(S)-(-)-N-[4-[4-(ethylamino)-1-hydroxy-4-oxobutyl]phenyl]methanesulfonamide | 180918-69-8

• 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: (S)-(-)-N-[4-[4-(ethylamino)-1-hydroxy-4-oxobutyl]phenyl]methanesulfonamide
• 英文别名: (S)-(-)-N-Ethyl-γ-hydroxy-4-(methanesulfonylamino)benzenebutanamide；(4S)-N-ethyl-4-hydroxy-4-[4-(methanesulfonamido)phenyl]butanamide
• CAS: 180918-69-8
• 化学式: C₁₃H₂₀N₂O₄S
• 分子量: 300.379
• InChiKey: IMIVPMBAZNYUHG-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-(-)-N-[4-[4-(ethylamino)-1-hydroxy-4-oxobutyl]phenyl]methanesulfonamide 在 红铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 18.0h， 以66.8%的产率得到(S)-(-)-N-[4-[4-(ethylamino)-1-hydroxybutyl]phenyl]methanesulfonamide
  参考文献：
  名称：

  Progress toward the Development of a Safe and Effective Agent for Treating Reentrant Cardiac Arrhythmias:  Synthesis and Evaluation of Ibutilide Analogues with Enhanced Metabolic Stability and Diminished Proarrhythmic Potential

  摘要：

  A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.

  DOI：

  10.1021/jm0004289
• 作为产物：
  描述：

  4-[(4-甲磺酰胺基)苯基]-4-氧代丁酸 在 三乙胺 、 (-)-diisopinocamphenylborane chloride 作用下， 以 四氢呋喃 为溶剂， 反应 26.0h， 生成 (S)-(-)-N-[4-[4-(ethylamino)-1-hydroxy-4-oxobutyl]phenyl]methanesulfonamide
  参考文献：
  名称：

  Progress toward the Development of a Safe and Effective Agent for Treating Reentrant Cardiac Arrhythmias:  Synthesis and Evaluation of Ibutilide Analogues with Enhanced Metabolic Stability and Diminished Proarrhythmic Potential

  摘要：

  A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.

  DOI：

  10.1021/jm0004289

文献信息

• Antiarrhythmic (S)-enantiomers of methanesulfonamides
  申请人：Pharmacia & Upjohn Company

  公开号：US05874475A1

  公开（公告）日：1999-02-23

  Compounds of formula (I) and pharmacologically acceptable salts thereof wherein: n is 1 to 3, R is an alkyl, R.sub.1 is hydrogen or alkyl, R.sub.2 is alkyl, R.sub.3 is an alkyl; b) alkyl substituted with an aryl, heteroaryl or cycloalkyl; c) alkyl substituted with one to eight fluorine atoms; d) cycloalkyl; e) alkenyl; f) alkyl substituted with one to three hydroxy, acyloxy or alkoxy substituents, and where the sum of carbons in R.sub.2 and R.sub.3 is greater than five br where R.sub.2 and R.sub.3 with the nitrogen atom form a saturated heterocyclic group having one nitrogen and form 4-8 carbon atoms or a 4-substituted piperazine group in which the 4-substituent can be alkyl, aryl, benzyl, or heteroaryl, and X is hydrogen, hydroxy, alkoxy, alkyl, carbon trifluoride or a halogen, or compounds of formula (I') and pharmacologically acceptable salts thereof wherein: n is 1 to 3, R is an alkyl, R.sub.1 is hydrogen or alkyl, R.sub.2 is an alkyl, R.sub.3 is an alkyl substituted with an aryl, heteroaryl or cycloalkyl, or an alkyl substituted with one to eight fluorine atoms, one to three hydroxy, acyloxy or alkoxy substituents, and where the sum of carbons in R.sub.2 and R.sub.3 is greater than five; X is hydrogen, hydroxy, alkoxy, alkyl, carbon trifluoride or a halogen, useful as class III antiarrhythmic agents.

  式（I）的化合物及其药理学上可接受的盐，其中：n为1至3，R为烷基，R.sub.1为氢或烷基，R.sub.2为烷基，R.sub.3为烷基；b）烷基与芳基，杂环烷基或环烷基取代；c）烷基取代一个至八个氟原子；d）环烷基；e）烯烃基；f）烷基取代一个至三个羟基，乙酰氧基或烷氧基取代基，其中R.sub.2和R.sub.3中碳的总和大于五br，其中R.sub.2和R.sub.3与氮原子形成一个饱和的杂环基，含有一个氮原子并形成4-8个碳原子，或者形成一个4-取代哌嗪基团，其中4-取代基可以是烷基，芳基，苄基或杂环基，X为氢，羟基，烷氧基，烷基，三氟甲基或卤素，或者式（I'）的化合物及其药理学上可接受的盐，其中：n为1至3，R为烷基，R.sub.1为氢或烷基，R.sub.2为烷基，R.sub.3为烷基，取代一个芳基，杂环烷基或环烷基，或者取代一个至八个氟原子，一个至三个羟基，乙酰氧基或烷氧基取代基，其中R.sub.2和R.sub.3中碳的总和大于五；X为氢，羟基，烷氧基，烷基，三氟甲基或卤素，作为III类抗心律失常药物。
• [EN] ANTIARRHYTHMIC (S)-ENANTIOMERS OF METHANESULFONAMIDES<br/>[FR] ENANTIOMERES (S) DE METHANE-SULFONAMIDES ANTIARYTHMIQUES
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：WO1996021643A1

  公开（公告）日：1996-07-18

  (EN) (S)-Enantiomeric methanesulfonamides are structurally depicted by formula (I) or its pharmacologically acceptable salts where R3 is a C1-9 alkyl substituted with one fluorine atom. These compounds are useful as Class III antiarrhythmic agents without the undesirable side effect of polymorphic ventricular tachycardia (PVT) and are stable against rapid metabolism. Use of the compounds of formula (I) in the preparation of compositions for treating cardiac arrhythmias are also described.(FR) Méthane-sulfonamides énantiomères (S) décrits, au point de vue de la structure, par la formule (I) ou les sels pharmacologiquement acceptables du composé décrit par celle-ci, où R3 est un alkyle en C1-C9 substitué avec un atome de fluor. Ces composés sont utiles en tant qu'agents antiarythmiques de classe III n'ayant pas l'effet secondaire indésirable qu'est la tachycardie ventriculaire polymorphe et sont stables vis-à-vis d'un métabolisme rapide. L'invention décrit également l'utilisation desdits composés de formule (I) dans des préparations servant au traitement d'arythmies cardiaques.

  （EN）（S）-对映甲磺酰胺的结构式如公式（I）或其药学上可接受的盐所示，其中R3是一个C1-9烷基，被一个氟原子取代。这些化合物可用作III类抗心律失常药物，不会产生多形性室性心动过速（PVT）的不良副作用，并且稳定不易被迅速代谢。本发明还描述了将公式（I）化合物用于制备治疗心律失常的组合物的用途。 （FR）（S）-对映甲磺酰胺的结构式如公式（I）或其药学上可接受的盐所示，其中R3是一个C1-9烷基，被一个氟原子取代。这些化合物可用作III类抗心律失常药物，不会产生多形性室性心动过速（PVT）的不良副作用，并且稳定不易被迅速代谢。本发明还描述了将公式（I）化合物用于制备治疗心律失常的组合物的用途。
• ANTIARRHYTHMIC (S)-ENANTIOMERS OF METHANESULFONAMIDES
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0802900A1

  公开（公告）日：1997-10-29
• US5874475A
  申请人：——

  公开号：US5874475A

  公开（公告）日：1999-02-23
• Progress toward the Development of a Safe and Effective Agent for Treating Reentrant Cardiac Arrhythmias:  Synthesis and Evaluation of Ibutilide Analogues with Enhanced Metabolic Stability and Diminished Proarrhythmic Potential
  作者：Jackson B. Hester、John K. Gibson、Lewis V. Buchanan、Madeline G. Cimini、Michael A. Clark、D. Edward Emmert、Michael A. Glavanovich、Rick J. Imbordino、Richelle J. LeMay、Moses W. McMillan、Salvatore C. Perricone、Donald M. Squires、Rodney R. Walters

  DOI：10.1021/jm0004289

  日期：2001.3.1

  A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.