2-(3-(氯甲基)苯氧基)-5-(三氟甲基)吡啶 | 1020325-30-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-(3-(氯甲基)苯氧基)-5-(三氟甲基)吡啶
• 英文名称: 2-[3-(chloromethyl)phenoxy]-5-(trifluoromethyl)pyridine
• 英文别名: 2-(3-(Chloromethyl)phenoxy)-5-(trifluoromethyl)pyridine
• CAS: 1020325-30-7
• 化学式: C₁₃H₉ClF₃NO
• 分子量: 287.669
• InChiKey: HKECJZLWUZMCIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  2-(3-(氯甲基)苯氧基)-5-(三氟甲基)吡啶 在 盐酸 、 potassium tert-butylate 、 水 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙腈 为溶剂， 反应 32.0h， 生成 N-哒嗪-3-基-4-(3-{[5-(三氟甲基)吡啶-2-基]醚}苯亚甲基丙酮)哌啶-1-羧酰胺
  参考文献：
  名称：

  Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor

  摘要：

  Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase that degrades the fatty acid amide family of signaling lipids, including the endocannabinoid anandamide. Genetic or pharmacological inactivation of FAAH leads to analgesic and anti-inflammatory phenotypes in rodents without showing the undesirable side effects observed with direct cannabinoid receptor agonists, indicating that. FAAH may represent an attractive therapeutic target for the treatment of inflammatory pain and other nervous system disorders. Herein, we report the discovery and characterization of a highly efficacious and selective FAAH inhibitor PR-04457845 (23). Compound 23 inhibits FAAH by a covalent, irreversible mechanism involving carbamylation of the active-site serine nucleophile of FAAH with high in vitro potency (k(inact)/K(i) and IC(50) values of 40300 M(-1) s(-1) and 7.2 nM, respectively, for human FAAH). Compound 23 has exquisite selectivity for FAAH relative to other members of the serine hydrolase superfamily as demonstrated by competitive activity-based protein profiling. Oral administration of 23 at 0.1 mg/kg results in efficacy comparable to that of naproxen at 10 mg/kg in a rat model of inflammatory pain. Compound 23 is being evaluated in human clinical trials.

  DOI：

  10.1021/ml100190t
• 作为产物：
  描述：

  3-((5-(三氟甲基)吡啶-2-基)氧基)苯甲醛 在 sodium tetrahydroborate 、 氯化亚砜 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-(3-(氯甲基)苯氧基)-5-(三氟甲基)吡啶
  参考文献：
  名称：

  在神经性疼痛模型中发现和评估新型FAAH抑制剂

  摘要：

  化学型PF-3845 / 04457845（一种基准标记的脂肪酸酰胺水解酶（FAAH）的不可逆抑制剂）中尿素部分的概念设计和修饰导致发现了一种新型的具有可逆作用机理的基于烟酰胺的铅12a。在12a中将SAR集中在吡啶杂环（Ar）周围（表1和2）（表1和表2），形成了四个候选化合物（-）- 12a，（-）- 12i，（-）- 12l – m。通过新型手性不对称中间体15的非对映异构体拆分获得所需的（-）-对映体。基于FAAH效力，在肝微粒体代谢稳定性的比较曲线，抑制主要hCYP450同种型，大鼠PK，和脑渗透能力的责任，二SAR优化化合物，（ - ） - 12升和（ - ） - 12米，被选择用于功效化疗诱发的周围神经病变（CIPN）大鼠模型的研究。当以3–30 mg / kg口服7天后，这两种化合物均显示出与剂量相关的抗痛觉过敏作用。30 mg / kg的作用与PF-04457845（10

  DOI：

  10.1016/j.bmcl.2018.11.048

文献信息

• Biaryl Ether Urea Compounds
  申请人：FAY Lorraine Kathleen

  公开号：US20080261941A1

  公开（公告）日：2008-10-23

  The present invention relates to compounds of Formula (I) or a pharmaceutically acceptable salt thereof; processes for the preparation of the compounds; intermediates used in the preparation of the compounds; compositions containing the compounds; and uses of the compounds in treating diseases or conditions associated with fatty acid amide hydrolase (FAAH) activity.

  本发明涉及式(I)的化合物或其药用可接受的盐；制备该化合物的方法；制备该化合物所用的中间体；含有该化合物的组合物；以及利用该化合物治疗与脂肪酸酰胺水解酶(FAAH)活性相关的疾病或症状。
• [EN] AMIDE COMPOUNDS, COMPOSITIONS AND APPLICATIONS THEREOF<br/>[FR] COMPOSÉS AMIDES, COMPOSITIONS ET APPLICATIONS DE CEUX-CI
  申请人：ADVINUS THERAPEUTICS LTD

  公开号：WO2013042139A1

  公开（公告）日：2013-03-28

  The present disclosure relates to substituted amide compounds that are inhibitors of Fatty Acid Amide Hydrolase (FAAH), their stereoisomers, tautomers, prodrugs, polymorphs, solvates, pharmaceutically acceptable salts, and pharmaceutical compositions containing them. These compounds are useful in the treatment, prevention, prophylaxis, management, or adjunct treatment of all medical conditions related to inhibition of Fatty Acid Amide Hydrolase (FAAH), such as pain including acute and post operative pain, chronic pain, cancer pain, cancer chemotherapy induced pain, neuropathic pain, nociceptive pain, inflammatory pain, back pain, pain due to disease of various origin such as: diabetic neuropathy, neurotropic viral disease including human immunodeficient virus (HIV), herpes zoster such as post herpetic neuralgia; polyneuropathy, neurotoxicity, mechanical nerve injury, carpal tunnel syndrome, immunologic mechanisms like multiple sclerosis; sleep disorders, anxiety and depression disorders, inflammatory disorders, weight and eating disorders, Parkinson's disease, addiction, spasticity, hypertension or other disorders. The disclosure also relates to the process of preparation of the amide compounds. Formula (1). The present disclosure also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.

  本公开涉及替代酰胺化合物，这些化合物是脂肪酸酰胺水解酶（FAAH）的抑制剂，包括它们的立体异构体、互变异构体、前药、多型体、溶剂合物、药用盐以及含有它们的药物组合物。这些化合物在治疗、预防、预防、管理或辅助治疗与脂肪酸酰胺水解酶（FAAH）抑制相关的所有医疗状况中非常有用，例如疼痛，包括急性和术后疼痛，慢性疼痛，癌症疼痛，癌症化疗引起的疼痛，神经痛，伤害性疼痛，炎症性疼痛，背部疼痛，疾病引起的疼痛，如糖尿病性神经病变，神经病毒性疾病，包括人类免疫缺陷病毒（HIV），带状疱疹，如带状疱疹后神经痛；多发性神经病，神经毒性，机械神经损伤，腕管综合症，类似多发性硬化的免疫机制；睡眠障碍，焦虑和抑郁症，炎症性疾病，体重和进食障碍，帕金森病，成瘾，痉挛，高血压或其他疾病。该公开还涉及酰胺化合物的制备过程。公式（1）。本公开还涉及制备这类化合物的方法，以及含有它们的药物组合物。
• AMIDE COMPOUNDS, COMPOSITIONS AND APPLICATIONS THEREOF
  申请人：ADVINUS THERAPEUTICS LIMITED

  公开号：US20150065464A1

  公开（公告）日：2015-03-05

  The present disclosure relates to substituted amide compounds that are inhibitors of Fatty Acid Amide Hydrolase (FAAH), their stereoisomers, tautomers, prodrugs, polymorphs, solvates, pharmaceutically acceptable salts, and pharmaceutical compositions containing them. These compounds are useful in the treatment, prevention, prophylaxis, management, or adjunct treatment of all medical conditions related to inhibition of Fatty Acid Amide Hydrolase (FAAH), such as pain including acute and post operative pain, chronic pain, cancer pain, cancer chemotherapy induced pain, neuropathic pain, nociceptive pain, inflammatory pain, back pain, pain due to disease of various origin such as: diabetic neuropathy, neurotropic viral disease including human immunodeficient virus (HIV), herpes zoster such as post herpetic neuralgia; polyneuropathy, neurotoxicity, mechanical nerve injury, carpal tunnel syndrome, immunologic mechanisms like multiple sclerosis; sleep disorders, anxiety and depression disorders, inflammatory disorders, weight and eating disorders, Parkinson's disease, addiction, spasticity, hypertension or other disorders. The disclosure also relates to the process of preparation of the amide compounds. The present disclosure also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.

  本公开涉及替代酰胺化合物，它们是脂肪酸酰胺水解酶（FAAH）的抑制剂，包括它们的立体异构体、互变异构体、前药、多型体、溶剂合物、药用可接受盐以及含有它们的药物组合物。这些化合物在治疗、预防、预防、管理或辅助治疗与脂肪酸酰胺水解酶（FAAH）抑制相关的所有医疗状况中非常有用，如疼痛，包括急性和术后疼痛，慢性疼痛，癌症疼痛，癌症化疗引起的疼痛，神经痛，伤害性疼痛，炎症性疼痛，背部疼痛，疾病引起的疼痛，如糖尿病性神经病变，神经病毒性疾病，包括人类免疫缺陷病毒（HIV），带状疱疹，如带状疱疹后神经痛；多发性神经病，神经毒性，机械神经损伤，腕管综合症，免疫机制如多发性硬化症；睡眠障碍，焦虑和抑郁症，炎症性疾病，体重和进食障碍，帕金森病，成瘾，痉挛，高血压或其他疾病。本公开还涉及酰胺化合物的制备过程。本公开还涉及制备这类化合物的方法，以及含有它们的药物组合物。
• 4-[3-(ARYLOXY)BENZYLIDENE]-3-METHYL PIPERIDINE 5-MEMBERED ARYL CARBOXAMIDE COMPOUNDS USEFUL AS FAAH INHIBITORS
  申请人：Meyers Marvin Jay

  公开号：US20110060012A1

  公开（公告）日：2011-03-10

  The present invention relates to compounds of Formula (I), wherein Ar is a 5-membered heteroaryl moiety and X, Y and Z are independently N or CH; or a pharmaceutically acceptable salt thereof; processes for the preparation of the compounds; intermediates used in the preparation of the compounds; compositions containing the compounds; and uses of the compounds in treating diseases or conditions associated with fatty acid amide hydrolase (FAAH) activity.

  本发明涉及公式（I）的化合物，其中Ar是5-成员杂环芳基基团，X，Y和Z分别是N或CH；或其药学上可接受的盐；制备该化合物的方法；用于制备该化合物的中间体；含有该化合物的组合物；以及用于治疗与脂肪酸酰胺水解酶（FAAH）活性相关的疾病或病况的化合物的用途。
• 4-[3-(ARYLOXY)BENZYLIDENE]-3-METHYL PIPERIDINE ARYL CARBOXAMIDE COMPOUNDS USEFUL AS FAAH INHIBITORS
  申请人：Meyers Marvin Jay

  公开号：US20110053949A1

  公开（公告）日：2011-03-03

  The present invention relates to compounds of Formula (I), wherein Ar is optionally substituted phenyl or heteroaryl and X, Y and Z are independently N or CH; or a pharmaceutically acceptable salt thereof; processes for the preparation of the compounds; intermediates used in the preparation of the compounds; compositions containing the compounds; and uses of the compounds in treating diseases or conditions associated with fatty acid amide hydrolase (FAAH) activity.

  本发明涉及式（I）的化合物，其中Ar是可选取代的苯基或杂环芳基，X、Y和Z分别是N或CH；或其药学上可接受的盐；制备该化合物的方法；制备该化合物所用的中间体；含有该化合物的组合物；以及使用该化合物治疗与脂肪酸酰胺水解酶（FAAH）活性相关的疾病或症状。