(R)-去甲肾上腺素 | 2282-53-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: (R)-去甲肾上腺素
• 英文名称: (R)-normetanephrine
• 英文别名: L-Normetanephrine；4-[(1R)-2-amino-1-hydroxyethyl]-2-methoxyphenol
• CAS: 2282-53-3
• 化学式: C₉H₁₃NO₃
• 分子量: 183.207
• InChiKey: YNYAYWLBAHXHLL-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-去甲肾上腺素 在 recombinant human sulfotransferase 1A₃ 、 6-氨基-9-[3-羟基-5-[(羟基-磺基氧基-磷酰)氧基甲基]-4-膦酰氧基-四氢呋喃-2-基]-嘌呤 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.07h， 生成 rac-normetanephrine
  参考文献：
  名称：

  SULT1A3催化去甲肾上腺素对映体的磺基缀合中对映体选择性的缺乏：体外和计算研究。

  摘要：

  （1 R）-去甲肾上腺素是磺基转移酶1A3（SULT1A3）催化磺化的天然立体异构底物。尽管该反应的对映选择性在肾上腺素能胺的代谢和临床生物化学中具有潜在的意义，但对它的对映选择性却一无所知。我们面对了重组人SULT1A3将合成的（1 R）-去甲肾上腺素和（1 S）-去甲肾上腺素磺缀合至每个具有SULT1A3和3'-磷腺苷-5'配合物稳定性的分子建模和分子动力学模拟的基础。该ķ中号，V最大和（1 R）-去甲肾上腺素，（1 S）-去甲肾上腺素和外消旋去甲肾上腺素磺化的k cat值相似。硅计算机模型与这些发现一致，因为它们表明两种对映异构体的结合模式几乎相同。总之，SULT1A3对去甲肾上腺素没有底物-对映体选择性，这是一个意外的发现，可以通过配体和SULT1A3之间的相互适应性通过催化口袋中的“诱导拟合模型”来解释。手征性，2012年25：28-34。©2012 Wiley Periodicals，Inc

  DOI：

  10.1002/chir.22108
• 作为产物：
  描述：

  O-tert-butyldimethylsilylvanillin 在 吡啶 、 sodium azide 、 AD-mix-α 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 95.84h， 生成 (R)-去甲肾上腺素
  参考文献：
  名称：

  SULT1A3催化去甲肾上腺素对映体的磺基缀合中对映体选择性的缺乏：体外和计算研究。

  摘要：

  （1 R）-去甲肾上腺素是磺基转移酶1A3（SULT1A3）催化磺化的天然立体异构底物。尽管该反应的对映选择性在肾上腺素能胺的代谢和临床生物化学中具有潜在的意义，但对它的对映选择性却一无所知。我们面对了重组人SULT1A3将合成的（1 R）-去甲肾上腺素和（1 S）-去甲肾上腺素磺缀合至每个具有SULT1A3和3'-磷腺苷-5'配合物稳定性的分子建模和分子动力学模拟的基础。该ķ中号，V最大和（1 R）-去甲肾上腺素，（1 S）-去甲肾上腺素和外消旋去甲肾上腺素磺化的k cat值相似。硅计算机模型与这些发现一致，因为它们表明两种对映异构体的结合模式几乎相同。总之，SULT1A3对去甲肾上腺素没有底物-对映体选择性，这是一个意外的发现，可以通过配体和SULT1A3之间的相互适应性通过催化口袋中的“诱导拟合模型”来解释。手征性，2012年25：28-34。©2012 Wiley Periodicals，Inc

  DOI：

  10.1002/chir.22108

文献信息

• Pharmaceutically active pyrrolidine derivatives as bax inhibitors
  申请人：——

  公开号：US20030171309A1

  公开（公告）日：2003-09-11

  The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating-up to an inhibitory-activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CR<6>R<7>, NOR<6>, NNR<6>R<7>; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO2-, —SO2NH—; —CH2-; B is either a group —(C═O)—NR<8>R<9> or represents a heterocyclic residue having the formula (II) wherein Q is NR<10>, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.

  本发明涉及新的取代吡咯烷衍生物的化学式(I)。所述化合物通常用作药用活性化合物。具体来说，化学式(I)的吡咯烷衍生物在治疗和/或预防神经退行性疾病、与多谷氨酸氨基酸序列相关的疾病、癫痫、缺血、不孕症、心血管疾病、肾脏缺氧、肝炎和艾滋病方面具有用处。所述吡咯烷衍生物显示出对细胞死亡促进子Bax和/或导致Bax激活途径的调节作用，最显著地是下调至抑制活性，并因此允许阻止细胞色素(c)的释放。本发明还涉及新的具有药用活性的取代吡咯烷衍生物，以及它们的制备方法，其中X选自O、S、CR<6>R<7>、NOR<6>、NNR<6>R<7>组成的群；A选自—(C═O)—、—(C═O)—O—、—C(═NH)—、—(C═O)—NH—、—(C═S)—NH、—SO2-、—SO2NH—；—CH2-；B是一个群—(C═O)—NR<8>R<9>或代表具有化学式(II)的杂环残基，其中Q是NR<10>、O或S；n是选自0、1或2的整数；Y、Z和E与它们连接的两个碳共同形成一个5-6成员芳香族或杂芳族环。
• Pharmaceutically active pyrrolidine derivatives
  申请人：——

  公开号：US20030212012A1

  公开（公告）日：2003-11-13

  The present invention is related to pyrrolidine derivatives of formula (I). Said 1 compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of premature labor, premature birth and dysmenorrhea. In particular, the present invention is related to pyrrolidine derivatives displaying a substantial modulatory, notably an antagonist activity of the oxytocin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin, including premature labor, premature birth and dysmenorrhea. The present invention is furthermore related to novel pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of CR6R7, NOR6, NNR6R7; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO22—, —SO2NH—, —CH2—,B is either a group —(C═O)—NR8R9 or represents a heterocyclic residue having the formula (a) wherein Q is NR10, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.

  本发明涉及式(I)的吡咯烷衍生物。所述化合物优选用作药用活性化合物。具体而言，式(I)的吡咯烷衍生物在治疗和/或预防早产、早产和痛经方面是有用的。特别是，本发明涉及显示出氧催产素受体显著调节作用，特别是拮抗剂活性的吡咯烷衍生物。更具体地，所述化合物在治疗和/或预防由氧催产素介导的疾病状态，包括早产、早产和痛经方面是有用的。本发明还涉及新型吡咯烷衍生物以及其制备方法，其中X从CR6R7、NOR6、NNR6R7组中选择；A从—(C═O)—、—(C═O)—O—、—C(═NH)—、—(C═O)—NH—、—(C═S)—NH、—SO22—、—SO2NH—、—CH2—中选择；B是一个群—(C═O)—NR8R9或表示具有式(a)的杂环残基，其中Q是NR10、O或S；n是选择的整数0、1或2；Y、Z和E与它们连接的2个碳一起形成一个5-6成员芳基或杂芳基环。
• [EN] PHARMACEUTICALLY ACTIVE PYRROLIDINE DERIVATIVES AS BAX INHIBITORS<br/>[FR] DERIVES DE LA PYRROLIDINE PHARMACEUTIQUEMENT ACTIFS COMME INHIBITEURS DE BAX
  申请人：APPLIED RESEARCH SYSTEMS

  公开号：WO2001074769A1

  公开（公告）日：2001-10-11

  The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating - up to an inhibitory - activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CR?6R7, NOR6, NNR6R7¿; A is selected from the group consisting of -(C=O)-, -(C=O)-O-, -C(=NH)-, -(C=O)-NH-, -(C=S)-NH, -SO¿2?-, -SO2NH-; -CH2-; B is either a group -(C=O)-NR?8R9¿ or represents a heterocyclic residue having the formula (II) wherein Q is NR10, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.

  本发明涉及公式（I）的新取代吡咯烷衍生物。所述化合物优选用作药物活性化合物。具体而言，公式（I）的吡咯烷衍生物在神经退行性疾病、与多谷氨酸重复序列相关的疾病、癫痫、缺血、不孕症、心血管疾病、肾脏缺氧、肝炎和艾滋病的治疗和/或预防中有用。所述吡咯烷衍生物显示出调节性，尤其是对于细胞死亡促进剂Bax和/或导致Bax的激活途径具有下调至抑制性的活性，并因此允许阻止细胞色素（c）的释放。本发明还涉及新型药物活性取代吡咯烷衍生物以及其制备方法，其中X选自O，S，CR?6R7，NOR6，NNR6R7¿的群；A选自-(C=O)-，-(C=O)-O-，-C（=NH）-，-(C=O)-NH-，-(C=S)-NH，-SO¿2?，-SO2NH-；-CH2-；B是一个-(C=O)-NR?8R9¿基团或代表具有公式（II）的杂环残基，其中Q是NR10，O或S；n是选择的0、1或2的整数；Y、Z和E与它们所连接的2个碳一起形成一个5-6成员芳基或杂芳基环。
• [EN] PHARMACEUTICALLY ACTIVE PYRROLIDINE DERIVATIVES AS BAX INHIBITORS<br/>[FR] DERIVES PYRROLIDINE ACTIFS SUR LE PLAN PHARMACEUTIQUE UTILISES EN TANT QU'INHIBITEURS DE BAX
  申请人：APPLIED RESEARCH SYSTEMS

  公开号：WO2001072705A1

  公开（公告）日：2001-10-04

  The present invention is related to pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of premature labor, premature birth and dysmenorrhea. In particular, the present invention is related to pyrrolidine derivatives displaying a substantial modulatory, notably an antagonist activity of the oxytocin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin, including premature labor, premature birth and dysmenorrhea. The present invention is furthermore related to novel pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of CR?6R7, NOR6, NNR6R7¿; A is selected from the group consisting of -(C=O)-, -(C=O)-O-, -C(=NH)-, -(C=O)-NH-, -(C=S)-NH, -SO¿2?2-, -SO2NH-, -CH2-,B is either a group -(C=O)-NR?8R9¿ or represents a heterocyclic residue having the formula (a) wherein Q is NR10, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.

  本发明涉及式（I）的吡咯烷衍生物。所述化合物最好用作药物活性化合物。具体而言，式（I）的吡咯烷衍生物在治疗和/或预防早产、早产和痛经方面是有用的。特别是，本发明涉及显示氧合胃素受体重要调节作用，特别是拮抗剂活性的吡咯烷衍生物。更具体地说，所述化合物在治疗和/或预防由氧合胃素介导的疾病状态方面是有用的，包括早产、早产和痛经。本发明还涉及新的吡咯烷衍生物以及其制备方法，其中X选自CR？6R7，NOR6，NNR6R7¿组成的群；A选自-(C=O)-，-(C=O)-O-，-C（=NH）-，-(C=O)-NH-，-(C=S)-NH，-SO¿2？2-，-SO2NH-，-CH2-；B是-(C=O)-NR？8R9¿或表示具有公式（a）的杂环残基，其中Q是NR10，O或S；n是选择的整数0、1或2；Y、Z和E与它们附着的2个碳原子一起形成一个5-6成员芳香族或杂芳基环。
• Processes for producing optically active 2-amino-1-phenylethanol derivatives
  申请人：Daicel Chemical Industries, Ltd.

  公开号：US20030143701A1

  公开（公告）日：2003-07-31

  An (R)-2-amino-1-phenylethanol derivative shown by the general formula (IIa) 1 wherein R 1 and R 5 represent a hydrogen atom, etc.; R 2 , R 3 and R 4 independently represent a halogen atom, etc., or a salt thereof, can readily be produced (1) by permitting a microorganism belonging to the genus Rhodosporidium, the genus Comamonas or the like to act on a mixture of corresponding (R)-form and (S)-form to asymmetrically utilize, or (2) by permitting a microorganism belonging to the genus Lodderomyces, the genus Pilimelia or the like to act on a corresponding aminoketone derivative to asymmetrically reduce. An (R,R)-1-phenyl-2-[(2-phenyl-1-alkylethyl)amino]ethanol derivative having a high optical purity can easily be obtained from the compound of the formula (IIa) or a salt thereof. Said derivative is useful as an intermediate for producing an anti-obesity agent and so on.

  通式（IIa）所示的（R）-2-氨基-1-苯乙醇衍生物，其中R1和R5代表氢原子等；R2、R3和R4分别独立地表示卤素原子等，或其盐，可以通过（1）让属于红孢霉属、普通小杆菌属或类似菌属的微生物作用于相应（R）-型和（S）-型的混合物以不对称利用，或（2）让属于洛德罗霉属、皮利米利亚属或类似菌属的微生物作用于相应的氨基酮衍生物以不对称还原而轻松制备。可以从式（IIa）化合物或其盐中轻松获得具有高光学纯度的（R，R）-1-苯基-2-［（2-苯基-1-烷基乙基）氨基］乙醇衍生物。所述衍生物可用作生产抗肥胖剂等中间体。