(2R)-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-N-[(2R)-1-(4-carbamimidoyl-1,4-diazepan-1-yl)-6-(methylamino)-1-oxohexan-2-yl]-4-methylpentanamide | 1024828-74-7

• 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: (2R)-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-N-[(2R)-1-(4-carbamimidoyl-1,4-diazepan-1-yl)-6-(methylamino)-1-oxohexan-2-yl]-4-methylpentanamide
• CAS: 1024828-74-7
• 化学式: C₃₇H₅₇N₉O₄
• 分子量: 691.917
• InChiKey: BWOLOWBBCGTZIF-SEVDZJIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  50
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  199
• 氢给体数：
  7
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  在 三氟甲磺酸三甲基硅酯 、 间甲酚 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (2R)-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-N-[(2R)-1-(4-carbamimidoyl-1,4-diazepan-1-yl)-6-(methylamino)-1-oxohexan-2-yl]-4-methylpentanamide
  参考文献：
  名称：

  Synthetic peptide amides

  摘要：

  该发明涉及合成肽酰胺配体与kappa阿片受体，特别是kappa阿片受体激动剂，表现出低的P450 CYP抑制作用和低的脑内渗透性。该发明的合成肽酰胺符合以下结构的结构：含有这些化合物的药物组合物在预防和治疗与多种疾病和病况相关的疼痛和炎症方面是有用的。这种可治疗的疼痛包括内脏疼痛、神经病性疼痛和过敏症。与疾病如炎症性肠病和肠易激综合症、眼部和耳部炎症、其他疾病和病况如瘙痒、水肿、低钠血症、低钾血症、肠梗阻、咳嗽和青光眼相关的炎症可以通过该发明的药物组合物进行治疗或预防。

  公开号：

  US07402564B1

文献信息

• SYNTHETIC PEPTIDE AMIDES
  申请人：Schteingart Claudio D.

  公开号：US20090075907A1

  公开（公告）日：2009-03-19

  The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P 450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.

  本发明涉及合成肽酰胺类κ-阿片受体配体，特别涉及表现出低P450CYP抑制和低脑内渗透的κ-阿片受体激动剂。本发明的合成肽酰胺符合公式I的结构：含有这些化合物的药物组合物在预防和治疗与各种疾病和病况相关的疼痛和炎症方面非常有用。这种可治疗的疼痛包括脏器疼痛，神经病理性疼痛和过度疼痛反应。与条件，如炎症相关的炎症，眼部和耳部炎症，其他疾病和病况，如瘙痒，水肿，低钠血症，低钾血症，肠梗阻，咳嗽和青光眼，均可通过本发明的药物组合物得到治疗或预防。
• SYNTHETIC PEPTIDE AMIDES AND DIMERIC FORMS THEREOF
  申请人：Schteingart Claudio D.

  公开号：US20100075910A1

  公开（公告）日：2010-03-25

  The invention relates to synthetic peptide amides that are ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P 450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: wherein Xaa is a D-amino acid and G is selected from the following three groups: The compounds are useful in the prophylaxis and treatment of pain, pruritus and inflammation associated with a variety of diseases and conditions.

  本发明涉及合成的肽酰胺，它们是kappa阿片受体的配体，特别是kappa阿片受体的激动剂，表现出低的P450CYP抑制和低的进入大脑的能力。本发明的合成肽酰胺符合以下结构：其中Xaa是D-氨基酸，G选择自以下三个组：这些化合物在预防和治疗与各种疾病和情况相关的疼痛、瘙痒和炎症方面非常有用。
• USES OF KAPPA OPIOID SYNTHETIC PEPTIDE AMIDES
  申请人：Schteingart Claudio D.

  公开号：US20110212882A1

  公开（公告）日：2011-09-01

  The invention relates to methods of use of synthetic peptide amides that are ligands of the kappa opioid receptor in the treatment and prevention of kappa opioid receptor-associated diseases and conditions; and particularly to uses of these agonists in the prophylaxis, inhibition and treatment of pain, inflammation and pruritis associated with a variety of diseases, disorders and conditions. Inflammatory conditions preventable or treatable by the methods of the invention include diseases and conditions associated with elevated levels of a proinflammatory cytokines, such as TNF-α, IL-β, IL-6, MMP-1 and MMP-3. Such diseases and conditions include cardiovascular inflammation, neurological inflammation, skeletal inflammation, muscular inflammation, gastrointestinal inflammation, ocular inflammation, otic inflammation, inflammation due to insect bites and inflammation due to wound healing; atherosclerosis, ischemia, restenosis and vasculitis; of asthma, Sjogren's syndrome, pulmonary inflammation, chronic airway inflammation and chronic obstructive pulmonary disease (COPD), allergy, psoriasis, psoriatic arthritis, eczema, scleroderma, atopic dermatitis and systemic lupus erythematosus, arthritis, synovitis, osteomyelitis, rheumatoid arthritis, osteoarthritis and ankylosing spondylitis; septicemia and septic shock, diabetes, glucose intolerance, insulin resistance and obesity, colitis, ulcerative colitis, Crohn's disease, IBD and IBS, and the inflammatory diseases and conditions due to tumor proliferation, tumor metastasis or transplantation rejection.

  本发明涉及使用合成肽酰胺作为κ-阿片受体配体在预防和治疗κ-阿片受体相关疾病和病况中的方法；特别是在预防、抑制和治疗与多种疾病、障碍和病况相关的疼痛、炎症和瘙痒方面使用这些激动剂。本发明方法可预防或治疗与促炎性细胞因子水平升高有关的炎症疾病和病况，如TNF-α、IL-β、IL-6、MMP-1和MMP-3。这些疾病和病况包括心血管炎症、神经炎症、骨骼炎症、肌肉炎症、胃肠炎症、眼部炎症、耳部炎症、由昆虫叮咬引起的炎症和由伤口愈合引起的炎症；动脉粥样硬化、缺血、再狭窄和血管炎；哮喘、Sjogren综合症、肺部炎症、慢性气道炎症和慢性阻塞性肺病（COPD）、过敏、银屑病、银屑病性关节炎、湿疹、硬皮病、特应性皮炎和系统性红斑狼疮、关节炎、滑膜炎、骨髓炎、类风湿性关节炎、骨关节炎和强直性脊柱炎；败血症和感染性休克、糖尿病、葡萄糖不耐受、胰岛素抵抗和肥胖、结肠炎、溃疡性结肠炎、克罗恩病、炎症性肠病和肠易激综合症，以及由肿瘤增殖、肿瘤转移或移植排斥引起的炎症疾病和病况。
• Methods and compositions for treating vasomotor symptoms
  申请人：UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION

  公开号：US11083726B2

  公开（公告）日：2021-08-10

  The present disclosure is generally directed to compositions and methods for treating or limiting development of vasomotor symptoms in a subject.

  本公开总体上涉及用于治疗或限制受试者血管运动症状发展的组合物和方法。
• Oral formulations of kappa opioid receptor agonists
  申请人：Cara Therapeutics, Inc.

  公开号：US11033629B2

  公开（公告）日：2021-06-15

  The invention provides formulations for oral delivery of a therapeutic agent wherein the formulation comprises a kappa opioid receptor agonist and an absorption enhancer, the absorption enhancer includes a medium chain fatty acid or a salt of a medium chain fatty acid; and a medium chain fatty acid glyceride. The kappa opioid receptor agonist may be embedded in an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists and the absorption enhancer of the invention and methods use of these formulations for the prophylaxis and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation; the method comprising administering to the mammal the formulation comprising the kappa opioid receptor agonist and an absorption enhancer.

  本发明提供了用于口服给药的制剂，其中制剂包括卡巴阿片受体激动剂和吸收促进剂，吸收促进剂包括中链脂肪酸或中链脂肪酸的盐；以及中链脂肪酸甘油酯。卡巴阿片受体激动剂可以包埋在低聚糖中，例如树胶糖。还提供了含有本发明卡巴阿片受体激动剂和吸收促进剂口服制剂的胶囊，以及使用这些制剂预防和治疗各种卡巴阿片受体相关疾病和病症（如疼痛、瘙痒和炎症）的方法；该方法包括向哺乳动物施用包含卡巴阿片受体激动剂和吸收促进剂的制剂。