2-己酮,1-氯-3-丙基- | 178609-26-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-己酮,1-氯-3-丙基-
• 英文名称: 1-chloro-3-propyl-2-hexanone
• 英文别名: chloro-3-propyl-2-hexanone；1-chloro-3-propylhexan-2-one
• CAS: 178609-26-2
• 化学式: C₉H₁₇ClO
• 分子量: 176.686
• InChiKey: NZMRJUYBKVFDFI-UHFFFAOYSA-N

物化性质

• 沸点：
  210.7±8.0 °C(Predicted)
• 密度：
  0.950±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  11
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-己酮,1-氯-3-丙基- 在 sodium hydroxide 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 21.0h， 生成
  参考文献：
  名称：

  2,4-Diarylpyrrolidine-3-carboxylic AcidsPotent ET_A Selective Endothelin Receptor Antagonists. 1. Discovery of A-127722

  摘要：

  We have discovered a novel class of endothelin (ET) receptor antagonists through pharmacophore analysis of the existing non-peptide ET antagonists. On the basis of this analysis, we determined that a pyrrolidine ring might replace the indan ring in SE 209670. The resultant compounds were readily prepared and amenable to extensive SAR studies. Thus a series of N-substituted trans,trans-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl) pyrrolidine-3-carboxylic acids (8) have been synthesized and evaluated for binding at ET(A) and ET(B) receptors. Compounds with N-acyl and simple N-alkyl substituents had weak activity. Compounds with N-alkyl substituents containing ethers, sulfoxides, or sulfones showed increased activity. Much improved activity resulted from compounds where the N-substituents were acetamides. Compound 17u (A-127722) with the N,N-dibutylacetamide substituent is the best of the series. It has an IC50 = 0.36 nM for inhibition of ET-1 radioligand binding at the ETA(A) receptor, with a 1000-fold selectivity for the ET(A) vs the ET(B) receptor. It is also a potent inhibitor (IC50 = 0.16 nM) of phosphoinositol hydrolysis stimulated by ET-1, and it antagonized the ET-l-induced contraction of the rabbit aorta with a pA(2) = 9.20. The compound has 70% oral bioavailability in rats.

  DOI：

  10.1021/jm9505369
• 作为产物：
  描述：

  丙戊酸 在 盐酸 、 草酰氯 作用下， 以 1,4-二氧六环 、 乙醚 为溶剂， 反应 18.0h， 生成 2-己酮,1-氯-3-丙基-
  参考文献：
  名称：

  2,4-Diarylpyrrolidine-3-carboxylic AcidsPotent ET_A Selective Endothelin Receptor Antagonists. 1. Discovery of A-127722

  摘要：

  We have discovered a novel class of endothelin (ET) receptor antagonists through pharmacophore analysis of the existing non-peptide ET antagonists. On the basis of this analysis, we determined that a pyrrolidine ring might replace the indan ring in SE 209670. The resultant compounds were readily prepared and amenable to extensive SAR studies. Thus a series of N-substituted trans,trans-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl) pyrrolidine-3-carboxylic acids (8) have been synthesized and evaluated for binding at ET(A) and ET(B) receptors. Compounds with N-acyl and simple N-alkyl substituents had weak activity. Compounds with N-alkyl substituents containing ethers, sulfoxides, or sulfones showed increased activity. Much improved activity resulted from compounds where the N-substituents were acetamides. Compound 17u (A-127722) with the N,N-dibutylacetamide substituent is the best of the series. It has an IC50 = 0.36 nM for inhibition of ET-1 radioligand binding at the ETA(A) receptor, with a 1000-fold selectivity for the ET(A) vs the ET(B) receptor. It is also a potent inhibitor (IC50 = 0.16 nM) of phosphoinositol hydrolysis stimulated by ET-1, and it antagonized the ET-l-induced contraction of the rabbit aorta with a pA(2) = 9.20. The compound has 70% oral bioavailability in rats.

  DOI：

  10.1021/jm9505369

文献信息

• [EN] NOVEL BENZO-1,3-DIOXOLYL- AND BENZOFURANYL SUBSTITUTED PYRROLIDINE DERIVATIVES AS ENDOTHELIN ANTAGONISTS<br/>[FR] DERIVES DE PYRROLIDINE A SUBSTITUTION BENZO-1,3-DIOXOLYL ET BENZOFURANYL SERVANT D'ANTAGONISTES DE L'ENDOTHELINE
  申请人：ABBOTT LABORATORIES

  公开号：WO1997030045A1

  公开（公告）日：1997-08-21

  (EN) A compound of formula (I), or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.(FR) La présente invention concerne un composé représenté par la formule générale (I) ou l'un de ses sels galéniques. L'invention, qui concerne également des procédés convenant à leur préparation, concerne aussi des intermédiaires pour de telles préparations. L'invention concerne enfin un procédé de réalisation d'une fonction antagoniste de l'endothéline.

  该发明涉及一种化合物，其化学式为(I)，或其药学上可接受的盐，以及其制备的过程和中间体，以及一种拮抗内皮素的方法。(翻译后)
• [EN] ENDOTHELIN ANTAGONISTS<br/>[FR] ANTAGONISTES D'ENDOTHELINE
  申请人：ABBOTT LABORATORIES

  公开号：WO1996006095A1

  公开（公告）日：1996-02-29

  (EN) A compound of formula (I) or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.(FR) Composé de formule (I) ou sel pharmaceutiquement acceptable dudit composé, ainsi que procédés et intermédiaires destinés à la préparation dudit composé, et procédé permettant d'obtenir un effet antagoniste par rapport à l'endothéline.

  揭示了化合物式(I)或其药学上可接受的盐，以及其制备过程中的中间体和制备方法，并且揭示了拮抗内皮素的方法。
• Endothelin antagonists
  申请人：Abbott Laboratories

  公开号：US05622971A1

  公开（公告）日：1997-04-22

  A compound of the formula (I): ##STR1## or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

  公开了一种式(I)的化合物： ##STR1## 或其药学上可接受的盐，以及其制备过程和中间体，以及一种拮抗内皮素的方法。
• Treatment of diseases using endothelin antagonists
  申请人：Abbott Laboratories

  公开号：US06380241B1

  公开（公告）日：2002-04-30

  A compound of the formula (I): or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

  本发明揭示了化合物(I)的公式或其药学上可接受的盐，以及其制备过程中的中间体和方法，以及拮抗内皮素的方法。
• Processes for preparing endothelin antagonists
  申请人：Abbott Laboratories

  公开号：EP1186603A2

  公开（公告）日：2002-03-13

  Processes for preparing endothelin antagonists of formula (I) and pharmaceutically acceptable salts thereof and processes for preparing intermediates thereof.

  制备式(I)内皮素拮抗剂及其药学上可接受的盐的工艺，以及制备其中间体的工艺。