cis-dimethyl piperidine-3,5-dicarboxylate

• 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: cis-dimethyl piperidine-3,5-dicarboxylate
• 英文别名: Rel-dimethyl (3S,5R)-piperidine-3,5-dicarboxylate；dimethyl (3R,5S)-piperidine-3,5-dicarboxylate
• 化学式: C₉H₁₅NO₄
• 分子量: 201.222
• InChiKey: FOEXRJBHOCBGFH-KNVOCYPGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  cis-dimethyl piperidine-3,5-dicarboxylate 在 碳酸氢钠 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 96.0h， 生成 (3R,5S)-1-[(叔丁氧基)羰基]哌啶-3,5-二羧酸
  参考文献：
  名称：

  Structure-Based Design of Substituted Piperidines as a New Class of Highly Efficacious Oral Direct Renin Inhibitors

  摘要：

  A cis-configured 3,5-disubstituted piperidine direct renin inhibitor, (syn,rac)-1, was discovered as a high-throughput screening hit from a target-family tailored library. Optimization of both the prime and the nonprime site residues flanking the central piperidine transition-state surrogate resulted in analogues with improved potency and pharmacokinetic (PK) properties, culminating in the identification of the 4-hydroxy-3,5-substituted piperidine 31. This compound showed high in vitro potency toward human renin with excellent off-target selectivity, 60% oral bioavailability in rat, and dose-dependent blood pressure lowering effects in the double-transgenic rat model.

  DOI：

  10.1021/ml500137b
• 作为产物：
  描述：

  3,5-吡啶二甲酸 在 4-二甲氨基吡啶 、 氯化亚砜 、 Adam’s catalyst 、 氢气 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 247.0h， 生成 cis-dimethyl piperidine-3,5-dicarboxylate
  参考文献：
  名称：

  피페리딘-3,5-디카복시아마이드 유도체 및 이를 유효성분으로 함유하는 항암용 약학적 조성물

  摘要：

  本发明涉及吡啶-3,5-二羧酰亚胺衍生物或其药学上可接受的盐及包含其作为有效成分的用于预防或治疗癌症的药学组合物，根据本发明的化合物具有优越的抑制逆转录淋巴瘤激酶（ALK）活性的效果，因此对具有EML4-ALK、NPM-ALK等逆转录淋巴瘤激酶（ALK）融合蛋白的癌细胞的治疗效果可能得到提高，且预计能有效防止癌症复发，因此可用作癌症预防或治疗的药学组合物。

  公开号：

  KR101577430B1

文献信息

• 피페리딘-3,5-디카복시아마이드 유도체 및 이를 유효성분으로 함유하는 항암용 약학적 조성물
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY 한국화학연구원(319980077651)

  公开号：KR101577430B1

  公开（公告）日：2015-12-14

  본 발명은 피페리딘-3,5-디카복시아마이드 유도체 또는 이의 약학적으로 허용가능한 염 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물에 관한 것으로, 본 발명에 의한 화합물은 역형성 림프종 키나아제(ALK) 활성을 억제하는 효과가 우수하므로 이에 따른 EML4-ALK, NPM-ALK 등의 역형성 림프종 키나아제(ALK) 융합 단백질을 가진 암세포에 대한 치료효과가 향상될 수 있으며, 암의 재발을 막는데 효과적일 것으로 예상되므로 암의 예방 또는 치료용 약학적 조성물로 유용하게 사용될 수 있다.

  本发明涉及吡啶-3,5-二羧酰亚胺衍生物或其药学上可接受的盐及包含其作为有效成分的用于预防或治疗癌症的药学组合物，根据本发明的化合物具有优越的抑制逆转录淋巴瘤激酶（ALK）活性的效果，因此对具有EML4-ALK、NPM-ALK等逆转录淋巴瘤激酶（ALK）融合蛋白的癌细胞的治疗效果可能得到提高，且预计能有效防止癌症复发，因此可用作癌症预防或治疗的药学组合物。
• Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 1: Exploration of Antibody Linker, Payload Loading, and Payload Molecular Properties
  作者：Peter S. Dragovich、Thomas H. Pillow、Robert A. Blake、Jack D. Sadowsky、Emel Adaligil、Pragya Adhikari、Sunil Bhakta、Nicole Blaquiere、Jinhua Chen、Josefa dela Cruz-Chuh、Karen E. Gascoigne、Steven J. Hartman、Mingtao He、Susan Kaufman、Tracy Kleinheinz、Katherine R. Kozak、Liang Liu、Liling Liu、Qi Liu、Ying Lu、Fanwei Meng、Melinda M. Mulvihill、Aimee O’Donohue、Rebecca K. Rowntree、Leanna R. Staben、Steven T. Staben、John Wai、Jian Wang、BinQing Wei、Catherine Wilson、Jianfeng Xin、Zijin Xu、Hui Yao、Donglu Zhang、Hongyan Zhang、Hao Zhou、Xiaoyu Zhu

  DOI：10.1021/acs.jmedchem.0c01845

  日期：2021.3.11

  related chimeric molecules that effect intracellular degradation of target proteins via ubiquitin ligase-mediated ubiquitination continue to grow. However, these chimeric entities are relatively large compounds that often possess molecular characteristics, which may compromise oral bioavailability, solubility, and/or in vivo pharmacokinetic properties. We therefore explored the conjugation of such

  靶向蛋白水解的嵌合体（PROTAC）和相关的嵌合分子通过泛素连接酶介导的泛素化影响靶蛋白胞内降解的生物学和医学影响继续增长。但是，这些嵌合实体是相对较大的化合物，通常具有分子特征，这可能会损害口服生物利用度，溶解度和/或体内药代动力学特性。因此，我们使用最初为细胞毒性有效载荷开发的技术，探索了此类分子与单克隆抗体的缀合，以便为这些新型药物提供替代的递送选择。在本报告中，我们描述了从含溴结构域蛋白4（BRD4）靶向嵌合降解体实体衍生的抗体-药物偶联物（ADC）系统开发的第一阶段。我们证明了降解物有效载荷对PC3-S1前列腺癌细胞的抗原依赖性传递以及对MYC转录和细胞内BRD4水平的相关影响。这些实验以鉴定一种降解物缀合物达到高潮，该缀合物在LNCaP前列腺癌细胞中表现出抗原依赖性的抗增殖作用。
• Design, Synthesis, and Evaluation of 2-Anilino-4-(3,5-dicarboxamidespiperidine)-pyrimidines as Anaplastic Lymphoma Kinase Inhibitors
  作者：Muhammad Latif、Sangjun Park、Imran Ali、Hyeonjeong Choe、Chong Hak Chae、Chi Hoon Park、Hyoung Rae Kim、Chang-Soo Yun、Kwangho Lee

  DOI：10.1002/bkcs.10454

  日期：2015.9
• SUBSTITUTED (HETERO)ANILINES AND THEIR USE
  申请人：[en]ASTRAZENECA AB

  公开号：WO2024149728A1

  公开（公告）日：2024-07-18

  The present disclosure relates to substituted anilines and heteroanilines and their use as TRPV4 antagonists. In some embodiments, the disclosure provides a compound of Formula (I): (I), or a pharmaceutically acceptable salt thereof, wherein ring A, R groups, X, Y, Z, m, p, q, and s are defined herein.
• Structure-Based Design of Substituted Piperidines as a New Class of Highly Efficacious Oral Direct Renin Inhibitors
  作者：Takeru Ehara、Osamu Irie、Takatoshi Kosaka、Takanori Kanazawa、Werner Breitenstein、Philipp Grosche、Nils Ostermann、Masaki Suzuki、Shimpei Kawakami、Kazuhide Konishi、Yuko Hitomi、Atsushi Toyao、Hiroki Gunji、Frederic Cumin、Nikolaus Schiering、Trixie Wagner、Dean F. Rigel、Randy L. Webb、Jürgen Maibaum、Fumiaki Yokokawa

  DOI：10.1021/ml500137b

  日期：2014.7.10

  A cis-configured 3,5-disubstituted piperidine direct renin inhibitor, (syn,rac)-1, was discovered as a high-throughput screening hit from a target-family tailored library. Optimization of both the prime and the nonprime site residues flanking the central piperidine transition-state surrogate resulted in analogues with improved potency and pharmacokinetic (PK) properties, culminating in the identification of the 4-hydroxy-3,5-substituted piperidine 31. This compound showed high in vitro potency toward human renin with excellent off-target selectivity, 60% oral bioavailability in rat, and dose-dependent blood pressure lowering effects in the double-transgenic rat model.