2,2-diphenyl-4-(4-hydroxy-4-phenyl)piperidinobutyronitrile | 50329-86-7

• 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: 2,2-diphenyl-4-(4-hydroxy-4-phenyl)piperidinobutyronitrile
• 英文别名: 4-(4-hydroxy-4-phenyl-piperidin-1-yl)-2,2-diphenyl-butyronitrile；4-(4-Hydroxy-4-phenylpiperidin-1-yl)-2,2-diphenylbutanenitrile
• CAS: 50329-86-7
• 化学式: C₂₇H₂₈N₂O
• 分子量: 396.532
• InChiKey: OTIRSAHHBSNELX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  47.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2-diphenyl-4-(4-hydroxy-4-phenyl)piperidinobutyronitrile 、 乙酸酐 生成 1-[3-(5-methyl-[1,3,4]oxadiazol-2-yl)-3,3-diphenyl-propyl]-4-phenyl-piperidin-4-ol
  参考文献：
  名称：

  3,3-Diphenyl-3-(2-alkyl-1,3,4-oxadiazol-5-yl)propylcycloalkylamines, a novel series of antidiarrheal agents

  摘要：

  A series of 4-amino-2,2-diarylbutyronitriles (3) prepared for testing as inhibitors of gastrointestinal propulsive activity did not show any enhancement over such existing agents as diphenoxylate and loperamide. However, conversion of the nitrile group to a 2-methyl-1,3,4-oxadiazol-5-yl function led to compounds 5g and 5j, statistically equipotent to diphenoxylate and loperamide in the mouse and showing a very low order of analgesic activity. Structural modifications determined that the best separation of antipropulsive and analgesic effects was obtained when the amino group was bicyclic and the oxadiazole ring had a 2-methyl substituent. The most potent compounds were and analogues of diphenoxylate and loperamide where the oxadiazole ring was present, but these compounds had marked analgesic activity.

  DOI：

  10.1021/jm00232a010
• 作为产物：
  描述：

  4-苯基-4-羟基哌啶 、 溴乙基二苯乙腈 在 N,N-二异丙基乙胺 作用下， 以66 mg的产率得到2,2-diphenyl-4-(4-hydroxy-4-phenyl)piperidinobutyronitrile
  参考文献：
  名称：

  Structure–activity relationship exploration of Kv1.3 blockers based on diphenoxylate

  摘要：

  Diphenoxylate, a well-known opioid agonist and anti-diarrhoeal agent, was recently found to block Kv1.3 potassium channels, which have been proposed as potential therapeutic targets for a range of autoimmune diseases. The molecular basis for this Kv1.3 blockade was assessed by the selective removal of functional groups from the structure of diphenoxylate as well as a number of other structural variations. Removal of the nitrile functional group and replacement of the C-4 piperidinyl substituents resulted in several compounds with submicromolar IC50 values. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.080

文献信息

• Anti-diarrheal oxadiazoles
  申请人：G. D. Searle & Co.

  公开号：US04003904A1

  公开（公告）日：1977-01-18

  The present invention encompasses a compound of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein Y is alkylene having 1-4 carbon atoms; R.sub.1 and R.sub. 2 together with N is a heterocyclic ring system consisting of an azamonocyclic ring of the formula ##STR2## wherein Z is oxygen, methylene, phenylhydroxymethylene, phenylcarboxymethylene or, phenylloweralkoxymethylene, or an azabicycloalkane structure having 6-9 carbon atoms and having at least 5 atoms in each ring of the azabicycloalkane structure; X is hydrogen, halogen, loweralkyl having 1-7 carbon atoms, or loweralkoxy having 1-7 carbon atoms; and Ar is phenyl, pyridyl, or monosubstituted phenyl wherein the substituent is halogen, loweralkyl having 1-7 carbon atoms, or loweralkoxy having 1-7 carbon atoms when R.sub.3 is hydrogen or Ar is 3 or 4 pyridyl when R.sub.3 is lower alkyl having 1-7 carbon atoms. The compounds of the present invention are prepared by converting the corresponding nitriles to 1H-tetrazoles and in turn reacting the 1H-tetrazole with ethyl chloroglyoxylate, hydrolyzing the resulting ester to the acid and decarboxylation to provide compounds wherein R.sub.3 is hydrogen. Compounds of the present invention are anti diarrheal agents.

  本发明涵盖了以下公式的化合物及其药学上可接受的酸加合盐：其中Y是具有1-4个碳原子的烷基；R.sub.1和R.sub.2与N一起形成一个由以下公式的氮杂单环环组成的杂环环系统：其中Z是氧、亚甲基、苯基羟甲基、苯基羧甲基或苯基低碳基氧甲基，或者是具有6-9个碳原子且在每个环中至少有5个原子的氮杂双环戊烷结构；X是氢、卤素、具有1-7个碳原子的低烷基或具有1-7个碳原子的低烷氧基；Ar是苯基、吡啶基或单取代苯基，其中取代基是卤素、具有1-7个碳原子的低烷基或具有1-7个碳原子的低烷氧基，当R.sub.3为氢或Ar为3或4吡啶基时，取代基为具有1-7个碳原子的低烷基。本发明的化合物是通过将相应的腈转化为1H-四唑，然后将1H-四唑与氯乙酰乙酸乙酯反应，水解得到酯，脱羧得到R.sub.3为氢的化合物。本发明的化合物是抗腹泻剂。
• 1,1-Diaryl-1H-tetrazole amines
  申请人：G. D. Searle & Co.

  公开号：US04017491A1

  公开（公告）日：1977-04-12

  The present invention relates to compounds of the following formula ##STR1## wherein Y is straight or branched chain alkylene containing 1-4 carbon atoms; X is hydrogen, halo such as fluoro, chloro, bromo or iodo, or lower alkyl containing 1-7 carbon atoms; Ar is phenyl, pyridyl, mono-substituted phenyl, wherein the substituent is halo such as fluoro, chloro, or bromo, or lower alkyl having 1-7 carbon atoms; and R.sub.2 and R.sub.3 are lower alkyl having 1-7 carbon atoms, or R.sub.2 and R.sub.3 together with N is an azamonocyclic ring selected from the group comprising 1-pyrrolidinyl, piperidino, 4-phenyl-4-hydroxypiperidino, 4-phenyl-4-hydroxymethylene, 4-phenyl-4-carboxypiperidino, 4-phenyl-4-carbloweralkoxypiperidino, or 4-phenyl-4-acetoxypiperidino substituted piperidino and morpholino, or an azabicycloalkanyl containing 6 to 9 carbon atoms and having at least 5 atoms in each ring of the azabicycloalkane. These compounds are useful intermediates for preparing potent antidiarrheal compounds.

  本发明涉及以下式的化合物：##STR1## 其中，Y是直链或支链烷基，含1-4个碳原子；X是氢，卤素，如氟、氯、溴或碘，或含1-7个碳原子的低级烷基；Ar是苯基、吡啶基、单取代苯基，其中取代基是卤素，如氟、氯或溴，或含1-7个碳原子的低级烷基；R.sub.2和R.sub.3是含1-7个碳原子的低级烷基，或R.sub.2和R.sub.3与N一起是从1-吡咯啉基、哌啶基、4-苯基-4-羟基哌啶基、4-苯基-4-羟甲基、4-苯基-4-羧基哌啶基、4-苯基-4-羧低级烷氧基哌啶基或4-苯基-4-乙酰氧基哌啶基取代的哌啶基和吗啡啉，或含有6-9个碳原子的氮杂环烷，每个环中至少有5个原子。这些化合物是制备有效的抗腹泻化合物的有用中间体。
• US4003904A
  申请人：——

  公开号：US4003904A

  公开（公告）日：1977-01-18
• US4017491A
  申请人：——

  公开号：US4017491A

  公开（公告）日：1977-04-12
• USRE29556E
  申请人：——

  公开号：USRE29556E

  公开（公告）日：1978-02-28