MM1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: MM1
• 英文别名: (5S)-(1H-imidazol-1-ylmethyl)-1-(phenylmethyl)-2-pyrrolidinone；(5S)-1-benzyl-5-(1H-imidazol-1-ylmethyl)-2-pyrrolidinone；(5S)-1-benzyl-5-(imidazol-1-ylmethyl)pyrrolidin-2-one
• 化学式: C₁₅H₁₇N₃O
• 分子量: 255.319
• InChiKey: GWEITBZPJXCDEE-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  38.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-benzyl-L-pyroglutamic acid 在 sodium tetrahydroborate 、 硫酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 22.5h， 生成 MM1
  参考文献：
  名称：

  An efficient and straight forward synthesis of (5S)-1-benzyl-5- (1H-imidazol-1-ylmethyl)-2-pyrrolidinone (MM1): a novel antihypertensive agent

  摘要：

  (5S)-1-苯甲基-5-(1H-咪唑-1-基甲基)-2-吡咯酮及其密切相关同类物通过Mitsunobu反应由(S)-吡咯谷氨醇和咪唑或其衍生物合成，其中以Mitsunobu反应为关键步骤。

  DOI：

  10.1007/s00044-010-9536-6

文献信息

• Synthesis, in silico docking experiments of new 2-pyrrolidinone derivatives and study of their anti-inflammatory activity
  作者：Panagiota Moutevelis-Minakakis、Eleni Papavassilopoulou、George Michas、Kalliopi Georgikopoulou、Maria-Eleni Ragoussi、Niki Neophytou、Panagiotis Zoumpoulakis、Thomas Mavromoustakos、Dimitra Hadjipavlou-Litina

  DOI：10.1016/j.bmc.2011.03.044

  日期：2011.5

  peroxidation inhibition. The molecular features that govern their bioactivity were explored through in silico docking experiments. The results showed that acidic moieties must be placed in certain distance and orientation in the active site of LOX enzyme in order to productively exhibit inhibitory activity. In addition, the 2-pyrrolidinone template significantly contributes in the inhibitory properties

  设计，合成并测试了新型的2-吡咯烷酮衍生物的抗氧化和抗炎活性。评价化合物对LOX的抑制活性。还测试了其中最有效的14d [IC 50 0.08（±0.005）mM]和14e [IC 50 0.0705（±0.003）mM]。化合物14d诱导了对大鼠爪水肿的等电位抑制，这与常用标准吲哚美辛（47％）产生的效果非常接近。化合物14e的LOX抑制活性脂质过氧化抑制百分比的值平行进行，这意味着该LOX抑制活性由脂质过氧化抑制支持。通过计算机对接实验探索了控制其生物活性的分子特征。结果表明，酸性部分必须在LOX酶的活性位点以一定的距离和方向放置，以便有效地发挥抑制活性。另外，2-吡咯烷酮模板对新化合物的抑制特性有显着贡献。
• Synthesis, binding studies and in vivo biological evaluation of novel non-peptide antihypertensive analogues
  作者：T. Mavromoustakos、P. Moutevelis-Minakakis、C.G. Kokotos、P. Kontogianni、A. Politi、P. Zoumpoulakis、J. Findlay、A. Cox、A. Balmforth、A. Zoga、E. Iliodromitis

  DOI：10.1016/j.bmc.2006.02.044

  日期：2006.7

  theoretical docking studies showed that MM1 acts on the same site of the receptor as losartan. They exert hydrophobic interactions with amino acid Val108 of the third helix of the AT(1) receptor and other hydrophobic amino acids in spatial vicinity. In addition, losartan favours multiple hydrogen bondings between its tetrazole group with Lys199. These additional interactions may in part explain its higher

  AT（1）拮抗剂（SARTAN）构成了用于治疗高血压的最新一代药物，其设计和合成为模仿血管收缩激素血管紧张素II（AngII）的C末端片段。他们通过阻止AngII与AT（1）受体的结合来发挥作用。迄今为止，已经批准了八种AT（1）拮抗剂用于调节高血压。尽管这些分子具有共同的结构特征，并被设计为以相同的机制起作用，但它们在药理特性和抗高血压功效方面存在差异。因此，仍然需要具有更好的药理和财务特性的新型类似物。MM1是一个新颖的合成非肽AT（1）拮抗剂，它没有SARTAN的经典模板。体内研究表明，MMK分子 属于同一类MM1的产品具有显着的降压活性（与氯沙坦相比为40-80％）。但是，体外亲和力研究表明，氯沙坦具有相当高的亲和力。理论上的对接研究表明，MM1与氯沙坦在受体的同一部位起作用。他们与AT（1）受体第三螺旋的氨基酸Val108和空间附近的其他疏水氨基酸发挥疏水作用。此外，氯沙坦利于其
• Design and synthesis of novel antihypertensive drugs
  作者：P Moutevelis-Minakakis、M Gianni、H Stougiannou、P Zoumpoulakis、A Zoga、A.D Vlahakos、E Iliodromitis、T Mavromoustakos

  DOI：10.1016/s0960-894x(03)00251-8

  日期：2003.5

  AT1 antagonists constitute a new generation of drugs for the treatment of hypertension and are designed and synthesized to mimic the C-terminal segment of Angiotensin II (Ang II) and to block its binding action on AT1 receptor. For this reason, the conformational analysis of Ang II and its derivatives as well as the AT1 antagonists belonging to SARTANs class of molecules were studied. Such studies offer the possibility to reveal the stereoelectronic factors responsible for bioactivity of AT1 antagonists and to design and synthesize new analogues with better pharmacological and financial profiles. An example of a novel synthetic non-peptide molecule is given which mimics the HiS(6)-Pro(7)-Phe(8) part of Ang II and is based on the (S)-pyroglutamic acid. (C) 2003 Elsevier Science Ltd. All rights reserved.
• An efficient and straight forward synthesis of (5S)-1-benzyl-5- (1H-imidazol-1-ylmethyl)-2-pyrrolidinone (MM1): a novel antihypertensive agent
  作者：Jagdish Prasad、Manoher Bhushan Pathak、Sharad Kumar Panday

  DOI：10.1007/s00044-010-9536-6

  日期：2012.3

  (5S)-1-benzyl-5-(1H-imidazol-1-ylmethyl)-2-pyrrolidinone and its closely related analog was synthesized from (S)-pyroglutaminol and imidazole or substituted imidazole using Mitsunobu reaction as the key step.

  (5S)-1-苯甲基-5-(1H-咪唑-1-基甲基)-2-吡咯酮及其密切相关同类物通过Mitsunobu反应由(S)-吡咯谷氨醇和咪唑或其衍生物合成，其中以Mitsunobu反应为关键步骤。