1-哌嗪羧酸,4-[2-[(二甲氨基)甲基]苯基]-,1,1-二甲基乙基酯 | 199105-23-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-哌嗪羧酸,4-[2-[(二甲氨基)甲基]苯基]-,1,1-二甲基乙基酯
• 英文名称: 1-tert-butoxycarbonyl-4-[2-((dimethylamino)methyl)phenyl]piperazine
• 英文别名: tert-butyl 4-{2-[(dimethylamino)methyl]phenyl}piperazinecarboxylate；1-Boc-4-(2-dimethylaminomethyl-phenyl)-piperazine；tert-butyl 4-[2-[(dimethylamino)methyl]phenyl]piperazine-1-carboxylate
• CAS: 199105-23-2
• 化学式: C₁₈H₂₉N₃O₂
• 分子量: 319.447
• InChiKey: KYTRUOQDLDBVNL-UHFFFAOYSA-N

物化性质

• 沸点：
  417.2±45.0 °C(Predicted)
• 密度：
  1.077±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  36
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-哌嗪羧酸,4-[2-[(二甲氨基)甲基]苯基]-,1,1-二甲基乙基酯 在 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 dimethyl[(2-piperazinylphenyl)methyl]amine
  参考文献：
  名称：

  Substituted piperazines and methods of use

  摘要：

  选择的替代哌嗪化合物对于预防和治疗疾病，如肥胖等，具有有效性。该发明涵盖了新型化合物、类似物、前药和其药用盐，以及用于预防和治疗涉及黑素皮质素受体激活的疾病和其他疾病或病症的药物组合物和方法。该发明还涉及制备这类化合物的方法，以及在这些过程中有用的中间体。

  公开号：

  US20030220324A1
• 作为产物：
  描述：

  聚合甲醛 、 4-(2-(氨基甲基)苯基)哌嗪-1-羧酸叔丁酯 在 水 、 sodium cyanoborohydride 作用下， 以 乙腈 为溶剂， 生成 1-哌嗪羧酸,4-[2-[(二甲氨基)甲基]苯基]-,1,1-二甲基乙基酯
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Novel Arylpiperazines as Potent and Selective Agonists of the Melanocortin Subtype-4 Receptor

  摘要：

  The melanocortin receptors have been implicated as potential targets for a number of important therapeutic indications, including inflammation, sexual dysfunction, and obesity. We identified compound 1, an arylpiperazine attached to the dipeptide H-D-Tic-D-p-Cl-Phe-OH, as a novel melanocortin subtype-4 receptor (MC4R) agonist through iterative directed screening of nonpeptidyl G-protein-coupled receptor biased libraries. Structure-activity relationship (SAR) studies demonstrated that substitutions at the ortho position of the aryl ring improved binding and functional potency. For example, the o-isopropyl-substituted compound 29 (K-i = 720 nM) possessed 9-fold better binding affinity compared to the unsubstituted aryl ring (K-i = 6600 nM). Sulfonamide 39 (K-i = 220 nM) fills this space with a polar substituent, resulting in a further 2-fold improvement in binding affinity. The most potent compounds such as the diethylamine 44 (K-i = 60 nM) contain a basic group at this position. Basic heterocycles such as the imidazole 50 (K-i = 110 nM) were similarly effective. We also demonstrated good oral bioavailability for sulfonamide 39.

  DOI：

  10.1021/jm0304109

文献信息

• [EN] SUBSTITUTED PIPERAZINES AS MODULATORS OF THE MELANOCORTIN RECEPTOR<br/>[FR] PIPERAZINES SUBSTITUEES COMME MODULATEURS DU RECEPTEUR DE MELANOCORTINE
  申请人：AMGEN INC

  公开号：WO2003009850A1

  公开（公告）日：2003-02-06

  Selected substituted piperazine compounds are effective for prophylaxis and treatment of diseases, such as obesity and the like. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving activation of the melanocortin receptor. The subject invention also relates to processes For making such compounds as well as to intermediates useful in such processes.

  选定的取代哌嗪化合物可用于预防和治疗疾病，如肥胖症等。该发明涵盖了新化合物、类似物、前药及其药学上可接受的盐、制药组合物以及用于预防和治疗涉及黑色素皮质素受体激活的疾病和其他疾病或病症的方法。该发明还涉及制造这些化合物的过程，以及在此类过程中有用的中间体。
• Melanocortin receptor agonists
  申请人：——

  公开号：US20040092507A1

  公开（公告）日：2004-05-13

  The present invention relates to melanocortin receptor agonists of formula (I), which is useful in the treatment of obesity, diabetes and male and/or female sexual dysfunction. 1

  本发明涉及公式（I）的黑色素皮质素受体激动剂，其在肥胖症、糖尿病和男性和/或女性性功能障碍的治疗中有用。
• Substituted piperazinyl amides and methods of use
  申请人：Amgen Inc.

  公开号：US07115607B2

  公开（公告）日：2006-10-03

  Selected substituted piperazine compounds of Formula I are effective for prophylaxis and treatment of diseases, such as obesity and the like. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving activation of the melanocortin receptor. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  公式I中选择的取代哌嗪化合物对于预防和治疗肥胖症等疾病有效。本发明涵盖了新型化合物、类似物、前药和其药学上可接受的盐、药物组合物以及预防和治疗激活黑色素细胞受体相关的疾病和其他疾病或病情的方法。本发明还涉及制备这种化合物的过程以及在这种过程中有用的中间体。
• Serine derivatives and their use as therapeutic agents
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05885999A1

  公开（公告）日：1999-03-23

  The present invention relates to compounds of formula (I): ##STR1## wherein m is zero, 1 or 2; and n is zero or 1, with the proviso that the sum total of m+n is 1 or 2; R.sup.1 represents phenyl; naphthyl; benzhydryl; or benzyl, where the naphthyl group or any phenyl moiety may be substituted; R.sup.2 represents hydrogen; phenyl; heteroaryl selected from indazolyl, thienyl, furanyl, pyridyl, thiazolyl, tetrazolyl and quinolinyl; naphthyl; benzhydryl; or benzyl; wherein each heteroaryl, the naphthyl group and any phenyl moiety may be substituted; R.sup.3 and R.sup.4 each independently represents hydrogen or C.sub.1-6 alkyl or R.sup.3 and R.sup.4 together are linked so as to form a C.sub.1-3 alkylene chain; Q represents CR.sup.5 R.sup.6 or NR.sup.5 ; X and Y each independently represents hydrogen, or together form a group .dbd.O; and Z represents a bond, O, S, SO, SO.sub.2, NR.sup.c or --(CR.sup.c R.sup.d)--, where R.sup.c and R.sup.d each independently represent hydrogen or C.sub.1-6 alkyl; or a pharmaceutically acceptable salt thereof. The compounds are of particular use in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.

  本发明涉及式（I）的化合物：##STR1## 其中，m为零，1或2；n为零或1，但须满足m+n的总和为1或2；R.sup.1代表苯基；萘基；苯基甲基；或苄基，其中萘基或任何苯基基团可以被取代；R.sup.2代表氢；苯基；从吲唑基、噻吩基、呋喃基、吡啶基、噻唑基、四唑基和喹啉基中选择的杂环基；萘基；苯基甲基；或苄基；其中每个杂环基、萘基和任何苯基基团可以被取代；R.sup.3和R.sup.4各自独立地代表氢或C.sub.1-6烷基，或者R.sup.3和R.sup.4一起连接形成C.sub.1-3烷基链；Q代表CR.sup.5R.sup.6或NR.sup.5；X和Y各自独立地代表氢，或者一起形成.dbd.O基团；Z代表键，O，S，SO，SO.sub.2，NR.sup.c或--(CR.sup.cR.sup.d)--，其中R.sup.c和R.sup.d各自独立地代表氢或C.sub.1-6烷基；或其药学上可接受的盐。这些化合物特别适用于治疗或预防疼痛、炎症、偏头痛、恶心和带状疱疹后神经痛。
• PIPERAZINE DERIVATIVES AS MELANOCORTIN RECEPTOR AGONISTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1368340A1

  公开（公告）日：2003-12-10