selepressin | 876296-47-8

• 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: selepressin
• 英文别名: [Phe²,Hgn⁴,Orn(i-Pr)⁸]VT；[Phe2.Ile3,Hgn4,Orn(iPr)8]VP；FE 202158；(2S)-1-[(4R,7S,10S,13S,16S,19R)-19-amino-10-(4-amino-4-oxobutyl)-7-(2-amino-2-oxoethyl)-16-benzyl-13-[(2S)-butan-2-yl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-1-oxo-5-(propan-2-ylamino)pentan-2-yl]pyrrolidine-2-carboxamide
• CAS: 876296-47-8
• 化学式: C₄₆H₇₃N₁₃O₁₁S₂
• 分子量: 1048.3
• InChiKey: JCVQBJTWWDYUFQ-MRUTUVJXSA-N

物化性质

• 沸点：
  1512.1±65.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  72
• 可旋转键数：
  21
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  442
• 氢给体数：
  12
• 氢受体数：
  15

制备方法与用途

加压素（FE 202158）是一种选择性的加压素V1A受体激动剂。作为一种强大的血管加压素，加压素常用于研究脓毒性休克。

反应信息

• 作为产物：
  描述：

  在 碘 、 三氟乙酸 作用下， 以 甲醇 、 水 为溶剂， 以168 mg的产率得到selepressin
  参考文献：
  名称：

  USE OF PEPTIDIC VASOPRESSIN RECEPTOR AGONISTS

  摘要：

  公开号：

  EP1984012B1

文献信息

• FLOUROUS METABOLICALLY STABLE PEPTIDE ANALOGS
  申请人：Université de Strasbourg

  公开号：EP3257863A1

  公开（公告）日：2017-12-20

  The present invention relates to metabolically stable and non-immunogen analogs completely hydrosoluble at physiological pH, and their use for the prevention or treatment of diseases mediated by G-protein coupled receptor (GPCR), in particular (Central Nervous System) CNS and cardiovascular diseases or disorders.

  本发明涉及在生理 pH 值下完全水溶的代谢稳定的非免疫原类似物，以及它们在预防或治疗由 G 蛋白偶联受体（GPCR）介导的疾病，特别是（中枢神经系统）中枢神经系统和心血管疾病或紊乱方面的用途。
• 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.
• METABOLICALLY STABLE PEPTIDE ANALOGS
  申请人：UNIVERSITÉ DE STRASBOURG

  公开号：US20190328887A1

  公开（公告）日：2019-10-31

  The present invention relates to metabolically stable and non-immunogen analogs completely hydrosolubleat physiological pH, and their use for the prevention or treatment of diseases mediated by G-protein coupled receptor (GPCR), in particular (Central Nervous System) CNS and cardiovascular diseases or disorders, or their use in diagnostic methods.
• COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING SEPSIS
  申请人：FERRING B.V.

  公开号：US20220008499A1

  公开（公告）日：2022-01-13

  There are disclosed herein compositions comprising selepressin for use in treating sepsis in a patient. The composition comprising selepressin may be administered within six hours from when the patient requires vasopressor therapy. The patients may have a serum lactate concentration of less than about 2 mmol/L prior to treatment and/or a ratio of partial pressure arterial oxygen to fraction of inspired oxygen (PaO 2 /F i O 2 ) of greater than about 200 prior to treatment. Related methods also are disclosed.
• USE OF PEPTIDIC VASOPRESSIN RECEPTOR AGONISTS
  申请人：Ferring B.V.

  公开号：EP1984012B1

  公开（公告）日：2015-12-30