1-(3-chloro-4-methylphenyl)-2-methylpiperazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(3-chloro-4-methylphenyl)-2-methylpiperazine
• 化学式: C₁₂H₁₇ClN₂
• 分子量: 224.733
• InChiKey: NMAJBBPAZUZNGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  苯基N-2-(5-甲基噻唑基)氨基甲酸酯 、 1-(3-chloro-4-methylphenyl)-2-methylpiperazine 在 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以18%的产率得到4-(3-chloro-4-methylphenyl)-3-methyl-N-(5-methylthiazol-2-yl)piperazine-1-carboxamide
  参考文献：
  名称：

  Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents

  摘要：

  A persistent latent reservoir of virus in CD4(+) T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC(50)s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112254
• 作为产物：
  描述：

  2-甲基哌嗪 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 31.0h， 生成 1-(3-chloro-4-methylphenyl)-2-methylpiperazine
  参考文献：
  名称：

  Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents

  摘要：

  A persistent latent reservoir of virus in CD4(+) T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC(50)s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112254

文献信息

• [EN] N-PHENYL-PIPERAZINE DERIVATIVES AND METHODS OF PROPHYLAXIS OR TREATMENT OF 5HT2C RECEPTOR ASSOCIATED DISEASES<br/>[FR] DERIVES DE N-PHENYL-PIPERAZINE ET METHODES DE PROPHYLAXIE OU DE TRAITEMENT DE MALADIES ASSOCIEES AU RECEPTEUR 5HT2C
  申请人：ARENA PHARM INC

  公开号：WO2005016902A1

  公开（公告）日：2005-02-24

  The present invention relates to certain substituted N-phenyl-piperazine derivatives of Formula: (I) that are modulators of the 5HT2c receptor. Accordingly, compounds of the present invention are useful for the prophylaxis or treatment of 5HT2c receptor associated diseases or disorders, such as, obesity, Alzheimer Disease, erectile dysfunction and related disorders.

  本发明涉及某些Formula: (I)的取代N-苯基哌嗪衍生物，它们是5HT2c受体的调节剂。因此，本发明的化合物对于预防或治疗与5HT2c受体相关的疾病或紊乱，如肥胖症、阿尔茨海默病、勃起功能障碍及相关疾病，是有用的。
• N-phenyl-piperazine derivatives and methods of prophylaxis or treatment of 5ht2c receptor associated diseases
  申请人：Smith Brian

  公开号：US20070179155A1

  公开（公告）日：2007-08-02

  The present invention relates to certain substituted N-phenyl-piperazine derivatives of Formula: (I) that are modulators of the 5HT 2c receptor. Accordingly, compounds of the present invention are useful for the prophylaxis or treatment of 5HT 2c receptor associated diseases or disorders, such as, obesity, Alzheimer Disease, erectile dysfunction and related disorders.

  本发明涉及某些替代N-苯基哌嗪衍生物，其化学式为：(I)，它们是5HT2c受体的调节剂。因此，本发明的化合物对于预防或治疗与5HT2c受体相关的疾病或疾病，如肥胖症、阿尔茨海默病、勃起功能障碍和相关疾病是有用的。
• THERAPEUTIC AGENT FOR STRESS URINARY INCONTINENCE AND FECAL INCONTINENCE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP3733204A1

  公开（公告）日：2020-11-04

  The present invention provides a medicament for use in treating stress urinary incontinence with fewer adverse effects including a body weight lowering effect. The present invention also provides a medicament for use in treating a disease such as incontinence of feces and further provide a medicament for use in treating a disease such as incontinence of feces with fewer adverse effects including a body weight lowering effect. A medicament for use in treating stress urinary incontinence, comprising a 5-HT2C receptor agonist, wherein the medicament is administered at a dosage lower than the minimum dosage of the agonist as an anti-obesity drug. A medicament for use in treating incontinence of feces, etc., comprising a 5-HT2C receptor agonist. A medicament for use in treating incontinence of feces, comprising a 5-HT2C receptor agonist, wherein the medicament is administered at a dosage lower than the minimum dosage of the agonist as an anti-obesity drug.

  本发明提供了一种用于治疗压力性尿失禁的药物，其不良反应较少，包括降低体重的效果。本发明还提供了一种用于治疗大便失禁等疾病的药物，并进一步提供了一种用于治疗大便失禁等疾病的药物，其不良反应较少，包括有降低体重的作用。 一种用于治疗压力性尿失禁的药物，包含一种5-HT2C受体激动剂，其中该药物的给药剂量低于作为抗肥胖药物的激动剂的最小剂量。一种用于治疗大便失禁等的药物，包含一种 5-HT2C 受体激动剂。一种用于治疗大便失禁等的药物，包含一种5-HT2C受体激动剂，其中该药物作为抗肥胖药物以低于该激动剂最小剂量的剂量给药。
• N-PHENYL-PIPERAZINE DERIVATIVES AND METHODS OF PROPHYLAXIS OR TREATMENT OF 5HT sb 2C /sb RECEPTOR ASSOCIATED DISEASES
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP1644347A1

  公开（公告）日：2006-04-12
• THERAPEUTIC AGENTS FOR STRESS URINARY INCONTINENCE AND INCOTINENCE OF FECES
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20210052600A1

  公开（公告）日：2021-02-25

  The present invention provides a medicament for use in treating stress urinary incontinence with fewer adverse effects including a body weight lowering effect. The present invention also provides a medicament for use in treating a disease such as incontinence of feces and further provide a medicament for use in treating a disease such as incontinence of feces with fewer adverse effects including a body weight lowering effect. A medicament for use in treating stress urinary incontinence, comprising a 5-HT 2C receptor agonist, wherein the medicament is administered at a dosage lower than the minimum dosage of the agonist as an anti-obesity drug. A medicament for use in treating incontinence of feces, etc., comprising a 5-HT 2C receptor agonist. A medicament for use in treating incontinence of feces, comprising a 5-HT 2C receptor agonist, wherein the medicament is administered at a dosage lower than the minimum dosage of the agonist as an anti-obesity drug.