N-[(1R,2S)-2-((2-[(4-chlorophenyl)carbonyl]amino-6-methylquinazolin-4-yl)amino)cyclohexyl]-N',N"-bis(tert-butoxycarbonyl)guanidine | 1123685-30-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-[(1R,2S)-2-((2-[(4-chlorophenyl)carbonyl]amino-6-methylquinazolin-4-yl)amino)cyclohexyl]-N',N"-bis(tert-butoxycarbonyl)guanidine
• 英文别名: (1R,2S)-N-[N,N'-bis(t-butoxycarbonyl)]amidino-2-{[2-(4-chlorobenzoylamino)-6-methylquinazolin-4-yl]amino}cyclohexylamine；(1R,2S)-N-[N,N'-bis(t-butoxycarbonyl)]amidino-2-[2-(4-chlorobenzoylamino)-6-methylquinazolin-4-yl]aminocyclohexylamine；tert-butyl N-[N'-[(1R,2S)-2-[[2-[(4-chlorobenzoyl)amino]-6-methylquinazolin-4-yl]amino]cyclohexyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• CAS: 1123685-30-2
• 化学式: C₃₃H₄₂ClN₇O₅
• 分子量: 652.193
• InChiKey: GKLJUOVKIWQSMV-LOSJGSFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  156
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-[(1R,2S)-2-((2-[(4-chlorophenyl)carbonyl]amino-6-methylquinazolin-4-yl)amino)cyclohexyl]-N',N"-bis(tert-butoxycarbonyl)guanidine 在 盐酸 、 甲醇 作用下， 以 氯仿 、 乙酸乙酯 为溶剂， 反应 24.0h， 生成 N-[(1R,2S)-2-((2-[(4-chlorophenyl)carbonyl]amino-6-methylquinazolin-4-yl)amino)cyclohexyl]guanidine dihydrochloride
  参考文献：
  名称：

  Discovery and structure–activity relationships of 4-aminoquinazoline derivatives, a novel class of opioid receptor like-1 (ORL1) antagonists

  摘要：

  Synthesis and structure-activity relationship studies of a series of 4-aminoquinazoline derivatives led to the identification of (1R, 2S)-17, N-[(1R, 2S)-2-({2-[(4-chlorophenyl) carbonyl] amino-6-methylquinazolin-4-yl} amino) cyclohexyl] guanidine dihydrochloride, as a highly potent ORL1 antagonist with up to 3000-fold selectivity over the mu, delta, and kappa opioid receptors. Molecular modeling clarified the structural factors contributing to the high affinity and selectivity of (1R, 2S)-17. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.11.012
• 作为产物：
  描述：

  2,4-二氯-6-甲基喹唑啉 在 4-二甲氨基吡啶 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 136.5h， 生成 N-[(1R,2S)-2-((2-[(4-chlorophenyl)carbonyl]amino-6-methylquinazolin-4-yl)amino)cyclohexyl]-N',N"-bis(tert-butoxycarbonyl)guanidine
  参考文献：
  名称：

  EP1371376

  摘要：

  公开号：

文献信息

• Antipruritics
  申请人：——

  公开号：US20040116450A1

  公开（公告）日：2004-06-17

  The present invention relates to an antipruritic agent comprising a nociceptin antagonist as an active ingredient. The nociceptin antagonist can be used as a preventive or remedy for diseases associated with itching (for example, atopic dermatitis and urticaria), local pruritus cutaneous caused by insect excretion and secretion, nodular prurigo, kidney dialysis, diabetes, blood disease, liver disease, kidney disease, incretion and metabolic disorder, viscera malignant tumor, hyperthyroidism, autoimmune disease, multiple sclerosis, neurologic disease, psychoneurosis, allergic conjunctivitis, spring catarrh, atopic keratoconjunctivitis, or itching caused by excess use of laxuries and drugs because it has excellent scrtaching behavior suppressing effect, that is, antiitching effect and antipruritic effect.

  本发明涉及一种抗瘙痒剂，其包含一种镇痛肽拮抗剂作为活性成分。该镇痛肽拮抗剂可用作与瘙痒有关的疾病的预防或治疗（例如，特应性皮炎和荨麻疹），由昆虫排泄物和分泌物引起的局部皮肤瘙痒，结节性瘙痒，肾透析，糖尿病，血液疾病，肝脏疾病，肾脏疾病，内分泌和代谢紊乱，内脏恶性肿瘤，甲状腺功能亢进，自身免疫疾病，多发性硬化症，神经系统疾病，精神神经症，过度使用泻药和药物引起的瘙痒，因为它具有出色的抓痒行为抑制作用，即抗瘙痒作用和抗瘙痒作用。
• ANTIPRURITICS
  申请人：Nippon Shinyaku Co., Ltd.

  公开号：EP1371376A1

  公开（公告）日：2003-12-17

  The present invention relates to an antipruritic agent comprising a nociceptin antagonist as an active ingredient. The nociceptin antagonist can be used as a preventive or remedy for diseases associated with itching (for example, atopic dermatitis and urticaria), local pruritus cutaneous caused by insect excretion and secretion, nodular prurigo, kidney dialysis, diabetes, blood disease, liver disease, kidney disease, incretion and metabolic disorder, viscera malignant tumor, hyperthyroidism, autoimmune disease, multiple sclerosis, neurologic disease, psychoneurosis, allergic conjunctivitis, spring catarrh, atopic keratoconjunctivitis, or itching caused by excess use of laxuries and drugs because it has excellent scrtaching behavior suppressing effect, that is, antiitching effect and antipruritic effect.

  本发明涉及一种止痒剂，其活性成分包括一种神经痛素拮抗剂。痛觉素拮抗剂可用于预防或治疗与瘙痒有关的疾病（例如特应性皮炎和荨麻疹）、昆虫排泄和分泌物引起的局部皮肤瘙痒症、结节性瘙痒症、肾透析、糖尿病、血液病、肝病、肾病、增生和代谢紊乱、内脏恶性肿瘤、甲状腺机能亢进症、自身免疫性疾病、多发性硬化症、神经系统疾病、精神神经症、过敏性结膜炎、春季白内障、特应性角结膜炎，或过量使用泻药和药物引起的瘙痒，因为它具有出色的抑制瘙痒行为的效果，即止痒效果和止痒效果。
• Discovery and structure–activity relationships of 4-aminoquinazoline derivatives, a novel class of opioid receptor like-1 (ORL1) antagonists
  作者：Masahiko Okano、Jun Mito、Yasufumi Maruyama、Hirofumi Masuda、Tomoko Niwa、Shin-ichiro Nakagawa、Yoshitaka Nakamura、Akira Matsuura

  DOI：10.1016/j.bmc.2008.11.012

  日期：2009.1

  Synthesis and structure-activity relationship studies of a series of 4-aminoquinazoline derivatives led to the identification of (1R, 2S)-17, N-[(1R, 2S)-2-(2-[(4-chlorophenyl) carbonyl] amino-6-methylquinazolin-4-yl} amino) cyclohexyl] guanidine dihydrochloride, as a highly potent ORL1 antagonist with up to 3000-fold selectivity over the mu, delta, and kappa opioid receptors. Molecular modeling clarified the structural factors contributing to the high affinity and selectivity of (1R, 2S)-17. (c) 2008 Elsevier Ltd. All rights reserved.
• EP1371376
  申请人：——

  公开号：——

  公开（公告）日：——