2-[4-[(1R)-1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-ium-1-yl]butyl]phenyl]-2-methylpropanoate

• 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-[4-[(1R)-1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-ium-1-yl]butyl]phenyl]-2-methylpropanoate
• 化学式: C32H39NO4
• 分子量: 501.7
• InChiKey: RWTNPBWLLIMQHL-GDLZYMKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  81
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  非索芬那定 、 2,3-di-p-toluoyl-L-tartaric acid monohydrate 、 在 methanol+acetone 作用下， 以 丙酮 为溶剂， 反应 96.0h， 以a purified crystalline product (6.00 g, 85% chem. yield, 0.96% de)的产率得到2-[4-[(1R)-1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-ium-1-yl]butyl]phenyl]-2-methylpropanoate
  参考文献：
  名称：

  Process and diastereomeric salts useful for the optical resolution of racemic alpha-(4-(1, 1-dimethylethyl) phenyl] -4- (hydroxydiphenylmethyl) -1-piperidinebutanol and derivative compounds

  摘要：

  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。

  公开号：

  US20060014793A1

文献信息

• Stereoisomers with high affinity for adrenergic receptors
  申请人：——

  公开号：US20030105332A1

  公开（公告）日：2003-06-05

  The present invention provides stereoscopically-pure diastereomers of Formula I: 1 In a preferred embodiment, the stereoisomers of the present invention are of Formula II, depicted below: 2 R 2 , R 3 and le are independently H, OH, OCH 3 , CH 2 OH, NHCONH 2 , NH 2 , halogen or CF 3 , and R 1 is pyridine, or an amine which may be substituted with hydrogen, lower alkyl, lower alkylenearyl, lower alkylenephenyl, lower alkylenehydroxyphenyl, lower alkyleneamine, lower alkyleneaminoaryl, lower alkylaminohydroxyphenyl, or a similar functional group. TV is hydrogen, hydroxyl or methyl; R 6 is hydrogen, lower alkyl, lower alkylenaryl, lower alkylenephenyl, lower alkylenehydroxyphenyl, lower alkyleneamine, lower alkyleneaminoaryl, lower alkylaminohydroxyphenyl, and the like. For both Formula I and Formual II, the firs carbon on the side chain progressing from the ring is preferably in the R-configuration. The second carbon atom on the side chain of Formula II, which is attached to IV, may or may not be a chiral center. However, when the second carbon atom is a chiral center, it is preferably in the S-configuration. The present invention contemplates each stereoisomer of Formula I and II in substantially-pure form. The present invention also provides methods of relieving nasal, sinus and bronchial congestion and of treating attention deficit hyperactivity disorder and obesity. The present stereoisomers may also be used to induce pupil dilation. These methods include administering to a mammal a composition containing a therapeutically effective amount of a stereoscopically-pure stereoisomer of Formula I or II with a pharmaceutically acceptable excipient.

  本发明提供了公式I的立体纯异构体：在一种优选实施方式中，本发明的立体异构体为下图所示的公式II：R2、R3和le分别独立地为H、OH、OCH3、CH2OH、NHCONH2、NH2、卤素或CF3，而R1为吡啶，或者可能被氢、低烷基、低烷基芳基、低烷基苯基、低烷基羟基苯基、低烷基胺基、低烷基氨基芳基、低烷基氨基羟基苯基或类似官能团取代的胺。TV为氢、羟基或甲基；R6为氢、低烷基、低烷基芳基、低烷基苯基、低烷基羟基苯基、低烷基胺基、低烷基氨基芳基、低烷基氨基羟基苯基等。对于公式I和公式II，从环中延伸的侧链上的第一个碳原子最好处于R构型。公式II侧链上与IV相连的第二个碳原子可能是手性中心，也可能不是。然而，当第二个碳原子是手性中心时，最好处于S构型。本发明考虑了公式I和II的每个立体异构体基本纯净形式。本发明还提供了缓解鼻腔、鼻窦和支气管充血、治疗注意力缺陷多动障碍和肥胖的方法。本发明的立体异构体也可用于诱导瞳孔扩张。这些方法包括向哺乳动物投与含有公式I或II的立体纯异构体的药学可接受的赋形剂的治疗有效量的组合物。
• 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] METHOD OF PREPARATION OF TERFENADINE AND ITS DERIVATIVES<br/>[FR] PROCEDE DE PREPARATION DE TERFENADINE ET DE SES DERIVES
  申请人：ZENTIVA AS

  公开号：WO2004043922A1

  公开（公告）日：2004-05-27

  The invention relates to a new method of preparation of derivatives of piperidinyl butylphenylacetic acids. The compounds are histaminically active. The substances are prepared by Grignard reaction of alkylhalohydrins and suitably substituted aromatic aldehydes. The resulting diols are subjected to subsequent substitution reaction.

  本发明涉及一种制备哌啶丁基苯乙酸衍生物的新方法。该化合物具有组胺活性。该物质是通过烷基卤代醇和适当取代的芳香醛的格氏反应制备而成。所得的二醇经过后续的取代反应。
• Process for the production of piperidine derivatives with microorganisms
  申请人：——

  公开号：US20020087003A1

  公开（公告）日：2002-07-04

  The present invention relates to the production of a product compound having a structure according to Formulae IA and/or IB: 1 wherein n is 0 or 1; R 1 is hydrogen or hydroxy; R 2 is hydrogen; or, when n is 0, R 1 and R 2 taken together form a second bond between the carbon atoms bearing R 1 and R 2 , provided that when n is 1, R 1 and R 2 are each hydrogen; R 3 is —COOH or —COOR 4 ; R 4 is an alkyl or aryl moiety; A, B, and D are the substituents of their rings, each of which may be different or the same, and are selected from the group consisting of hydrogen, halogens, alkyl, hydroxy, and alkoxy. This process involves incubating a starting compound having a structure according to Formulae IIA and/or IIB: 2 wherein R 3 is —CH 3 and R 1 , R 2 , A, B, and D are defined above. in the presence of a microorganism under conditions effective to produce the product compound. The microorganism can be from the genus Streptomyces, Stemphylium, Gliocladium, Bacillus, Botrytis, Cyathus, Rhizopus, Pycniodosphora, Psuedomonas, Helicostylum, Aspergillus, Mucor, Gelasinospora, Rhodotorula, Candida, Mycobacterium, or Pennicillium. Alternatively, the microorganism can be Cunninghamella bainieri.

  本发明涉及生产一个化合物，其结构符合公式IA和/或IB，其中n为0或1；R1为氢或羟基；R2为氢；或者，当n为0时，R1和R2共同形成连接R1和R2的碳原子之间的第二个键，但当n为1时，R1和R2均为氢；R3为—COOH或—COOR4；R4为烷基或芳基基团；A、B和D为它们的环的取代基，每个取代基可以不同也可以相同，且选择自氢、卤素、烷基、羟基和烷氧基的群。该过程涉及在微生物的存在下孵育一个具有符合公式IIA和/或IIB的起始化合物，其中R3为—CH3，R1、R2、A、B和D如上所定义，以有效的条件产生产品化合物。该微生物可以来自属于链霉菌、茎腐菌、灰葡萄孢、芽孢杆菌、灰霉菌、杯状孢、根霉菌、小球孢菌、假单胞菌、螺旋菌属、曲霉属、毛霉属、肉座菌属、红酵母、念珠菌、结核分枝杆菌或青霉菌的微生物。或者，该微生物可以是拟青霉属真菌。
• [EN] TERFENADINE METABOLITES AND THEIR OPTICALLY PURE ISOMERS FOR TREATING ALLERGIC DISORDERS<br/>[FR] METABOLITES DE TERFENADINE ET LEURS ISOMERES OPTIQUEMENT PURS UTILISES DANS LE TRAITEMENT DES AFFECTIONS ALLERGIQUES
  申请人：SEPRACOR INC.

  公开号：WO1994003170A1

  公开（公告）日：1994-02-17

  (EN) A pharmaceutical composition comprising a compound of formula (I): wherein Z is COOH, COOCH3 or CH2OH, or a pharmaceutically acceptable salt thereof, for use in an anti-histaminic treatment which does not induce any significant cardiac arrhythmia, comprising administering a therapeutically effective amount of a compound of formula (I) to a human patient.(FR) L'invention se rapporte à une composition pharmaceutique comprenant un composé de la formule (I) dans laquelle Z représente COOH, COOH3 ou CH2OH, ou un sel pharmaceutiquement acceptable de ce composé. Cette composition peut être utilisée dans un traitement anti-histaminique qui ne provoque aucune arythmie cardiaque importante, et le procédé consiste à administrer une quantité thérapeutiquement efficace d'un composé de la formule (I) à un être humain.

  一种药物组合物，包括公式(I)中的化合物：其中Z为COOH，COOCH3或CH2OH，或其药学上可接受的盐，用于抗组胺治疗，不引起任何显著的心律失常，包括向人类患者给予公式(I)中的化合物的治疗有效量。