5-(4-氯苯基)-1H-吡唑-3-羧酸 | 54006-63-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-(4-氯苯基)-1H-吡唑-3-羧酸
• 中文别名: 5-(4-氯苯基)-1H-吡唑-3-甲酸
• 英文名称: 5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid
• 英文别名: 5-(4-chloro-phenyl)-1(2)H-pyrazole-3-carboxylic acid；5-(4-Chlorphenyl)-pyrazol-3-carboxylsaeure；3-(4-chlorophenyl)-1H-pyrazole-5-carboxylic acid
• CAS: 54006-63-2
• 化学式: C₁₀H₇ClN₂O₂
• 分子量: 222.631
• InChiKey: WYTQCLKZYRFUIQ-UHFFFAOYSA-N

物化性质

• 熔点：
  250-251 °C
• 沸点：
  515.7±40.0 °C(Predicted)
• 密度：
  1.476±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 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：
  66
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933199090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 5-(4-Chlorophenyl)-1h-pyrazole-3-carboxylic acid
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 5-(4-Chlorophenyl)-1h-pyrazole-3-carboxylic acid
CAS number: 54006-63-2

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C10H7ClN2O2
Molecular weight: 222.6

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  5-(4-氯苯基)-1H-吡唑-3-羧酸 在 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (3-(4-chlorophenyl)-1H-pyrazol-5-yl)(piperidin-1-yl)methanone
  参考文献：
  名称：

  Pyrazole derivatives as inhibitors of arachidonic acid-induced platelet aggregation

  摘要：

  Antiplatelet drugs are promising therapeutics to intervene with platelet aggregation in arterial thrombosis, most prominently in myocardial infarction and ischemic stroke. Here, we describe the synthesis and structure activity relationships of potent inhibitors of platelet aggregation based on the 1,5-diarylpyrazol-3-carboxamide scaffold. Analogs from this series demonstrated potent anti-aggregatmy activities against arachidonic acid-induced platelet aggregation, as measured by turbidimetric method of Born. 1,5-Diarylpyrazole-3-carboxamides obtained with small-basic amines (7, 8, 50, 51, 61, 62) displayed the strongest activity with IC50 values in low nanomolar range (5.7-83 nM). On the basis of their high potency in cellular environment, these straightforward pyrazole derivatives may possess potential in the design of more potent compounds for intervention with cardiovascular diseases. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.048
• 作为产物：
  描述：

  4-(4-chlorophenyl)-2,4-dioxobutyric acid ethyl ester sodium salt 在 sodium hydroxide 、 一水合肼 、 溶剂黄146 作用下， 以 1,4-二氧六环 为溶剂， 反应 28.0h， 生成 5-(4-氯苯基)-1H-吡唑-3-羧酸
  参考文献：
  名称：

  吡唑衍生物作为烟酸受体的部分激动剂。

  摘要：

  烟酸作为降血脂药显得独特，因为它比其他药物具有更大程度地增加HDL胆固醇水平的潜力。但是，它有一些副作用，其中严重的皮肤潮红是最常见的，并且经常限制患者的依从性。在寻找新的激动剂，用于最近鉴定和克隆的G蛋白偶联的烟酸受体中，我们合成了一系列取代的吡唑-3-羧酸，它们被证明对该受体具有显着的亲和力。通过抑制[（3）H]烟酸与大鼠脾膜的结合来测量亲和力。相对于烟酸的效能和内在活性是通过它们对[（35）S] GTPgammaS与大鼠脂肪细胞和脾膜结合的影响来确定的。有趣的是，大多数化合物是部分激动剂。特别是，证明2-重氮双环[3,3,0（4,8）]八-3,8-二烯-3-羧酸（4c）和5-丙基吡唑-3-羧酸（4f）具有K（i）值约0.15 microM的EC（50）值和约6 microM的EC（50）值，而与烟酸相比，它们的固有活性仅为约50％。活性稍强的是5-丁基吡唑-3-羧酸（4g），K（i）值为0

  DOI：

  10.1021/jm030888c
• 作为试剂：
  描述：

  (R)-tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate 、 5-(4-氯苯基)-1H-吡唑-3-羧酸 在 (S)-tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate 、 5-(4-氯苯基)-1H-吡唑-3-羧酸 、 3-苯基吡唑-5-羧酸水合物 作用下， 生成 (R)-3-(4-chlorophenyl)-N-(4-(morpholin-2-yl)phenyl)-1H-pyrazole-5-carboxamide hydrochloride
  参考文献：
  名称：

  PYRAZOLE DERIVATIVES

  摘要：

  本发明涉及式IA和式IB的化合物，其中R1、R2、R3、R4和Z如本文所定义，或其药学上适宜的酸加盐。式IA和式IB的化合物对微量胺相关受体（TAARs）具有良好的亲和力，特别是对TAAR1。这些化合物可用于治疗抑郁症、焦虑症、双相情感障碍、注意力缺陷多动障碍（ADHD）、应激相关障碍、精神疾病如精神分裂症、神经疾病如帕金森病、神经退行性疾病如阿尔茨海默病、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、脂质代谢异常、能量消耗和吸收障碍、体温稳态障碍和功能障碍、睡眠和昼夜节律障碍，以及心血管疾病。

  公开号：

  US20120316172A1

文献信息

• [EN] PYRAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRAZOLE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012168260A1

  公开（公告）日：2012-12-13

  The invention relates to compounds of formula wherein R1 is hydrogen or phenyl, optionally substitutes by halogen, CN or lower alkoxy or lower alkoxy substituted by halogen; R2 is hydrogen or lower alkyl; R3 is hydrogen or lower alkyl or is phenyl optionally substituted by one or more substituents, selected from halogen, cyano or lower alkoxy substituted by halogen, or is pyridinyl, optionally substituted by halogen or lower alkyl substituted by halogen, or is pyrimidinyl, optionally substituted by lower alkyl substituted by halogen, or is pyrazinyl, optionally substituted by halogen, cyano or lower alkyl substituted by halogen; R4 is hydrogen, lower alkyl or phenyl; Z is a bond, -CH2- or -O-; or to a pharmaceutically suitable acid addition salt thereof. It has now been found that the compounds of formulas IA and IB 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 Parkinson's disease, neurodegenerative disorders such as Alzheimer's 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.

  该发明涉及以下式中的化合物，其中R1是氢或苯基，可选择由卤素、CN或较低的烷氧基或由卤素取代的较低的烷氧基取代；R2是氢或较低的烷基；R3是氢或较低的烷基或是苯基，可选择由卤素、氰基或由卤素取代的较低的烷氧基取代，或是吡啶基，可选择由卤素或由卤素取代的较低的烷基取代，或是嘧啶基，可选择由较低的烷基取代的较低的烷基取代，或是吡嗪基，可选择由卤素、氰基或由卤素取代的较低的烷基取代；R4是氢、较低的烷基或苯基；Z是键，-CH2-或-O-；或其药学上适宜的酸盐。现已发现，IA和IB式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、如精神分裂症等精神疾病、帕金森病等神经系统疾病、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、能量消耗和吸收障碍、体温稳态障碍、睡眠和昼夜节律障碍以及心血管疾病。
• Fragment-Based Lead Generation of 5-Phenyl-1H-pyrazole-3-carboxamide Derivatives as Leads for Potent Factor Xia Inhibitors
  作者：Qunchao Wei、Zhichao Zheng、Shijun Zhang、Xuemin Zheng、Fancui Meng、Jing Yuan、Yongnan Xu、Changjiang Huang

  DOI：10.3390/molecules23082002

  日期：——

  FXIa is suggested as a major target for anticoagulant drug discovery because of reduced risk of bleeding. In this paper, we defined 5-phenyl-1H-pyrazole-3-carboxylic acid derivatives as privileged fragments for FXIa inhibitors’ lead discovery. After replacing the (E)-3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylamide moiety in compound 3 with 5-(3-chlorophenyl)-1H-pyrazole-3-carboxamide, we traveled from FXIa inhibitor3 to a scaffold that fused the privileged fragments into a pharmacophore for FXIa inhibitors. Subsequently, we synthesized and assessed the FXIa inhibitory potency of a series of 5-phenyl-1H-pyrazole-3-carboxamide derivatives with different P1, P1′ and P2′moiety. Finally, the SAR of them was systematically investigated to afford the lead compound 7za (FXIa Ki = 90.37 nM, 1.5× aPTT in rabbit plasma = 43.33μM) which exhibited good in vitro inhibitory potency against FXIa and excellent in vitro coagulation activities. Furthermore, the binding mode of 7za with FXIa was studied and the results suggest that the 2-methylcyclopropanecarboxamide group of 7za makes 2 direct hydrogen bonds with Tyr58B and Thr35 in the FXIa backbone, making 7za binds to FXIa in a highly efficient manner.

  FXIa被认为是抗凝药物发现的主要靶点，因为减少了出血风险。在这篇论文中，我们将5-苯基-1H-吡唑-3-羧酸衍生物定义为FXIa抑制剂的引物片段，用于引物发现。在将化合物3中的(E)-3-(5-氯-2-(1H-四唑-1-基)苯基)丙烯酰胺基团替换为5-(3-氯苯基)-1H-吡唑-3-羧酰胺后，我们从FXIa抑制剂3转变为将引物片段融合成FXIa抑制剂的药效团的支架。随后，我们合成并评估了一系列具有不同P1、P1'和P2'基团的5-苯基-1H-吡唑-3-羧酰胺衍生物的FXIa抑制活性。最后，对它们的结构活性关系进行了系统研究，得到了引物化合物7za（FXIa Ki = 90.37 nM，在兔血浆中1.5× aPTT = 43.33μM），该化合物表现出良好的体外抑制FXIa活性和优秀的体外凝血活性。此外，研究了7za与FXIa的结合方式，结果表明7za的2-甲基环丙烷甲酰胺基团与FXIa骨架中的Tyr58B和Thr35直接形成两个氢键，使7za以高效的方式结合到FXIa上。
• Design, Synthesis, Biological Evaluation and In Silico Studies of Pyrazole-Based NH2-Acyl Oseltamivir Analogues as Potent Neuraminidase Inhibitors
  作者：Jiqing Ye、Lin Lin、Jinyi Xu、Paul Kay-sheung Chan、Xiao Yang、Cong Ma

  DOI：10.3390/ph14040371

  日期：——

  Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150-cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C-5-NH2-acyl derivatives of OC

  奥司他韦是当前抗流感治疗中最成功的神经氨酸酶（NA）抑制剂之一。 NA 的 150 个空腔被确定为一个额外的结合袋，并且根据羧酸奥司他韦 ( OC ) 与 NA 复合物的结构信息，设计了新型 NA 抑制剂来占据 150 个空腔。本研究合成了一系列含有吡唑部分的OC的C-5-NH 2 -酰基衍生物。几种衍生物对 NA 表现出显着的抑制活性。此外，计算机ADME评估表明，该衍生物具有类似药物的特性，比OC具有更高的口服吸收率和更大的细胞渗透性。此外，分子对接研究表明，衍生物与 NA 酶活性位点和 150 腔相互作用，正如预期的那样。研究结果为OC的进一步结构优化提供了有用的信息。
• Nitrogen-containing heterocyclic compound and use thereof
  申请人：Ikeura Yoshinori

  公开号：US20090156572A1

  公开（公告）日：2009-06-18

  The present invention relates to a compound represented by the formula wherein ring A is a nitrogen-containing heterocycle optionally further having substituent(s), ring B is an aromatic ring optionally having substituent(s), ring C is a cyclic group optionally having substituent(s), R 1 is a hydrogen atom, a hydrocarbon group optionally having substituent(s), an acyl group, a heterocyclic group optionally having substituent(s) or an amino group optionally having substituent(s), R 2 is an optionally halogenated C 1-6 alkyl group, m and n are each an integer of 0 to 5, m+n is an integer of 2 to 5, and is a single bond or a double bond, or a salt thereof and the like. Since the compound has a superior tachykinin receptor antagonistic action, and is useful as an agent for the prophylaxis or treatment of various diseases such as lower urinary tract diseases, gastrointestinal diseases, central nervous system diseases and the like.

  本发明涉及一种由下式表示的化合物：其中环A是含氮杂环，可选择地进一步具有取代基，环B是芳香环，可选择地具有取代基，环C是环状基团，可选择地具有取代基，R1是氢原子，一个碳氢基团，可选择地具有取代基，酰基，一个杂环基团，可选择地具有取代基或一个氨基团，可选择地具有取代基，R2是可选择卤代的C1-6烷基基团，m和n分别是0到5的整数，m+n是2到5的整数，是单键或双键，或其盐等。由于该化合物具有优越的催吐肽受体拮抗作用，可用作预防或治疗多种疾病的药物，如下尿道疾病、胃肠道疾病、中枢神经系统疾病等。
• HETEROCYCLIC COMPOUND AND p27Kip1 DEGRADATION INHIBITOR
  申请人：Uchida Hiroshi

  公开号：US20130079306A1

  公开（公告）日：2013-03-28

  A novel heterocyclic compound or a salt thereof useful for selectively inhibiting the degradation of p27 Kip1 is provided. The compound or the salt thereof is represented by the following formula (1): wherein A represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic group, the group A may have a substituent; the ring B represents a 5- to 8-membered monocyclic heterocyclic ring or a condensed ring containing the monocyclic heterocyclic ring, the ring B may have a substituent; the ring C represents an aromatic ring, the ring C may have a substituent; L represents a linker comprising a main chain having 3 to 5 atoms selected from the group consisting of a carbon atom, a nitrogen atom, an oxygen atom and a sulfur atom, wherein at least one atom in the main chain is a hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, the linker L may have a substituent; and n is 0 or 1.

  提供了一种新型杂环化合物或其盐，用于选择性地抑制p27Kip1的降解。该化合物或其盐由以下式（1）表示：其中A代表烷基、环烷基、芳基或杂环基，基团A可能有取代基；环B代表5至8成员的单环杂环环或包含该单环杂环环的缩合环，环B可能有取代基；环C代表芳香环，环C可能有取代基；L代表包含3至5个原子的主链的连接物，所述原子选自碳原子、氮原子、氧原子和硫原子组成的群，其中主链中的至少一个原子是选自氮原子、氧原子和硫原子组成的杂原子，连接物L可能有取代基；n为0或1。