2-chloro-N-[(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenyl]acetamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-chloro-N-[(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenyl]acetamide
• 化学式: C₂₂H₃₆ClNO
• 分子量: 366.0
• InChiKey: WHAZXZVXLLMCTG-DOFZRALJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  25
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

文献信息

• [EN] PROCESSES FOR THE PREPARATION OF CANNABINOID RECEPTOR MODULATORS<br/>[FR] PROCÉDÉS DE PRÉPARATION DE MODULATEURS DES RÉCEPTEURS DE CANNABINOÏDES
  申请人：ARENA PHARM INC

  公开号：WO2016085941A1

  公开（公告）日：2016-06-02

  The present invention relates to processes, and process intermediates useful in the preparation of (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide (Compound 1) and crystalline forms thereof. The compound (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide has been identified as a modulator of the cannabinoid 2 (CB2) receptor and useful in the treatment of CB2 receptor-mediated disorders, for example, pain, disorders of the immune system (such as, autoimmune disorders, type 1 hypersensitivity and allergic response, conditions associated with CNS inflammation, conditions associated with vascular inflammation, and other disorders associated with aberrant or unwanted immune response), bone and joint diseases (such as, osteoporosis and arthritis), eye disease, cough, cancer, and regenerative medicine. The present invention further provides pharmaceutical compositions comprising Compound 1 and the use of the pharmaceutical compositions for the treatment of CB2 receptor-mediated disorders.

  本发明涉及用于制备(1aS,5aS)-2-(4-氧基吡嗪-2-基)-1a,2,5,5a-四氢-1H-2,3-二氮杂-环丙[a]戊二烯-4-羧酸((S)-1-羟甲基-2,2-二甲基-丙基)-酰胺(化合物1)及其结晶形式的过程和过程中间体。已确定该化合物(1aS,5aS)-2-(4-氧基吡嗪-2-基)-1a,2,5,5a-四氢-1H-2,3-二氮杂-环丙[a]戊二烯-4-羧酸((S)-1-羟甲基-2,2-二甲基-丙基)-酰胺为大麻素2(CB2)受体调节剂，并在治疗CB2受体介导的疾病中有用，例如疼痛、免疫系统疾病(如自身免疫疾病、1型超敏反应和过敏反应、与中枢神经系统炎症相关的疾病、与血管炎症相关的疾病以及其他与异常或不需要的免疫反应相关的疾病)、骨骼和关节疾病(如骨质疏松和关节炎)、眼疾、咳嗽、癌症和再生医学。本发明还提供包含化合物1的药物组合物以及用于治疗CB2受体介导的疾病的药物组合物的用途。
• [EN] CRYSTALLINE FORMS AND PROCESSES FOR THE PREPARATION OF CONDENSED AZACYCLES ( CANNABINOID RECEPTOR MODULATORS)<br/>[FR] FORMES CRISTALLINES ET PROCÉDÉS DE PRÉPARATION D'AZACYCLES CONDENSÉS (MODULATEURS DES RÉCEPTEURS DES CANNABINOÏDES)
  申请人：ARENA PHARM INC

  公开号：WO2012116276A1

  公开（公告）日：2012-08-30

  The present invention relates to crystalline forms of (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)- 1a,2,5.5a-tetrahydro- 1 H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)- 1 - hydroxymcthyl-2.2-dimcthyl-propyl)-amidc (Compound 1) and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor and are therefore useful in t treatment of CB2 receptor-mediated disorders, for example, osteoarthritis; pain; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions CNS inflammation for example; atherosclerosis; undesired immune cell activity, and inflammation associated with a disorder selected from: osteoarthritis, anaphylaxis, Behcet's disease, graft rejection, vasculitis, gout, spondylitis, viral disease, bacterial disease, lupus, inflammatory bowel disease, autoimmune hepatitis, and type 1 diabetes mellitus; age-related macular degeneration; cough; leukemia; lymphoma; CNS rumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis; and Parkinson's disease.

  本发明涉及（1aS,5aS）-2-(4-氧基吡嗪-2-基)-1a,2,5,5a-四氢-1H-2,3-二氮杂-环丙烯并[α]戊二烯-4-羧酸（(S)-1-羟甲基-2,2-二甲基-丙基）-酰胺（化合物1）的晶型及其调节大麻素CB2受体活性的药物组合物，因此在治疗CB2受体介导的疾病方面具有用处，例如骨关节炎；疼痛；过敏性疼痛；触痛；炎症性过敏性疼痛；神经病性过敏性疼痛；急性疼痛感知；骨质疏松症；多发性硬化相关的痉挛；自身免疫性疾病；过敏反应中枢神经系统炎症，例如；动脉粥样硬化；不良的免疫细胞活性，以及与所选疾病相关的炎症：骨关节炎，过敏反应，贝赫切特氏病，移植排斥反应，血管炎，痛风，脊柱炎，病毒性疾病，细菌性疾病，红斑狼疮，炎症性肠病，自身免疫性肝炎和1型糖尿病；年龄相关性黄斑变性；咳嗽；白血病；淋巴瘤；中枢神经系统肿瘤；前列腺癌；阿尔茨海默病；中风引起的损伤；痴呆症；肌萎缩侧索硬化；和帕金森病。
• [EN] CANNABINOID RECEPTOR MODULATORS<br/>[FR] MODULATEURS DES RÉCEPTEURS DES CANNABINOÏDES
  申请人：ARENA PHARM INC

  公开号：WO2012116279A1

  公开（公告）日：2012-08-30

  Provided are certain methods useful in the treatment of pain comprising administering a compound of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor.

  提供了一些在治疗疼痛方面有用的方法，包括给予化合物Ia的复方及其药物组合物，以调节大麻素CB2受体的活性。
• METHODS AND COMPOSITIONS FOR TREATING INFLAMMATION
  申请人：UNIVERSITY OF MASSACHUSETTS

  公开号：US20200138756A1

  公开（公告）日：2020-05-07

  Disclosed herein are methods and compositions for treating neutrophil-mediated inflammation by targeting, in any combination, the pro-inflammatory MRP2/HXA3 pathway and/or the anti-inflammatory P-gp/endocannabinoid pathway and/or the anti-inflammatory MRP 1/L-AMEND pathway, comprising administering to the subject a therapeutically effective amount of (a) one or more first compound that inhibits the activity and/or level of one or more of multidrug resistance protein 2 (MRP2) and hepoxilin A3 (HXA3) synthase, and/or (b) one or more second compound that increases the level and/or activity of one or more N-acylethanolamines (NAEs), and/or (c) one or more third compound that increases the level and/or activity of multidrug resistance protein 1 (MRP1), wherein the therapeutic amount of the first, second, and third compounds reduces migration of neutrophils into the target tissue.

  本文披露了一种治疗中性粒细胞介导炎症的方法和组合物，通过以任何组合方式靶向抗炎 MRP2/HXA3 途径和/或抗炎 P-gp/内源性大麻素途径和/或抗炎 MRP 1/L-AMEND 途径，包括向受试者施用治疗有效量的（a）抑制一种或多种多药耐药蛋白2（MRP2）和肝过氧化脂酸A3（HXA3）合酶的活性和/或水平的一种或多种第一化合物，和/或（b）增加一种或多种N-乙酰基乙醇胺（NAEs）的水平和/或活性的一种或多种第二化合物，和/或（c）增加一种或多种多药耐药蛋白1（MRP1）的水平和/或活性的一种或多种第三化合物，其中第一、第二和第三化合物的治疗量减少中性粒细胞向目标组织的迁移。
• [EN] COMPOSITIONS CONTAINING CANNABINOID ANALOG CONJUGATES AND METHODS OF USE<br/>[FR] COMPOSITIONS CONTENANT DES CONJUGUÉS D'ANALOGUES CANNABINOÏDES ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：VYRIPHARM ENTPR LLC

  公开号：WO2019018536A1

  公开（公告）日：2019-01-24

  Provided here are compositions containing a conjugate of a label, a chelator, and a cannabinoid analog and methods for diagnosing, treating, or monitoring the progression of a cancer or a neurologic disorder using these compositions. Also provided here are methods of synthesizing these compositions and kits for delivery of these compositions as imaging and therapeutic agents.

  在这里提供了包含标签的共轭物、螯合剂和大麻素类似物的组合物，以及使用这些组合物诊断、治疗或监测癌症或神经系统疾病进展的方法。还提供了合成这些组合物的方法以及用于传递这些组合物作为成像和治疗剂的工具包。