4-(4-Trifluoromethyl-piperidin-1-yl)-benzylamine | 1416351-77-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(4-Trifluoromethyl-piperidin-1-yl)-benzylamine
• 英文别名: [4-[4-(trifluoromethyl)piperidin-1-yl]phenyl]methanamine
• CAS: 1416351-77-3
• 化学式: C₁₃H₁₇F₃N₂
• mdl: MFCD20821463
• 分子量: 258.287
• InChiKey: AFLDOYDSDIMPOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.538
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-Trifluoromethyl-piperidin-1-yl)-benzylamine 、 间硝基苯甲酸 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 3-nitro-N-(4-(4-(trifluoromethyl)piperidin-1-yl)benzyl)benzamide
  参考文献：
  名称：

  新型硝基苯甲酰胺衍生物的设计，合成及抗分枝杆菌活性

  摘要：

  摘要我们在此报告了一系列新型硝基苯甲酰胺衍生物的设计和合成。结果显示，它们中的许多显示出相当大的体外抗结核活性。四个3,5-二硝基苯甲酰胺的N-苄基或N-（吡啶-2-基）甲基A6，A11，C1和C4不仅具有相同的1500优异的MIC值，为进一步发展开辟了新的方向。

  DOI：

  10.1016/j.cclet.2018.08.005
• 作为产物：
  描述：

  4-(4-Trifluoromethyl-piperidin-1-yl)-benzonitrile 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 4-(4-Trifluoromethyl-piperidin-1-yl)-benzylamine
  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

• 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。
• N-苄基苯甲酰胺类化合物及其制备方法
  申请人：浙江司太立制药股份有限公司

  公开号：CN106543106B

  公开（公告）日：2018-10-30

  本发明涉及式(I)所示N‑苄基苯甲酰胺类化合物，其制备方法和医药用途以及以其为有效成分的抗结核药物组合物。更具体地讲，本发明涉及的N‑苄基苯甲酰胺类化合物，其苄基对位上的取代基是含氮杂环片段，其中，式(I)中R代表三氟甲基、硝基；X代表4‑硫代吗啉基、八氢‑2H‑异吲哚‑2‑基、异吲哚啉‑2‑基、4‑取代哌啶‑1‑基、(4‑取代苯基)哌啶‑1‑基、(4‑取代苯基)哌嗪‑1‑基。
• Design, Synthesis, and Biological Evaluation of Pyrazolo[1,5-<i>a</i>]pyridine-3-carboxamides as Novel Antitubercular Agents
  作者：Jian Tang、Bangxing Wang、Tian Wu、Junting Wan、Zhengchao Tu、Moses Njire、Baojie Wan、Scott G. Franzblauc、Tianyu Zhang、Xiaoyun Lu、Ke Ding

  DOI：10.1021/acsmedchemlett.5b00176

  日期：2015.7.9

  A series of pyrazolo[1,5-a]pyridine-3-carboxamide derivatives were designed and synthesized as new anti-Mycobacterium tuberculosis (Mtb) agents. The compounds exhibit promising in vitro potency with nanomolar MIC values against the drug susceptive H37Rv strain and a panel of clinically isolated multidrug-resistant Mtb (MDR-TB) strains. One of the representative compounds (5k) significantly reduces the bacterial burden in an autoluminescent H37Ra infected mouse model, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.
• 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.
• Design, synthesis and antimycobacterial activity of novel nitrobenzamide derivatives
  作者：Hongjian Wang、Kai Lv、Xiaoning Li、Bo Wang、Apeng Wang、Zeyu Tao、Yunhe Geng、Bin Wang、Menghao Huang、Mingliang Liu、Huiyuan Guo、Yu Lu

  DOI：10.1016/j.cclet.2018.08.005

  日期：2019.2

  Abstract We report herein the design and synthesis of a series of novel nitrobenzamide derivatives. Results reveal that many of them display considerable in vitro antitubercular activity. Four N-benzyl or N-(pyridine-2-yl)methyl 3,5-dinitrobenzamides A6, A11, C1 and C4 have not only the same excellent MIC values of 1500), opening a new direction for further development.

  摘要我们在此报告了一系列新型硝基苯甲酰胺衍生物的设计和合成。结果显示，它们中的许多显示出相当大的体外抗结核活性。四个3,5-二硝基苯甲酰胺的N-苄基或N-（吡啶-2-基）甲基A6，A11，C1和C4不仅具有相同的1500优异的MIC值，为进一步发展开辟了新的方向。