(S)-4,6-dichloro-N-(1-methoxypropan-2-yl)pyrimidin-2-amine | 879609-61-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (S)-4,6-dichloro-N-(1-methoxypropan-2-yl)pyrimidin-2-amine
• 英文别名: 4,6-dichloro-N-[(2S)-1-methoxypropan-2-yl]pyrimidin-2-amine
• CAS: 879609-61-7
• 化学式: C₈H₁₁Cl₂N₃O
• 分子量: 236.101
• InChiKey: RYHCUSRCINTJMO-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-4,6-dichloro-N-(1-methoxypropan-2-yl)pyrimidin-2-amine 在 氢碘酸 、 sodium iodide 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 (S)-4,6-diiodo-N-(1-methoxypropan-2-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Vanilloid receptor ligands and their use in treatments

  摘要：

  取代吡啶和嘧啶以及含有它们的组合物，用于治疗急性、炎症性和神经痛、牙痛、普通头痛、偏头痛、集簇头痛、混合血管和非血管综合征、紧张性头痛、一般炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠道疾病、炎症性眼部疾病、炎症性或不稳定的膀胱疾病、牛皮癣、具有炎症成分的皮肤问题、慢性炎症症状、炎症性疼痛及相关的痛觉过敏和触痛、神经痛及相关的痛觉过敏和触痛、糖尿病性神经病痛、烧灼性神经痛、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、呼吸系统、泌尿系统、消化系统或血管区域内脏动力障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道障碍、胃溃疡、十二指肠溃疡、腹泻、由坏死性药剂引起的胃损伤、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。

  公开号：

  US20060058308A1
• 作为产物：
  描述：

  2,4,6-三氯嘧啶 、 (S)-(+)-1-甲氧基-2-丙胺 以 乙醇 为溶剂， 反应 0.25h， 以12%的产率得到(S)-4,6-dichloro-N-(1-methoxypropan-2-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Design and Synthesis of Peripherally Restricted Transient Receptor Potential Vanilloid 1 (TRPV1) Antagonists

  摘要：

  Transient receptor potential vanilloid 1 (TRPV 1) channel antagonists may have clinical utility for the treatment of chronic nociceptive and neuropathic pain. We recently advanced a TRPV1 antagonist, 3 (AMG 517), into clinical trials as a new therapy for the treatment of pain. However, in addition to the desired analgesic effects, this TRPV1 antagonist significantly increased body core temperature following oral administration in rodents. Here, we, report one of our approaches to eliminate or minimize the on-target hyperthermic effect observed with this and other TRPV1 antagonists. Through modifications of our clinical candidate, 3 a series of potent and peripherally restricted TRPV1 antagonists have been prepared. These analogues demonstrated on-target coverage in vivo but caused increases in body core temperature, suggesting that peripheral restriction was not sufficient to separate antagonism mediated antihyperalgesia from hyperthermia. Furthermore, these studies demonstrate that the site of action for TRPV1 blockade elicited hyperthermia is outside the blood-brain barrier.

  DOI：

  10.1021/jm7014638

文献信息

• Vanilloid receptor ligands and their use in treatments
  申请人：Norman H. Mark

  公开号：US20060058308A1

  公开（公告）日：2006-03-16

  Substituted pyridines and pyrimidines 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, burns, 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.

  取代吡啶和嘧啶以及含有它们的组合物，用于治疗急性、炎症性和神经痛、牙痛、普通头痛、偏头痛、集簇头痛、混合血管和非血管综合征、紧张性头痛、一般炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠道疾病、炎症性眼部疾病、炎症性或不稳定的膀胱疾病、牛皮癣、具有炎症成分的皮肤问题、慢性炎症症状、炎症性疼痛及相关的痛觉过敏和触痛、神经痛及相关的痛觉过敏和触痛、糖尿病性神经病痛、烧灼性神经痛、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、呼吸系统、泌尿系统、消化系统或血管区域内脏动力障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道障碍、胃溃疡、十二指肠溃疡、腹泻、由坏死性药剂引起的胃损伤、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。
• US7335672B2
  申请人：——

  公开号：US7335672B2

  公开（公告）日：2008-02-26
• Design and Synthesis of Peripherally Restricted Transient Receptor Potential Vanilloid 1 (TRPV1) Antagonists
  作者：Nuria Tamayo、Hongyu Liao、Markian M. Stec、Xianghong Wang、Partha Chakrabarti、Dan Retz、Elizabeth M. Doherty、Sekhar Surapaneni、Rami Tamir、Anthony W. Bannon、Narender R. Gavva、Mark H. Norman

  DOI：10.1021/jm7014638

  日期：2008.5.1

  Transient receptor potential vanilloid 1 (TRPV 1) channel antagonists may have clinical utility for the treatment of chronic nociceptive and neuropathic pain. We recently advanced a TRPV1 antagonist, 3 (AMG 517), into clinical trials as a new therapy for the treatment of pain. However, in addition to the desired analgesic effects, this TRPV1 antagonist significantly increased body core temperature following oral administration in rodents. Here, we, report one of our approaches to eliminate or minimize the on-target hyperthermic effect observed with this and other TRPV1 antagonists. Through modifications of our clinical candidate, 3 a series of potent and peripherally restricted TRPV1 antagonists have been prepared. These analogues demonstrated on-target coverage in vivo but caused increases in body core temperature, suggesting that peripheral restriction was not sufficient to separate antagonism mediated antihyperalgesia from hyperthermia. Furthermore, these studies demonstrate that the site of action for TRPV1 blockade elicited hyperthermia is outside the blood-brain barrier.