(4-trifluoromethylphenyl)-[7-(3-trifluoromethylpyridin-2-yl)-quinazolin-4-yl]amine | 573678-04-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (4-trifluoromethylphenyl)-[7-(3-trifluoromethylpyridin-2-yl)-quinazolin-4-yl]amine
• 英文别名: 4-(4'-trifluoromethylanilino)-7-(3'-trifluoromethylpyridin-2-yl)quinazoline；N-(4-(trifluoromethyl)phenyl)-7-(3-(trifluoromethyl)-2-pyridinyl)-4-quinazolinamine；N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)-2-pyridinyl]-4-quinazolinamine；N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]quinazolin-4-amine
• CAS: 573678-04-3
• 化学式: C₂₁H₁₂F₆N₄
• 分子量: 434.343
• InChiKey: VTANGSDRFFLTSQ-UHFFFAOYSA-N

物化性质

• 沸点：
  500.9±50.0 °C(Predicted)
• 密度：
  1.440±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  10

制备方法与用途

MK-2295（NGD-8243）是一种TRPV1拮抗剂，具有镇痛作用，适用于疼痛研究领域。[1][2]

反应信息

• 作为产物：
  描述：

  2-amino-4-(3-trifluoromethylpyridin-2-yl)benzoic acid 在 异丙醇 、 三氯氧磷 作用下， 生成 (4-trifluoromethylphenyl)-[7-(3-trifluoromethylpyridin-2-yl)-quinazolin-4-yl]amine
  参考文献：
  名称：

  从芳基脲到联芳基酰胺再到氨基喹唑啉：发现新型有效的TRPV1拮抗剂。

  摘要：

  铅VR1拮抗剂1中芳基环的哌嗪生物等位取代导致了联芳基酰胺系列的产生。B环SAR的发展导致构象受限的类似物70。所得氨基喹唑啉70代表一种新型VR1拮抗剂，与先导系列的类似化合物相比，具有更高的体外效价和口服生物利用度。

  DOI：

  10.1016/j.bmcl.2006.07.010

文献信息

• Vanilloid receptor ligands and their use in treatments
  申请人：Norman H. Mark

  公开号：US20050165032A1

  公开（公告）日：2005-07-28

  Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  具有一般结构的化合物及其组合物，用于治疗急性、炎症性和神经性疼痛、牙痛、普通头痛、偏头痛、集群头痛、混合血管和非血管综合征、紧张性头痛、一般炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠道疾病、炎症性眼部疾病、炎症性或不稳定膀胱疾病、牛皮癣、伴有炎症成分的皮肤疾病、慢性炎症症状、炎症性疼痛及相关的过敏性疼痛和触痛、神经性疼痛及相关的过敏性疼痛和触痛、糖尿病性神经病痛、烧伤性神经痛、交感神经维持性疼痛、感觉缺失综合征、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿、消化或血管区域内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道疾病、胃溃疡、十二指肠溃疡、腹泻、坏死性剂引起的胃病变、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。
• Methods and compositions for prevention and treatment of cardiac hypertrophy
  申请人：University of Hawaii

  公开号：US10137123B2

  公开（公告）日：2018-11-27

  Methods are provided of treating cardiac hypertrophy in a mammalian subject comprising administering to the subject an anti-hypertrophic effective amount of an ion channel TR-PV1 inhibitor. The methods include treatment of a symptom of cardiac hypertrophy in the subject comprises cardiac remodeling, cardiac fibrosis, apoptosis, hypertension, or heart failure.

  提供了治疗哺乳动物心脏肥大的方法，包括向受试者施用抗肥大有效量的离子通道 TR-PV1 抑制剂。这些方法包括治疗受试者的心脏肥大症状，包括心脏重塑、心脏纤维化、细胞凋亡、高血压或心力衰竭。
• Aminoquinazolines as TRPV1 antagonists: Modulation of drug-like properties through the exploration of 2-position substitution
  作者：Charles A. Blum、Xiaozhang Zheng、Harry Brielmann、Kevin J. Hodgetts、Rajagopal Bakthavatchalam、Jayaraman Chandrasekhar、James E. Krause、Daniel Cortright、David Matson、Marci Crandall、Chu K. Ngo、Lawrence Fung、Marta Day、Mark Kershaw、Stéphane De Lombaert、Bertrand L. Chenard

  DOI：10.1016/j.bmcl.2008.07.036

  日期：2008.8

  A focused SAR exploration of the lead 4-aminoquinazoline TRPV1 antagonist 2 led to the discovery of compound 18. In rats, compound 18 is readily absorbed following oral dosing and demonstrates excellent in vivo potency and efficacy in an acute inflammatory pain model. (C) 2008 Elsevier Ltd. All rights reserved.
• Discovery of Novel 6,6-Heterocycles as Transient Receptor Potential Vanilloid (TRPV1) Antagonists
  作者：Charles A. Blum、Timothy Caldwell、Xiaozhang Zheng、Rajagopal Bakthavatchalam、Scott Capitosti、Harry Brielmann、Stéphane De Lombaert、Mark T. Kershaw、David Matson、James E. Krause、Daniel Cortright、Marci Crandall、William J. Martin、Beth Ann Murphy、Susan Boyce、A. Brian Jones、Glenn Mason、Wayne Rycroft、Helen Perrett、Rachael Conley、Nicola Burnaby-Davies、Bertrand L. Chenard、Kevin J. Hodgetts

  DOI：10.1021/jm100051g

  日期：2010.4.22

  The transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is a nonselective cation channel that can be activated by a wide range of noxious stimuli, including capsaicin, acid, and heat. Blockade of TRPV1 activation by selective antagonists is under investigation in an attempt to identify novel agents for pain treatment. The design and synthesis of a series of novel TRPV1 antagonists with a variety of different 6,6-heterocyclic cores is described, and an extensive evaluation of the pharmacological and pharmacokinetic properties of a number of these compounds is reported. For example, the 1,8-naphthyridine 52 was characterized as an orally bioavailable and brain penetrant TRPV1 antagonist. In vivo, 52 fully reversed carrageenan-induced thermal hyperalgesia (CITH) in rats and dose-dependently potently reduced complete Freund's adjuvant (CFA) induced chronic inflammatory pain after oral administration.
• VANILLOID RECEPTOR LIGANDS AND THEIR USE IN TREATMENTS
  申请人：AMGEN INC.

  公开号：EP1713807A1

  公开（公告）日：2006-10-25