(1S,3S,2'S,4'R)-[3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-1-(4'-methyl-5-oxo-tetrahydro-furan-2'-yl)-pentyl]-carbamic acid tert-butyl ester | 956035-15-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1S,3S,2'S,4'R)-[3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-1-(4'-methyl-5-oxo-tetrahydro-furan-2'-yl)-pentyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(1S,3S)-3-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-4-methyl-1-[(2S,4R)-4-methyl-5-oxooxolan-2-yl]pentyl]carbamate
• CAS: 956035-15-7
• 化学式: C₂₈H₄₅NO₇
• 分子量: 507.668
• InChiKey: WAXNXUFIYJTGCQ-LTYHASHMSA-N

物化性质

• 熔点：
  86-88 °C(Solvent: Diethyl ether; Hexane)
• 沸点：
  635.3±50.0 °C(predicted)
• 密度：
  1.069±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  36
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  92.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,3S,2'S,4'R)-[3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-1-(4'-methyl-5-oxo-tetrahydro-furan-2'-yl)-pentyl]-carbamic acid tert-butyl ester 在 lithium hydroxide 作用下， 以 乙二醇二甲醚 为溶剂， 反应 1.0h， 生成 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid
  参考文献：
  名称：

  Novel 2,7-Dialkyl-Substituted 5(S)-Amino-4(S)-hydroxy-8-phenyl-octanecarboxamide Transition State Peptidomimetics Are Potent and Orally Active Inhibitors of Human Renin

  摘要：

  The action of renin is the rate-limiting step of the renin-angiotensin system (RAS), a key regulator of blood pressure. Effective renin inhibitors directly block the RAS entirely at source and, thus, may provide a vital weapon for hypertension therapy. Our efforts toward identifying novel small-molecule peptidomimetic renin inhibitors have resulted in the design of transition-state isosteres such as I bearing an all-carbon 8-phenyl-octanecarboxamide framework. Optimization of the extended P3 portion of I and extensive P2' modifications provided analogues with improved in vitro potencies in the presence of plasma. X-ray resolution of rhrenin/38a in the course of SAR work surprisingly unveiled the exploitation of a previously unexplored pocket (S3(SP)) important for strong binding affinities. Several inhibitors demonstrated oral efficacy in sodium-depleted marmosets. The most potent, 38a, induced dose-dependently a pronounced reduction in mean arterial blood pressure, paralleled by complete blockade of active plasma renin, up to 8 h post-dose. Oral bioavailability of 38a was 16% in marmosets.

  DOI：

  10.1021/jm070314y
• 作为产物：
  描述：

  (1S,2S,4R,2'S)-(4-butylcarbamoyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3'-methyl-butyl}-pentyl)-carbamic acid tert-butyl ester 在 对甲苯磺酸 作用下， 以 氯仿 为溶剂， 反应 18.0h， 以75%的产率得到(1S,3S,2'S,4'R)-[3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-1-(4'-methyl-5-oxo-tetrahydro-furan-2'-yl)-pentyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Novel 2,7-Dialkyl-Substituted 5(S)-Amino-4(S)-hydroxy-8-phenyl-octanecarboxamide Transition State Peptidomimetics Are Potent and Orally Active Inhibitors of Human Renin

  摘要：

  The action of renin is the rate-limiting step of the renin-angiotensin system (RAS), a key regulator of blood pressure. Effective renin inhibitors directly block the RAS entirely at source and, thus, may provide a vital weapon for hypertension therapy. Our efforts toward identifying novel small-molecule peptidomimetic renin inhibitors have resulted in the design of transition-state isosteres such as I bearing an all-carbon 8-phenyl-octanecarboxamide framework. Optimization of the extended P3 portion of I and extensive P2' modifications provided analogues with improved in vitro potencies in the presence of plasma. X-ray resolution of rhrenin/38a in the course of SAR work surprisingly unveiled the exploitation of a previously unexplored pocket (S3(SP)) important for strong binding affinities. Several inhibitors demonstrated oral efficacy in sodium-depleted marmosets. The most potent, 38a, induced dose-dependently a pronounced reduction in mean arterial blood pressure, paralleled by complete blockade of active plasma renin, up to 8 h post-dose. Oral bioavailability of 38a was 16% in marmosets.

  DOI：

  10.1021/jm070314y