rac-4-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: rac-4-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
• 英文别名: 4-(4-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydrothieno[3,2-c]-pyridine；4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine；4-[4-(Trifluoromethyl)phenyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
• 化学式: C₁₄H₁₂F₃NS
• 分子量: 283.317
• InChiKey: KIPRTQNWIXZVKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  40.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-甲氧基苯甲酸 、 rac-4-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 [4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(3-methoxyphenyl)-methanone
  参考文献：
  名称：

  葡萄糖-6-磷酸酶催化酶抑制剂：新型4,5,6,7-四氢噻吩并[3,2-c]-和-[2,3-c]吡啶的合成及体外评估。

  摘要：

  描述了发现第一类有效的葡萄糖-6-磷酸酶催化位点抑制剂，即取代的4,5,6,7-四氢噻吩并[3,2-c]-和-[2,3-c]吡啶。该系列的优化涉及溶液相组合合成，并且制备的强效化合物的IC50值低至140 nM。这些化合物的结构活性关系（SAR）表明：四氢噻吩并[3,2-c]吡啶核环系统和异构体[2,3-c]系统是等位的，并且比相应的苯并类似物好得多，1 2,3,4-四氢异喹啉。四氢噻吩并[3，2-c]吡啶环的4-取代基必须是苯基，任选被亲脂性4-取代基如三氟甲氧基或氯取代。四氢噻吩并[3，2-c]吡啶环的5-取代基必须是取代的苯甲酰基；异戊基和（E）-3-呋喃-3-基丙烯酰基是所研究的最佳基团。似乎禁止在苯甲酰基邻位取代，而仅当存在甲氧基对位取代基时才容许在间位取代。这些SAR结果与在4,5,6,7-四氢噻吩并[2,3-c]吡啶系统中获得的结果相似。在酶识别中观察到对映选择性，并且该活性仅在一种对映异构体中存在于所有情况下。

  DOI：

  10.1016/s0968-0896(00)00153-x
• 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 rac-4-[4-(trifluoromethyl)phenyl]-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

• 4,5,6,7-tetrahydro-thieno&lsqb;3, 2-C&rsqb;pyridine derivatives, their preparation and use
  申请人：Novo Nordisk A/S

  公开号：US06177443B1

  公开（公告）日：2001-01-23

  The present invention relates to pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent and a compound of formula I wherein A together with the double bond of formula I is benzene or thiophene; R1 is optionally substituted C1-6 alkyl or optionally substituted aryl; R2 is optionally substituted C1-6-alkyl, optionally substituted aralkyl, or —COR3, wherein R3 is optionally substituted C1-6-alkyl, optionally substituted aralkyl, or optionally substituted aryl; R4 and R5 independently are hydrogen, halogen, perhalomethyl, optionally substituted C1-6-alkyl, hydroxy, optionally substituted C1-6-alkoxy, nitro, cyano, amino, optionally substituted mono- or optionally substituted di-C1-6-alkylamino, acylamino, C1-6-alkoxycarbonyl, carboxy or carbamoyl; n is 0, and m is 1, and methods of treating or preventing a disease of the endocrinologic system.

  本发明涉及含有药用可接受载体或稀释剂以及式I化合物的制药组合物，其中A与式I的双键一起为苯或噻吩；R1为可选的取代C1-6烷基或可选的取代芳基；R2为可选的取代C1-6烷基，可选的取代芳基烷基，或—COR3，其中R3为可选的取代C1-6烷基，可选的取代芳基烷基，或可选的取代芳基；R4和R5独立地为氢、卤素、全卤甲基、可选的取代C1-6烷基、羟基、可选的取代C1-6-氧基、硝基、氰基、氨基、可选的取代单或可选的取代二C1-6烷基氨基、酰胺基、C1-6-烷氧羰基、羧基或氨基甲酰；n为0，m为1，并且治疗或预防内分泌系统疾病的方法。
• [EN] 4,5,6,7-TETRAHYDRO-THIENO[3,2-c]PYRIDINE DERIVATIVES, THEIR PREPARATION AND USE<br/>[FR] DERIVES DE 4,5,6,7-TETRAHYDRO-THIENO[3,2-c]PYRIDINE, LEUR PREPARATION ET LEUR UTILISATION
  申请人：NOVO NORDISK A/S

  公开号：WO1998040385A1

  公开（公告）日：1998-09-17

  (EN) 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine derivative modulate the activity of molecules with glucose-6-phosphate recognition units, including glucose-6-phosphatases (G-6-Pases) in $i(in vitro ) systems, microorganisms, eukaryotic cells, whole animals and human beings, and are useful in the treatment of diseases related to glucose metabolic pathways.(FR) Les dérivés de 4,5,6,7-tétrahydro-thiéno[3,2-c]pyridine modulent l'activité de molécules à l'aide d'unités de reconnaissance glucose-6-phosphate, notamment des glucose-6-phosphatases dans des systèmes $i(in vitro), des micro-organismes, des cellules eucaryotes, des animaux entiers et des humains, et sont utiles dans le traitement de maladies associées aux voies métaboliques du glucose.

  (EN) 4,5,6,7-四氢-3,2-c-位吡咯四氢并噻吩的衍生物调节了含有葡萄糖六磷酸识别单元的分子活性，包括体外实验( $i(in vitro ) $)、微生物、真核细胞、完整动物和人类，对治疗与葡萄糖代谢途径相关的疾病有 usefulness。 (FR) Les dérivés de 4,5,6,7-四氢-3,2-c-位吡咯四氢并噻吩 modulent l'activité de molécules au moyen d'unités de reconnaissance de glucose six-phosphaté, notamment de glucose six-phosphatases dans des $systèmes (i( in vitro )), des micro-organismes, des cellules eucaryotes, des animaux entiers et des humains, et sont utiles dans le traitement des maladies liées aux voies métaboliques du glucose.
• 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
  作者：Lars Wortmann、Bernhard Lindenthal、Peter Muhn、Alexander Walter、Reinhard Nubbemeyer、Dieter Heldmann、Lothar Sobek、Federica Morandi、Anna K. Schrey、Dieter Moosmayer、Judith Günther、Joachim Kuhnke、Marcus Koppitz、Ulrich Lücking、Ulrike Röhn、Martina Schäfer、Katrin Nowak-Reppel、Ronald Kühne、Hilmar Weinmann、Gernot Langer

  DOI：10.1021/acs.jmedchem.9b01382

  日期：2019.11.27

  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.
• 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
• 4,5,6,7-TETRAHYDRO-THIENO 3,2-c]PYRIDINE DERIVATIVES, THEIR PREPARATION AND USE
  申请人：NOVO NORDISK A/S

  公开号：EP0973778A1

  公开（公告）日：2000-01-26