2-(4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)-butyl)-phenyl)-2-methyl-propanol | 76815-56-0

• 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-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)-butyl)-phenyl)-2-methyl-propanol
• 英文别名: [3H]-Hydroxyterfenadine；Hydroxyterfenadine；1-(4-(1-hydroxy-2-methylpropan-2-yl)phenyl)-4-(4-((hydroxy)diphenylmethyl)piperidin-1-yl)butan-1-ol；terfenadine alcohol；4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]-1-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]butan-1-ol
• CAS: 76815-56-0
• 化学式: C₃₂H₄₁NO₃
• 分子量: 487.682
• InChiKey: ZIQKFOOBIMENJF-UHFFFAOYSA-N

物化性质

• 熔点：
  104-109 °C (decomp)
• 沸点：
  664.0±55.0 °C(Predicted)
• 密度：
  1.131±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  63.9
• 氢给体数：
  3
• 氢受体数：
  4

ADMET

代谢

羟基特非那丁是特非那丁已知的人体代谢物。

Hydroxyterfenadine is a known human metabolite of terfenadine.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  2-(4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)-butyl)-phenyl)-2-methyl-propanol 在 N-氯代丁二酰亚胺 、 2,2,6,6-四甲基哌啶氧化物 、 四丁基氯化铵 、 碳酸氢钠 、 potassium carbonate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.0h， 以45%的产率得到Terfenadine aldehyde metabolite
  参考文献：
  名称：

  Biooxidation of methyl group: Part 2. Evidences for the involvement of cytochromes P450 in microbial multistep oxidation of terfenadine

  摘要：

  The actinomycete Streptomyces platensis grown in culture medium containing soybean peptones can transform terfenadine, an antihistamine drug, into its active metabolite fexofenadine. The microbial oxidation of methyl group of terfenadine into carboxylic acid could be an alternative to chemical ways to produce fexofenadine. This bioconversion requires three oxidation steps: a hydroxylation of one methyl group followed by the oxidation of the corresponding alcohol into the aldehyde and finally its oxidation into the carboxylic acid. The oxidation reaction of each step has been studied. Terfenadine and intermediates incubated with whole cells were not oxidized under argon whereas their biotransformation under O-18(2)-enriched atmosphere gave labeled fexofenadine. P450 inhibitors, such as clotrimazole or fluconazole, inhibited oxidation activity of each step. While the two last steps could be catalyzed by dehydrogenases or oxidases, this study strongly demonstrates the role of at least one, or possibly several cytochromes P450, in the oxidation of terfenadine into fexofenadine by S. platensis cells. To our knowledge, this is one of the few examples of involvement of P450s in such three steps oxidation of a xenobiotic. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2010.07.017
• 作为产物：
  描述：

  特非那定 在 Streptomyces platensis NRRL 2364 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 以51%的产率得到2-(4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)-butyl)-phenyl)-2-methyl-propanol
  参考文献：
  名称：

  甲基的生物氧化：在特非那定，依巴斯汀及其类似物的醇和酸代谢产物的制备中的应用

  摘要：

  这项研究的目的是找到制备特非那定，依巴斯汀及其类似物代谢物的最佳条件。为此，我们研究了氧化全细胞活性所需的结构底物要求，并选择了获得每种化合物的最有效条件。我们的结果表明，由甲基氧化产生的醇或酸衍生物是主要产物，其比例取决于所用微生物和细胞培养条件。氧化代谢产物以制备规模进行合成，并在表征之前以35–88％的产率分离。

  DOI：

  10.1016/j.tet.2008.09.098

文献信息

• Intermediates useful for the preparation of antihistaminic piperidine derivatives
  申请人：Merrell Pharmaceuticals, Inc.

  公开号：US06348597B2

  公开（公告）日：2002-02-19

  The present invention is related to a novel intermediates and processes which are useful in the preparation of certain antihistaminic piperidine derivatives of the formula wherein W represents —C(═O)— or —CH(OH)—; R1 represents hydrogen or hydroxy; R2 represents hydrogen; R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2; n is an integer of from 1 to 5; m is an integer 0 or 1; R3 is —COOH or —COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched each of A is hydrogen or hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R1 and R2 are taken together to form a second bond between the carbon atoms bearing R1 and R2 or where R1 represented hydroxy, m is an integer 0.

  本发明涉及一种新型中间体和过程，该中间体和过程在制备某些抗组胺酸哌啶衍生物的过程中非常有用，其化学式为 其中 W代表—C(═O)—或—CH(OH)—; R1代表氢或羟基; R2代表氢; R1和R2一起形成连接R1和R2的碳原子之间的第二键; n为1至5的整数; m为0或1的整数; R3为—COOH或—COO烷基，其中烷基基团具有1至6个碳原子，直链或支链，A的每个是氢或羟基;以及其药用可接受盐和各自的光学异构体， 但是当R1和R2一起形成连接R1和R2的碳原子之间的第二键或当R1代表羟基时，m为0。
• Intermediates useful for the preparation of antihistaminic piperidine
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US06147216A1

  公开（公告）日：2000-11-14

  The present invention is related to a novel intermediates and processes which are useful in the preparation of certain antihistaminic piperidine derivatives of the formula ##STR1## wherein W represents --C(.dbd.O)-- or --CH(OH)--; R.sub.1 represents hydrogen or hydroxy; R.sub.2 represents hydrogen; R.sub.1 and R.sub.2 taken together form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 ; n is an integer of from 1 to 5; m is an integer 0 or 1; R.sub.3 is --COOH or --COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched each of A is hydrogen or hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R.sub.1 and R.sub.2 are ta to form a second bond between the carbon R.sub.1 and R.sub.2 or where R.sub.1 represented hydroxy integer 0.

  本发明涉及一种新型中间体和工艺，可用于制备某些抗组胺酸哌啶衍生物，其化学式为##STR1##其中W代表--C(.dbd.O)--或--CH(OH)--；R.sub.1代表氢或羟基；R.sub.2代表氢；R.sub.1和R.sub.2共同形成连接R.sub.1和R.sub.2的碳原子之间的第二键；n为1至5的整数；m为0或1的整数；R.sub.3为--COOH或--COOalkyl，其中alkyl基含有1至6个碳原子，是直链或支链；每个A都是氢或羟基；以及其药用盐和单体光学异构体，但其中R.sub.1和R.sub.2形成连接R.sub.1和R.sub.2的碳原子之间的第二键或R.sub.1代表羟基时除外。
• [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。
• [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。
• Intermediates for the preparation of antihistaminic 4-diphenylmethyl/diphenylmethoxy piperidine derivatives
  申请人：Aventisub II Inc.

  公开号：EP2261208A1

  公开（公告）日：2010-12-15

  The present invention is related to novel intermediates and processes which are useful in the preparation of certain antihistaminic piperidine derivatives of formula (I) wherein W represents -C(=O)- or -CH(OH)-; R1 represents hydrogen or hydroxy; R2 represents hydrogen; R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2; n is an integer of from 1 to 5; m is an integer 0 or 1; R3 is -COOH or -COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; each of A is hydrogen or hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R1 and R2 are taken together to form a second bond between the carbon atoms bearing R1 and R2 or where R1 represented hydroxy, m is an integer 0.

  本发明涉及一种新型中间体和制备某些抗组胺哌啶衍生物的方法，其化学式为(I)，其中W代表-C（=O）-或-CH（OH）-；R1代表氢或羟基；R2代表氢；R1和R2一起形成连接带有R1和R2的碳原子之间的第二个键；n为1至5的整数；m为0或1的整数；R3为-COOH或-COOalkyl，其中烷基具有1至6个碳原子，是直链或支链；每个A是氢或羟基；以及其药学上可接受的盐和单一光学异构体，但当R1和R2一起形成连接带有R1和R2的碳原子之间的第二个键或当R1代表羟基时，m为0。