5-(4-isopropylpiperazin-1-yl)-2-cyanobenzene | 186650-79-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-(4-isopropylpiperazin-1-yl)-2-cyanobenzene
• 英文别名: 4-(4-isopropyl-1-piperazinyl)benzonitrile；4-[4-(1-Methylethyl)-1-piperazinyl]benzonitrile；4-(4-propan-2-ylpiperazin-1-yl)benzonitrile
• CAS: 186650-79-3
• 化学式: C₁₄H₁₉N₃
• mdl: MFCD11038452
• 分子量: 229.325
• InChiKey: RGSLNGLNMXFZFE-UHFFFAOYSA-N

物化性质

• 沸点：
  375.9±37.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  30.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-isopropylpiperazin-1-yl)-2-cyanobenzene 在 二异丁基氢化铝 作用下， 以 正己烷 、 甲苯 为溶剂， 反应 1.5h， 以81%的产率得到4-(4-isopropylpiperazin-1-yl)benzaldehyde
  参考文献：
  名称：

  合成具有5,11-二氢-6H-吡啶并[2,3-b] [1,4]苯并二氮杂-6-骨架作为有效和选择性的M2毒蕈碱受体拮抗剂的新型琥珀酰胺衍生物。二。

  摘要：

  制备了一系列含有5,11-二氢-6H-吡啶并[2,3-b] [1,4]苯并二氮杂-6-6骨架（6a-z）的琥珀酰胺衍生物，并评估了其与毒蕈碱受体的结合亲和力。与AF-DX 116（1a）相比在体外以及对心动过缓和体内唾液的拮抗作用。体外结构-活性关系（SAR）研究表明，4-（4-烷基-1-哌嗪基）苄氨基部分在增强与M2毒蕈碱受体的亲和力中起关键作用。含有4-（4-异丙基-1-哌嗪基）苄基甲基氨基的化合物6y对M2毒蕈碱受体的亲和力最高（pKi = 9.2），效力是1a的200倍，而化合物6u含有4-（与M3毒蕈碱受体相比，4-乙基-1-哌嗪基）苄基乙基氨基部分显示出最高的M2选择性（M3 / M2比= 320）。静脉或口服给药后，6y和6u均能拮抗氧代雷斯莫林诱导的大鼠心动过缓。有意识的狗的口服评估表明，提高心率的功效至少是1a的3倍。

  DOI：

  10.1248/cpb.45.1458
• 作为产物：
  描述：

  1-异丙基哌嗪 、 对氟苯腈 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 生成 5-(4-isopropylpiperazin-1-yl)-2-cyanobenzene
  参考文献：
  名称：

  鉴定自PBTZ169衍生的N-苄基3,5-二硝基苯甲酰胺作为抗结核药

  摘要：

  通过PBTZ169的噻嗪酮开环设计并合成了一系列苯甲酰胺支架，最终鉴定出N-苄基3,5-二硝基苯甲酰胺是抗结核药物。3,5- Dinitrobenzamides D5，6，7，和12表现出优异的体外对抗药物易感活性的结核分枝杆菌H37Rv的菌株（MIC：0.0625微克/毫升）和两个临床分离多药耐药性菌株（MIC <0.016-0.125微克/毫升）。化合物D6与PBTZ169相比，显示出可接受的安全性和更好的药代动力学特征，表明其有望成为未来抗结核药物发现的先导化合物。

  DOI：

  10.1021/acsmedchemlett.8b00177

文献信息

• Lead Optimization of a Novel Series of Imidazo[1,2-<i>a</i>]pyridine Amides Leading to a Clinical Candidate (Q203) as a Multi- and Extensively-Drug-Resistant Anti-tuberculosis Agent
  作者：Sunhee Kang、Ryang Yeo Kim、Min Jung Seo、Saeyeon Lee、Young Mi Kim、Mooyoung Seo、Jeong Jea Seo、Yoonae Ko、Inhee Choi、Jichan Jang、Jiyoun Nam、Seijin Park、Hwankyu Kang、Hyung Jun Kim、Jungjun Kim、Sujin Ahn、Kevin Pethe、Kiyean Nam、Zaesung No、Jaeseung Kim

  DOI：10.1021/jm5003606

  日期：2014.6.26

  A critical unmet clinical need to combat the global tuberculosis epidemic is the development of potent agents capable of reducing the time of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis therapy. In this paper, we report on the optimization of imidazo[1,2-a]pyridine amide (IPA) lead compound 1, which led to the design and synthesis of Q203 (50). We found that the amide linker with IPA core is very important for activity against Mycobacterium tuberculosis H37Rv. Linearity and lipophilicity of the amine part in the IPA series play a critical role in improving in vitro and in vivo efficacy and pharmacokinetic profile. The optimized IPAs 49 and 50 showed not only excellent oral bioavailability (80.2% and 90.7%, respectively) with high exposure of the area under curve (AUC) but also displayed significant colony-forming unit (CFU) reduction (1.52 and 3.13 log10 reduction at 10 mg/kg dosing level, respectively) in mouse lung.
• COMPOUNDS AND METHODS FOR TARGETING PATHOGENIC BLOOD VESSELS
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20210147385A1

  公开（公告）日：2021-05-20

  The disclosure provides compounds, and compositions, including pharmaceutical compositions, kits that include the compounds, and methods of using (or administering) and making the compounds. The disclosure further provides compounds or compositions thereof for use in a method of modulating PLXDC1 (TEM7) and/or PLXDC2 or killing pathogenic blood vessles. The disclosure further provides compounds or compositions thereof for use in a method of treating a disease, disorder, or condition that is mediated, at least in part, by PEDF receptors or by angiogenesis.
• Synthesis of Novel Succinamide Derivatives Having a 5,11-Dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepin-6-one Skeleton as Potent and Selective M2 Muscarinic Receptor Antagonists. II
  作者：Toshihiro WATANABE、Akio KAKEFUDA、Isao KINOYAMA、Kenji TAKIZAWA、Seiko HIRANO、Hiroshi SHIBATA、Isao YANAGISAWA

  DOI：10.1248/cpb.45.1458

  日期：——

  A series of succinamide derivatives containing the 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton (6a-z) was prepared and evaluated for binding affinity to muscarinic receptors in vitro and for antagonism of bradycardia and salivation in vivo in comparison with AF-DX 116 (1a). Structure-activity relationships (SAR) studies in vitro indicated that the 4-(4-alkyl-1-piperazinyl)benzylamino

  制备了一系列含有5,11-二氢-6H-吡啶并[2,3-b] [1,4]苯并二氮杂-6-6骨架（6a-z）的琥珀酰胺衍生物，并评估了其与毒蕈碱受体的结合亲和力。与AF-DX 116（1a）相比在体外以及对心动过缓和体内唾液的拮抗作用。体外结构-活性关系（SAR）研究表明，4-（4-烷基-1-哌嗪基）苄氨基部分在增强与M2毒蕈碱受体的亲和力中起关键作用。含有4-（4-异丙基-1-哌嗪基）苄基甲基氨基的化合物6y对M2毒蕈碱受体的亲和力最高（pKi = 9.2），效力是1a的200倍，而化合物6u含有4-（与M3毒蕈碱受体相比，4-乙基-1-哌嗪基）苄基乙基氨基部分显示出最高的M2选择性（M3 / M2比= 320）。静脉或口服给药后，6y和6u均能拮抗氧代雷斯莫林诱导的大鼠心动过缓。有意识的狗的口服评估表明，提高心率的功效至少是1a的3倍。
• Identification of <i>N</i>-Benzyl 3,5-Dinitrobenzamides Derived from PBTZ169 as Antitubercular Agents
  作者：Linhu Li、Kai Lv、Yupeng Yang、Jingquan Sun、Zeyu Tao、Apeng Wang、Bin Wang、Hongjian Wang、Yunhe Geng、Mingliang Liu、Huiyuan Guo、Yu Lu

  DOI：10.1021/acsmedchemlett.8b00177

  日期：2018.7.12

  A series of benzamide scaffolds were designed and synthesized by the thiazinone ring opening of PBTZ169, and N-benzyl 3,5-dinitrobenzamides were finally identified as anti-TB agents in this work. 3,5-Dinitrobenzamides D5, 6, 7, and 12 exhibit excellent in vitro activity against the drug susceptive Mycobacterium tuberculosis H37Rv strain (MIC: 0.0625 μg/mL) and two clinically isolated multidrug-resistant

  通过PBTZ169的噻嗪酮开环设计并合成了一系列苯甲酰胺支架，最终鉴定出N-苄基3,5-二硝基苯甲酰胺是抗结核药物。3,5- Dinitrobenzamides D5，6，7，和12表现出优异的体外对抗药物易感活性的结核分枝杆菌H37Rv的菌株（MIC：0.0625微克/毫升）和两个临床分离多药耐药性菌株（MIC <0.016-0.125微克/毫升）。化合物D6与PBTZ169相比，显示出可接受的安全性和更好的药代动力学特征，表明其有望成为未来抗结核药物发现的先导化合物。