1-(4-甲氧基苯基)吡唑-4-甲酸 | 138907-79-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-(4-甲氧基苯基)吡唑-4-甲酸
• 英文名称: 1-(4-methoxyphenyl)-1H-pyrazole-4-carboxylic acid
• 英文别名: 1-(4-Methoxyphenyl)-4-pyrazolecarboxylic acid；1-(4-methoxyphenyl)pyrazole-4-carboxylic acid
• CAS: 138907-79-6
• 化学式: C₁₁H₁₀N₂O₃
• mdl: MFCD09971832
• 分子量: 218.212
• InChiKey: YXDPASMCMVABFS-UHFFFAOYSA-N

物化性质

• 熔点：
  235-237 °C
• 沸点：
  411.9±25.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933199090
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  1-(4-甲氧基苯基)吡唑-4-甲酸 在 氯化亚砜 作用下， 反应 0.5h， 生成 1-(4-methoxyphenyl)pyrazole-4-carbonyl chloride
  参考文献：
  名称：

  Synthesis and leishmanicidal activities of 1-(4-X-phenyl)-N′-[(4-Y-phenyl)methylene]-1H-pyrazole-4-carbohydrazides

  摘要：

  1H-pyrazole-4-carbohydrazides were synthesized and their leishmanicidal in vitro activities and cytotoxic effects were investigated. The drugs prototypes of these new compounds (ketoconazole, benznidazole, allopurinol and pentamidine) were also tested. It was found that among all the 1H-pyrazole-4-carbohydrazides derivatives examined, the most active compounds were those with X = Br, Y = NO2 (27) and X = NO2, Y = Cl (15) derivatives which showed to be most effective on promastigotes forms of L. amazonensis than on L. chagasi and L. braziliensis species. When tested against murine peritoneal macrophages as mammalian host cell controls of toxicity, 1-(4-Br-phenyl)-N'-[(4-NO2-phenyl)methylene]-1H-pyrazole-4-carbohydrazides (27) (EC50 = 50 mu M 1(-1)) and 1-(4-NO2-phenyl)-N'-[(4-Cl-phenyl)methylene]-1H-pyrazole-4-carbohydrazides (15) EC50 = 80 mu M 1(-1))] was reasonably toxic. However, both compounds were less toxic than pentamidine and ketoconazole. These results provide new perspectives on the development of drugs with activities against Leishmania parasite. (c) 2005 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2005.10.007
• 作为产物：
  描述：

  ethyl 3-amino-1-(4-methoxyphenyl)-1H-pyrazole-4-carboxylate 在 sodium hydroxide 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 1-(4-甲氧基苯基)吡唑-4-甲酸
  参考文献：
  名称：

  Synthesis and structure–activity relationships of 1-Phenylpyrazoles as xanthine oxidase inhibitors

  摘要：

  A series of 1-phenylpyrazoles was evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds prepared, 1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid (Y-700) had the most potent enzyme inhibition and displayed longer-lasting hypouricemic action than did allopurinol in a rat model of hyperuricemia induced by the uricase inhibitor potassium oxonate. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00093-2

文献信息

• 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。
• Synthesis of Pyrazole-Carboxamides and Pyrazole-Carboxylic Acids Derivatives: Simple Methods to Access Powerful Building Blocks
  作者：Byanca Silva Ferreira、Rafaela Corrêa Silva、Bernardo Araújo Souto、Maurício Silva dos Santos

  DOI：10.2174/1570178617999200728215322

  日期：2021.5

  Hybrid systems containing pyrazole moiety show a wide spectrum of biological activities. To access novel hybrids with pyrazole ring, in this work we synthesized twenty pyrazole-carboxylic acids and twenty pyrazole-carboxamides, using simple synthetic methods, to be used as building blocks in the development of new structures.

  摘要：含有吡唑基团的混合系统展示了广泛的生物活性。为了获得含有吡唑环的新型混合物，本研究合成了二十种吡唑羧酸和二十种吡唑羧酰胺，采用简单的合成方法，作为开发新结构的基础。
• [EN] COMPOSITIONS AND METHODS FOR TREATING CANCER<br/>[FR] COMPOSITIONS ET PROCÉDÉS POUR LE TRAITEMENT DU CANCER
  申请人：UNIV CALIFORNIA

  公开号：WO2018112420A1

  公开（公告）日：2018-06-21

  Disclosed herein, inter alia, are compositions and methods for modulating Ras and treating cancer.

  本文披露了用于调节Ras和治疗癌症的组合物和方法。
• [EN] PYRAZOLE CARBOXAMIDE DERIVATIVES AS TAAR MODULATORS FOR USE IN THE TREATMENT OF SEVERAL DISORDERS, SUCH AS DEPRESSION, DIABETES AND PARKINSON'S DISEASE<br/>[FR] DÉRIVÉS DE PYRAZOLE-CARBOXAMIDE EN TANT QUE MODULATEURS DE TAAR POUR UTILISATION DANS LE TRAITEMENT DE PLUSIEURS TROUBLES, TELS QUE LA DÉPRESSION, LE DIABÈTE ET LA MALADIE DE PARKINSON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014041007A1

  公开（公告）日：2014-03-20

  The present invention relates to compounds of formula (I) wherein R1 is phenyl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkoxy, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, lower alkoxy substituted by halogen or lower alkoxy substituted by hydroxy; or is pyridine-2, 3 or 4-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, lower alkoxy, lower alkoxy substituted by halogen or lower alkoxy substituted by hydroxyl; or is pyrimidin-2, 4 or 5-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkyl substituted by hydroxy or lower alkyl substituted by halogen; or is pyrazin-2-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy or cyano; or is 2,2-difluorobenzo[d][l,3]dioxol-5-yl, or is thiazolyl, optionally substituted by lower alkyl substituted by halogen; R2 is hydrogen or lower alkyl; R3 is hydrogen, amino or lower alkyl; 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 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 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.

  本发明涉及以下式（I）的化合物，其中R1是苯基，可以被卤素、较低烷基、较低环烷基、较低烷氧基、氰基、被卤素取代的较低烷基、被羟基取代的较低烷基、被卤素取代的较低烷氧基或被羟基取代的较低烷氧基；或是吡啶-2、3或4-基，可以被卤素、较低烷基、较低环烷基、氰基、被卤素取代的较低烷基、被羟基取代的较低烷基、较低烷氧基、被卤素取代的较低烷氧基或被羟基取代的较低烷氧基取代；或是嘧啶-2、4或5-基，可以被卤素、较低烷基、较低环烷基、被羟基取代的较低烷基或被卤素取代的较低烷基取代；或是吡嗪-2-基，可以被卤素、较低烷基、较低环烷基、被卤素取代的较低烷基、被羟基取代的较低烷基或氰基取代；或是2,2-二氟苯并[d][1,3]二氧杂环-5-基，或是噻唑基，可以被被卤素取代的较低烷基取代；R2是氢或较低烷基；R3是氢、氨基或较低烷基；Z是键，-CH2-或-O-；或其药学上适用的酸盐。现已发现，式I的化合物对追踪胺相关受体（TAARs）有很好的亲和力，尤其是对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）、与压力相关的障碍、精神分裂症等精神障碍、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、物质滥用以及代谢障碍，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。
• Pyrazole-amides and -sulfonamides
  申请人：Atkinson N. Robert

  公开号：US20050049237A1

  公开（公告）日：2005-03-03

  Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-dependent sodium channels. More particularly, the invention provides pyrazole-amides and -sulfonamides, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrance of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a channel that includes a PN3 subunit.

  本发明提供了一种通过抑制电压依赖性钠通道中的钠离子流来治疗疾病的化合物、组合物和方法。更具体地，本发明提供了吡唑酰胺和磺酰胺，以及其组合物和方法，这些化合物、组合物和方法对于治疗中枢或外周神经系统疾病特别是疼痛和慢性疼痛非常有用，通过阻止与所述疾病的发作或复发有关的钠通道。本发明的化合物、组合物和方法特别适用于通过抑制包括PN3亚基的通道中的离子流来治疗神经病理性或炎性疼痛。