西酞普兰甲醛 | 227954-87-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 西酞普兰甲醛
• 英文名称: 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbaldehyde
• 英文别名: 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbaldehyde；5-Formyl-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran；Citalopram Carboxaldehyde；1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3H-2-benzofuran-5-carbaldehyde
• CAS: 227954-87-2
• 化学式: C₂₀H₂₂FNO₂
• 分子量: 327.399
• InChiKey: GRNCGIVYWGYYLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  西酞普兰甲醛 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 12.5h， 生成 3-(5-((((1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl)methyl)amino)methyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine
  参考文献：
  名称：

  Design and Synthesis of 1-(3-(Dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (Citalopram) Analogues as Novel Probes for the Serotonin Transporter S1 and S2 Binding Sites

  摘要：

  The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N, 4, 5, and 4' positions of (+/-)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT Si site, including two dimeric ligands (15 and 51). In addition, eight analogues were identified with similar potencies to S-1 for decreasing the dissociation of [H-3]S-1 from the S1 site via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT Si site (K-i = 19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [H-3]S-1 via S2.

  DOI：

  10.1021/jm4014136
• 作为产物：
  描述：

  西酞普兰 在 nickel-aluminum alloy 作用下， 以46 %的产率得到西酞普兰甲醛
  参考文献：
  名称：

  以乙腈为氰源的镍催化(杂)芳基卤化物的氰化反应

  摘要：

  我们提出了一种高效的方法来氰化具有挑战性的基材，特别关注芳基氟化物。这种创新方法已成功扩展到涵盖多种芳基卤化物，强调了其多功能性和广泛的适用性。镍催化方案在温和的温度条件下利用乙腈，为氰化提供了清洁、安全的替代方案。值得注意的是，它采用无害、非气态、不含金属的氰化物源，并具有广泛的底物范围，可容纳芳基氯、氟化物、溴化物和碘化物。该反应对于乙腈特别有效。这种催化氰化过程是合成来曲唑、西酞普兰和其他 NNRTI 药物等药物的宝贵途径。从机理上讲，我们认为涉及零价镍和二价镍的催化循环对于该反应更为合理。

  DOI：

  10.1021/acscatal.3c05836

文献信息

• Method for the preparation of citalopram
  申请人：H. Lundbeck A/S

  公开号：US20020040153A1

  公开（公告）日：2002-04-04

  A method for the preparation of citalopram comprising reductive hydrolysis of a compound of Formula (IV) 1 wherein R is a N,N-disubstituted amid group or an optionally substituted 4,5-dihydro-1,3-oxazol-2-yl group, and conversion of the resulting 5-formyl compound to citalopram.

  一种制备西酞普兰的方法，包括对式（IV）的化合物进行还原水解，其中R是N,N-二取代酰胺基团或可选择取代的4,5-二氢-1,3-噁唑-2-基基团，并将所得的5-甲醛化合物转化为西酞普兰。
• Histamine-3 Receptor Antagonists
  申请人：Godek Dennis Michael

  公开号：US20160237052A1

  公开（公告）日：2016-08-18

  The invention is directed to a compound of formula I, as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula I; and a method of treatment of a disorder or condition selected from the list consisting of acute myocardial infarction; memory processes disorders; dementia; cognition disorders such as Alzheimer's disease; attention deficit disorder (ADD); attention-deficit hyperactivity disorder (ADHD); cancers such as cutaneous carcinoma, medullary thyroid carcinoma and melanoma; Meniere's disease; gastrointestinal disorders; inflammation; migraine; motion sickness; obesity; pain; septic shock; respiratory disorders (including allergic rhinitis, nasal congestion and allergic congestion) in a mammal, including a human, that may be effected by administering to said mammal a pharmacologically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

  本发明涉及一种公式I的化合物，如本文所定义，或其药用盐；含有公式I化合物的药物组合物；以及治疗从急性心肌梗死；记忆过程障碍；痴呆症；认知障碍，如阿尔茨海默病；注意力缺陷障碍（ADD）；注意力缺陷多动障碍（ADHD）；癌症，如皮肤癌、髓样甲状腺癌和黑色素瘤；美尼尔氏病；胃肠道障碍；炎症；偏头痛；晕动病；肥胖症；疼痛；脓毒性休克；哺乳动物，包括人类，的呼吸道障碍（包括过敏性鼻炎、鼻塞和过敏性充血），可通过向该哺乳动物施用公式I化合物或其药用盐的药理有效量和药用载体来实现的一种治疗方法。
• Method for the Preparation of Escitalopram
  申请人：Paulon Antonio

  公开号：US20090247772A1

  公开（公告）日：2009-10-01

  The invention relates to intermediates and the use thereof in a method for the preparation of escitalopram:

  本发明涉及中间体及其在制备艾司西酞普兰的方法中的使用。
• Process for the preparation of 5-substituted isobenzofurans
  申请人：——

  公开号：US20040230065A1

  公开（公告）日：2004-11-18

  There is described a process for the preparation of citalopram and of its pharmaceutically acceptable salts, which comprises treating a 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5 isobenzofurancarbaldoxime, O-substituted preferably with a diphenylmethyl or triphenylmethyl group, with formic-acetic anhydride. Furthermore, the total synthesis of citalopram, as free base or in form of its pharmaceutically acceptable salt, starting from 5-formylphthalide is described.

  描述了一种制备西酞普兰及其药用可接受盐的方法，包括用甲酸-乙酸酐处理1-[3-(二甲氨基)丙基]-1-(4-氟苯基)-1,3-二氢-5-异苯并呋喃羰肟，O-取代物最好是二苯甲基或三苯甲基基团。此外，还描述了从5-甲酰基邻苯二甲酸酯开始，合成西酞普兰的全合成方法，作为自由碱基或其药用可接受盐的形式。
• Process for the preparation of 5-subtituted isobenzofurans
  申请人：INFOSINT SA

  公开号：EP1281707B1

  公开（公告）日：2004-12-29