4-三氟甲基-3-甲酰基吡啶 | 1083197-78-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 4-三氟甲基-3-甲酰基吡啶
• 英文名称: 4-(trifluoromethyl)pyridine-3-carbaldehyde
• 英文别名: 4-(trifluoromethyl)nicotinaldehyde；4-(trifluoromethyl)-3-pyridinecarboxaldehyde
• CAS: 1083197-78-7
• 化学式: C₇H₄F₃NO
• 分子量: 175.11
• InChiKey: LNHXJOJOYYLHIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险类别：
  6.1
• 危险性防范说明：
  P261,P280,P301+P310,P305+P351+P338
• 危险品运输编号：
  2810
• 危险性描述：
  H301,H315,H317,H319,H335
• 包装等级：
  III

反应信息

• 作为反应物：
  描述：

  4-三氟甲基-3-甲酰基吡啶 在 盐酸 、 二异丁基氢化铝 、 copper(II) sulfate 、 magnesium 作用下， 以 1,4-二氧六环 、 乙醚 、 二氯甲烷 为溶剂， 反应 70.17h， 生成 (S)-(4-(trifluoromethyl)phenyl)(4-(trifluoromethyl)pyridin-3-yl)methanamine hydrochloride
  参考文献：
  名称：

  Discovery of TRPM8 Antagonist (S)-6-(((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinic Acid (AMG 333), a Clinical Candidate for the Treatment of Migraine

  摘要：

  Transient-receptor-potential melastatin 8 (TRPM8), the predominant mammalian cold-temperature thermosensor, is a non-selective cation channel expressed in a subpopulation of sensory neurons in the peripheral nervous system, including nerve circuitry implicated in migraine pathogenesis: the trigeminal and pterygopalatine ganglia. Genomewide association studies have identified an association between TRPM8 and reduced risk of migraine. This disclosure focuses on medicinal-chemistry efforts to improve the druglike properties of initial leads, particularly removal of CYP3A4-induction liability and improvement of pharmacokinetic properties. A novel series of biarylmethanamide TRPM8 antagonists was developed, and a subset of leads were evaluated in preclinical toxicology studies to identify a clinical candidate with an acceptable preclinical safety profile leading to clinical candidate AMG 333, a potent and highly selective antagonist of TRPM8 that was evaluated in human clinical trials.

  DOI：

  10.1021/acs.jmedchem.8b00518
• 作为产物：
  描述：

  4-三氟甲基烟酸 在 diisopropylaluminium hydride 、 HATU 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 4-三氟甲基-3-甲酰基吡啶
  参考文献：
  名称：

  [EN] TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS
  [FR] ANTAGONISTES DE TRPM8 ET LEUR UTILISATION DANS DES TRAITEMENTS

  摘要：

  公开号：

  WO2012177893A3

文献信息

• [EN] 1,4-DISUBSTITUTED PIPERIDINE DERIVATIVES AND THEIR USE AS 11-BETAHSD1 INHIBITORS<br/>[FR] DERIVES DE PIPERIDINE 1,4 DISUBSTITUEE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE 11-BETAHSD1
  申请人：ASTRAZENECA AB

  公开号：WO2004033427A1

  公开（公告）日：2004-04-22

  The use of a compound of formula (I) in the manufacture of a medicament for use in the inhibition of 11βHSD1 is described.

  使用式(I)的化合物制造用于抑制11βHSD1的药物。
• COMPOUNDS USEFUL AGAINST KINETOPLASTIDEAE PARASITES
  申请人：Davioud-Charvet Elisabeth

  公开号：US20120214996A1

  公开（公告）日：2012-08-23

  Dibenzylidene and heterobenzylideneacetone derivatives, related 4-piperidones, related 4-thiopyranones and the corresponding sulfinyl- and sulfonyl-analogues for their use for prophylaxis or treatment of trypanosomiasis and leishmaniasis.

  二苄基亚烷和杂二苄基亚烷乙酮衍生物，相关的4-哌啶酮，相关的4-噻opyranones以及相应的亚磺酰基和磺酰基类似物，用于预防或治疗锥虫病和利什曼病。
• [EN] PYRAZOLOPYRIDINES AS INHIBITORS OF THE KINASE LRRK2<br/>[FR] PYRAZOLOPYRIDINES EN TANT QU'INHIBITEURS DE LA KINASE LRRK2
  申请人：MEDICAL RES COUNCIL TECHNOLOGY

  公开号：WO2011141756A1

  公开（公告）日：2011-11-17

  A compound of formula la or formula lb, or a pharmaceutically acceptable salt or ester thereof, wherein R1 is selected from: aryl; heteroaryl; -NHR3; fused aryl-C4-7-heterocycloalkyl; - CONR4R5; -NHCOR6; -C3-7-cycloalkyl; -0-C3-7-cycloalkyl; -NR3R6; and optionally substituted -C1-6 alkyl; wherein said aryl, heteroaryl, fused aryl-C4-7-heterocycloalkyl and C4-7- heterocycloalkyl are each optionally substituted; Q is CN, halogen, or is selected from C1-6-alkyl, C3-7-cycloalkyl, heterocycloalkyl, aryl and heteroaryl, each of which is optionally substituted with one or more substituents A; R2 is selected from hydrogen, aryl, C1-6-alkyl, C2-6-alkenyl,C3-7-cycloalkyl, heteroaryl, C4-7 heterocycloalkyl and halogen, wherein said C1-6-alkyl,, Cz-B-alkenyl, aryl, heteroaryl and C4-7-heterocycloalkyl are each optionally substituted;R3 is selected from aryl, heteroaryl, C4-7-heterocycloalkyl, C3-7- cycloalkyl, fused aryl-C-heterocycloalkyl and C1-6-alkyl, each of which is optionally substituted; R4 and R5 are each independently hydrogen, or optionally substituted C3-7- cycloalkyl, aryl, heteroaryl, C1-6-alkyl or C3-6-heterocycloalkyl; or R4 and R5 together with the N to which they are attached form a C3-6-heterocycloalkyl ring; each R6 is independently selected from C1-6-alkyl, C3-7 cycloalkyl, C-heterocycloalkyl, aryl and heteroaryl, each of which is optionally substituted; each R7 is selected from hydrogen, optionally substituted C1-6-alkyl and C3-7-cycloalkyl; each of R8 and R9 is independently hydrogen or optionally substituted C1-6-alkyl; or R8 and R9 together with the N to which they are attached form a C4-6-heterocycloalkyl; each R10 is selected from C3-7- cycloalkyl and optionally substituted C1-6-alkyl; each R11 is independently selected from C1-6-alkyl, C3-7-cycloalkyl, C1-6-alkyl-C3-7-cycloalkyl, C4-7-heterocycloalkyl, aryl and heteroaryl, each of which is optionally substituted; A is selected from halogen, - NR4S02R5, -CN, -OR6, -NR4R5, -NR7R11, hydroxyl, -CF3, -CONR4R5, -NR4COR5, -NR7(CO)NR4R5, -N02, -C02H, -C02R6, -S02R6, -S02NR4R5, -NR4COR5 ,-NR4COOR5, 6-alkyl and -COR6. Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formulae la and lb.

  一种具有化学式la或化学式lb的化合物，或其在药学上可接受的盐或酯，其中R1选择自：芳基；杂环芳基；-NHR3；融合芳基-C4-7-杂环烷基；-CONR4R5；-NHCOR6；-C3-7-环烷基；-0-C3-7-环烷基；-NR3R6；以及可选择地取代的-C1-6烷基；其中所述的芳基、杂环芳基、融合芳基-C4-7-杂环烷基和C4-7-杂环烷基均可选择地取代；Q选择自CN、卤素，或选择自C1-6-烷基、C3-7-环烷基、杂环烷基、芳基和杂环芳基，每种均可选择地取代一个或多个取代基A；R2选择自氢、芳基、C1-6-烷基、C2-6-烯烃基、C3-7-环烷基、杂环芳基、C4-7-杂环烷基和卤素，其中所述的C1-6-烷基、C2-6-烯烃基、芳基、杂环芳基和C4-7-杂环烷基均可选择地取代；R3选择自芳基、杂环芳基、C4-7-杂环烷基、C3-7-环烷基、融合芳基-C-杂环烷基和C1-6-烷基，每种均可选择地取代；R4和R5各自独立地为氢，或可选择地取代的C3-7-环烷基、芳基、杂环芳基、C1-6-烷基或C3-6-杂环烷基；或R4和R5与其连接的N一起形成一个C3-6-杂环烷基环；每个R6独立地选择自C1-6-烷基、C3-7-环烷基、C-杂环烷基、芳基和杂环芳基，每种均可选择地取代；每个R7选择自氢、可选择地取代的C1-6-烷基和C3-7-环烷基；每个R8和R9各自独立地为氢或可选择地取代的C1-6-烷基；或R8和R9与其连接的N一起形成一个C4-6-杂环烷基；每个R10选择自C3-7-环烷基和可选择地取代的C1-6-烷基；每个R11独立地选择自C1-6-烷基、C3-7-环烷基、C1-6-烷基-C3-7-环烷基、C4-7-杂环烷基、芳基和杂环芳基，每种均可选择地取代；A选择自卤素、-NR4S02R5、-CN、-OR6、-NR4R5、-NR7R11、羟基、-CF3、-CONR4R5、-NR4COR5、-NR7(CO)NR4R5、-N02、-C02H、-C02R6、-S02R6、-S02NR4R5、-NR4COR5、-NR4COOR5、6-烷基和-COR6。进一步涉及到具有化学式la和lb的化合物的制药组合物、治疗用途和制备过程。
• [EN] FUNCTIONALIZED HETROARYL ENONES EXHIBITING NRF2 ACTIVATION AND THEIR METHOD OF USE<br/>[FR] ÉNONES D'HÉTÉROARYLE FONCTIONNALISÉES PRÉSENTANT UNE ACTIVATION NRF2 ET LEUR MÉTHODE D'UTILISATION
  申请人：CUREVEDA LLC

  公开号：WO2015187934A1

  公开（公告）日：2015-12-10

  Pharmaceutical compositions are disclosed, which include functionalized hetroaryl enones and are useful for treating or preventing a disease, disorder or condition associated with an NRF2-regulated pathway and/or which involves oxidative stress.

  揭示了包括功能化杂环烯酮在内的药物组合物，适用于治疗或预防与NRF2调节途径相关或涉及氧化应激的疾病、紊乱或状况。
• SPIROCYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20190127362A1

  公开（公告）日：2019-05-02

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of famesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式（I）的化合物或其立体异构体、互变异构体或药学上可接受的盐或溶剂，其中所有变量均如本说明中所定义。这些化合物调节法尼索德X受体（FXR）的活性，例如作为激动剂。本发明还涉及包含这些化合物的药物组合物以及使用这些化合物和药物组合物治疗与FXR失调相关的疾病、紊乱或情况的方法，例如病理纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。