3-Ethyl-5-amino-pyrazol-4-carbonsaeureethylester | 1904-23-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-Ethyl-5-amino-pyrazol-4-carbonsaeureethylester
• 英文别名: 3-amino-5-ethyl-1(2)H-pyrazole-4-carboxylic acid ethyl ester；Ethyl 5-amino-3-ethyl-1H-pyrazole-4-carboxylate；ethyl 3-amino-5-ethyl-1H-pyrazole-4-carboxylate
• CAS: 1904-23-0
• 化学式: C₈H₁₃N₃O₂
• mdl: MFCD09953595
• 分子量: 183.21
• InChiKey: HQIVWLMIGLVBJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  3-Ethyl-5-amino-pyrazol-4-carbonsaeureethylester 在 palladium 10% on activated carbon 、 氢气 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 甲乙醚 、 水 为溶剂， 反应 4.0h， 生成 2-ethyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid
  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

文献信息

• Substituted pyrazolo (1,5-a)pyrimidines and their use as anxiolytic
  申请人：American Cyanamid Company

  公开号：US04281000A1

  公开（公告）日：1981-07-28

  This disclosure describes substituted pyrazolo[1,5-a]pyrimidines which possess anxiolytic activity.

  这份披露描述了具有抗焦虑活性的取代嘧啶并[1,5-a]嘧啶。
• Synthesis and Evaluation of Novel Pyrazolo(1,5-a)pyrimidine Derivatives as Nonpeptide Angiotensin II Receptor Antagonists.
  作者：Ryuichi KIYAMA、Kunio HAYASHI、Mariko HARA、Masafumi FUJIMOTO、Tomoji KAWABATA、Masaru KAWAKAMI、Shigeyuki NAKAJIMA、Toshio FUJISHITA

  DOI：10.1248/cpb.43.960

  日期：——

  boxyli c acid derivatives was prepared as angiotensin II (AII) receptor antagonists. When evaluated in an in vitro binding assay using COS cells transfected with a cDNA encoding a human AT1 angiotensin II receptor, the compounds in this series showed Ki values in the range of 0.4-4.0 nM. In anesthetized spontaneously hypertensive rats (SHRs), administration of the 6-propyl derivative 4d (1 mg/kg, i

  制备了一系列新的6-烷基-7-氧代-4，7-二氢吡唑并[1，5-α-嘧啶-3-羧基]酸衍生物作为血管紧张素II（AII）受体拮抗剂。当在体外结合测定中使用转染了编码人AT1血管紧张素II受体的cDNA的COS细胞进行评估时，该系列化合物的Ki值在0.4-4.0 nM范围内。在麻醉的自发性高血压大鼠（SHRs）中，使用6-丙基衍生物4d（1 mg / kg，iv）可使平均血压（MBP）与正常值相比最多降低了30 mmHg以上。
• Pyrazolo[1,5-a]pyrimidines and imidazo-[1,5-a]pyrimidines
  申请人：American Cyanamid Company

  公开号：US04178449A1

  公开（公告）日：1979-12-11

  This disclosure describes substituted pyrazolo[1,5-a]pyrimidines and imidazo[1,5-a]pyrimidines which possess anxiolytic activity.

  这份披露描述了具有抗焦虑活性的取代嘧啶并[1,5-a]吡唑嘧啶和咪唑[1,5-a]吡咯啉。
• Imidazo[1,5-a]pyrimidines
  申请人：American Cyanamid Company

  公开号：US04236005A1

  公开（公告）日：1980-11-25

  This disclosure describes substituted pyrazolo[1,5-a]pyrimidines and imidazo[1,5-a]pyrimidines which possess anxiolytic activity.

  本文披露了具有抗焦虑活性的取代嘧唑并[1,5-a]嘧啶和咪唑并[1,5-a]嘧啶。
• Substituted pyrazolo (1,5-a) pyrimidines, and their preparation
  申请人：AMERICAN CYANAMID COMPANY

  公开号：EP0025819A1

  公开（公告）日：1981-04-01

  Compoundsoftheformula: wherein R1 is hydrogen or alkyl having from 1 to 3 carbon atoms; R2 is selected from the group consisting of wherein R' is hydrogen or alkyl having from 1 to 3 carbon atoms; R3 is hydrogen, fluoro, chloro, bromo, cyano, cyanomethyl, carbamoyl or alkyl having from 1 to 3 carbon atoms; R4 is selected from the group consisting of hydrogen, fluoro, chloro, bromo, formyl, carboxyl, cyano, hydroxymethyl, N-hydroxyformimidoyl, alkyl having from 1 to 3 carbon atoms and moieties of the formulae: where R is alkyl having from 1 to 3 carbon atoms, and the pharmacologically acceptable acid-addition salts thereof, possess anxiolytic activity.

  其中 R1 为氢或具有 1 至 3 个碳原子的烷基；R2 选自以下组成的组：其中 R' 为氢或具有 1 至 3 个碳原子的烷基；R3 为氢、氟、氯、溴、氰基、氰基甲基、氨基甲酰基或具有 1 至 3 个碳原子的烷基；R4 选自以下组成的组：氢、氟、氯、溴、甲酰基、羧基、氰基、羟甲基、N-羟基甲酰亚胺基、具有 1 至 3 个碳原子的烷基和以下式子的分子：其中 R 为具有 1 至 3 个碳原子的烷基及其药理上可接受的酸加成盐，具有抗焦虑活性。