1-[4-chlorophenyl-(pyridin-2-yl)methyl]piperazine | 142404-72-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[4-chlorophenyl-(pyridin-2-yl)methyl]piperazine
• 英文别名: 1-[4-chlorophenyl-(2-pyridyl)methyl]piperazine；1-[(4-chlorophenyl)-pyridin-2-ylmethyl]piperazine
• CAS: 142404-72-6
• 化学式: C₁₆H₁₈ClN₃
• 分子量: 287.792
• InChiKey: BQTAQGYXDFYILL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-吡啶乙酸 、 1-[4-chlorophenyl-(pyridin-2-yl)methyl]piperazine 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 1-[(4-chlorophenyl)-2-pyridinylmethyl]-4-(3-pyridinylacetyl)piperazine
  参考文献：
  名称：

  Inhibitors of Farnesyl Protein Transferase. 4-Amido, 4-Carbamoyl, and 4-Carboxamido Derivatives of 1-(8-Chloro-6,11-dihydro-5H-benzo[5,6]- cyclohepta[1,2-b]pyridin-11-yl)piperazine and 1-(3-Bromo-8-chloro-6,11- dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine

  摘要：

  The synthesis of a variety of novel 4-amido, 4-carbamoyl and 4-carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin -11-yl)piperazine to explore the SAR of of this series of FPT inhibitors is described. This resulted in the synthesis of the 4- and 3-pyridylacetyl analogues 45a and 50a, respectively, both of which were orally active but were found to be rapidly metabolized in vivo. Identification of the principal metabolites led to the synthesis of a variety of new compounds that would be less readily metabolized, the most interesting of which were the 3- and 4-pyridylacetyl N-oxides 80a and 83a. Novel replacements for the pyridylacetyl moiety were also sought, and this resulted in the discovery of the 4-N-methyl and 4-N-carboxamidopiperidinylacetyl derivatives 135a and 160a, respectively. All of these derivatives exhibited greatly improved pharmacokinetics. The synthesis of the corresponding 3-bromo analogues resulted in the discovery of the 4-pyridylacetyl N-oxides 83b (+/-) and 85b [11S(-)] and the 4-carboxamidopiperidinylacetamido derivative 160b (+/-), all of which exhibited potent FPT inhibition in vitro. All three showed excellent oral bioavailability in vivo in nude mice and cynomolgus monkeys and exhibited excellent antitumor efficacy against a series of tumor cell lines when dosed orally in nude mice.

  DOI：

  10.1021/jm970462w
• 作为产物：
  描述：

  α-(4-氯苯基)吡啶-2-甲醇 在 氯化亚砜 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 21.0h， 生成 1-[4-chlorophenyl-(pyridin-2-yl)methyl]piperazine
  参考文献：
  名称：

  Inhibitors of Farnesyl Protein Transferase. 4-Amido, 4-Carbamoyl, and 4-Carboxamido Derivatives of 1-(8-Chloro-6,11-dihydro-5H-benzo[5,6]- cyclohepta[1,2-b]pyridin-11-yl)piperazine and 1-(3-Bromo-8-chloro-6,11- dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine

  摘要：

  The synthesis of a variety of novel 4-amido, 4-carbamoyl and 4-carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin -11-yl)piperazine to explore the SAR of of this series of FPT inhibitors is described. This resulted in the synthesis of the 4- and 3-pyridylacetyl analogues 45a and 50a, respectively, both of which were orally active but were found to be rapidly metabolized in vivo. Identification of the principal metabolites led to the synthesis of a variety of new compounds that would be less readily metabolized, the most interesting of which were the 3- and 4-pyridylacetyl N-oxides 80a and 83a. Novel replacements for the pyridylacetyl moiety were also sought, and this resulted in the discovery of the 4-N-methyl and 4-N-carboxamidopiperidinylacetyl derivatives 135a and 160a, respectively. All of these derivatives exhibited greatly improved pharmacokinetics. The synthesis of the corresponding 3-bromo analogues resulted in the discovery of the 4-pyridylacetyl N-oxides 83b (+/-) and 85b [11S(-)] and the 4-carboxamidopiperidinylacetamido derivative 160b (+/-), all of which exhibited potent FPT inhibition in vitro. All three showed excellent oral bioavailability in vivo in nude mice and cynomolgus monkeys and exhibited excellent antitumor efficacy against a series of tumor cell lines when dosed orally in nude mice.

  DOI：

  10.1021/jm970462w
• 作为试剂：
  描述：

  1-[4-chlorophenyl-(pyridin-2-yl)methyl]piperazine 、 N-cyclopropyl-6-chlorohexanesulfonamide 在 水 、 氯仿 、 magnesium sulfate 、 crude product 、 silica gel 、 chloroform methanol 、 1-[4-chlorophenyl-(pyridin-2-yl)methyl]piperazine 作用下， 以 N,N-二异丙基乙胺 为溶剂， 反应 6.0h， 以N-cyclopropyl-6-[4-[4-chlorophenyl-(2-pyridyl)methyl]-1-piperazinyl]hexanesulfonamide (6.29 g) as an oil (yield based on 1-[4-chlorophenyl-(2-pyridyl)methyl]piperazine: 92.7%)的产率得到N-cyclopropyl-6-[4-[4-chlorophenyl-(pyridin-2-yl)methyl]-1-piperazinyl]hexanesulfonamide
  参考文献：
  名称：

  US06172228B2

  摘要：

  公开号：

文献信息

• Substituted imidazoles as dual histamine H1 and H3 agonists or antagonists
  申请人：——

  公开号：US20020082278A1

  公开（公告）日：2002-06-27

  The present invention discloses novel substituted imidazole compounds which have H 3 receptor antagonist or dual histamine-H 1 and H 3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, nasal congestion, inflammatory and CNS-related diseases and others.

  本发明揭示了一种新型取代咪唑化合物，具有H3受体拮抗剂或双重组织胺H1和H3受体拮抗剂活性，以及制备这种化合物的方法。在另一种实施方案中，本发明揭示了包含这些咪唑环化合物的药物组成物，以及使用它们治疗过敏、鼻塞、炎症和中枢神经系统相关疾病等方法。
• PROCESS FOR PRODUCING PIPERAZINESULFONAMIDE DERIVATIVES AND SALTS THEREOF
  申请人：Azwell Inc.

  公开号：EP1020443A1

  公开（公告）日：2000-07-19

  A process for advantageously producing compounds of general formula (III), wherein R1 represents hydrogen, alkyl having 1 to 6 carbon atoms, alkoxyl having 1 to 4 carbon atoms, halogen, hydroxyl, trifluoromethyl, nitro or amino, R2 represents substituted or unsubstituted phenyl or pyridyl, R3 and R4 each represents hydrogen, alkyl having 1 to 6 carbon atoms, hydroxyalkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, or substituted or unsubstituted phenyl; and Y represents alkylene having 1 to 12 carbon atoms, and salts thereof.

  一种有利地生产通式(III)化合物的工艺，其中 R1 代表氢、具有 1 至 6 个碳原子的烷基、具有 1 至 4 个碳原子的烷氧基、卤素、羟基、三氟甲基、硝基或氨基，R2 代表取代或未取代的苯基或吡啶基，R3 和 R4 各自代表氢、具有 1 至 6 个碳原子的烷基、具有 1 至 4 个碳原子的羟烷基、具有 3 至 8 个碳原子的环烷基或取代或未取代的苯基；Y 代表具有 1 至 12 个碳原子的亚烷基及其盐类。
• SUBSTITUTED IMIDAZOLES AS DUAL HISTAMINE H1 AND H3 AGONISTS OR ANTAGONISTS
  申请人：Schering Corporation

  公开号：EP1318996A2

  公开（公告）日：2003-06-18
• US6172228B1
  申请人：——

  公开号：US6172228B1

  公开（公告）日：2001-01-09
• US6762186B2
  申请人：——

  公开号：US6762186B2

  公开（公告）日：2004-07-13