(6R/S)-1-benzyl-6-ethoxycarbonyl-4-methyl-3,4-didehydropiperidine | 127897-25-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (6R/S)-1-benzyl-6-ethoxycarbonyl-4-methyl-3,4-didehydropiperidine
• 英文别名: 1-benzyl-4-methyl-1,2,3,6-tetrahydropyridine-2(R,S)-carboxylic acid ethyl ester；Ethyl 1-benzyl-4-methyl-1,2,3,6-tetrahydropyridine-2-carboxylate；ethyl 1-benzyl-4-methyl-3,6-dihydro-2H-pyridine-2-carboxylate
• CAS: 127897-25-0
• 化学式: C₁₆H₂₁NO₂
• 分子量: 259.348
• InChiKey: LYATWKHNENCBKK-UHFFFAOYSA-N

物化性质

• 沸点：
  347.7±42.0 °C(Predicted)
• 密度：
  1.075±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6R/S)-1-benzyl-6-ethoxycarbonyl-4-methyl-3,4-didehydropiperidine 以 盐酸 、 二氯甲烷 、 甲苯 为溶剂， 生成 1-Benzyl-4-methyl-1,2,3,6-tetrahydropyridine-2(R,S)-carboxylic acid hydrochloride
  参考文献：
  名称：

  Antithrombotic amidinotetrahydropyridylalanine derivatives

  摘要：

  本发明涉及化合物的结构式(I) ##STR1## 及其药学上可接受的盐和任一实体的药学上可接受的溶剂结晶体，其中Y是可选择地具有C.sub.3 -C.sub.5的不饱和的烷基，可选择地取代有C.sub.1 -C.sub.4烷基或亚甲基; R.sup.1是H; 可选择地取代有C.sub.1 -C.sub.4烷基的C.sub.1 -C.sub.4烷氧基、OH、NR.sup.5 R.sup.6、CONR.sup.5 R.sup.6、C.sub.3 -C.sub.6环烷基或芳基; 或C.sub.3 -C.sub.6烯基; R.sup.2是H; 可选择地取代有C.sub.1 -C.sub.4烷基的C.sub.1 -C.sub.4烷氧基、OH、NR.sup.5 R.sup.6、CONR.sup.5 R.sup.6、C.sub.3 -C.sub.6环烷基或芳基; 或CONR.sup.5 R.sup.6; R.sup.3和R.sup.4各自独立地选择自H; 可选择地取代有NR.sup.5 R.sup.6的C.sub.1 -C.sub.4烷基; C.sub.1 -C.sub.4烷氧基; 卤素; CONR.sup.5 R.sup.6和芳基; 芳基是苯基，可选择地取代有一个、两个或三个从C.sub.1 -C.sub.4烷基、C.sub.1 -C.sub.4烷氧基、OH、卤素和CF.sub.3中独立选择的取代基; R.sup.5和R.sup.6各自独立地选择自H和C.sub.1 -C.sub.4烷基; m和n各自独立地选择为1、2或3; 这些化合物是有效且选择性的凝血酶抑制剂，在治疗包括深静脉血栓形成、溶栓治疗后再闭塞、慢性动脉阻塞、周围血管疾病、急性心肌梗死、不稳定性心绞痛、心房颤动、血栓性中风、短暂性缺血发作、血管成形术后再狭窄和闭塞，或神经退行性疾病等方面有用。

  公开号：

  US05798352A1
• 作为产物：
  描述：

  、 天然橡胶 以43%的产率得到
  参考文献：
  名称：

  BAILEY, PATRICK D.;WILSON, ROBERT D.;BROWN, GEORGE R., TETRAHEDRON LETT., 30,(1989) N8, C. 6781-6784

  摘要：

  DOI：

文献信息

• Antithrombotic amidinotetrahydropyridylalanine derivatives
  申请人：Pfizer Inc.

  公开号：US05798352A1

  公开（公告）日：1998-08-25

  This invention is directed to compounds of formula (I), ##STR1## pharmaceutically acceptable salts thereof, and pharmaceutically acceptable solvates of either entity, wherein Y is optionally monounsaturated C.sub.3 -C.sub.5 alkylene optionally substituted with C.sub.1 -C.sub.4 alkyl or methylene; R.sup.1 is H; C.sub.1 -C.sub.4 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy, OH, NR.sup.5 R.sup.6, CONR.sup.5 R.sup.6, C.sub.3 -C.sub.6 cycloalkyl or aryl; or C.sub.3 -C.sub.6 alkenyl; R.sup.2 is H; C.sub.1 -C.sub.4 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy, OH, NR.sup.5 R.sup.6, CONR.sup.5 R.sup.6, C.sub.3 -C.sub.6 cycloalkyl or aryl; or CONR.sup.5 R.sup.6 ; R.sup.3 and R.sup.4 are each independently selected from H; C.sub.1 -C.sub.4 alkyl optionally substituted with NR.sup.5 R.sup.6 ; C.sub.1 -C.sub.4 alkoxy; halo; CONR.sup.5 R.sup.6 and aryl; aryl is phenyl optionally substituted with one, two or three substituents independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, OH, halo and CF.sub.3 ; R.sup.5 and R.sup.6 are each independently selected from H and C.sub.1 -C.sub.4 alkyl; and m and n are each independently 1, 2 or 3; which are potent and selective thrombin inhibitors useful in the treatment of inter alia, deep vein thrombosis; reocclusion following thrombolytic therapy; chronic arterial obstruction; peripheral vascular disease; acute myocardial infarction; unstable angina; atrial fibrillation; thrombotic stroke; transient ischaemic attacks; restenosis and occlusion following angioplasty; or neurodegenerative disorders.

  本发明涉及化合物的结构式(I) ##STR1## 及其药学上可接受的盐和任一实体的药学上可接受的溶剂结晶体，其中Y是可选择地具有C.sub.3 -C.sub.5的不饱和的烷基，可选择地取代有C.sub.1 -C.sub.4烷基或亚甲基; R.sup.1是H; 可选择地取代有C.sub.1 -C.sub.4烷基的C.sub.1 -C.sub.4烷氧基、OH、NR.sup.5 R.sup.6、CONR.sup.5 R.sup.6、C.sub.3 -C.sub.6环烷基或芳基; 或C.sub.3 -C.sub.6烯基; R.sup.2是H; 可选择地取代有C.sub.1 -C.sub.4烷基的C.sub.1 -C.sub.4烷氧基、OH、NR.sup.5 R.sup.6、CONR.sup.5 R.sup.6、C.sub.3 -C.sub.6环烷基或芳基; 或CONR.sup.5 R.sup.6; R.sup.3和R.sup.4各自独立地选择自H; 可选择地取代有NR.sup.5 R.sup.6的C.sub.1 -C.sub.4烷基; C.sub.1 -C.sub.4烷氧基; 卤素; CONR.sup.5 R.sup.6和芳基; 芳基是苯基，可选择地取代有一个、两个或三个从C.sub.1 -C.sub.4烷基、C.sub.1 -C.sub.4烷氧基、OH、卤素和CF.sub.3中独立选择的取代基; R.sup.5和R.sup.6各自独立地选择自H和C.sub.1 -C.sub.4烷基; m和n各自独立地选择为1、2或3; 这些化合物是有效且选择性的凝血酶抑制剂，在治疗包括深静脉血栓形成、溶栓治疗后再闭塞、慢性动脉阻塞、周围血管疾病、急性心肌梗死、不稳定性心绞痛、心房颤动、血栓性中风、短暂性缺血发作、血管成形术后再狭窄和闭塞，或神经退行性疾病等方面有用。
• Stereoselective synthesis of pipecolic acid derivatives using aza-diels-alder reactions
  作者：Patrick D. Bailey、Robert D. Wilson、George R. Brown

  DOI：10.1016/s0040-4039(00)70675-7

  日期：——

  Pipecolic acid derivatives can be prepared by the aza-Diels-Alder reaction of dienes with the iminium salt derived from benzylamine and ethyl glyoxylate in DMF; the presence of a catalytic quantity of water is essential, and acyclic dienes react with high regio- and diastereoselectivity.

  胡椒酸衍生物可以通过二烯的二氮杂-Diels-Alder反应与衍生自苄胺和乙醛酸乙酯的亚胺盐在DMF中制备。催化量的水的存在是必不可少的，无环二烯的区域和非对映选择性很高。
• Asymmetric synthesis of pipecolic acid derivatives using the aza-Diels-Alder reaction
  作者：Patrick D. Bailey、George R. Brown、Pritiof Korber、Amanda Reed、Robert D. Wilson

  DOI：10.1016/s0957-4166(00)80025-7

  日期：1991.1

  Imines of the type R-N=CHCO2Et can be coerced into undergoing a (4 + 2) cycloaddition with substituted dienes if the reaction is carried out in DMF in the presence of both water and acid; these reactions show extremely high regio- and diastereoselectivity. Use of the 1-phenylethyl group as a chiral auxiliary leads to moderate asymmetric induction (typical d.e. ca. 70%); moreover, the diastereoisomers are surprisingly easy to separate, giving a short general route to optically pure substituted pipecolic acid derivatives.
• BAILEY, PATRICK D.;WILSON, ROBERT D.;BROWN, GEORGE R., TETRAHEDRON LETT., 30,(1989) N8, C. 6781-6784
  作者：BAILEY, PATRICK D.、WILSON, ROBERT D.、BROWN, GEORGE R.

  DOI：——

  日期：——
• Antithrombotic amidinophenylalanine and amidinopyridylalanine derivatives
  申请人：Pfizer Inc.

  公开号：US05750520A1

  公开（公告）日：1998-05-12

  This invention relates to compounds of formula (I), ##STR1## pharmaceutically acceptable salt thereof, and pharmaceutically acceptable solvates of either entity, wherein X is CH or N; Y is optionally monousaturated C.sub.3 -C.sub.5 alkylene optionally substituted with C.sub.1 -C.sub.4 alkyl or methylene; R.sup.1 is H; C.sub.1 -C.sub.4 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy, OH, NR.sup.5 R.sup.6, CONR.sup.5 R.sup.6, C.sub.3 -C.sub.6 cycloalkyl or aryl; or C.sub.3 -C.sub.6 alkenyl; R.sup.2 is H; C.sub.1 -C.sub.4 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy, OH, NR.sup.5 R.sup.6, CONR.sup.5 R.sup.6, C.sub.3 -C.sub.6 cycloalkyl or aryl; or CONR.sup.5 R.sup.6 ; R.sup.3 and R.sup.4 are each independently selected from H; C.sub.1 -C.sub.4 alkyl optionally substituted with NR.sup.5 R.sup.6 ; C.sub.1 -C.sub.4 alkoxy; halo; CONR.sup.5 R.sup.6 and aryl; R.sup.5 and R.sup.6 are each independently selected from H and C.sub.1 -C.sub.4 alkyl; and m and n are each independently 1, 2 or 3; are potent and selective thrombin inhibitors useful in the treatment of, inter alia, deep vein thrombosis; reocclusion following thrombolytic therapy; chronic arterial obstruction; peripheral vascular disease; acute myocardial infarction; unstable angina; atrial fibrillation; thrombotic stroke; transient ischaemic attacks; restenosis and occlusion following angioplasty; or neurodegenerative disorders.

  本发明涉及式(I)的化合物，其中X为CH或N；Y为可选择的单不饱和C.sub.3-C.sub.5烷基，可选择地取代为C.sub.1-C.sub.4烷基或亚甲基；R.sup.1为H；C.sub.1-C.sub.4烷基，可选择地取代为C.sub.1-C.sub.4烷氧基，OH，NR.sup.5R.sup.6，CONR.sup.5R.sup.6，C.sub.3-C.sub.6环烷基或芳基；或C.sub.3-C.sub.6烯基；R.sup.2为H；C.sub.1-C.sub.4烷基，可选择地取代为C.sub.1-C.sub.4烷氧基，OH，NR.sup.5R.sup.6，CONR.sup.5R.sup.6，C.sub.3-C.sub.6环烷基或芳基；或CONR.sup.5R.sup.6；R.sup.3和R.sup.4各自独立地选自H；C.sub.1-C.sub.4烷基，可选择地取代为NR.sup.5R.sup.6；C.sub.1-C.sub.4烷氧基；卤素；CONR.sup.5R.sup.6和芳基；R.sup.5和R.sup.6各自独立地选自H和C.sub.1-C.sub.4烷基；m和n各自独立地为1、2或3；这些化合物是有效且选择性的凝血酶抑制剂，可用于治疗深静脉血栓形成等疾病。