10-Ethyl-1,5,6,14-tetrahydroxy-8,13-dioxo-5,6-dihydrobenzo[a]tetracene-2-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 并四苯
• 英文名称: 10-Ethyl-1,5,6,14-tetrahydroxy-8,13-dioxo-5,6-dihydrobenzo[a]tetracene-2-carboxylic acid
• 英文别名: 10-ethyl-1,5,6,14-tetrahydroxy-8,13-dioxo-5,6-dihydrobenzo[a]tetracene-2-carboxylic acid
• 化学式: C₆₈H₈₃N₁₂O₁₂PolS₂
• 分子量: 446.4
• InChiKey: AHUAWCUMCSDHQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  152
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  BOC-甘氨酸 、 BOC-L-脯氨酸 、 BOC-L-异亮氨酸 、 BOC-L-天冬酰胺 、 2-(3,4-dihydroxyphenyl)-3-[(2S,3R,4S,5R,6R)-4,5-dihydroxy-3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-6-[[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxy-5-hydroxy-6,7-dimethoxychromen-4-one 、 BOC-L-苯丙氨酸 、 Boc-S-(4-甲氧基苄基)-L-半胱氨酸 、 BOC-L-天门冬氨酸Β-9-芴甲氧羰酰甲酯 、 N-叔丁氧羰基-N'-苄氧羰基-L-2,4-二氨基丁酸二环己胺盐 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N'-二环己基碳二亚胺 、 间甲酚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 10-Ethyl-1,5,6,14-tetrahydroxy-8,13-dioxo-5,6-dihydrobenzo[a]tetracene-2-carboxylic acid
  参考文献：
  名称：

  New, Potent, Selective, and Short-Acting Peptidic V_1a Receptor Agonists

  摘要：

  [Arg(8)]vasopressin (AVP) produces vasoconstriction via V-1a receptor (V1aR)-mediated vascular smooth muscle cell contraction and is being used to increase blood pressure in septic shock, a form of vasodilatory hypotension. However, AVP also induces V-2 receptor (V2R)-mediated antidiuresis, vasodilation, and coagulation factor release, all deleterious in septic shock. The V1aR agonist terlipressin (H-Gly(3)[Lys(8)]VP) also lacks selectivity vs the V2R and has sizably longer duration of action than AVP, preventing rapid titration of its vasopressor effect in the clinic. We designed and synthesized new short acting V1aR selective analogues of general structure [Xaa(2),Ile(3),Yaa(4), Zaa(8)]VP. The most potent and selective compounds in in vitro functional assays (e.g., [Phe(2),Ile(3),Asn(Me-2)(4),Orn(8)]VP (31), [Phe(2), Ile(3),Asn((CH2)(3)OH)(4),Orn(8)]VP (34), [Phe(2),Ile(3),Hgn(4),Orn(iPr)(8)]VP (45), [Phe(2),Ile(3),Asn(Et)(4),Dab(8)]VP (49), [Thi(2),Ile(3),Orn(iPr)(8)]VP (59), [Cha(2),Ile(3),Asn(4),Orn(iPr)(8)]VP (68)) were tested by intravenous bolus in rats for duration of vasopressive action. Analogues 31, 34, 45, and 49 were as short-acting as AVP. Compound 45, FE 202158, is currently undergoing clinical trials in septic shock.

  DOI：

  10.1021/jm200278m

文献信息

• New, Potent, Selective, and Short-Acting Peptidic V_1a Receptor Agonists
  作者：Kazimierz Wiśniewski、Robert Galyean、Hiroe Tariga、Sudarkodi Alagarsamy、Glenn Croston、Joshua Heitzmann、Arash Kohan、Halina Wiśniewska、Régent Laporte、Pierre J-M. Rivière、Claudio D. Schteingart

  DOI：10.1021/jm200278m

  日期：2011.7.14

  [Arg(8)]vasopressin (AVP) produces vasoconstriction via V-1a receptor (V1aR)-mediated vascular smooth muscle cell contraction and is being used to increase blood pressure in septic shock, a form of vasodilatory hypotension. However, AVP also induces V-2 receptor (V2R)-mediated antidiuresis, vasodilation, and coagulation factor release, all deleterious in septic shock. The V1aR agonist terlipressin (H-Gly(3)[Lys(8)]VP) also lacks selectivity vs the V2R and has sizably longer duration of action than AVP, preventing rapid titration of its vasopressor effect in the clinic. We designed and synthesized new short acting V1aR selective analogues of general structure [Xaa(2),Ile(3),Yaa(4), Zaa(8)]VP. The most potent and selective compounds in in vitro functional assays (e.g., [Phe(2),Ile(3),Asn(Me-2)(4),Orn(8)]VP (31), [Phe(2), Ile(3),Asn((CH2)(3)OH)(4),Orn(8)]VP (34), [Phe(2),Ile(3),Hgn(4),Orn(iPr)(8)]VP (45), [Phe(2),Ile(3),Asn(Et)(4),Dab(8)]VP (49), [Thi(2),Ile(3),Orn(iPr)(8)]VP (59), [Cha(2),Ile(3),Asn(4),Orn(iPr)(8)]VP (68)) were tested by intravenous bolus in rats for duration of vasopressive action. Analogues 31, 34, 45, and 49 were as short-acting as AVP. Compound 45, FE 202158, is currently undergoing clinical trials in septic shock.