sarilesin | 37827-06-8

• 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: sarilesin
• 英文别名: 1,Ile⁵,Ile⁸>-angiotensin II；1-Ile⁸>-angiotensin II；[sarcosine¹,Ile⁸]-angiotensin II；(Sar¹, Ile⁸)angiotensin II；[Sar¹,Ile⁸]-angiotensin II；[Sar¹,Ile⁸]angiotensin II；(2S,3S)-2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylpentanoic acid
• CAS: 37827-06-8
• 化学式: C₄₆H₇₃N₁₃O₁₀
• 分子量: 968.167
• InChiKey: ZVUNAQTWOGAJRE-VRZYMZKVSA-N

物化性质

• 密度：
  1.37±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  69
• 可旋转键数：
  28
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  358
• 氢给体数：
  12
• 氢受体数：
  13

制备方法与用途

生物活性

[Sar1, Ile8]-Angiotensin II 是一种多肽，在血管平滑肌细胞中具有多种作用，包括正常动脉的收缩、培养细胞或病变血管的肥大或增生等。

体外研究

血管紧张素Ⅱ (Angiotensin II) 在血管平滑肌细胞中有多种效应，如引起正常动脉收缩、促进培养细胞或病理性血管的肥大或增生。它能够激活 NADPH 和 NADH 氧化酶，并刺激超氧阴离子在血管平滑肌细胞中的形成。

反应信息

• 作为产物：
  描述：

  N-Boc-L-缬氨酸 、 叔丁氧羰酰基肌氨酸 、 N-Boc-L-精氨酸 、 Boc-L-酪氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 sarilesin
  参考文献：
  名称：

  Potent angiotensin II antagonists with non-.beta.-branched amino acids in position 5

  摘要：

  Amino acids with lipophilic side chains that contain more than one functional group on the beta-carbon, i.e. a beta-branched hydrocarbon moiety, are required in position 5 of angiotensin II (AII) analogue with potent agonist activity. This requirement for agonist activity does not follow for AII analogues with potent antagonist activity. Straight-chain amino acids may be substituted into position 5 of [Sar1,X5,Ile8]AII with retention or enhancement of antagonist activity, e.g. (X5,pA2 rabbit aorta) Phe, 9.15; Tyr, 9.6; His, 9.0; Glu,9.0; Nle, 8.85, compared to Ile, 9.1. beta-Branched side chains can still enhance the antagonist activities of [Sar1,X5,Ile8]AII analogues, e.g. X5 = (beta Me)Phe, pA2 = 9.3. An X-ray crystal structure of the Boc-(beta Me)Phe DCHA salt, prepared for the synthesis of [Sar1,-(beta Me)Phe5, Ile8]AII, revealed an S,S configuration of alpha- and beta-carbon atoms. Contrary to previous literature reports, chemical nonequivalence of the deta-protons of Pro was observed in the 1H NMR spectra of [Sar1,X5,Ile8]AII analogues bearing both beta-branched X5 side chains (X5 = Ile) and non-beta-branched X5 side chains (X5 = Ala, His).

  DOI：

  10.1021/jm00122a030

文献信息

• An investigation of angiotensin II agonist and antagonist analogs with 5,5-dimethylthiazolidine-4-carboxylic acid and other constrained amino acids
  作者：J. Samanen、T. Cash、D. Narindray、E. Brandeis、W. Adams、H. Weideman、T. Yellin、D. Regoli

  DOI：10.1021/jm00114a012

  日期：1991.10

  [Sar1]ANG II and [Sar1,Ile8]ANG II containing a C7 conformation in position 7 are preferred for both ANG II agonist and antagonist activity. Incorporation of the L,L-lactam-Phe modification into [Sar1]ANG II gives a pure ANG II antagonist (pA2 8.3), comparable to saralasin (pA2 8.6). In positions 3, 5, and 7 the conformational requirements for the ANG II agonist [Sar1]ANG II and the ANG II antagonist [Sar1

  为了探测血管紧张素II（ANG II）八肽激动剂和拮抗剂的受体结合构象要求，[Sar1] ANG II激动剂和[Sar1，X8] ANG II拮抗剂类似物的合成和生物学活性（X8 = Ile，D-Phe （或Aib）在位置3、5和7处受到构象约束的情况进行了研究，并与以前的文献进行了比较。检查的构象限制条件包括Pro，Dtc（5,5-二甲基噻唑烷-4-羧酸），Aib，Cle，（NMe）Ala，（NMe）Ile和内酰胺修饰，L，L-内酰胺-Phe，先前由Freidinger等人描述。（J.Org.Chem.1982，47，104-109）。[Sar1，（NMe）Ala3和Pro3] ANG II均保留激动剂活性，而仅[Sar1，（NMe）Ala3，Ile8] ANGII保留拮抗剂活性。[Sar1，Dtc5] ANG II显示出优异的激动剂活性，而[Sar1，Dtc5和Cle5，Ile8] ANG
• Structure-activity relationships for the competitive angiotensin antagonist [sarcosine1, O-methyltyrosine4]angiotensin II (sarmesin)
  作者：Mahesh H. Goghari、Kevin J. Franklin、Graham J. Moore

  DOI：10.1021/jm00156a035

  日期：1986.6

  Ile8]ANG II were weaker antagonists (pA2 = 6.6 and 6.7, respectively) than [Sar1,Ile8]ANG II (pA2 apparent = 8.1) and, moreover, were reversible competitive antagonists. These findings demonstrate that the structural requirements for receptor blockade by sarmesin are remarkably stringent--modifications at positions 1, 4, and 8 markedly reduce the antagonist activity of this peptide.

  竞争性血管紧张素拮抗剂[Sar1，Tyr（Me）4] ANG II（sarmesin）的类似物已通过固相法合成，其中肌氨酸-1，O-甲基酪氨酸-4和苯丙氨酸-8残基被修饰。在大鼠离体子宫试验中确定了所合成的23种肽的激动剂和拮抗剂的效力。在位置1，用Asp，Ala或Pro取代Sar会产生无活性的类似物，而对于所有研究的类似物，N末端氨基酸的缺失都会产生无活性的七肽。在位置4，用Tyr（Et），D-Tyr，D-Phe，Ile，Thr或Hyp取代Tyr导致无效的类似物，而用Phe取代则产生了强大的竞争性拮抗剂（pA2 = 7.9），该拮抗剂具有显着的竞争性。激动剂活性（22％）。对于位置8，[Sar1，Tyr（Me）4，Ile8] ANG II和[Sar1，Phe4，Ile8] ANG II是较[Sar1，Ile8] ANG II（pA2明显= 8.1）更弱的拮抗剂（分别为pA2 = 6.6和6
• Peptidester, Verfahren zur Herstellung derselben und diese enthaltende Arzneimittel beziehungsweise Diagnostica
  申请人：RICHTER GEDEON VEGYESZETI GYAR R.T.

  公开号：EP0034259B1

  公开（公告）日：1985-06-12