4R-(1S,2-dimethylpropyl)pyrrolidin-2-one | 577040-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 4R-(1S,2-dimethylpropyl)pyrrolidin-2-one
• 英文别名: (4R)-4-[(2S)-3-methylbutan-2-yl]pyrrolidin-2-one
• CAS: 577040-92-7
• 化学式: C₉H₁₇NO
• 分子量: 155.24
• InChiKey: ZUUVATFHUDRRLA-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4R-(1S,2-dimethylpropyl)pyrrolidin-2-one 在 盐酸 、 Dowex-50 ion-exchange resin 作用下， 以 水 为溶剂， 以33%的产率得到(3R,4S)-3-Aminomethyl-4,5-dimethyl-hexanoic acid
  参考文献：
  名称：

  Structure−Activity Relationships of Pregabalin and Analogues That Target the α₂-δ Protein

  摘要：

  Pregabalin exhibits robust activity in preclinical assays indicative of potential antiepileptic, anxiolytic, and antihyperalgesic clinical efficacy. It binds with high affinity to the alpha(2)-delta subunit of voltage-gated calcium channels and is a substrate of the system L neutral amino acid transporter. A series of pregabalin analogues were prepared and evaluated for their alpha(2)-delta binding affinity as demonstrated by their ability to inhibit binding of [H-3]gabapentin to pig brain membranes and for their potency to inhibit the uptake of [H-3]leucine into CHO cells, a measure of their ability to compete with the endogenous substrate at the system L transporter. Compounds were also assessed in vivo for their ability to promote anxiolytic, analgesic, and anticonvulsant actions. These studies suggest that distinct structure activity relationships exist for alpha(2)-delta binding and system L transport inhibition. However, both interactions appear to play an important role in the in vivo profile of these compounds.

  DOI：

  10.1021/jm049762l
• 作为产物：
  描述：

  4R-(1S,2-dimethylpropyl)dihydrofuran-2-one 在 镍 sodium azide 、 氢溴酸 、 氢气 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 20.0~60.0 ℃ 、330.95 kPa 条件下， 反应 22.0h， 生成 4R-(1S,2-dimethylpropyl)pyrrolidin-2-one
  参考文献：
  名称：

  Structure−Activity Relationships of Pregabalin and Analogues That Target the α₂-δ Protein

  摘要：

  Pregabalin exhibits robust activity in preclinical assays indicative of potential antiepileptic, anxiolytic, and antihyperalgesic clinical efficacy. It binds with high affinity to the alpha(2)-delta subunit of voltage-gated calcium channels and is a substrate of the system L neutral amino acid transporter. A series of pregabalin analogues were prepared and evaluated for their alpha(2)-delta binding affinity as demonstrated by their ability to inhibit binding of [H-3]gabapentin to pig brain membranes and for their potency to inhibit the uptake of [H-3]leucine into CHO cells, a measure of their ability to compete with the endogenous substrate at the system L transporter. Compounds were also assessed in vivo for their ability to promote anxiolytic, analgesic, and anticonvulsant actions. These studies suggest that distinct structure activity relationships exist for alpha(2)-delta binding and system L transport inhibition. However, both interactions appear to play an important role in the in vivo profile of these compounds.

  DOI：

  10.1021/jm049762l

文献信息

• [EN] PREGABALIN DERIVATIVES FOR THE TREATMENT OF FIBROMYALGIA AND OTHER DISORDERS<br/>[FR] DERIVES DE PREGABALIN POUR LE TRAITEMENT DE LA FIBROMYALGIE ET D'AUTRES TROUBLES
  申请人：WARNER LAMBERT CO

  公开号：WO2004054566A1

  公开（公告）日：2004-07-01

  This invention relates to a method of treating a disorder selected from OCD, agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia, PTSD, restless legs syndrome, premenstrual dysphoric disorder, hot flashes, and fibromyalgia by administering a compound of the formula (1), or a pharmaceutically acceptable salt thereof, wherein; a) R1 is hydrogen, straight or branched alkyl of from 1 to 6 carbon atoms or phenyl; and b) R2 is straight or branched alkyl of from 4 to 8 carbon atoms, straight or branched alkenyl of from 2 to 8 carbon atoms, cycloalkyl of from 3 to 7 carbon atoms, alkoxy of from 1 to 6 carbon atoms, -alkylcycloalkyl, -alkylalkoxy, -alkyl OH, -alkylphenyl, -alkylphenoxy, or -substituted phenyl. The invention also relates to a method of treating the above disorders by administering the compound (3S, 5R)-3-Aminomethyl-5-methyl-octanoic acid.

  本发明涉及一种通过给予化合物（1）或其药学上可接受的盐来治疗选择自强迫症、广场恐惧症、无惊恐症状的广场恐惧症、特定恐惧症、社交恐惧症、创伤后应激障碍、不宁腿综合症、经前期情感性障碍、潮热和纤维肌痛等疾病的方法；其中：a）R1为氢、1至6个碳原子的直链或支链烷基或苯基；b）R2为4至8个碳原子的直链或支链烷基、2至8个碳原子的直链或支链烯基、3至7个碳原子的环烷基、1至6个碳原子的烷氧基、-烷基环烷基、-烷基烷氧基、-烷基羟基、-烷基苯基、-烷基苯氧基或-取代苯基。本发明还涉及一种通过给予化合物（3S，5R）-3-氨甲基-5-甲基-辛酸来治疗上述疾病的方法。
• Alpha 2 Delta Ligands For Fibromyalgia and Other Disorders
  申请人：Dooley David James

  公开号：US20080207755A1

  公开（公告）日：2008-08-28

  This invention relates to a method of treating certain disorders by administering a compound of the formula 1 or a pharmaceutically acceptable salt thereof, wherein: R 1 is hydrogen, straight or branched alkyl of from 1 to 6 carbon atoms or phenyl; and R 2 is straight or branched alkyl of from 4 to 8 carbon atoms, straight or branched alkenyl of from 2 to 8 carbon atoms, cycloalkyl of from 3 to 7 carbon atoms, alkoxy of from 1 to 6 carbon atoms, -alkylcycloalkyl, -alkylalkoxy, -alkyl OH, -alkylphenyl, -alkylphenoxy, or -substituted phenyl. The invention also relates to a method of treating the above disorders by administering the compound (3S, 5R)-3-aminomethyl-5-methyl-octanoic acid.

  本发明涉及一种通过给予公式1化合物或其药学上可接受的盐来治疗某些疾病的方法，其中：R1是氢、1至6个碳原子的直链或支链烷基或苯基；R2是4至8个碳原子的直链或支链烷基、2至8个碳原子的直链或支链烯基、3至7个碳原子的环烷基、1至6个碳原子的烷氧基、-烷基环烷基、-烷基烷氧基、-烷基羟基、-烷基苯基、-烷基苯氧基或-取代苯基。本发明还涉及一种通过给予化合物(3S, 5R)-3-氨甲基-5-甲基-辛酸来治疗上述疾病的方法。
• ALPHA 2 DELTA LIGANDS FOR FIBROMYALGIA AND OTHER DISORDERS
  申请人：Dooley James David

  公开号：US20070027212A1

  公开（公告）日：2007-02-01

  This invention relates to a method of treating a disorder selected from OCD, agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia, PTSD, restless legs syndrome, premenstrual dysphoric disorder, hot flashes, and fibromyalgia by administering a compound of the formula 1 or a pharmaceutically acceptable salt thereof, wherein: R 1 is hydrogen, straight or branched alkyl of from 1 to 6 carbon atoms or phenyl; and R 2 is straight or branched alkyl of from 4 to 8 carbon atoms, straight or branched alkenyl of from 2 to 8 carbon atoms, cycloalkyl of from 3 to 7 carbon atoms, alkoxy of from 1 to 6 carbon atoms, -alkylcycloalkyl, -alkylalkoxy, -alkyl OH, -alkylphenyl, -alkylphenoxy, or -substituted phenyl. The invention also relates to a method of treating the above disorders by administering the compound (3S,5R)-3-Aminomethyl-5-methyl-octanoic acid.

  本发明涉及通过给予式1化合物或其药学上可接受的盐治疗选自强迫症、广场恐惧症、无惊恐障碍史的广场恐惧症、特定恐惧症、社交恐惧症、创伤后应激障碍、不宁腿综合症、月经前期失调症、潮热和纤维肌痛的方法，其中：R1是氢、1至6个碳原子的直链或支链烷基或苯基；R2是4至8个碳原子的直链或支链烷基、2至8个碳原子的直链或支链烯基、3至7个碳原子的环烷基、1至6个碳原子的烷氧基、-烷基环烷基、-烷基烷氧基、-烷基-OH、-烷基苯基、-烷基苯氧基或-取代苯基。本发明还涉及通过给予化合物(3S,5R)-3-氨甲基-5-甲基-辛酸治疗上述疾病的方法。
• Alpha 2 Delta Ligands for Fibromyalgia and Other Disorders
  申请人：Dooley David James

  公开号：US20090203782A1

  公开（公告）日：2009-08-13

  This invention relates to a method of treating certain disorders by administering a compound of the formula 1 or a pharmaceutically acceptable salt thereof, wherein: R 1 is hydrogen, straight or branched alkyl of from 1 to 6 carbon atoms or phenyl; and R 2 is straight or branched alkyl of from 4 to 8 carbon atoms, straight or branched alkenyl of from 2 to 8 carbon atoms, cycloalkyl of from 3 to 7 carbon atoms, alkoxy of from 1 to 6 carbon atoms, -alkylcycloalkyl, -alkylalkoxy, -alkyl OH, -alkylphenyl, -alkylphenoxy, or -substituted phenyl. The invention also relates to a method of treating the above disorders by administering the compound (3S,5R)-3-aminomethyl-5-methyl-octanoic acid.

  本发明涉及通过给予式1化合物或其药学上可接受的盐来治疗某些疾病的方法，其中： R1为氢，1-6个碳原子的直链或支链烷基或苯基；和 R2为4-8个碳原子的直链或支链烷基，2-8个碳原子的直链或支链烯基，3-7个碳原子的环烷基，1-6个碳原子的烷氧基，-烷基环烷基，-烷基烷氧基，-烷基羟基，-烷基苯基，-烷基苯氧基或-取代苯基。本发明还涉及通过给予化合物(3S,5R)-3-氨甲基-5-甲基-辛酸来治疗上述疾病的方法。
• Mono- and disubstituted 3-propyl gamma-aminobutyric acids
  申请人：Warner-Lambert Company LLC

  公开号：EP1840117A1

  公开（公告）日：2007-10-03

  The instant invention is a series of novel mono- and disubstituted 3-propyl gamma aminobutyric acids of Formula I The compounds are useful as therapeutic agents in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, arthritis, sleep disorders, IBS, and gastric damage. Methods of preparing the compounds and useful intermediates are also part of the invention.

  本发明是一系列新型单-和二取代 3-丙基γ-氨基丁酸，其式为 I 这些化合物可作为治疗剂用于治疗癫痫、晕厥发作、运动机能减退、颅脑疾病、神经退行性疾病、抑郁症、焦虑症、恐慌症、疼痛、神经病理学疾病、关节炎、睡眠障碍、肠易激综合征和胃损伤。制备化合物和有用中间体的方法也是本发明的一部分。