N-methyl-N-[(piperidin-1-yl)sulfonyl]-3-(4-chloropheny)-4-phenyl-4,5-dihydro-(1H)-pyrazole-1-carboxamidine | 505031-07-2

• 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: N-methyl-N-[(piperidin-1-yl)sulfonyl]-3-(4-chloropheny)-4-phenyl-4,5-dihydro-(1H)-pyrazole-1-carboxamidine
• 英文别名: 3-(4-chlorophenyl)-N-methyl-4-phenyl-N'-(piperidin-1-ylsulfonyl)-4,5-dihydro-1H-pyrazole-1-carboxamidine；3-(4-chlorophenyl)-N-methyl-4-phenyl-N'-((piperidin-1-yl)sulfonyl)-4,5-dihydro-1H-pyrazole-1-carboxamidine；5-(4-chlorophenyl)-N'-methyl-4-phenyl-N-piperidin-1-ylsulfonyl-3,4-dihydropyrazole-2-carboximidamide
• CAS: 505031-07-2
• 化学式: C₂₂H₂₆ClN₅O₂S
• 分子量: 460.0
• InChiKey: VXVYAAXIGIEBPP-UHFFFAOYSA-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

• 作为反应物：
  描述：

  N-methyl-N-[(piperidin-1-yl)sulfonyl]-3-(4-chloropheny)-4-phenyl-4,5-dihydro-(1H)-pyrazole-1-carboxamidine 生成 (S)-3-(4-chloropheny)-4-phenyl-4,5-dihydro-(1H)-pyrazole-1-[N-methyl-N'-(piperidin-1-yl)sulfonyl]carboxamidine 、 (R)-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
• 作为产物：
  描述：

  3-(4-氯苯基)-4- 苯基-4,5-二氢-1H-吡唑 以 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 35.0h， 生成 N-methyl-N-[(piperidin-1-yl)sulfonyl]-3-(4-chloropheny)-4-phenyl-4,5-dihydro-(1H)-pyrazole-1-carboxamidine
  参考文献：
  名称：

  An expedient atom-efficient synthesis of the cannabinoid CB1 receptor inverse agonist ibipinabant

  摘要：

  A novel synthetic route to the highly selective and orally active cannabinoid CB, receptor inverse agonist ibipinabant is described which combines the use of inexpensive, commercially available reagents and mild reaction conditions with a high degree of atom-efficiency. The method is expected to enable the rapid synthesis of a variety of sulfonylguanidines. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.01.068

文献信息

• [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。
• 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。
• FLUORO-SUBSTITUTED 3,4-DIARYL-4,5-DIHYDRO-1H-PYRAZOLE-1-CARBOXAMIDINE DERIVATIVES HAVING CB1-ANTAGONISTIC ACTIVITY
  申请人：Lange Josephus H.M.

  公开号：US20110172274A1

  公开（公告）日：2011-07-14

  This invention concerns fluorinated 3,4-diaryl-4,5-dihydro-1H-pyrazole-1-carboxamidine derivatives as cannabinoid-CB 1 receptor antagonists, methods for preparing these compounds, novel intermediates useful for the synthesis of said compounds, methods for the preparation of these intermediates, pharmaceutical compositions containing one or more of these dihydropyrazole derivatives as active ingredient, as well as the use of these pharmaceutical compositions for the treatment of obesity and obesity-related cardiovascular disorders, drug addiction, cognition deficits, liver fibrosis and inflammatory disorders. The compounds have the general formula (I) wherein the symbols have the meanings given in the specification.

  本发明涉及氟化的3,4-二芳基-4,5-二氢-1H-吡唑-1-羧酰胺衍生物，作为大麻素CB1受体拮抗剂，制备这些化合物的方法，用于合成上述化合物的新型中间体，制备这些中间体的方法，含有一种或多种这些二氢吡唑衍生物作为活性成分的制药组合物，以及利用这些制药组合物治疗肥胖和肥胖相关心血管疾病、药物成瘾、认知缺陷、肝纤维化和炎症性疾病的用途。这些化合物的一般式为(I)，其中符号的含义在说明书中给出。
• SYNTHESIS OF 3,4-DIARYL-4,5-DIHYDRO-(H)-PYRAZOLE-1-CARBOXAMIDINE DERIVATIVES
  申请人：Lange Josephus H.M.

  公开号：US20110137040A1

  公开（公告）日：2011-06-09

  The invention relates to a novel chemical route to 3,4-diaryl-4,5-dihydro-(1H)-pyrazole-1-carbox-amidine derivatives, known as potent cannabinoid-CB 1 receptor antagonists, and to novel intermediates of these compounds. The synthetic route produced considerably higher yields than those reported, without the use of corrosive reagents. The process concerns the preparation of a compound of formula (I): wherein the symbols have the meanings given in the description.

  该发明涉及一种新型化学路线，用于制备3,4-二芳基-4,5-二氢-(1H)-吡唑-1-羧酸脒衍生物，也称为有效的大麻素-CB1受体拮抗剂，并涉及这些化合物的新型中间体。该合成路线产生的产率比报道的高得多，而且不使用腐蚀性试剂。该过程涉及制备式（I）的化合物：其中符号具有描述中给出的含义。