(-)-Terfenadine | 126588-96-3

• 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: (-)-Terfenadine
• 英文别名: (S)-1-(4-(tert-butyl)phenyl)-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butan-1-ol；(S)-(-)-terfenadine；S-terfenadine；terfenadine；KSC-335-069；S-(-)-1-{4-[4-(1,1-dimethylethyl)phenyl]-4-hydroxybutyl}-α,α,-diphenyl-4-piperidinomethanol；Terfenadine, (S)-；(1S)-1-(4-tert-butylphenyl)-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butan-1-ol
• CAS: 126588-96-3
• 化学式: C₃₂H₄₁NO₂
• 分子量: 471.683
• InChiKey: GUGOEEXESWIERI-PMERELPUSA-N

物化性质

• 沸点：
  626.8±55.0 °C(Predicted)
• 密度：
  1.088±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

特非那丁已知的人类代谢物包括羟基特非那丁和氮杂环醇。

Terfenadine has known human metabolites that include hydroxyterfenadine and azacyclonol.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  特非那定 在 pyridinium chlorochromate 、 (+)-二异松蒎基氯硼烷 作用下， 生成 (-)-Terfenadine
  参考文献：
  名称：

  Mechanism of block of a human cardiac potassium channel by terfenadine racemate and enantiomers

  摘要：

  The cardiac toxicity of racemic terfenadine (marked QT prolongation and polymorphic ventricular arrhythmias) is probably due to potassium channel blockade. To test whether one of its enantiomers would be a less efficient potassium channel blocker, we compared the mechanism of action of the racemate with that of the individual enantiomers. We synthesized the individual enantiomers of terfenadine and examined under whole cell voltage‐clamp conditions the mechanism of action of the racemate, both enantiomers and a major metabolite on a cloned human cardiac potassium channel, hKvl.5. This delayed rectifier is sensitive to quinidine, clofilium and other ‘class III’ antiarrhythmic drugs at clinically relevant concentrations. Upon depolarization, racemic terfenadine and its enantiomers induced a fast decline of hKvl.5 current towards a reduced steady state current level. During subsequent repolarization the tail currents deactivated more slowly than the control, resulting in a ‘crossover’ phenomenon. The voltage‐dependence of block was biphasic with a steep increase in block over the voltage range of channel opening (−30 to 0 mV), and a more shallow phase positive to O mV (where the channel is fully open). The latter was consistent with a binding reaction sensing 21% of the transmembrane electrical field (with reference to the cell interior). The EC50 for hKvl.5 block by racemic terfenadine was 0.88 μm, while the values for R‐ and S‐terfenadine were 1.19 μm and 1.16 μm, respectively. In contrast, the acid metabolite reduced hKvl.5 current by only 5% at a concentration of 50 μm. These findings suggest that terfenadine blocks the hKvl.5 channel after it opens by entering into the internal mouth of the channel. We have previously shown that quinidine blocks hKvl.5 in a similar manner but with an apparent affinity of ∼6 μm. Thus, terfenadine and its enantiomers are approximately equipotent open state blockers of this human K+ channel and about 6 times more potent than quinidine. The similar state‐, time‐, and voltage‐dependence of hKvl.5 block by both enantiomers also indicates that the chiral centre does not significantly constrain the orientation of critical binding determinants of terfenadine with respect to the receptor site.

  DOI：

  10.1111/j.1476-5381.1995.tb15873.x

文献信息

• METHODS AND COMPOSITIONS FOR TREATING INFECTION
  申请人：UNIVERSITY OF ROCHESTER

  公开号：US20150238473A1

  公开（公告）日：2015-08-27

  Provided herein are compositions and methods for treating or preventing infection.

  本文提供了用于治疗或预防感染的组合物和方法。
• Process and diastereomeric salts useful for the optical resolution of racemic a-[4- (1,1-dimethylethy) phenyl) -4- (hydroxydipenylmethyl) -1-piperidinebutanol and derivative compounds
  申请人：——

  公开号：US20030078429A1

  公开（公告）日：2003-04-24

  A process and diastereomeric salts useful for the optical resolution of racemic &agr;-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol, 4-[4-[4-(hydroxydiphenylmethyl)- 1 -piperidinyl]- 1 -hydroxybutyl]-&agr;,&agr;-dimethylbenzeneacetic acid and lower alkyl 4-[4-[4-(hydroxydiphenylmethyl)- 1 -piperidinyl]- 1 -hydroxybutyl]-&agr;,&agr;-dimethylbenzeneacetates. The process comprises placing into solution a chiral resolving agent, either (+)/(−)-di-paratoluoyltartaric acid or (−)/(+)-mandelic acid, in an amount equimolar to a compound corresponding to the desired enantiomer of the above compound, precipitating the resulting diastereomeric salt between the chiral resolving agent and the target enantiomer and separating the enantiomer.

  本发明涉及一种用于拆分外消旋α-[4-(1,1-二甲基乙基)苯基]-4-(羟基二苯甲基)-1-哌啶丁醇、4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-α,α-二甲基苯乙酸和较低烷基4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-α,α-二甲基苯乙酸酯的对映体盐的过程和对映体盐。该过程包括将手性分辨剂（+）/（−）-二对甲苯酰酸或（−）/(+)甘酸以当量的量置于溶液中，与所需对映体的化合物相对应，沉淀结果的手性分辨剂和目标对映体之间的对映异构体盐，并分离对映体。
• [EN] PROCESS AND DIASTEREOMERIC SALTS USEFUL FOR THE OPTICAL RESOLUTION OF RACEMIC alpha -[4-(1,1-DIMETHYLETHYL)PHENYL]-4-(HYDROXYDIPHENYLMETHYL)-1-PIPERIDINEBUTANOL AND DERIVATIVE COMPOUNDS<br/>[FR] PROCEDE ET SELS DIASTEREOMERES UTILES POUR LA RESOLUTION OPTIQUE DE alpha -[4-(1,1-DIMETHYLETHYL)PHENYL]-4-(HYDROXYDIPHENYLMETHYL)-1-PIPERIDINEBUTANOL RACEMIQUE ET DE COMPOSES DERIVES
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：WO1995031436A1

  公开（公告）日：1995-11-23

  (EN) A process and diastereomeric salts useful for the optical resolution of racemic $g(a)-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol, 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-$g(a),$g(a)-dimethylbenzeneacetic acid and lower alkyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-$g(a),$g(a)-dimethylbenzeneacetates. The process comprises placing into solution a chiral resolving agent, either (+)/(-)-di-paratoluoyltartaric acid or (-)/(+)-mandelic acid, in an amount equimolar to a compound corresponding to the desired enantiomer of the above compound, precipitating the resulting diastereomeric salt between the chiral resolving agent and the target enantiomer and separating the enantiomer.(FR) Procédé et sels diastéréomères utilisés pour effectuer la résolution optique d'acide $g(a)-[4-(1,1-diméthyléthyl)phényl]-4-(hydroxydiphénylméthyl)-1-pipéridinebutanol, 4-[4-[4-(hydroxydiphénylméthyl)-1-pipéridinyl]-1-hydroxybutyl]-$g(a),$g(a)-acide diméthylbenzèneacétique racémique et 4-[4-[4-(hydroxydiphénylméthyl)-1-pipéridinyl]-1-hydroxybutyl]-$g(a),$g(a)-diméthylbenzèneacétates d'alkyle inférieur. Ce procédé consiste à placer en solution un agent de résolution chiral, tel que de l'acide (+)/(-)-di-paratoluoyltartique ou de l'acide (-)/(+)-mandélique, selon une quantité équimolaire à un composé correspondant à l'énantiomère désiré du composé précité, à précipiter le sel diastomère résultant entre l'agent de résolution chiral et l'énantiomère cible puis à séparer l'énantiomère.

  一种用于光学分辨手性混合物$g(a)-[4-(1,1-二甲基乙基)苯基]-4-(羟基二苯甲基)-1-哌啶丁醇、4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-$g(a),$g(a)-二甲基苯乙酸盐和较低烷基4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-$g(a),$g(a)-二甲基苯乙酸盐的过程和对映异构体盐。该过程包括将手性分离剂(+)/(-)-邻苯二甲酸或(-)/(+)-苯甲酸以相当于所需对映体的化合物的当量加入溶液中，沉淀产生的对映异构体盐在手性分离剂和目标对映体之间，然后分离对映体。
• Process and diastereomeric salts useful for the optical resolution of racemic alpha-(4-(1, 1-dimethylethyl) phenyl] -4- (hydroxydiphenylmethyl) -1-piperidinebutanol and derivative compounds
  申请人：Nakamura Mitsuo

  公开号：US20060014793A1

  公开（公告）日：2006-01-19

  A process and diastereomeric salts useful for the optical resolution of racemic α-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1 -piperidinebutanol, 4-[4-[4-(hydroxydiphenylmethyl)-1 -piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid and lower alkyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetates. The process comprises placing into solution a chiral resolving agent, either (+)/(−)-di-paratoluoyltartaric acid or (−)/(+)-mandelic acid, in an amount equimolar to a compound corresponding to the desired enantiomer of the above compound, precipitating the resulting diastereomeric salt between the chiral resolving agent and the target enantiomer and separating the enantiomer.

  一种用于光学分辨手性α-[4-(1,1-二甲基乙基)苯基]-4-(羟基二苯甲基)-1-哌啶丁醇、4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-α,α-二甲基苯乙酸和较低烷基4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-α,α-二甲基苯乙酸酯的过程和对映异构体盐。该过程包括将手性分离剂（+）/（−）-对甲苯酰酒石酸或（−）/（+）-苯乙酸曼德酸溶解到与所需对映体化合物等摩尔的量中，使手性分离剂与目标对映体之间形成沉淀的对映异构体盐，并分离对映体。
• Process and diastereomeric salts useful for the optical resolution of racemic alpha-(4-(1,1-dimethylethyl)phenyl)-4-(hydroxydiphenylmethyl)-1-piperidinebutanol and derivative compounds
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US20040186137A1

  公开（公告）日：2004-09-23

  A process and diastereomeric salts useful for the optical resolution of racemic &agr;-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol, 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-&agr;,&agr;-dimethylbenzeneacetic acid and lower alkyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-&agr;,&agr;-dimethylbenzeneacetates. The process comprises placing into solution a chiral resolving agent, either (+)/(−)-di-paratoluoyltartaric acid or (−)/(+)-mandelic acid, in an amount equimolar to a compound corresponding to the desired enantiomer of the above compound, precipitating the resulting diastereomeric salt between the chiral resolving agent and the target enantiomer and separating the enantiomer.

  一种过程和对映异构盐，用于光学分离外消旋的α-[4-(1,1-二甲基乙基)苯基]-4-(羟基二苯甲基)-1-哌啶丁醇，4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-α,α-二甲基苯乙酸和较低的烷基4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-α,α-二甲基苯乙酸酯的光学分辨。该过程包括将手性分离剂（+）/（-）-对甲苯酰酒石酸或（-）/(+)-苯乙酸曼德酯，以与所需对映体的化合物相当的摩尔量置于溶液中，使手性分离剂和目标对映体之间形成沉淀的对映异构盐，并分离对映体。