4-(8-Chloro-5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11-ylidene)piperidine | 126570-60-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噁庚英
• 英文名称: 4-(8-Chloro-5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11-ylidene)piperidine
• 英文别名: 4-(8-chloro-5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11-ylidene)-piperidine；8-chloro-11-piperidin-4-ylidene-5H-[1]benzoxepino[4,3-b]pyridine
• CAS: 126570-60-3
• 化学式: C₁₈H₁₇ClN₂O
• 分子量: 312.799
• InChiKey: SBSDDZJRNWZLIP-UHFFFAOYSA-N

物化性质

• 沸点：
  486.0±45.0 °C(Predicted)
• 密度：
  1.274±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  34.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(8-Chloro-5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11-ylidene)piperidine 以 乙腈 为溶剂， 反应 6.5h， 生成 4-(8-chloro-5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11-ylidene)-N-cyano-N'-(4-pyridinylmethyl)-1-piperidine-carboximidamide
  参考文献：
  名称：

  Inhibitors of farnesyl protein transferase. synthesis and biological activity of amide and cyanoguanidine derivatives containing a 5,11-dihydro[1]benzthiepin, benzoxepin, and benzazepin [4,3-b]pyridine ring system

  摘要：

  Bioisosteric replacement of the C-6 carbon atom in piperidine I and piperazine II with S, O, and N heteroatoms is described. Amide and cyanoguanidine derivatives of these compounds were evaluated in vitro and found to be good inhibitors of farnesyl-protein transferase. An improved method of preparing the 5,11-dihydro-[1]-benzthiepin nucleus 6 was accomplished in high yield and with excellent regioselectivity using an AlCl3 melt protocol. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00439-9
• 作为产物：
  描述：

  ethyl 4-(8-chloro-5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11-ylidene)-1-piperidine-carboxylate 在 aqueous KOH 作用下， 以 CH₃ CH₂ OH 为溶剂， 生成 4-(8-Chloro-5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11-ylidene)piperidine
  参考文献：
  名称：

  Benzopyrido piperidine, piperidylidene and piperazine compounds,

  摘要：

  揭示了一种新型苯并吡啶二烯、吡啶基亚烯和哌嗪化合物，其广义化学式为##STR1##，用于治疗哮喘、过敏和炎症。还公开了含有这些化合物的新型药物组合物以及生产这些化合物的方法。

  公开号：

  US05104876A1

文献信息

• Bis-benzo or benzopyrido cyclohepta piperidene, piperidylidene and
  申请人：Schering Corporation

  公开号：US05422351A1

  公开（公告）日：1995-06-06

  Bis-benzo or benzopyrido piperidene, piperidylidene and piperazine compounds of the formula: ##STR1## and pharmaceutically acceptable salts thereof are disclosed, wherein Z represents --(C(R.sup.a).sub.2).sub.m --Y--(C(R.sup.a).sub.2).sub.n -- or ##STR2## The compounds of Formula I possess anti-allergic and anti-inflammatory activity. Methods for preparing and using the compounds are also described.

  本发明揭示了一种具有以下结构的双苯或苯并吡啶哌啶烯，哌啶基亚甲基和哌嗪类化合物的药用盐：其中Z代表--(C(R^a)_2)_m--Y--(C(R^a)_2)_n--或##STR2##。式I的化合物具有抗过敏和抗炎活性。还描述了制备和使用这些化合物的方法。
• Amphoteric Drugs. 3. Synthesis and Antiallergic Activity of 3-[(5,11-Dihydro[1]benzoxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic Acid Derivatives and Related Compounds
  作者：Nobuhiko Iwasaki、Tetsuo Ohashi、Keiichi Musoh、Hiroyuki Nishino、Noriyuki Kado、Shingo Yasuda、Hideo Kato、Yasuo Ito

  DOI：10.1021/jm00003a013

  日期：1995.2

  penetration into the central nervous system (CNS) is described. A series of 3-[(5,11- dihydro[1]benzoxepino[4,3-b]-pyridin-11-ylidene)piperidino]propion ic acid derivatives (31-47) and related compounds (48-54) were synthesized and evaluated for antiallergic activity and penetration of a compound into the CNS in comparison with the corresponding 6H-dibenz[b,e]oxepin derivative (3). Combination of zwitterionization

  描述了设计减少进入中枢神经系统（CNS）的抗过敏剂的重要方法。一系列3-[（5,11-二氢[1]苯并氧杂吡啶[4,3-b]-吡啶-11-亚基]哌啶子基]丙酸衍生物（31-47）及相关化合物（48-54）为与相应的6H-dibenz [b，e] oxepin衍生物（3）相比，合成并评估了化合物的抗过敏活性和对化合物的渗透性。两性离子化和引入吡啶组分的结合导致抗过敏活性的增加和对CNS的渗透性大大降低，通过中央系统的抗组胺活性的选择性（B / A）[离体H1与小鼠脑膜结合的ID50值（B）]和周围系统的抗组胺活性[ED50值对组胺的抑制作用]诱导的小鼠血管通透性增加] 可以基于两性离子化和吡啶组分的引入引起的亲水性的增加来考虑这种令人惊奇的渗透到CNS中的减少。3- [4-（8-氟-5,11-二氢[1]苯并xepino [4,3-b]吡啶基-11亚基）哌啶子基]丙酸（33）在各种实验模型中均表
• Tricyclic compounds having activity as RAS-FPT inhibitors
  申请人：Schering Corporation

  公开号：US06130229A1

  公开（公告）日：2000-10-10

  Compounds of Formula I: ##STR1## wherein: X.sup.1 is hydrogen, halogen, CF.sub.3, nitro, NH.sub.2 or lower alkyl; each X.sup.2 is independently selected from the group consisting of hydrogen, halogen, lower alkoxy and lower alkyl; n is 1 or 2; Y is selected from the group consisting of S(O).sub.p, O, and NR.sup.5, wherein p is 0, 1 or 2, and R.sup.5 is hydrogen, alkyl, aryl, cycloalkyl, loweralkoxycarbonyl, aminocarbonyl or acyl; R.sup.1 and R.sup.2, which may be the same or different, are selected from the group consisting of hydrogen and lower alkyl groups, or taken together can form an oxygen atom when Y is NR.sup.5 ; A . . . is C=, CH-- or N--; R is --CZ--Y.sup.1 --Y.sup.2 --R.sup.3, wherein: Z is O, =CH--CN, or =N--CN; one of Y.sup.1 and Y.sup.2 is a bond, --CO--, O, S, or --NR.sup.4 --, and the other is (CH.sub.2).sub.m, where m is 0 or an integer of 1 to 4, and R.sup.4 is H or alkyl, with the proviso that when Z is O and m is 0 then Y.sup.1 or Y.sup.2 is selected from --CO--, O, S, or --NR.sup.4 ; R.sup.3 is aryl, heteroaryl or heterocycloalkyl, with the proviso that R.sup.3 can also be lower alkyl when Z is =N--CN; and their pharmaceutically acceptable acid addition salts; have activity as Ras-FPT inhibitors. They can be used, e.g., in pharmaceutical compositions, for inhibiting the abnormal growth of cells and for inhibiting proliferative diseases. Processes for their preparation, and useful intermediates, are also disclosed.

  公式I的化合物：##STR1## 其中：X.sup.1是氢，卤素，CF.sub.3，硝基，NH.sub.2或低烷基；每个X.sup.2独立地选自由氢，卤素，低烷氧基和低烷基组成的群；n为1或2；Y选自S（O）.sub.p，O和NR.sup.5组成的群，其中p为0，1或2，R.sup.5为氢，烷基，芳基，环烷基，低烷氧羰基，氨基羰基或酰基；R.sup.1和R.sup.2，可以相同也可以不同，选自氢和低烷基组，或者当Y为NR.sup.5时，它们可以结合成一个氧原子；A…为C=，CH-或N-；R为--CZ--Y.sup.1--Y.sup.2--R.sup.3，其中：Z为O，=CH-CN或=N-CN；Y.sup.1和Y.sup.2中的一个是键，--CO--，O，S或--NR.sup.4--，另一个为（CH.sub.2）.sub.m，其中m为0或1到4的整数，R.sup.4为H或烷基，但当Z为O且m为0时，Y.sup.1或Y.sup.2选自--CO--，O，S或--NR.sup.4；R.sup.3为芳基，杂芳基或杂环烷基，但当Z为=N-CN时，R.sup.3也可以是低烷基；它们的药学上可接受的酸盐具有Ras-FPT抑制剂的活性。它们可以用于制备药物组合物，用于抑制细胞的异常生长和抑制增殖性疾病。还披露了它们的制备过程和有用的中间体。
• Benzopyrido piperidine, piperidylidene and piperazine compounds, compositions, methods of manufacture and methods of use
  申请人：SCHERING CORPORATION

  公开号：EP0341860A1

  公开（公告）日：1989-11-15

  Novel benzopyrido piperidine, piperidylidene and piperazine compounds of the generalized formula are disclosed as useful for the treatment of asthma, allergy and inflammation. Novel pharmaceutical compositions containing such compounds and processes for producing the compounds are also disclosed.

  通式为哌啶、亚哌啶和哌嗪的新型苯并吡啶化合物 公开了可用于治疗哮喘、过敏和炎症的新型苯并吡啶哌啶、亚哌啶和哌嗪化合物。此外，还公开了含有此类化合物的新型药物组合物以及生产此类化合物的工艺。
• Novel benzopyrido piperidylidene compounds, compositions, methods of manufacture and methods of use
  申请人：SCHERING CORPORATION

  公开号：EP0515158A1

  公开（公告）日：1992-11-25

  Disclosed is a compound of Formula I: or a pharmaceutically acceptable salt or solvate thereof, wherein R represents H or a halogen atom selected from the group consisting of: Cl, Br, F, and l. Preferably R represents Cl. Also disclosed is a pharmaceutical composition comprising a compound of Formula I and a pharmaceutically acceptable carrier. Further disclosed is a method of treating asthma, allergy and/or inflammation comprising administering to a mammal in need of such treatment an anti-asthmatic, anti-allergic and/or an anti-inflammatory, respectively, effective amount of a compound of Formula I.

  公开了一种式 I 的化合物： 或其药学上可接受的盐或溶液，其中 R 代表 H 或选自以下组成的组的卤原子：Cl、Br、F 和 l：优选 R 代表 Cl。 还公开了一种药物组合物，包含式 I 的化合物和药学上可接受的载体。 进一步公开了一种治疗哮喘、过敏和/或炎症的方法，该方法包括向需要这种治疗的哺乳动物分别施用有效量的式Ⅰ化合物来抗哮喘、抗过敏和/或抗炎。