4-cyclopropyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine | 869472-59-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 4-cyclopropyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
• CAS: 869472-59-3
• 化学式: C₁₀H₁₃NS
• mdl: MFCD07345654
• 分子量: 179.286
• InChiKey: YLISNFNPLLPBMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  40.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  4-cyclopropyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 在 copper(l) iodide 、 正丁基锂 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-(4-cyclopropyl-5-tert-butoxyformyl-6,7-dihydrothieno[3,2-c]pyridin-2-yl)-5-chloro-pyrrolo[1,2-b]pyridazine-7-carboxylic acid methyl ester
  参考文献：
  名称：

  鉴定 2-取代的吡咯并[1,2-b]哒嗪衍生物作为新的 PARP-1 抑制剂

  摘要：

  一个新的 2-取代吡咯并[1,2- b ]哒嗪衍生物文库被快速组装并鉴定为 PARP 抑制剂。这类抑制剂的构效关系导致发现了最有效的化合物15a和15b，它们对 PARP-1 的选择性活性分别是 PARP-2 的 29 和 5 倍。通过在 BRCA2 缺陷型 V-C8 和 BRCA1 缺陷型 MDA-MB-436 细胞系中的进一步细胞测定证明了所制备化合物的抗增殖活性，表明化合物15b可以用 CC 50强力降低相应的细胞增殖和生长s 分别为 340 和 106 nM。15b的PK属性 这里也被调查了。

  DOI：

  10.1016/j.bmcl.2020.127710
• 作为产物：
  描述：

  4-cyclopropyl-5-Formyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以94%的产率得到4-cyclopropyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
  参考文献：
  名称：

  An Efficient and Convenient Synthesis of 4,5,6,7-Tetrahydrothieno[3,2-c]pyridines by a Modified Pictet-Spengler Reaction via a Formyliminium Ion Intermediate

  摘要：

  A synthesis of N-formyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridines (5) was achieved in a highly efficient manner via trifluoroacetic acid catalyzed cyclization of formyliminium ion (4), which was produced by imination of 2-(2-thienyl)ethylamine (1) and a carbonyl compound (2) using titanium(IV) tetraisopropoxide followed by formylation with acetic-formic anhydride in a one-pot procedure. This modified Pictet-Spengler reaction provides a convenient method for preparing 4,5,6,7-tetahydrothieno[3,2-c]pyridines (6) possessing various substituents at C-4.

  DOI：

  10.3987/com-10-11992

文献信息

• Fused Piperidines as a Novel Class of Potent and Orally Available Transient Receptor Potential Melastatin Type 8 (TRPM8) Antagonists
  作者：Nuria A. Tamayo、Yunxin Bo、Vijay Gore、Vu Ma、Nobuko Nishimura、Phi Tang、Hong Deng、Lana Klionsky、Sonya G. Lehto、Weiya Wang、Brad Youngblood、Jiyun Chen、Tiffany L. Correll、Michael D. Bartberger、Narender R. Gavva、Mark H. Norman

  DOI：10.1021/jm2013634

  日期：2012.2.23

  The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (< 25 degrees C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS).
• SUBSTITUIERTE 4,5,6,7-TETRAHYDROTHIENOPYRIDINE ALS KCNQ2/3 MODULATOREN ZUR BEHANDLUNG VON SCHMERZ, EPILEPSIE UND HARNINKONTINENZ
  申请人：Grünenthal GmbH

  公开号：EP2350093B1

  公开（公告）日：2012-10-03
• Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors
  作者：Hao-Yue Xiang、Jian-Yang Chen、Xia-Juan Huan、Yi Chen、Zhao-bing Gao、Jian Ding、Ze-Hong Miao、Chun-Hao Yang

  DOI：10.1016/j.bmcl.2020.127710

  日期：2021.1

  A library of new 2-substituted pyrrolo[1,2-b]pyridazine derivatives were rapidly assembled and identified as PARP inhibitors. Structure-activity relationship for this class of inhibitor resulted in the discovery of most potent compounds 15a and 15b that exhibited about 29- and 5- fold selective activity against PARP-1 over PARP-2 respectively. The antiproliferative activity of the as-prepared compounds

  一个新的 2-取代吡咯并[1,2- b ]哒嗪衍生物文库被快速组装并鉴定为 PARP 抑制剂。这类抑制剂的构效关系导致发现了最有效的化合物15a和15b，它们对 PARP-1 的选择性活性分别是 PARP-2 的 29 和 5 倍。通过在 BRCA2 缺陷型 V-C8 和 BRCA1 缺陷型 MDA-MB-436 细胞系中的进一步细胞测定证明了所制备化合物的抗增殖活性，表明化合物15b可以用 CC 50强力降低相应的细胞增殖和生长s 分别为 340 和 106 nM。15b的PK属性 这里也被调查了。
• An Efficient and Convenient Synthesis of 4,5,6,7-Tetrahydrothieno[3,2-c]pyridines by a Modified Pictet-Spengler Reaction via a Formyliminium Ion Intermediate
  作者：Yoshie Horiguchi、Michikazu Kitabatake、Aki Hashimoto、Toshiaki Saitoh、Takehiro Sano、Kunihiko Mohri

  DOI：10.3987/com-10-11992

  日期：——

  A synthesis of N-formyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridines (5) was achieved in a highly efficient manner via trifluoroacetic acid catalyzed cyclization of formyliminium ion (4), which was produced by imination of 2-(2-thienyl)ethylamine (1) and a carbonyl compound (2) using titanium(IV) tetraisopropoxide followed by formylation with acetic-formic anhydride in a one-pot procedure. This modified Pictet-Spengler reaction provides a convenient method for preparing 4,5,6,7-tetahydrothieno[3,2-c]pyridines (6) possessing various substituents at C-4.