(S)-3-(4-chloropheny)-4-phenyl-4,5-dihydro-(1H)-pyrazole-1-[N-methyl-N'-(piperidin-1-yl)sulfonyl]carboxamidine | 505031-78-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (S)-3-(4-chloropheny)-4-phenyl-4,5-dihydro-(1H)-pyrazole-1-[N-methyl-N'-(piperidin-1-yl)sulfonyl]carboxamidine
• 英文别名: SLV330；piperidin-1-sulfonic acid [3-(4-chloro-phenyl)-4-phenyl-4,5-dihydro-pyrazol-1-yl]-methylamino-methyleneamide；piperidine-1-sulfonic acid [3-(4-chloro-phenyl)-4-phenyl-4,5-dihydro-pyrazol-1-yl]-methylamino-methyleneamide；(-)-(4S)-3-(4-Chlorophenyl)-N-methyl-4-phenyl-N'-((piperidin-1-yl)sulfonyl)-4,5-dihydro-1H-pyrazole-1-carboxamidine；(4S)-5-(4-chlorophenyl)-N'-methyl-4-phenyl-N-piperidin-1-ylsulfonyl-3,4-dihydropyrazole-2-carboximidamide
• CAS: 505031-78-7
• 化学式: C₂₂H₂₆ClN₅O₂S
• 分子量: 460.0
• InChiKey: VXVYAAXIGIEBPP-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  85.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  在 三乙胺 、 氯甲酸三氯甲酯 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 40.0h， 生成 (S)-3-(4-chloropheny)-4-phenyl-4,5-dihydro-(1H)-pyrazole-1-[N-methyl-N'-(piperidin-1-yl)sulfonyl]carboxamidine
  参考文献：
  名称：

  Novel 3,4-diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity

  摘要：

  Novel 3,4-diarylpyrazolines 1 as potent CB1 receptor antagonists with lipophilicity lower than that of SLV319 are described. The key change is the replacement of the arylsulfonyl group in the original series by a dialkylaminosulfonyl moiety. The absolute configuration (4S) of eutomer 24 was established by X-ray diffraction analysis and 24 showed a close molecular fit with rimonabant in a CB1 receptor-based model. Compound 17 exhibited the highest CB1 receptor affinity (K-i = 24 nM) in this series, as well as very potent CB1 antagonistic activity (pA(2) = 8.8) and a high CB1/CB2 subtype selectivity (similar to 147-fold). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.054

文献信息

• COMPOUNDS WITH A COMBINATION OF CANNABINOID-CB1 ANTAGONISM AND ACETYLCHOLINESTERASE INHIBITION
  申请人：Lange Josephus H.M.

  公开号：US20080153867A1

  公开（公告）日：2008-06-26

  Embodiments of this invention relate to compounds having a combination of cannabinoid-CB 1 antagonism and cholinesterase inhibition, to pharmaceutical compositions comprising these compounds, to methods for preparing these compounds, methods for preparing novel intermediates useful for the synthesis of these compounds, and methods for preparing compositions comprising these compounds. The invention also relates to methods of treating Alzheimer's disease, cognitive disorders, memory disorders, dementia, attention deficit disorder, traumatic brain injury, drug dependence, addiction or substance abuse by administering a pharmaceutical composition comprising these compounds to a patient in need thereof. A compound with a combination of cannabinoid-CB 1 antagonism and cholinesterase inhibition is a compound of formula (1) wherein the symbols have the meanings given in the specification.

  本发明实施例涉及具有大麻素-CB1拮抗和胆碱酯酶抑制作用的化合物，包括这些化合物的制药组合物，制备这些化合物的方法，制备用于合成这些化合物的新型中间体的方法，以及制备包含这些化合物的组合物的方法。本发明还涉及通过向需要此类治疗的患者投与包含这些化合物的制药组合物来治疗阿尔茨海默病、认知障碍、记忆障碍、痴呆、注意力缺陷障碍、创伤性脑损伤、药物依赖、成瘾或药物滥用的方法。具有大麻素-CB1拮抗和胆碱酯酶抑制作用的化合物是式（1）中符号具有规范中给出的含义的化合物。
• [EN] 4,5-DIHYDRO-1H-PYRAZOLE DERIVATIVES HAVING POTENT CB1-ANTAGONISTIC ACTIVITY<br/>[FR] DERIVES 4,5-DIHYDRO-1H-PYRAZOLE PRESENTANT UNE PUISSANTE ACTIVITE ANTAGONISTE DU RECEPTEUR CB1
  申请人：SOLVAY PHARM BV

  公开号：WO2003026648A1

  公开（公告）日：2003-04-03

  The present invention relates to a group of novel 4,5-dihydro-1H-pyrazole derivatives which are potent cannabinoid (CB1) receptor antagonists with utility for the treatment of diseases connected with disorders of the cannabinoid system. The compounds have the general formula (Ia) or (Ib) wherein the symbols have the meanings given in the specification. The invention also relates to methods for the preparation of these compounds, and to pharmaceutical compositions containing one or more of these compounds as an active component.

  本发明涉及一组新型的4,5-二氢-1H-吡唑衍生物，它们是有效的大麻素受体（CB1）拮抗剂，适用于治疗与大麻素系统紊乱相关的疾病。这些化合物具有通式（Ia）或（Ib），其中符号具有规范中给出的含义。本发明还涉及制备这些化合物的方法，以及包含其中一种或多种化合物作为活性成分的制药组合物。
• 4,5-Dihydro-1h-pyrazole derivatives having potent cb1-antagonistic activity
  申请人：——

  公开号：US20040106800A1

  公开（公告）日：2004-06-03

  The present invention relates to a group of novel 4,5-dihydro-1H-pyrazole derivatives which are potent cannabinoid (CB 1 ) receptor antagonists with utility for the treatment of diseases connected with disorders of the cannabinoid system. The compounds have the general formula (Ia) or (Ib) wherein the symbols have the meanings given in the specification. The invention also relates to methods for the preparation of these compounds, and to pharmaceutical compositions containing one or more of these compounds as an active component. 1

  本发明涉及一类新型的4,5-二氢-1H-吡唑衍生物，它们是有效的大麻素（CB1）受体拮抗剂，可用于治疗与大麻素系统紊乱相关的疾病。这些化合物具有通式（Ia）或（Ib），其中符号的含义如规范中所述。本发明还涉及制备这些化合物的方法，以及包含其中一种或多种这些化合物作为活性成分的制药组合物。
• COMPOUNDS WITH A COMBINATION OF CANNABINOID CB1 ANTAGONISM AND SEROTONIN REUPTAKE INHIBITION
  申请人：Lange Josephus H.M.

  公开号：US20080214559A1

  公开（公告）日：2008-09-04

  Compounds with a combination of cannabinoid CB 1 antagonism and serotonin re-uptake inhibition, pharmaceutical compositions containing these compounds, methods for preparing these compounds, methods for preparing novel intermediates useful for their synthesis, and methods for preparing these compositions are disclosed. Uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in psychosis, anxiety, depression, attention deficits, cognitive disorders, obesity, drug dependence, Parkinson's disease, Alzheimer's disease, pain disorders, neuropathic pain disorders and sexual disorders are disclosed. In at least one embodiment, the invention relates to compounds of the general formula (1); wherein the substitutents have the definitions given in the specification.

  本发明涉及一种具有大麻素CB1拮抗和血清素再摄取抑制的化合物组合，含有这些化合物的制药组合物，制备这些化合物的方法，制备用于其合成的新型中间体的方法，以及制备这些组合物的方法。本发明还涉及这些化合物和组合物的用途，特别是将它们用于给患者施用，以在精神病、焦虑、抑郁、注意力缺陷、认知障碍、肥胖症、药物依赖、帕金森病、阿尔茨海默病、疼痛障碍、神经痛障碍和性障碍中实现治疗效果。在至少一个实施例中，本发明涉及一般式（1）的化合物；其中取代基具有规范中给出的定义。
• 4,5-Dihydro-1H-pyrazole derivatives having potent CB1-antagonistic activity
  申请人：Lange H.M. Josephus

  公开号：US20070259884A1

  公开（公告）日：2007-11-08

  The present invention relates to a group of novel 4,5-dihydro-1H-pyrazole derivatives which are potent cannabinoid (CB 1 ) receptor antagonists with utility for the treatment of diseases connected with disorders of the cannabinoid system. The compounds have the general formula (Ia) or (Ib) wherein the symbols have the meanings given in the specification. The invention also relates to methods for the preparation of these compounds, and to pharmaceutical compositions containing one or more of these compounds as an active component.

  本发明涉及一组新型的4,5-二氢-1H-吡唑衍生物，它们是具有治疗与大麻素系统紊乱相关疾病的功效的强效大麻素（CB1）受体拮抗剂。这些化合物具有通式（Ia）或（Ib），其中符号具有规范中所给定的含义。本发明还涉及制备这些化合物的方法，以及含有这些化合物之一或多个作为活性成分的制药组合物。