5-氨基-3-苯基-1H-吡唑-4-羧酸乙酯 | 1572-11-8

• 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-氨基-3-苯基-1H-吡唑-4-羧酸乙酯
• 英文名称: 5-amino-3-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester
• 英文别名: ethyl 5-amino-3-phenyl-1H-pyrazole-4-carboxylate；3-amino-4-ethoxycarbonyl-5-phenylpyrazole；ethyl 3-amino-5-phenyl-1H-pyrazole-4-carboxylate
• CAS: 1572-11-8
• 化学式: C₁₂H₁₃N₃O₂
• mdl: MFCD00980421
• 分子量: 231.254
• InChiKey: JRUYBHHBBGZBGS-UHFFFAOYSA-N

物化性质

• 熔点：
  167-169 °C
• 沸点：
  489.7±45.0 °C(Predicted)
• 密度：
  1.264±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  81
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-氨基-3-苯基-1H-吡唑-4-羧酸乙酯 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 oil 为溶剂， 生成 ethyl 7,7-dimethyl-2,5-diphenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylate
  参考文献：
  名称：

  Novel and potent calcium-sensing receptor antagonists: Discovery of (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate (TAK-075) as an orally active bone anabolic agent

  摘要：

  The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient PTH secretion in rats. However, compound 1 showed poor physical and chemical stability. In order to work out this compound's chemical stability and further understand its in vivo efficacy, we focused on modifying the 2-position of the tetrahydropyrazolopyrimidine. As a result of chemical modification, we discovered (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate 10m (TAK-075), which showed improved solubility, chemical stability, and in vivo efficacy. Furthermore, we describe that evaluating the active metabolite is important during repeated treatment with short-acting CaSR antagonists. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.001
• 作为产物：
  描述：

  苯甲酰基氰基乙酸乙酯 在 肼 作用下， 以 乙醇 为溶剂， 生成 5-氨基-3-苯基-1H-吡唑-4-羧酸乙酯
  参考文献：
  名称：

  [EN] COMPOUNDS THAT MODULATE INTRACELLULAR CALCIUM
  [FR] COMPOSITIONS QUI MODULANT LE CALCIUM INTRACELLULAIRE

  摘要：

  公开号：

  WO2009076454A3

文献信息

• [EN] PIPERIDINYLPYRAZOLOPYRIMIDINONES AND THEIR USE<br/>[FR] PIPÉRIDINYLPYRAZOLOPYRIMIDINONES ET LEUR UTILISATION
  申请人：BAYER PHARMA AG

  公开号：WO2016071216A1

  公开（公告）日：2016-05-12

  The present application relates to novel substituted piperidinylpyrazolopyrimidinones, to processes for their preparation, the compounds for use alone or in combinations in a method for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of acute and recurrent bleeding in patients with or without underlying hereditary or acquired hemostatic disorders, wherein the bleeding is associated with a disease or medical intervention selected from the group consisting of heavy menstrual bleeding, postpartum hemorrhage, hemorrhagic shock, hemorrhagic cystitis, gastrointestinal hemorrhage, trauma, surgery, transplantation, stroke, liver diseases, hereditary angioedema, nosebleed, and synovitis and cartilage damage following hemarthrosis.

  本申请涉及新型取代哌啶基吡唑吡嘧啶酮，以及它们的制备方法，这些化合物可单独或组合使用于治疗和/或预防疾病的方法中，特别是用于治疗和/或预防患有或不患有基础遗传或获得性止血障碍的患者的急性和复发性出血，其中出血与从重经期出血、产后出血、出血性休克、出血性膀胱炎、胃肠道出血、创伤、手术、移植、中风、肝脏疾病、遗传性血管性水肿、鼻血、以及血液积聚后的滑膜炎和软骨损伤等一组疾病或医疗干预有关。
• [EN] SATURATED BICYCLIC HETEROCYCLIC DERIVATIVES AS SMO ANTAGONISTS<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES BICYCLIQUES SATURÉS EN TANT QU'ANTAGONISTES DE SMO
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2010023480A1

  公开（公告）日：2010-03-04

  The present invention relates to compounds of formula I: and pharmaceutically acceptable salts or tautomers thereof which are inhibitors of the Sonic Hedgehog pathway, in particular Smoantagonists. Thus the compounds of this invention are useful for the treatment of diseases associated with abnormal hedgehog pathway activation, including cancer, for example basal cell carcinoma, medulloblastoma, prostate, pancreatic, breast, colon, bone and small cell lung cancers, and cancers of the upper GI tract.

  本发明涉及公式I的化合物及其药用可接受的盐或互变异构体，这些化合物是Sonic Hedgehog通路的抑制剂，特别是Smo拮抗剂。因此，本发明的化合物可用于治疗与异常刺刺通路激活相关的疾病，包括癌症，例如基底细胞癌、髓母细胞瘤、前列腺、胰腺、乳腺、结肠、骨骼和小细胞肺癌，以及上消化道癌症。
• Synthesis and Antimicrobial Evaluations of Novel Spiro Cyclic 2-Oxindole Derivatives of N-(1H-Pyrazol-5-Yl)-Hexahydroquinoline Derivatives
  作者：Amr Mohamed Abdelmoniem、Ismail Abdelshafy Abdelhamid、Said Ahmed Soliman Ghozlan、Muhammed Ali Ramadan

  DOI：10.3987/com-16-13451

  日期：——

  A novel series of interesting spiro cyclic 2-oxindole derivatives of N-(1H-pyrazol-5-yl)hexahydroquinoline derivatives were prepared via the versatile readily accessible cyclic β-enaminones incorporating pyrazole. Antimicrobial evaluations were performed on the prepared compounds. Most of these compounds exhibited high to moderate antimicrobial activity.

  N-(1H-pyrazol-5-yl)hexahydroquinoline 衍生物的一系列有趣的螺环 2-oxindole 衍生物是通过含有吡唑的多功能、易于获得的环状 β-烯胺酮制备的。对制备的化合物进行抗菌评估。大多数这些化合物表现出高到中等的抗微生物活性。
• Heteroarenobenzodiazepines. Part 7. Synthesis and pharmacological evaluation of a series of 4-piperazinylpyrazolo[3,4-b] and [4,3-b][1,5]benzodiazepines as potential anxiolytics
  作者：Jiban K. Chakrabarti、Terrence M. Hotten、Ian A. Pullar、Nicholas C. Tye

  DOI：10.1021/jm00132a012

  日期：1989.12

  The synthesis and pharmacological evaluation of a series of pyrazolo[b][1,5]benzodiazepines are described. Some of the 4-piperazinyl-2,10-dihydropyrazolo[3,4-b][1,5]benzodiazepine derivatives demonstrated potent anxiolytic activity in the three-part operant anticonflict test in rats. Compounds 21 and 30 were more active than the clinically effective anxiolytic chlordiazepoxide in releasing conflict-suppressed

  描述了一系列吡唑并[b] [1,5]苯并二氮杂s的合成和药理学评价。在大鼠的三部分操作性抗冲突试验中，一些4-哌嗪基-2,10-二氢吡唑并[3,4-b] [1,5]苯并二氮杂卓衍生物具有较强的抗焦虑活性。化合物21和30在释放冲突抑制行为方面比临床上有效的抗焦虑药氯氮卓更具活性。这项研究表明，分别在噻吩和二苯并二氮杂卓衍生物氟美沙平和氯氮平中发现的抗焦虑和抗多巴胺能活性已解离。描述并评估了其他三个其他二氢吡唑并[b] [1,5]苯并二氮杂ring环系统的实例，发现它们的活性较低。
• New Synthesis of<i>N</i>-(1<i>H</i>-pyrazol-5-yl)-hexahydroquinoline-3-carbonitrile and octahydropyrazolo[4′,3′:5,6]pyrimido[1,2-<i>a</i>]quinoline-6-carbonitrile Derivatives from the Cyclic<i>β</i>-Enaminones
  作者：Amr Mohamed Abdelmoniem、Muhammed Ali Ramadan、Said Ahmed Soliman Ghozlan、Ismail Abdelshafy Abdelhamid

  DOI：10.1002/jhet.2692

  日期：2017.3

  A facile and convenient synthesis of an interesting N‐(1H‐pyrazol‐5‐yl)‐hexahydroquinoline‐3‐carbonitrile and octahydropyrazolo[4′,3′:5,6]pyrimido[1,2‐a]quinoline‐6‐carbonitrile derivatives via the versatile readily accessible cyclic enaminones incorporating pyrazole moiety was accomplished.

  有趣的N-（1 H-吡唑-5-基）-六氢喹啉-3-腈和八氢吡唑并[4'，3'：5,6]嘧啶[1,2 - a ]喹啉-6的简便合成方法通过掺入吡唑部分的通用易得的环状烯胺酮，完成了腈衍生物。