4-oxo-4-(2-oxo-1-pyrrolidinyl)butyric acid | 130984-38-2

• 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: 4-oxo-4-(2-oxo-1-pyrrolidinyl)butyric acid
• 英文别名: 4-oxo-4-(2-oxopyrrolidin-1-yl)butanoic acid
• CAS: 130984-38-2
• 化学式: C₈H₁₁NO₄
• 分子量: 185.18
• InChiKey: NTQYLADLFLEGII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-oxo-4-(2-oxo-1-pyrrolidinyl)butyric acid 、 L-脯氨醇 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 在 N,N-二环己脲 、 氯仿 、 盐酸 、 magnesium sulfate 、 silica gel 、 chloroform methanol 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以to give 3.41 g of N-[(4-oxo-4-(2-oxo-1-pyrrolidinyl)butanoyl]-L-prolinol的产率得到(4-oxo-4-(2-oxo-1-pyrrolidinyl)butanoyl]-L-prolinol
  参考文献：
  名称：

  Amino acid derivatives possessing prolyl endopeptidase-inhibitory

  摘要：

  化合物的氨基酸衍生物的公式为##STR1## 其中：Q为W--(CH.sub.2).sub.m--(A).sub.n--CO--B-- 其中A为氧原子或--NH--；B为##STR2##或--(CH.sub.2).sub.l--其中X为硫原子或--CH.sub.2--，l为1到3的整数；W为##STR3##其中Hal为卤素原子；n为0或1的整数；m为0到3的整数；Y为硫原子或--CH.sub.2--；R为氢原子、甲酰基、C.sub.1-5烷氧羰基、--C.tbd.N或##STR4##其中R.sup.1为氢原子，R.sup.2为羟基、C.sub.1-5烷基羧基、苯基羧基、C.sub.1-5烷氧基或苯基C.sub.1-5烷氧基；但当R为氢原子、甲酰基或C.sub.1-5烷氧羰基时，W为##STR5## 上述化合物特异性抑制脯氨酰内切酶活性，并且作为治疗和预防痴呆和健忘症的药物。

  公开号：

  US05118811A1
• 作为产物：
  描述：

  2-吡咯烷酮 、 丁二酸酐 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 生成 4-oxo-4-(2-oxo-1-pyrrolidinyl)butyric acid
  参考文献：
  名称：

  Amino acid derivatives possessing prolyl endopeptidase-inhibitory

  摘要：

  该化合物的氨基酸衍生物的化学式为##STR1##其中：Q是W--(CH.sub.2).sub.m --(A).sub.n --CO--B--，其中A是氧原子或--NH--；B是##STR2##或--(CH.sub.2).sub.l --其中X是硫原子或--CH.sub.2--，l是1到3的整数；W是##STR3##其中Hal是卤素原子；n为0或1的整数；m是0到3的整数；Y是硫原子或--CH.sub.2--；R是氢原子、甲酰基、C.sub.1-5烷氧羰基、--C.tbd.N或##STR4##其中R.sup.1是氢原子，R.sup.2是羟基、C.sub.1-5烷基羧基、苯基羧基、C.sub.1-5烷氧基或苯基C.sub.1-5烷氧基；但当R为氢原子、甲酰基或C.sub.1-5烷氧羰基时，W是##STR5##上述化合物特异性抑制脯氨酸内切酶活性，并可用作治疗和预防痴呆和健忘症的药物。

  公开号：

  US05118811A1

文献信息

• NEW AMINO ACID DERIVATIVES HAVING PROLYLENDOPEPTIDASE INHIBITOR ACTIVITY
  申请人：Japan Tobacco Inc.

  公开号：EP0419683A1

  公开（公告）日：1991-04-03

  Amino acid derivatives of formula (I), which specifically inhibit prolylendopeptidase activity and are useful for treating or preventing dementia and amnesia, wherein Q represents W-(CH2)m-(A)n-CO-B-, A represents oxygen or imino, B represents (II) or -(CH2)1, X and Y represent each sulfur or methylene, W represents (III, IV) or (V), wherein Hal represents halogen, R represents hydrogen, formyl, C1 to C5 alkoxycarbonyl, cyano, or -CR1 = N - R2, R1 represents hydrogen, R2 represents hydroxy, C1 to C5 alkylcarboxy, phenylcarboxy, C1 to C5 alkoxy, or phenyl(C1 to Cs) alkoxy, and n, m and I represent integers of, respectively, 0 or 1, 0 to 3, and 1 to 3, provided that W represents (VI) when R represents hydrogen, formyl or C1 to Cs alkoxycarbonyl.

  式(I)的氨基酸衍生物，可特异性抑制脯氨酰内肽酶活性，用于治疗或预防痴呆症和健忘症，其中Q代表W-(CH2)m-(A)n-CO-B-，A代表氧或亚氨基，B代表(II)或-(CH2)1，X和Y分别代表硫或亚甲基，W代表(III、IV)或(V)，其中Hal代表卤素、R代表氢、甲酰基、C1～C5烷氧基羰基、氰基或-CR1＝N-R2，R1代表氢，R2代表羟基、C1～C5烷基羧基、苯基羧基、C1～C5烷氧基或苯基（C1～Cs）烷氧基，n、m和I分别代表0或1、0～3和1～3的整数，但当R代表氢、甲酰基或C1～Cs烷氧基羰基时，W代表(VI)。
• SASAKI, HITOSHI;MORI, YOSHIYKI;NAKAMURA, JUNZO;SHIBASAKI, JUICHIRO, J. MED. CHEM., 34,(1991) N, C. 628-633
  作者：SASAKI, HITOSHI、MORI, YOSHIYKI、NAKAMURA, JUNZO、SHIBASAKI, JUICHIRO

  DOI：——

  日期：——
• US5118811A
  申请人：——

  公开号：US5118811A

  公开（公告）日：1992-06-02
• Synthesis and anticonvulsant activity of 1-acyl-2-pyrrolidinone derivatives
  作者：Hitoshi Sasaki、Yoshiyuki Mori、Junzo Nakamura、Juichiro Shibasaki

  DOI：10.1021/jm00106a025

  日期：1991.2

  Several 1-acyl-2-pyrrolidinone derivatives were synthesized as derivatives of gamma-aminobutyric acid (GABA), and their pharmacological activities and stabilities were investigated. The derivatives showed anticonvulsant effect on picrotoxin-induced seizure at a dose of 200 mg/kg. In particular, 1-decanoyl-2-pyrrolidinone (7) and 1-dodecanoyl-2-pyrrolidinone (8) had a high activity. The anticonvulsant activity showed a dose dependency. Some of 1-acyl-2-pyrrolidinone derivatives prolonged sleeping time which was induced by sodium pentobarbital and showed a recovery from disruption of the memory of passive avoidance response, which was induced by an electroconvulsive shock. As shown by the results of the stability study of 1-acetyl-2-pyrrolidinone (1), it was degraded in an acidic buffer and an alkaline buffer although 2-pyrrolidinone was stable. 1-Acyl-2-pyrrolidinone derivatives were degraded in liver and brain homogenates of mouse and rat. They showed a degradation rate in rat plasma. Conversion of 8 to GABA in mouse liver homogenate was demonstrated. These results suggested that the pharmacological activity of 1-acyl-2-pyrrolidinone is probably due to the release of GABA by hydrolysis of derivatives although further work is necessary.
• Amino acid derivatives possessing prolyl endopeptidase-inhibitory
  申请人：Japan Tobacco Inc.

  公开号：US05118811A1

  公开（公告）日：1992-06-02

  Amino acid derivatives of the formula ##STR1## wherein: Q is W--(CH.sub.2).sub.m --(A).sub.n --CO--B-- wherein A is oxygen atom or --NH--; B is ##STR2## or --(CH.sub.2).sub.l -- wherein X is sulfur atom or --CH.sub.2 --, and l is an integer from 1 to 3; W is ##STR3## wherein Hal is halogen atom; n is an integer of 0 or 1; and m is an integer from 0 to 3; Y is sulfur atom or --CH.sub.2 --; and R is hydrogen atom, formyl group, C.sub.1-5 alkoxycarbonyl group, --C.tbd.N or ##STR4## wherein R.sup.1 is hydrogen atom, and R.sup.2 is hydroxyl group, C.sub.1-5 alkylcarboxy group, phenylcarboxy group, C.sub.1-5 alkoxy group or phenyl C.sub.1-5 alkoxy group; with the proviso that when R is hydrogen atom, formyl group or C.sub.1-5 alkoxycarbonyl group, W is ##STR5## The compounds mentioned above specifically inhibit prolyl endopeptidase activity and are useful as agents for the treatment and prevention of dementia and amnesia.

  该化合物的氨基酸衍生物的化学式为##STR1##其中：Q是W--(CH.sub.2).sub.m --(A).sub.n --CO--B--，其中A是氧原子或--NH--；B是##STR2##或--(CH.sub.2).sub.l --其中X是硫原子或--CH.sub.2--，l是1到3的整数；W是##STR3##其中Hal是卤素原子；n为0或1的整数；m是0到3的整数；Y是硫原子或--CH.sub.2--；R是氢原子、甲酰基、C.sub.1-5烷氧羰基、--C.tbd.N或##STR4##其中R.sup.1是氢原子，R.sup.2是羟基、C.sub.1-5烷基羧基、苯基羧基、C.sub.1-5烷氧基或苯基C.sub.1-5烷氧基；但当R为氢原子、甲酰基或C.sub.1-5烷氧羰基时，W是##STR5##上述化合物特异性抑制脯氨酸内切酶活性，并可用作治疗和预防痴呆和健忘症的药物。