4-[氯(苯基)乙酰基]吗啉 | 18504-71-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-[氯(苯基)乙酰基]吗啉
• 英文名称: N-<2-Chlor-2-phenyl-acetyl>-morpholin
• 英文别名: 4-(chloro-phenyl-acetyl)-morpholine；4-[Chloro(phenyl)acetyl]morpholine；2-chloro-1-morpholin-4-yl-2-phenylethanone
• CAS: 18504-71-7
• 化学式: C₁₂H₁₄ClNO₂
• mdl: MFCD06655932
• 分子量: 239.702
• InChiKey: FCAFIWSACLLPGG-UHFFFAOYSA-N

物化性质

• 沸点：
  396.5±42.0 °C(Predicted)
• 密度：
  1.244±0.06 g/cm3(Predicted)
• 溶解度：
  33.5 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  4-[氯(苯基)乙酰基]吗啉 、 7-羟基黄酮 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 4-[(4-oxo-2-phenyl-4H-chromen-7-yloxy)-phenyl-acetyl]-morpholine
  参考文献：
  名称：

  Klosa,J., Journal fur praktische Chemie (Leipzig 1954), 1963, vol. 19, p. 123 - 131

  摘要：

  DOI：

文献信息

• The Addition Reaction of Samarium Enolates and 2-Haloenolates Derived from Esters, and Amides to Imines. Totally Stereoselective Synthesis of Enantiopure 3,4-Diamino Esters or Amides
  作者：José M. Concellón、Humberto Rodríguez-Solla、Carmen Simal、Vicente del Amo、Santiago García-Granda、M. Rosario Díaz

  DOI：10.1002/adsc.200900534

  日期：2009.11

  addition reaction of samarium enolates and 2-haloenolates derived from esters and amides to imines takes place in an efficient manner. A novel protocol to perform the addition reaction of samarium enolates derived from esters or amides to chiral 2-aminoimines, with total stereoselectivity and without racemization, is also reported. The use of samarium enolates in place of other classic metallic enolates

  衍生自酯和酰胺的烯醇盐和2-卤代烯醇盐以有效的方式发生加成反应。还报道了一种新颖的方案，该方案可以进行酯或酰胺衍生的烯醇sa到手性2-氨基亚胺的加成反应，该反应具有总的立体选择性且没有消旋作用。当需要低碱性的烯醇盐时，使用sa烯醇盐代替其他经典的金属烯醇盐（锂，镁等）可能是获得对映纯3,4-二氨基酯或酰胺的有价值的选择。
• [EN] SUBSTITUTED 1,4-DI-PIPERIDIN-4-YL-PIPERAZINE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS<br/>[FR] DERIVES 1,4-DI-PIPERIDIN-4-YL-PIPERAZINES SUBSTITUES EN 1,4 ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DES NEUROKININES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2004033428A1

  公开（公告）日：2004-04-22

  The invention concerns substituted 1,4-di-piperidin-4-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment of emesis, anxiety, depression, pain, pancreatitis and IBS. The compounds according to the invention can be represented by general Formula (I), and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1. In view of their capability to antagonize the actions of neurokinins by blocking the neurokinin receptors, and in particular antagonizing the actions of substance P by blocking the NK1 receptor, the compounds according to the invention are useful as a medicine, in particular in the prophylactic and therapeutic treatment of neurokinin-mediated conditions, such as, for instance CNS disorders, in particular depression, anxiety disorders, stress-related disorders, sleep disorders, cognitive disorders, personality disorders, schizoaffective disorders, eating disorders, neurodegenerative diseases, addiction disorders, mood disorders, sexual dysfunction, pain and other CNS-related conditions; inflammation; allergic disorders; emesis; gastrointestinal disorders, in particular irritable bowel syndrome (IBS); skin disorders; vasospastic diseases; fibrosing and collagen diseases; disorders related to immune enhancement or suppression and rheumatic diseases and body weight control.

  该发明涉及具有神经激肽拮抗活性的替代1,4-二哌啶-4-基哌嗪衍生物，特别是NK1拮抗活性，它们的制备，包含它们的组合物以及它们作为药物的用途，特别是用于治疗呕吐、焦虑、抑郁、疼痛、胰腺炎和肠易激综合征。根据该发明的化合物可以用一般公式（I）表示，并且还包括其药用可接受的酸或碱盐，其立体化学异构体形式，其N-氧化物形式以及其前药，其中所有取代基的定义如权利要求书1所述。鉴于它们通过阻断神经激肽受体来拮抗神经激肽的作用，特别是通过阻断NK1受体来拮抗P物质的作用，根据该发明的化合物可用作药物，特别是在预防和治疗神经激肽介导的情况下，如中枢神经系统疾病，特别是抑郁症、焦虑症、与压力有关的疾病、睡眠障碍、认知障碍、人格障碍、分裂情感障碍、进食障碍、神经退行性疾病、成瘾障碍、情绪障碍、性功能障碍、疼痛和其他中枢神经系统相关疾病；炎症；过敏性疾病；呕吐；胃肠道疾病，特别是肠易激综合征（IBS）；皮肤疾病；血管痉挛性疾病；纤维化和胶原疾病；与免疫增强或抑制以及风湿疾病和体重控制相关的疾病。
• Novel formulations of opioid-based treatments of pain comprising substituted 1,4-di-piperidin-4-yl-piperazine derivatives
  申请人：Janssens Eduard Frans

  公开号：US20060128721A1

  公开（公告）日：2006-06-15

  This invention concerns novel formulations for opioid-based treatments of pain and/or nociception comprising opioid analgesics and 1,4-di-piperidin-4-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK 1 antagonistic activity, the use of said formulation for the manufacture of a medicament for the prevention and/or treatment of emesis, pain and/or nociception, in particular in opioid-based acute and chronic pain treatments, more in particular in inflammatory, post-operative, emergency room (ER), breakthrough, neuropathic and cancer pain treatments and the use of an NK 1 -receptor antagonist for the manufacture of a medicament for the prevention and/or treatment of respiratory depression in opioid-based treatments of pain. The pharmaceutical formulations according to the invention comprise a pharmaceutically acceptable carrier and, as active ingredients, a therapeutically effective amount of an opioid analgesic and NK 1 -antagonists according to the general Formula (I) the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in claim 1. The pharmaceutical composition according to the invention reduces to a large extent a number of unwanted side-effects associated with opioid analgesics, in particular emesis, respiratory depression and tolerance, thereby increasing the total tolerability of said opioids in pain treatment.

  本发明涉及基于阿片类药物治疗疼痛和/或痛觉的新型制剂，包括阿片类镇痛剂和具有神经激肽拮抗活性的 1,4-二哌啶-4-基哌嗪衍生物，特别是 NK 1 拮抗活性，使用所述制剂制造用于预防和/或治疗呕吐、疼痛和/或痛觉的药物，特别是在基于阿片类药物的急性和慢性疼痛治疗中，尤其是在炎症、术后、急诊室（ER）、突破性、神经病理性和癌症疼痛治疗中，以及使用 NK 1 -受体拮抗剂来制造预防和/或治疗以阿片类药物为主的疼痛治疗中的呼吸抑制的药物。 根据本发明的药物制剂包括药学上可接受的载体以及作为活性成分的治疗有效量的阿片类镇痛剂和 NK 1 -拮抗剂的通式（I） 其药学上可接受的酸或碱加成盐、其立体化学异构体形式、其 N-氧化物形式和其原药，其中所有取代基的定义如权利要求 1 所述。根据本发明的药物组合物在很大程度上减少了与阿片类镇痛药相关的一些不希望出现的副作用，特别是呕吐、呼吸抑制和耐受性，从而提高了所述阿片类药物在疼痛治疗中的总体耐受性。
• Substituted 1,4,-di-piperidin-4-yl-piperazine derivatives and their use as neurokinin antagonists
  申请人：Janssens Eduard Frans

  公开号：US20060167008A1

  公开（公告）日：2006-07-27

  The invention concerns substituted 1,4-di-piperidin-4-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK 1 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment of emesis, anxiety, depression, pain, pancreatitis and IBS. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in claim 1. In view of their capability to antagonize the actions of neurokinins by blocking the neurokinin receptors, and in particular antagonizing the actions of substance P by blocking the NK 1 receptor, the compounds according to the invention are useful as a medicine, in particular in the prophylactic and therapeutic treatment of neurokinin-mediated conditions, such as, for instance CNS disorders, in particular depression, anxiety disorders, stress-related disorders, sleep disorders, cognitive disorders, personality disorders, schizoaffective disorders, eating disorders, neurodegenerative diseases, addiction disorders, mood disorders, sexual dysfunction, pain and other CNS-related conditions; inflammation; allergic disorders; emesis; gastrointestinal disorders, in particular irritable bowel syndrome (IBS); skin disorders; vasospastic diseases; fibrosing and collagen diseases; disorders related to immune enhancement or suppression and rheumatic diseases and body weight control.

  本发明涉及具有神经激肽拮抗活性，特别是 NK 1 拮抗活性的取代的 1,4-二哌啶-4-基哌嗪衍生物、它们的制备方法、包含它们的组合物以及它们作为药物的用途，特别是用于治疗呕吐、焦虑、抑郁、疼痛、胰腺炎和肠易激综合征。 根据本发明的化合物可以由通式 (I) 表示 还包括其药学上可接受的酸或碱加成盐、其立体化学异构体形式、其 N-氧化物形式和其原药，其中所有取代基的定义如权利要求 1. 鉴于它们能够通过阻断神经激肽受体来拮抗神经激肽的作用，特别是通过阻断 NK 1 受体来拮抗 P 物质的作用，因此根据本发明的化合物可用作药物，特别是用于预防和治疗神经激肽介导的疾病，例如中枢神经系统疾病，尤其是抑郁症、焦虑症、压力相关疾病、睡眠障碍、认知障碍、人格障碍、精神分裂症、进食障碍、神经退行性疾病、成瘾性疾病、情绪障碍、性功能障碍、疼痛和其他中枢神经系统相关疾病；炎症；过敏性疾病；呕吐；胃肠道疾病，特别是肠易激综合征（IBS）；皮肤疾病；血管痉挛性疾病；纤维化和胶原疾病；与免疫增强或抑制有关的疾病以及风湿性疾病和体重控制。
• The Use of Samarium Enolates, A Novel Alternative in the Addition Reactions to Imines. Synthesis of 3-Amino Esters, Amides and Enantiopure 3,4-Diamino Esters
  作者：José M. Concellón、Humberto Rodríguez-Solla、Carmen Simal

  DOI：10.1002/adsc.200900189

  日期：2009.6

  Abstractmagnified imageAn efficient reaction of tosylimines with a range of samarium enolates (derived from esters, and amides) is reported. The reaction with the α‐dibenzylamino‐N‐tert‐butanesulfinimine derived from chiral phenylalaninal afforded the corresponding enantiopure 3,4‐diamino ester with very high diastereoselectivity.