Imidazolinopentamidine | 80498-67-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: Imidazolinopentamidine
• 英文别名: 1,5-bis(4-(4,5-dihydro-1H-imidazol-2-yl)phenoxy)pentane；5MAA089；1,5-bis(4-imidazolinophenoxy)pentane；1H-Imidazole, 2,2'-(1,5-pentanediylbis(oxy-4,1-phenylene))bis(4,5-dihydro-；2-[4-[5-[4-(4,5-dihydro-1H-imidazol-2-yl)phenoxy]pentoxy]phenyl]-4,5-dihydro-1H-imidazole
• CAS: 80498-67-5
• 化学式: C₂₃H₂₈N₄O₂
• 分子量: 392.501
• InChiKey: OIXYPNVIRVOZFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,5-二(4-氰基苯氧基)戊烷 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 Imidazolinopentamidine
  参考文献：
  名称：

  Small Molecule Inhibitors of Ca²⁺-S100B Reveal Two Protein Conformations

  摘要：

  The drug pentamidine inhibits calcium-dependent complex formation with p53 ((Ca)S100Bp53) in malignant melanoma (MM) and restores p53 tumor suppressor activity in vivo. However, off-target effects associated with this drug were problematic in MM patients. Structure-activity relationship (SAR) studies were therefore completed here with 23 pentamidine analogues, and X-ray structures of (Ca)S100Binhibitor complexes revealed that the C-terminus of S100B adopts two different conformations, with location of Phe87 and Phe88 being the distinguishing feature and termed the FF-gate. For symmetric pentamidine analogues ((Ca)S100B5a, (Ca)S100B6b) a channel between sites 1 and 2 on S100B was occluded by residue Phe88, but for an asymmetric pentamidine analogue ((Ca)S100B17), this same channel was open. The (Ca)S100B17 structure illustrates, for the first time, a pentamidine analog capable of binding the open form of the FF-gate and provides a means to block all three hot spots on (Ca)S100B, which will impact next generation (Ca)S100Bp53 inhibitor design.

  DOI：

  10.1021/acs.jmedchem.5b01369

文献信息

• Amidine derivatives for treating amyloidosis
  申请人：Chalifour J. Robert

  公开号：US20070021483A1

  公开（公告）日：2007-01-25

  The present invention relates to the use of amidine compounds in the treatment of amyloid-related diseases. In particular, the invention relates to a method of treating or preventing an amyloid-related disease in a subject comprising administering to the subject a therapeutic amount of an amidine compound. Among the compounds for use according to the invention are those according to the following Formula, such that, when administered, amyloid fibril formation, neurodegeneration, or cellular toxicity is reduced or inhibited:

  本发明涉及在治疗与淀粉样相关疾病中使用氨基脲类化合物。特别地，本发明涉及一种治疗或预防受试者淀粉样相关疾病的方法，包括向受试者施用治疗剂量的氨基脲类化合物。根据本发明使用的化合物包括以下化学式的化合物，当施用时，可减少或抑制淀粉样纤维形成、神经退行性或细胞毒性：
• On the Reactivity of Hydroximoyl Chlorides.Preparation of 2-Arylimidazolines
  作者：Héctor Salgado-Zamora、Elena Campos、Rogelio Jiménez、Humberto Cervantes

  DOI：10.3987/com-97-s(n)109

  日期：——

  Elimination of the hydroxylamino portion in arylhydroximoyl chlorides upon nucleophilic addition of ethylenediamine rendered an alternative procedure for 2-arylimidazolines preparation.
• Analogs of 1,5-bis(4-amidinophenoxy)pentane (pentamidine) in the treatment of experimental Pneumocystis carinii pneumonia
  作者：Richard R. Tidwell、Susan Kilgore Jones、J. Dieter Geratz、Kwasi A. Ohemeng、Michael Cory、James Edwin Hall

  DOI：10.1021/jm00166a026

  日期：1990.4

  A series of 33 analogues of the anti-Pneumocystis carinii drug 1,5-bis(4-amidinophenoxy)pentane (pentamidine) was synthesized for screening against a rat model of P. carinii pneumonia (PCP). Twenty-five of the compounds showed efficacy against PCP when compared to a saline-treated control group. Two compounds, 1,4-bis(4-amidinophenoxy)butane (butamidine, 6) and 1,3-bis(4-amidino-2-methoxyphenoxy)propane (DAMP, 16), were statistically more effective than the parent drug in treating PCP in the rat model of infection. In addition to their activity against PCP, the compounds were also evaluated for antitrypsin activity, ability to inhibit thymidylate synthetase, affinity for DNA, and toxicity. No correlation was observed between the tested molecular interactions of the diamidines and their effectiveness against PCP.
• Small Molecule Inhibitors of Ca²⁺-S100B Reveal Two Protein Conformations
  作者：Michael C. Cavalier、Mohd. Imran Ansari、Adam D. Pierce、Paul T. Wilder、Laura E. McKnight、E. Prabhu Raman、David B. Neau、Padmavani Bezawada、Milad J. Alasady、Thomas H. Charpentier、Kristen M. Varney、Eric A. Toth、Alexander D. MacKerell、Andrew Coop、David J. Weber

  DOI：10.1021/acs.jmedchem.5b01369

  日期：2016.1.28

  The drug pentamidine inhibits calcium-dependent complex formation with p53 ((Ca)S100Bp53) in malignant melanoma (MM) and restores p53 tumor suppressor activity in vivo. However, off-target effects associated with this drug were problematic in MM patients. Structure-activity relationship (SAR) studies were therefore completed here with 23 pentamidine analogues, and X-ray structures of (Ca)S100Binhibitor complexes revealed that the C-terminus of S100B adopts two different conformations, with location of Phe87 and Phe88 being the distinguishing feature and termed the FF-gate. For symmetric pentamidine analogues ((Ca)S100B5a, (Ca)S100B6b) a channel between sites 1 and 2 on S100B was occluded by residue Phe88, but for an asymmetric pentamidine analogue ((Ca)S100B17), this same channel was open. The (Ca)S100B17 structure illustrates, for the first time, a pentamidine analog capable of binding the open form of the FF-gate and provides a means to block all three hot spots on (Ca)S100B, which will impact next generation (Ca)S100Bp53 inhibitor design.