3,3′-(pentane-1,5-diylbis(oxy))dibenzonitrile | 61947-46-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3,3′-(pentane-1,5-diylbis(oxy))dibenzonitrile
• 英文别名: 1,5-bis(3-cyanophenoxy)pentane；3,3'-[Pentane-1,5-diylbis(oxy)]dibenzonitrile；3-[5-(3-cyanophenoxy)pentoxy]benzonitrile
• CAS: 61947-46-4
• 化学式: C₁₉H₁₈N₂O₂
• 分子量: 306.364
• InChiKey: QBWFEUIFTJMLQR-UHFFFAOYSA-N

物化性质

• 沸点：
  495.9±40.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  66
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,3′-(pentane-1,5-diylbis(oxy))dibenzonitrile 在 盐酸 、 乙醇 、 氨 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 48.0h， 以77%的产率得到1,5-bis(benzamidine-3-oxy)pentane dihydrochloride
  参考文献：
  名称：

  Structure−Activity Study of Pentamidine Analogues as Antiprotozoal Agents

  摘要：

  Diamidine 1 (pentamidine) and 65 analogues (2-66) have been tested for in vitro antiprotozoal activities against Trypanosoma brucei rhodesiense, Plasmodium. falciparum, and Leishmania donovani, and for cytotoxicity against mammalian cells. Dications 32, 64, and 66 exhibited antitrypanosomal potencies equal or greater than melarsoprol (IC50 = 4 nM). Nine congeners (2-4, 12, 27, 30, and 64-66) were more active against P. falciparum than artemisinin (IC50 = 6 nM). Eight compounds (12, 32, 33, 44, 59, 62, 64, and 66) exhibited equal or better antileishmanial activities than 1 (IC50 = 1.8 mu M). Several congeners were more active than I in vivo, curing at least 2/4 infected animals in the acute mouse model of trypanosomiasis. The diimidazoline 66 was the most promising compound in the series, showing excellent in vitro activities and high selectivities against T. b. rhodesiense, P. falciparum, and L. donovani combined with high antitrypanosomal efficacy in vivo.

  DOI：

  10.1021/jm801547t
• 作为产物：
  描述：

  1,5-二溴戊烷 、 3-氰基苯酚 在 sodium hydride 、 lithium hexamethyldisilazane 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.0h， 以63%的产率得到3,3′-(pentane-1,5-diylbis(oxy))dibenzonitrile
  参考文献：
  名称：

  使用双脒增强革兰氏阳性特异性抗生素对抗革兰氏阴性病原体的结构-活性研究

  摘要：

  喷他脒是一种 FDA 批准的抗寄生虫药，最近被鉴定为一种外膜破坏增效剂，可增强红霉素、利福平和新生霉素对革兰氏阴性菌的作用。同一项研究还描述了使用市售喷他脒类似物的初步构效关系。我们在这里报告了受喷他脒启发的更广泛的双脒组的设计、合成和评估。本研究既验证了先前观察到的喷他脒的协同活性，同时进一步评估了结构相似的双脒增强革兰氏阳性特异性抗生素对抗革兰氏阴性病原体的能力。在制备的双脒中，发现其中一些表现出比喷他脒更大的协同活性。鲍曼不动杆菌、肺炎克雷伯菌、铜绿假单胞菌和大肠杆菌，包括耐多粘菌素和碳青霉烯的菌株。

  DOI：

  10.1021/acsinfecdis.1c00466

文献信息

• [EN] COMPOUNDS WHICH INHIBIT TRYPTASE ACTIVITY<br/>[FR] COMPOSES INHIBANT L'ACTIVITE DE LA TRYPTASE
  申请人：ARRAY BIOPHARMA, INC.

  公开号：WO1999024395A1

  公开（公告）日：1999-05-20

  (EN) The present invention is directed to compounds which are capable of inhibiting the activity of tryptase. Such compounds are useful in the treatment or prevention of inflammatory disease, particularly those disease states which are mediated by mast cell activation. Also encompassed by the invention are formulations comprising the noted compound, processes for preparing such compounds and methods for treating or preventing an inflammatory disease.(FR) La présente invention concerne des composés capables d'inhiber l'activité de la tryptase. Ces composés sont utiles dans le traitement ou la prévention de maladies inflammatoires, notamment des états pathologiques induits par l'activation des mastocytes. L'invention concerne également des formulations comprenant les composés précités, des processus permettant de les préparer et des procédés de traitement et de prévention d'une maladie inflammatoire.

  (EN) 本发明涉及能够抑制组胺酸酶活性的化合物。这些化合物在治疗或预防炎症性疾病方面是有用的，特别是那些通过肥大细胞激活介导的疾病状态。本发明还包括含有上述化合物的配方、制备这些化合物的过程以及治疗或预防炎症性疾病的方法。 (FR) 本发明涉及能够抑制组胺酸酶活性的化合物。这些化合物在治疗或预防炎症性疾病方面是有用的，特别是那些通过肥大细胞激活介导的疾病状态。本发明还包括含有上述化合物的配方、制备这些化合物的过程以及治疗或预防炎症性疾病的方法。
• 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.
• TIDWELL, RICHARD R.;JONES, SUSAN KILGORE;GERATZ, J. DIETER;OHEMENG, KWASI+, J. MED. CHEM., 33,(1990) N, C. 1252-1257
  作者：TIDWELL, RICHARD R.、JONES, SUSAN KILGORE、GERATZ, J. DIETER、OHEMENG, KWASI+

  DOI：——

  日期：——
• US6221914B1
  申请人：——

  公开号：US6221914B1

  公开（公告）日：2001-04-24
• Structure–Activity Studies with Bis-Amidines That Potentiate Gram-Positive Specific Antibiotics against Gram-Negative Pathogens
  作者：Charlotte M. J. Wesseling、Cornelis J. Slingerland、Shanice Veraar、Samantha Lok、Nathaniel I. Martin

  DOI：10.1021/acsinfecdis.1c00466

  日期：2021.12.10

  observed synergistic activity reported for pentamidine, while further assessing the capacity for structurally similar bis-amidines to also potentiate Gram-positive specific antibiotics against Gram-negative pathogens. Among the bis-amidines prepared, a number of them were found to exhibit synergistic activity greater than pentamidine. These synergists were shown to effectively potentiate the activity of

  喷他脒是一种 FDA 批准的抗寄生虫药，最近被鉴定为一种外膜破坏增效剂，可增强红霉素、利福平和新生霉素对革兰氏阴性菌的作用。同一项研究还描述了使用市售喷他脒类似物的初步构效关系。我们在这里报告了受喷他脒启发的更广泛的双脒组的设计、合成和评估。本研究既验证了先前观察到的喷他脒的协同活性，同时进一步评估了结构相似的双脒增强革兰氏阳性特异性抗生素对抗革兰氏阴性病原体的能力。在制备的双脒中，发现其中一些表现出比喷他脒更大的协同活性。鲍曼不动杆菌、肺炎克雷伯菌、铜绿假单胞菌和大肠杆菌，包括耐多粘菌素和碳青霉烯的菌株。