2-[4-Benzo[1,3]dioxol-5-yl-2-(4-methoxyphenyl)-5-oxo-3-(3,4,5-trimethoxy-benzyl)-2,5-dihydro-furan-2-yloxycarbonylamino]-4-methyl-pentanoic acid ethyl ester

• 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: 2-[4-Benzo[1,3]dioxol-5-yl-2-(4-methoxyphenyl)-5-oxo-3-(3,4,5-trimethoxy-benzyl)-2,5-dihydro-furan-2-yloxycarbonylamino]-4-methyl-pentanoic acid ethyl ester
• 英文别名: 2-[4-Benzo[1,3]dioxol-5-yl-2-(4-methoxy-phenyl)-5-oxo-3-(3,4,5-trimethoxy-benzyl)-2,5-dihydro-furan-2-yloxycarbonylamino]-4-methyl-pentanoic acid ethyl ester；ethyl 2-[[4-(1,3-benzodioxol-5-yl)-2-(4-methoxyphenyl)-5-oxo-3-[(3,4,5-trimethoxyphenyl)methyl]furan-2-yl]oxycarbonylamino]-4-methylpentanoate
• 化学式: C₃₇H₄₁NO₁₂
• 分子量: 691.732
• InChiKey: AGWINCPCXUTIHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  50
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  146
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  ethyl 2-isocyanato-4-methyl-valerate 、 3-(1,3-苯并二氧戊环-5-基)-5-羟基-5-(4-甲氧基苯基)-4-(3,4,5-三甲氧基苄基)-2(5H)-呋喃酮 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 2-[4-Benzo[1,3]dioxol-5-yl-2-(4-methoxyphenyl)-5-oxo-3-(3,4,5-trimethoxy-benzyl)-2,5-dihydro-furan-2-yloxycarbonylamino]-4-methyl-pentanoic acid ethyl ester
  参考文献：
  名称：

  γ-Carbamate butenolide analogues as potent ETA selective endothelin receptor antagonists and prodrugs

  摘要：

  Continued SAR around our ET(A) selective series of butenolide antagonists, for example PD156707 (1) has yielded a new series of subnanomolar ET(A) selective antagonists. Depending upon solution pH, 1 exists as the ring closed butenolide form (shown) or as the tautomeric open chain keto-acid salt. Reaction of the butenolide gamma-hydroxyl with isocyanates yields carbamates with essentially identical ET(A) binding affinity and with improved ET(A) selectivity. As carbamates these derivatives may undergo facile hydrolysis, reverting back to their parent butenolides, and therefore may be useful as prodrugs of 1. Stability studies of PD163140 (7) indicate that the compound is stable in the binding assay conditions and hence has intrinsic activity. In addition 7 is readily hydrolyzed by rat intestinal perfusate to yield the parent compound 1. (C) 1997, Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00002-4

文献信息

• US6017951A
  申请人：——

  公开号：US6017951A

  公开（公告）日：2000-01-25
• [EN] BUTENOLIDE ENDOTHELIN ANTAGONISTS<br/>[FR] ANTAGONISTES DE l'ENDOTHELINE BUTENOLIDIQUE
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1997002265A1

  公开（公告）日：1997-01-23

  (EN) Novel nonpeptide antagonists of endothelin I are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, acute and chronic renal failure, hypertension, myocardial infarction, myocardial ischemia, cerebral vasospasm, cerebral ischemia, cerebral infarction, cirrhosis, septic shock, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, atherosclerotic disorders including Raynaud's disease and restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, hemorrhagic shock, ischemic bowel disease, stroke, benign prostatic hyperplasia (BPH), and diabetes.(FR) La présente invention se rapporte à de nouveaux antagonistes non peptidiques de l'endothéline I, ainsi qu'à leurs procédés de préparation et à leurs compositions pharmaceutiques, qui sont utiles pour le traitement de taux élevés d'endothéline, d'insuffisances rénales aiguës ou chroniques, de l'hypertension, de l'infarctus du myocarde, de l'ischémie myocardique, des spasmes vasculaires cérébraux, de l'ischémie cérébrale, de l'infarctus cérébral, de la cirrhose, du choc septique, de l'insuffisance cardiaque globale, du choc endotoxique, de l'hémorragie sous-arachnoïdienne, de l'arythmie, de l'asthme, de la prééclampsie, des troubles athéroscléreux comprenant la maladie de Raynaud et la resténose, de l'angine, du cancer, de l'hypertension pulmonaire, de la maladie ischémique, des lésions de la muqueuse gastrique, du choc hémorragique, de l'infarctus mésentérique, de l'accident cérébrosvasculaire, de l'hyperplasie prostatique bénigne et du diabète.
• γ-Carbamate butenolide analogues as potent ETA selective endothelin receptor antagonists and prodrugs
  作者：William C. Patt、Billy R. Reisdorph、Joseph T. Repine、Annette M. Doherty、Stephen J. Haleen、Donnelle M. Walker、Kathleen M. Welch、Michael A. Flynn、Hussein Hallak、Eric L. Reyner、Barbra H. Stewart

  DOI：10.1016/s0960-894x(97)00002-4

  日期：1997.2

  Continued SAR around our ET(A) selective series of butenolide antagonists, for example PD156707 (1) has yielded a new series of subnanomolar ET(A) selective antagonists. Depending upon solution pH, 1 exists as the ring closed butenolide form (shown) or as the tautomeric open chain keto-acid salt. Reaction of the butenolide gamma-hydroxyl with isocyanates yields carbamates with essentially identical ET(A) binding affinity and with improved ET(A) selectivity. As carbamates these derivatives may undergo facile hydrolysis, reverting back to their parent butenolides, and therefore may be useful as prodrugs of 1. Stability studies of PD163140 (7) indicate that the compound is stable in the binding assay conditions and hence has intrinsic activity. In addition 7 is readily hydrolyzed by rat intestinal perfusate to yield the parent compound 1. (C) 1997, Elsevier Science Ltd.