alberto Bernareggi、Paolo G. Cassarà、Germano D’Arasmo、Edmondo Ferretti、Sergio De Munari、Ambrogio Oliva、Gabriella Pezzoni、Cecilia Allievi、Ivan Strepponi、Bruce Ruggeri、Mark A. Ator、Michael Williams、John P. Mallamo

  DOI：10.1021/jm7010589

  日期：2008.2.1

  malignant cells. The successful development of the 20S human proteasome inhibitor bortezomib for the treatment of relapsed and refractory multiple myeloma has established this targeted intervention as an effective therapeutic strategy. Herein, the potent, selective, and orally bioavailable threonine-derived 20S human proteasome inhibitor that has been advanced to preclinical development, [(1R)-1-[[(2 S,3

  泛素-蛋白酶体途径在调节细胞蛋白的产生和破坏中起关键作用。这些途径介导增殖和细胞存活，特别是在恶性细胞中。用于治疗复发性和难治性多发性骨髓瘤的20S人类蛋白酶体抑制剂硼替佐米的成功开发已将这种靶向干预确立为有效的治疗策略。在本文中，有效，选择性和口服生物利用的苏氨酸来源的20S人蛋白酶体抑制剂已被推进到临床前开发，[（1R）-1-[[（2 S，3 R）-3-hydroxy-2-[[公开了6-苯基吡啶-2-羰基氨基] -1-氧丁基]氨基] -3-甲基丁基]硼酸20（CEP-18770）。
• Decarbonylative Methylation of Aromatic Esters by a Nickel Catalyst
  作者：Toshimasa Okita、Kei Muto、Junichiro Yamaguchi

  DOI：10.1021/acs.orglett.8b01233

  日期：2018.5.18

  A Ni-catalyzed decarbonylative methylation of aromatic esters was achieved using methylaluminums as methylating agents. Dimethylaluminum chlorides uniquely worked as the methyl source. Because of the Lewis acidity of aluminum reagents, less reactive alkyl esters could also undergo the present methylation. By controlling the Lewis acidity of aluminum reagents, a chemoselective decarbonylative cross-coupling

  使用甲基铝作为甲基化剂，可以实现镍催化的芳香族酯的脱羰甲基化。氯化二甲基铝独特地用作甲基源。由于铝试剂的路易斯酸度，反应性较低的烷基酯也可能会发生本甲基化。通过控制铝试剂的路易斯酸度，烷基酯和苯基酯之间的化学选择性脱羰交联是成功的。