(3R)-1-(3-氯吡啶-2-基)-3-甲基哌嗪 | 393513-95-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: (3R)-1-(3-氯吡啶-2-基)-3-甲基哌嗪
• 中文别名: (R)-1-(3-氯吡啶-2-基)-3-甲基哌嗪
• 英文名称: (R)-1-(3-chloropyridin-2-yl)-3-methylpiperazine
• 英文别名: (R)-4-(3-chloro-2-pyridinyl)-2-methylpiperazine；(3R)-1-(3-chloropyridin-2-yl)-3-methylpiperazine
• CAS: 393513-95-6
• 化学式: C₁₀H₁₄ClN₃
• 分子量: 211.694
• InChiKey: ZIHUFGHPYQTYIP-MRVPVSSYSA-N

物化性质

• 密度：
  1.157

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R)-1-(3-氯吡啶-2-基)-3-甲基哌嗪 在 四氧化锇 、 四(三苯基膦)钯 、 2,6-二叔丁基苯酚 、 溴 、 N-甲基吗啉氧化物 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 14.5h， 生成 1-(5-Chloro-6-{(R)-3-methyl-4-[6-trifluoromethyl-4-(3,4,5-trifluoro-phenyl)-1H-benzoimidazol-2-yl]-piperazin-1-yl}-pyridin-3-yl)-ethane-1,2-diol
  参考文献：
  名称：

  Design of Potent, Orally Available Antagonists of the Transient Receptor Potential Vanilloid 1. Structure−Activity Relationships of 2-Piperazin-1-yl-1H-benzimidazoles

  摘要：

  The vanilloid receptor-1 ( VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Herein, we describe the synthesis and the structure-activity relationships of a series of 2-(4-pyridin-2-ylpiperazin-1-yl)-1H-benzo-[ d] imidazoles as novel TRPV1 antagonists. Compound 46ad was among the most potent analogues in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. Compound 46ad also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund's adjuvant ( CFA).

  DOI：

  10.1021/jm060065y
• 作为产物：
  描述：

  2,3-二氯吡啶 、 (R)-(-)-2-甲基哌嗪 生成 (3R)-1-(3-氯吡啶-2-基)-3-甲基哌嗪
  参考文献：
  名称：

  VANILLOID RECEPTOR LIGANDS AND THEIR USE IN TREATMENTS

  摘要：

  治疗苯并咪唑及其含量物，用于急性、炎症性和神经痛、牙痛、一般头痛、偏头痛、集群性头痛、混合血管和非血管综合症、紧张型头痛、一般炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠病、炎症性眼病、炎症性或不稳定的膀胱疾病、牛皮癣、有炎症成分的皮肤病、慢性炎症状况、炎症性疼痛和相关的高敏感性和触痛、神经痛和相关的高敏感性和触痛、糖尿病神经病疼痛、烧伤后疼痛、交感神经维持的疼痛、去感觉综合症、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿、胃肠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、一般胃肠疾病、胃溃疡、十二指肠溃疡、腹泻、坏死性剂引起的胃损伤、头发生长、血管运动或过敏性鼻炎、支气管疾病或膀胱疾病。

  公开号：

  US20090143575A1

文献信息

• [EN] BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS VANILLOID RECEPTOR LIGANDS<br/>[FR] DERIVES DE BENZIMIDAZOLES ET UTILISATION DE CEUX-CI EN TANT QUE LIGANDS DU RECEPTEUR VANILLOIDE
  申请人：AMGEN INC

  公开号：WO2004035549A1

  公开（公告）日：2004-04-29

  Compounds of formula (I) are useful in the treatment of vanilloid-receptor-meditated diseases, such as inflammatory or neuropathic pain and diseases involving sensory nerve function such as asthma, rheumatoid arthritis, osteoarthritis, inflammatory bowel disorders, urinary incontinence, migraine and psoriasis.

  式（I）的化合物在治疗辣椒素受体介导的疾病方面很有用，如炎症性或神经病痛以及涉及感觉神经功能的疾病，如哮喘、类风湿性关节炎、骨关节炎、炎症性肠道疾病、尿失禁、偏头痛和牛皮癣。
• Capsaicin receptor ligands
  申请人：——

  公开号：US20020132853A1

  公开（公告）日：2002-09-19

  Disclosed are diaryl piperazines and related compounds. These compounds are selective modulators of capsaicin receptors, including human capsaicin receptors, that are, therefore, useful in the treatment of a chronic and acute pain conditions, itch and urinary incontinence. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of capsaicin receptors and as standards in assays for capsaicin receptor binding and capsaicin receptor mediated cation conductance. Methods of using the compounds in receptor localization studies are given.

  揭示了二芳基哌嗪和相关化合物。这些化合物是辣椒素受体的选择性调节剂，包括人类辣椒素受体，在慢性和急性疼痛症状、瘙痒和尿失禁的治疗中非常有用。还提供了治疗这些疾病的方法以及包装的药物组合物。该发明的化合物还可用作辣椒素受体的定位探针，并作为辣椒素受体结合和辣椒素受体介导的阳离子传导的测定中的标准。提供了使用这些化合物进行受体定位研究的方法。
• [EN] BENZOAZOLYPIPERAZINE DERIVATIVES HAVING MGLUR1- AND MGLUR5-ANTAGONISTIC ACTIVITY<br/>[FR] DERIVES DE BENZOAZOLYLPIPERAZINE PRESENTANT UNE ACTIVITE ANTAGONISTE VIS-A-VIS DE MGLUR1 ET DE MGLUR5
  申请人：EURO CELTIQUE SA

  公开号：WO2004058754A1

  公开（公告）日：2004-07-15

  A compound of formula (I) wherein Ar1, A, R3, x, and m are as disclosed herein and Ar2 is a benzothiazolyl, benzooxazolyl, or benzoimidazolyl group or a pharmaceutically acceptable salt thereof (a “Benzoazolylpiperazine Compound”), compositions comprising a Benzoazolylpiperazine Compound, and methods for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson’s disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, retricted brain function, Huntington’s chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal comprising administering to an animal in need thereof an effective amount of Benzoazolylpiperazine Compound are disclosed.

  公式（I）的化合物，其中Ar1，A，R3，x和m如本文所述，Ar2是苯并噻唑基，苯并噁唑基或苯并咪唑基或其药学上可接受的盐（“苯并咪唑基哌嗪化合物”），包含苯并咪唑基哌嗪化合物的组合物，并且揭示了治疗或预防疼痛，UI，溃疡，IBD，IBS，成瘾障碍，帕金森病，帕金森综合症，焦虑，癫痫，中风，癫痫发作，瘙痒症，精神病，认知障碍，记忆力缺失，受限的脑功能，亨廷顿舞蹈症，肌萎缩性侧索硬化症，痴呆症，视网膜病变，肌肉痉挛，偏头痛，呕吐，运动失调或抑郁症的方法，包括向需要治疗的动物中投与有效量的苯并咪唑基哌嗪化合物。
• Vanilloid receptor ligands and their use in treatments
  申请人：Amgen Inc.

  公开号：US20040152690A1

  公开（公告）日：2004-08-05

  Therapeutic benzimidazoles 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, bums, 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.

  治疗苯并咪唑和含有苯并咪唑的组合物，用于治疗急性、炎症性和神经痛、牙痛、普通头痛、偏头痛、集群头痛、混合血管和非血管综合症、紧张性头痛、一般炎症、关节炎、风湿病、骨关节炎、炎症性肠病、炎症性眼疾、炎症性或不稳定的膀胱疾病、牛皮癣、带有炎症成分的皮肤疾病、慢性炎症病状、炎症性疼痛及相关的高敏感性和痛觉过敏、神经痛及相关的高敏感性和痛觉过敏、糖尿病神经病疼痛、烧伤后疼痛、交感神经维持性疼痛、去神经症候群、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿、胃肠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、由坏死性剂引起的胃病变、头发生长、血管运动或过敏性鼻炎、支气管疾病或膀胱疾病。
• Therapeutic agents useful for treating pain
  申请人：——

  公开号：US20040106625A1

  公开（公告）日：2004-06-03

  A compound of formula: 1 wherein A, Ar, R 3 , R 6 , and m are disclosed herein, or a pharmaceutically acceptable salt thereof (a “Cyanoiminopiperazine Compound”), compositions comprising an effective amount of a Cyanoiminopiperazine Compound, and methods for treating or preventing pain, urinary incontinence, an ulcer, inflammatory-bowel disease, irritable-bowel syndrome, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia or depression in an animal comprising administering to an animal in need thereof an effective amount of a Cyanoiminopiperazine Compound are disclosed.

  本文披露了一种式为1的化合物，其中披露了A、Ar、R3、R6和m，或其药学上可接受的盐（“氰亚胺哌嗪化合物”），包括有效量的氰亚胺哌嗪化合物的组合物，以及治疗或预防动物的疼痛、尿失禁、溃疡、炎症性肠病、肠易激综合征、成瘾障碍、帕金森病、帕金森综合征、焦虑、癫痫、中风、癫痫发作、瘙痒症、精神病、认知障碍、记忆力缺陷、大脑功能受限、亨廷顿舞蹈症、肌肉痉挛、偏头痛、呕吐、运动障碍或抑郁症的方法，包括向需要治疗的动物中投与有效量的氰亚胺哌嗪化合物。