4-(2-fluorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine | 1224397-05-0

• 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-(2-fluorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
• 英文别名: 4-(2-Fluoro-phenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine
• CAS: 1224397-05-0
• 化学式: C₁₃H₁₂FNS
• 分子量: 233.309
• InChiKey: BTMQBCBKHKAVDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  40.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-fluorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 、 3,5-二氯苯异氰酸酯 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 以48%的产率得到rac-N-(3,5-dichlorophenyl)-4-(2-fluorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxamide
  参考文献：
  名称：

  Discovery of BAY-298 and BAY-899: Tetrahydro-1,6-naphthyridine-Based, Potent, and Selective Antagonists of the Luteinizing Hormone Receptor Which Reduce Sex Hormone Levels in Vivo

  摘要：

  The human luteinizing hormone receptor (hLH-R) is a member of the glycoprotein hormone family of G-protein-coupled receptors (GPCRs), activated by luteinizing hormone (hLH) and essentially involved in the regulation of sex hormone production. Thus, hLH-R represents a valid target for the treatment of sex hormone-dependent cancers and diseases (polycystic ovary syndrome, uterine fibroids, endometriosis) as well as contraception. Screening of the Bayer compound library led to the discovery of tetrahydrothienopyridine derivatives as novel, small-molecule (SMOL) hLH-R inhibitors and to the development of BAY-298, the first nanomolar hLH-R antagonist reducing sex hormone levels in vivo. Further optimization of physicochemical, pharmacokinetic, and safety parameters led to the identification of BAY-899 with an improved in vitro profile and proven efficacy in vivo. BAY-298 and BAY-899 serve as valuable tool compounds to study hLH-R signaling in vitro and to interfere with the production of sex hormones in vivo.

  DOI：

  10.1021/acs.jmedchem.9b01382
• 作为产物：
  描述：

  噻吩乙胺 在 sodium tetrahydroborate 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 22.0h， 生成 4-(2-fluorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
  参考文献：
  名称：

  Fused Piperidines as a Novel Class of Potent and Orally Available Transient Receptor Potential Melastatin Type 8 (TRPM8) Antagonists

  摘要：

  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).

  DOI：

  10.1021/jm2013634

文献信息

• Substituted 4,5,6,7-tetrahydrothienopyridines as KCNQ2/3 Modulators
  申请人：Kuehnert Sven

  公开号：US20100105722A1

  公开（公告）日：2010-04-29

  Substituted tetrahydrothienopyridines corresponding to formula (1) in which A 1 through A 3 and R 1 through R 12 have defined meanings, pharmaceutical compositions comprising such compounds, a process for preparing such compounds and the use of such compounds in treatment or inhibition of conditions mediated by the KCNQ 2/3 K + channel, e.g., pain.

  公式（1）对应的替代四氢噻吡啶，其中A1至A3和R1至R12具有定义的含义，包括这些化合物的药物组合物，制备这些化合物的方法以及利用这些化合物治疗或抑制由KCNQ 2/3 K+通道介导的疾病状态，例如疼痛。
• [EN] HEDGEHOG ACYLTRANSFERASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'ACYLTRANSFÉRASE HEDGEHOG ET UTILISATIONS DE CES DERNIERS
  申请人：MEMORIAL SLOAN KETTERING CANCER CENTER

  公开号：WO2017218874A1

  公开（公告）日：2017-12-21

  Hedgehog acyltransferase (Hhat), a membrane-bound O-acyl transferase (MBOAT) protein, is responsible for the palmitoylation of Shh and is crucial to proper Shh signaling. Hhat inhibitors that are capable of preventing Shh palmitoylation and mitigating Shh signaling, and therefore can be used in the treatment and/or prevention of diseases (e.g., proliferative diseases, such as cancer). Provided herein are Hhat inhibitors, such as compounds of Formula (I), (II), and (III), which are useful for the treatment and/or prevention of disease.

  刺猬酰基转移酶（Hhat）是一种膜结合型O-酰基转移酶（MBOAT）蛋白质，负责对Shh进行棕榈酰化，并且对于正确的Shh信号传导至关重要。具有能够阻止Shh棕榈酰化并减轻Shh信号传导的Hhat抑制剂，因此可以用于治疗和/或预防疾病（例如，增生性疾病，如癌症）。本文提供了Hhat抑制剂，例如Formula（I）、（II）和（III）的化合物，可用于治疗和/或预防疾病。
• Discovery and Structural Characterization of Small Molecule Binders of the Human CTLH E3 Ligase Subunit GID4
  作者：Chetan K. Chana、Pierre Maisonneuve、Ganna Posternak、Nicolas G.A. Grinberg、Juline Poirson、Samara M. Ona、Derek F. Ceccarelli、Pavel Mader、Daniel J. St-Cyr、Victor Pau、Igor Kurinov、Xiaojing Tang、Dongjing Deng、Weiren Cui、Wenji Su、Letian Kuai、Richard Soll、Mike Tyers、Hannes L. Röst、Robert A. Batey、Mikko Taipale、Anne-Claude Gingras、Frank Sicheri

  DOI：10.1021/acs.jmedchem.2c00509

  日期：2022.10.13
• 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
• HEDGEHOG ACYLTRANSFERASE INHIBITORS AND USES THEREOF
  申请人：Memorial Sloan Kettering Cancer Center

  公开号：EP3471723A1

  公开（公告）日：2019-04-24