3-(2-isopropyl-4-thiazolyl)propanoic acid | 1026694-44-9

• 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-(2-isopropyl-4-thiazolyl)propanoic acid
• 英文别名: 3-(2-Propan-2-yl-1,3-thiazol-4-yl)propanoic acid
• CAS: 1026694-44-9
• 化学式: C₉H₁₃NO₂S
• 分子量: 199.274
• InChiKey: PTXHQMYXHISAJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-isopropyl-4-thiazolyl)propanoic acid 、 [(1S,3S,4S)-4-((S)-2-Amino-3-methyl-butyrylamino)-1-benzyl-3-hydroxy-5-phenyl-pentyl]-carbamic acid pyridin-3-ylmethyl ester 在 N-ethyl-N’-(diethylaminopropyl)-carbodiimide 、 1-羟基苯并三唑一水物 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,3S,5S)-2-valinyl>amino>-5-carbonyl>amino>-1,6-diphenyl-3-hydroxyhexane
  参考文献：
  名称：

  Discovery of Ritonavir, a Potent Inhibitor of HIV Protease with High Oral Bioavailability and Clinical Efficacy

  摘要：

  The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption, Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 mu M) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.

  DOI：

  10.1021/jm970636+
• 作为产物：
  描述：

  2-异丙基噻唑-4-羧酸乙酯 在 甲醇 、 lithium hydroxide 、 sodium hydride 、 二异丁基氢化铝 、 magnesium 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 反应 1.41h， 生成 3-(2-isopropyl-4-thiazolyl)propanoic acid
  参考文献：
  名称：

  Discovery of Ritonavir, a Potent Inhibitor of HIV Protease with High Oral Bioavailability and Clinical Efficacy

  摘要：

  The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption, Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 mu M) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.

  DOI：

  10.1021/jm970636+

文献信息

• [EN] RETROVIRAL PROTEASE INHIBITING COMPOUNDS<br/>[FR] COMPOSES INHIBANT DES PROTEASES RETROVIRALES
  申请人：ABBOTT LABORATORIES

  公开号：WO1994014436A1

  公开（公告）日：1994-07-07

  (EN) A retroviral protease inhibiting compound of formula (A) is disclosed.(FR) L'invention se rapporte à un composé inhibant des protéases rétrovirales, qui est présenté par la formule (A).

  一种抑制反转录病毒蛋白酶的化合物公式（A）已被披露。(法语)本发明涉及一种通过公式（A）表示的抑制反转录病毒蛋白酶的化合物。
• [EN] RETROVIRAL PROTEASE INHIBITING COMPOUNDS<br/>[FR] COMPOSES INHIBITEURS DE PROTEASES RETROVIRALES
  申请人：ABBOTT LABORATORIES

  公开号：WO1999059994A1

  公开（公告）日：1999-11-25

  (EN) The present invention discloses novel compounds, compositions, and methods for inhibiting retroviral proteases and in particular for inhibiting human immunodeficiency virus (HIV) protease. The present invention also relates to compositions and methods for treating a retroviral infection and in particular a HIV infection, and to processes for making such compounds and synthetic intermediates employed in these processes.(FR) L'invention concerne des nouveaux composés, compositions, et procédés d'inhibition de protéases rétrovirales, et notamment d'inhibition de la protéase du virus du syndrome immunodéficitaire acquis (VIH). Elle concerne également des compositions et méthodes de traitement d'une infection rétrovirale, et notamment une infection au VIH, ainsi que des procédés de fabrication de tels composés, de même que des intermédiaires de synthèse employés dans ces procédés.

  本发明揭示了一种新型化合物、组合物和方法，用于抑制反转录病毒蛋白酶，特别是抑制人类免疫缺陷病毒（HIV）蛋白酶。本发明还涉及用于治疗反转录病毒感染，特别是HIV感染的组合物和方法，以及用于制备这些化合物和合成中间体的过程。
• Retroviral protease inhibiting compounds
  申请人：——

  公开号：US20010008892A1

  公开（公告）日：2001-07-19

  The present invention discloses novel compounds, compositions, and methods for inhibiting retroviral proteases and in particular for inhibiting human immunodeficiency virus (HIV) protease. The present invention also relates to compositions and methods for treating a retroviral infection and in particular an HIV infection, and to processes for making such compounds and synthetic intermediates employed in these processes.

  本发明揭示了新型化合物、组合物和方法，用于抑制逆转录病毒蛋白酶，特别是用于抑制人类免疫缺陷病毒（HIV）蛋白酶。本发明还涉及用于治疗逆转录病毒感染，特别是HIV感染的组合物和方法，以及用于制备这些化合物和合成中间体的过程。
• Processes and intermediates for manufacturing retroviral protease inhibiting compounds
  申请人：ABBOTT LABORATORIES

  公开号：EP1090914A2

  公开（公告）日：2001-04-11

  A retroviral protease inhibiting compound of formula (A) is disclosed for use in combination with other active pharmaceutical agents for treating a human infected by HIV. Intermediates and processes useful in the manufacture of compounds of formula (A) are also disclosed.

  本发明公开了一种抑制逆转录病毒蛋白酶的式(A)化合物，该化合物可与其他活性药剂联合使用，用于治疗受艾滋病毒感染的人。还公开了用于制造式（A）化合物的中间体和工艺。
• RETROVIRAL PROTEASE INHIBITING COMPOUNDS
  申请人：ABBOTT LABORATORIES

  公开号：EP0674513B1

  公开（公告）日：1996-09-25