(2R,3R,4S)-4-Benzo[1,3]dioxol-5-yl-1-butylcarbamoylmethyl-2-(4-methoxy-phenyl)-pyrrolidine-3-carboxylic acid | 1140617-21-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,3R,4S)-4-Benzo[1,3]dioxol-5-yl-1-butylcarbamoylmethyl-2-(4-methoxy-phenyl)-pyrrolidine-3-carboxylic acid
• 英文别名: (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(butylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid
• CAS: 1140617-21-5
• 化学式: C₂₅H₃₀N₂O₆
• 分子量: 454.523
• InChiKey: LKUAPKYGZSSJEK-FOVJLYNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-bromo-N-butylacetamide 、 ethyl trans-trans-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate 在 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 生成 (2R,3R,4S)-4-Benzo[1,3]dioxol-5-yl-1-butylcarbamoylmethyl-2-(4-methoxy-phenyl)-pyrrolidine-3-carboxylic acid
  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] CRYSTALLINE FORM OF ATRASENTAN HYDROCHLORIDE<br/>[FR] FORME CRISTALLINE DE L'HYDROCHLORURE D'ATRASENTAN
  申请人：ABBOTT LAB

  公开号：WO2006034085A1

  公开（公告）日：2006-03-30

  Substantially amorphous atrasentan hydrochloride, compositions containing it and methods of treatment of diseases and inhibition of adverse physiological events using it are disclosed.

  本文揭示了含有实质上无定形氯化羟氯嗪的组合物，以及使用它治疗疾病和抑制不良生理事件的方法。
• [EN] CRYSTALLINE FORM 1 OF ATRASENTAN HXDROCHLORIDE<br/>[FR] FORME CRISTALLINE 1 DE L'HYDROCHLORURE D'ATRASENTAN
  申请人：ABBOTT LAB

  公开号：WO2006034094A1

  公开（公告）日：2006-03-30

  Atrasentan Hydrochloride Crystalline Form 1, compositions containing it and methods of treatment of diseases and inhibition of adverse physiological events using it are disclosed.

  Atrasentan盐酸盐结晶形式1，含有它的组合物以及使用它进行疾病治疗和抑制不良生理事件的方法被披露。
• [EN] CRYSTALLINE FORM 3 OF ATRASENTAN HYDROCHLORIDE<br/>[FR] FORME CRISTALLINE 3 DE L'HYDROCHLORURE D'ATRASENTAN
  申请人：ABBOTT LAB

  公开号：WO2006034234A1

  公开（公告）日：2006-03-30

  Atrasentan Hydrochloride Crystalline Form 3, compositions containing it and methods of treatment of diseases and inhibition of adverse physiological events using it are disclosed

  Atrasentan盐酸盐结晶型态3，含有它的组合物以及使用它治疗疾病和抑制不良生理事件的方法被披露。
• ATRASENTAN HYDROCHLORIDE CRYSTALLINE FORM 2
  申请人：Henry Rodger F.

  公开号：US20080132710A1

  公开（公告）日：2008-06-05

  Atrasentan Hydrochloride Crystalline Form 2, compositions containing it and methods of treatment of diseases and inhibition of adverse physiological events using it are disclosed.

  Atrasentan盐酸晶型2，含有该晶型的组合物以及使用它进行疾病治疗和抑制不良生理事件的方法被披露。
• Crystalline form of a drug
  申请人：Dziki Walter

  公开号：US20060063825A1

  公开（公告）日：2006-03-23

  Atrasentan Hydrochloride Crystalline Form 2, compositions containing it and methods of treatment of diseases and inhibition of adverse physiological events using it are disclosed.

  Atrasentan盐酸盐结晶形式2，含有它的组合物以及使用它治疗疾病和抑制不良生理事件的方法已经公开。