4-(2-pyridin-3-ylacetyl)piperazine-1-carboxylic acid tert-butyl ester | 205044-32-2

• 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: 4-(2-pyridin-3-ylacetyl)piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: 1-Boc-4-[(3-pyridinyl)acetyl]piperazine；tert-butyl 4-(2-pyridin-3-ylacetyl)piperazine-1-carboxylate
• CAS: 205044-32-2
• 化学式: C₁₆H₂₃N₃O₃
• mdl: MFCD18260075
• 分子量: 305.377
• InChiKey: YWDKWQVIXKAENU-UHFFFAOYSA-N

物化性质

• 沸点：
  481.0±45.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.562
• 拓扑面积：
  62.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-pyridin-3-ylacetyl)piperazine-1-carboxylic acid tert-butyl ester 在 硫酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 1.5h， 生成 1-(4-chlorobenzoyl)-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：

  3-吡啶乙酸 、 N-Boc-哌嗪 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， 以80%的产率得到4-(2-pyridin-3-ylacetyl)piperazine-1-carboxylic acid tert-butyl ester
  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

文献信息

• [EN] SUBSTITUTED PIPERAZINE CARBAMATES FOR USE AS INHIBITORS OF HORMONE SENSITIVE LIPASE<br/>[FR] CARBAMATES DE PIPERAZINE A SUBSTITUTION UTILISES EN TANT QU'INHIBITEURS DE LA LIPASE HORMONOSENSIBLE
  申请人：NOVO NORDISK AS

  公开号：WO2004111004A1

  公开（公告）日：2004-12-23

  Novel substituted piperazine carbamates of formula (I), pharmaceutical compositions comprising them and use thereof in the treatment and/or prevention of diseases and disorders related to hormone sensitive lipase. More particularly, the compounds are useful for the treatment and/or prevention of diseases and disorders in which modulation of the activity of hormone sensitive lipase is beneficial.

  公式(I)的新取代哌嗪氨基甲酸酯，包含它们的药物组合物及其在治疗和/或预防与激素敏感脂肪酶相关的疾病和障碍中的用途。更具体地说，这些化合物对于治疗和/或预防调节激素敏感脂肪酶活性有益的疾病和障碍非常有用。
• [EN] FUSED-ARYL AND HETEROARYL DERIVATIVES AND METHODS OF THEIR USE<br/>[FR] DERIVES HETEROARYLE ET ARYLE FUSIONNE ET METHODES D'UTILISATION ASSOCIEES
  申请人：WYETH CORP

  公开号：WO2005037283A1

  公开（公告）日：2005-04-28

  The present invention is directed to fused-aryl and heteroaryl derivatives of formula I, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibrornyalgia, pain, diabetic neuropathy, and combinations thereof. FORMULA

  本发明涉及公式I的融合芳基和杂环芳基衍生物，含有这些衍生物的组合物，以及它们用于预防和治疗由单胺再摄取改善的病症的方法，包括但不限于血管运动症状（VMS）、性功能障碍、胃肠道和泌尿系统疾病、慢性疲劳综合征、纤维肌痛综合征、神经系统疾病等，尤其是从包括重性抑郁障碍、血管运动症状、压力和急迫性尿失禁、纤维肌痛综合征、疼痛、糖尿病神经病变等在内的一组病症中选择的那些病症。
• [EN] 1- 2' (1, 4'-BIPERIDIN-1'-YL)-1- (PHENYL) -ETHYL CYCLOHEXANOL DERIVATIVES AS MONOAMINE REUPTAKE MODULATORS FOR THE TREATMENT OF VISOMOTOR SYMPTOMS<br/>[FR] DERIVES DE 1- 2' (1, 4'-BIPERIDIN-1'-YL)-1- (PHENYL) ETHYL CYCLOHEXANOL UTILES COMME MODULATEURS DU RECAPTAGE DE MONOAMINE DANS LE TRAITEMENT DES SYMPTOMES VASOMOTEURS
  申请人：WYETH CORP

  公开号：WO2005037279A1

  公开（公告）日：2005-04-28

  The present invention is directed to substituted N-heterocycle derivatives of formula (I), compositions containing these derivatives, and their use in the manufacture of a medicament for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof wherein : A is phenyl, naphthyl, thiophenyl, pyridinyl, furanyl, benzofuranyl, isobenzofuranyl, xanthenyl, pyrrolyl, indolizinyl, isoindolyl, indolyl, or benzothiophenyl, where 1 to 3 carbon atoms of said A is optionally replaced with a nitrogen atom; U is N or O; W is H or OR8; the other substituents are defined in the claims.

  本发明涉及式（I）的取代N-杂环衍生物，含有这些衍生物的组合物，以及它们在制造用于预防和治疗由单胺再摄取改善的病况的药物中的应用，包括但不限于血管运动症状（VMS）、性功能障碍、胃肠道和泌尿系统疾病、慢性疲劳综合征、纤维肌痛综合征、神经系统疾病以及其中的组合，特别是从主要抑郁障碍、血管运动症状、压力和急迫性尿失禁、纤维肌痛、疼痛、糖尿病性神经病变以及其中的组合中选择的那些病况，其中：A是苯基、萘基、噻吩基、吡啶基、呋喃基、苯并呋喃基、异苯并呋喃基、黄色素基、吡咯基、吲哚啉基、异吲哚基、吲哚基或苯并噻吩基，其中所述A的1至3个碳原子可选择地被氮原子取代；U是N或O；W是H或OR8；其他取代基在权利要求中定义。
• [EN] SUBSTITUTED ARYL CYCLOALKANOL DERIVATIVES AND METHODS OF THEIR USE<br/>[FR] DERIVES DE CYCLOALCANOYL ARYLE SUBSTITUES ET PROCEDES D'UTILISATION DE CEUX-CI
  申请人：WYETH CORP

  公开号：WO2005037809A1

  公开（公告）日：2005-04-28

  The present invention is directed to substituted aryl cycloalkanoyl derivatives, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.

  本发明涉及取代芳基环烷酰衍生物，含有这些衍生物的组合物，以及它们用于预防和治疗由单胺再摄取改善的病况的方法，包括但不限于血管运动症状（VMS）、性功能障碍、胃肠道和泌尿系统疾病、慢性疲劳综合征、纤维肌痛综合征、神经系统疾病，以及这些疾病的组合，尤其是从包括重性抑郁障碍、血管运动症状、压力和急迫性尿失禁、纤维肌痛、疼痛、糖尿病神经病变等病况中选出的那些病况。
• [EN] ARYLALKYL- AND CYCLOALKYLALKYL-PIPERAZINE DERIVATIVES AND METHODS OF THEIR USE<br/>[FR] DERIVES D'ARYLALKYL-PIPERAZINE ET DE CYCLOALKYLALKYL-PIPERAZINE ET METHODES D'UTILISATION ASSOCIEES
  申请人：WYETH CORP

  公开号：WO2005037807A1

  公开（公告）日：2005-04-28

  The present invention is directed to arylalkyl- and cycloalkylalkyl-piperazine derivatives, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.

  本发明涉及芳基烷基和环烷基哌嗪衍生物，含有这些衍生物的组合物，以及它们用于预防和治疗由单胺再摄取改善的病况的方法，包括但不限于血管运动症状（VMS），性功能障碍，胃肠和泌尿系统疾病，慢性疲劳综合征，纤维肌痛综合征，神经系统疾病等，特别是那些选自主要抑郁症、血管运动症状、压力性和切望性尿失禁、纤维肌痛综合征、疼痛、糖尿病性神经病变等病况的组合物。