4-甲基-1,4-二氮杂环庚-1-甲脒 | 59775-29-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂卓
• 中文名称: 4-甲基-1,4-二氮杂环庚-1-甲脒
• 英文名称: 1-Methyl-4-guanyl-homopiperazin
• 英文别名: 4-methyl-[1,4]diazepane-1-carboximidic acid amide；4-Methyl-1,4-diazepane-1-carboximidamide
• CAS: 59775-29-0
• 化学式: C₇H₁₆N₄
• 分子量: 156.231
• InChiKey: VPKIYAFZAMGOMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  56.4
• 氢给体数：
  2
• 氢受体数：
  2

文献信息

• SYNTHETIC PEPTIDE AMIDES AND DIMERS THEREOF
  申请人：Schteingart Claudio D.

  公开号：US20090264373A1

  公开（公告）日：2009-10-22

  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: 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，特别是表现出低P450CYP抑制和低穿透脑血屏障的κ-阿片受体激动剂。本发明的合成肽酰胺符合以下结构：含有这些化合物的制药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内脏疼痛、神经病理性疼痛和过敏症。与炎症相关的病况，例如IBD和IBS、眼和耳炎症、其他疾病和病况，例如瘙痒、水肿、低钠血症、低钾血症、肠梗阻、咳嗽和青光眼，均可通过本发明的制药组合物进行治疗或预防。
• 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。
• SYNTHETIC PEPTIDE AMIDES
  申请人：Schteingart Claudio D.

  公开号：US20130012448A1

  公开（公告）日：2013-01-10

  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，特别是低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：包含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内脏疼痛、神经病理性疼痛和过敏症。与条件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通过本发明的药物组合物进行治疗或预防。
• POLYAMIDE COMPOUND AND USE THEREOF
  申请人：Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

  公开号：EP3521301A1

  公开（公告）日：2019-08-07

  The invention relates to a polyamide compound and a use thereof. Specifically, the invention relates to a type of polyamide compound (which preferably comprise one or more amide bonds formed by condensation of same or different L-amino acids or D-amino acids), or stereoisomers, crystalline polymorphs, solvates, metabolites, prodrugs or pharmaceutically acceptable salts or esters thereof, or pharmaceutical compositions thereof, as well as a method for preparing the polyamide compound and a use thereof in the prevention or treatment of diseases associated with κ-opioid receptor. The polyamide compound of the invention has excellent κ-opioid receptor agonistic activity and hydrophilicity, thus having a lesser ability of penetrating the blood-brain barrier and a lower capacity for entering the brain. The compound of the invention has higher selectivity for a κ-opioid receptor, lower addictiveness, improved pharmacokinetic properties, and improved safety (lower toxicity and/or fewer side effects), good patient compliance, and/or lesser propensity for developing tolerance, among other excellent medicinal properties.

  本发明涉及一种聚酰胺化合物及其用途。具体地说，本发明涉及一种聚酰胺化合物（优选包括由相同或不同的 L-氨基酸或 D-氨基酸缩合形成的一个或多个酰胺键），或其立体异构体、结晶多晶体、溶解物、代谢物、原药或药学上可接受的盐或酯，或其药物组合物，以及制备该聚酰胺化合物的方法及其在预防或治疗与 κ-阿片受体相关的疾病中的用途。本发明的聚酰胺化合物具有优异的κ-阿片受体激动活性和亲水性，因此穿透血脑屏障的能力较弱，进入大脑的能力较低。本发明化合物对κ-阿片受体具有更高的选择性、更低的成瘾性、更好的药代动力学特性、更好的安全性（更低的毒性和/或更少的副作用）、良好的患者依从性和/或更低的产生耐受性的倾向，以及其他优异的药用特性。