(4R)-dihydro-L-kynurenine | 135457-24-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4R)-dihydro-L-kynurenine
• 英文别名: (2S,4R)-2-amino-4-(2-aminophenyl)-4-hydroxybutanoic acid
• CAS: 135457-24-8
• 化学式: C₁₀H₁₄N₂O₃
• 分子量: 210.233
• InChiKey: JHFGLUQOFZHYDW-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  110
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  L-犬尿氨酸 在 sodium tetrahydroborate 、 水 作用下， 以7.2 mg的产率得到(4S)-dihydro-L-kynurenine
  参考文献：
  名称：

  Stereochemistry and mechanism of aldol reactions catalyzed by kynureninase

  摘要：

  Kynureninase from Pseudomonas has been reported to catalyze aldol and retro-aldol reactions, in addition to the physiological hydrolytic cleavage of L-kynurenine to anthranilic acid and L-alanine. However, the stereochemistry of these novel aldol reactions has not been previously determined. We have determined that the reaction of L-kynurenine and benzaldehyde catalyzed by kynureninase results in (2S,4R)-2-amino-4-hydroxy-4-phenylbutanoic acid. Similarly, the 4R isomer of dihydro-L-kynurenine readily undergoes retro-aldol cleavage, while the 4S isomer is unreactive as a substrate. Both isomers of dihydro-L-kynurenine are competitive inhibitors of kynureninase from Pseudomonas. However, the 4S isomer of dihydro-L-kynurenine is the most potent inhibitor, with a K(i) of 0.3-mu-M. These results provide additional support for a general base mechanism for kynureninase, and suggest that the hydration occurs on the re face of the carbonyl group of kynurenine to give an (S)-gem-diolate intermediate.

  DOI：

  10.1021/ja00019a039

文献信息

• Treatment of aneurysms
  申请人：Georgia State University Research Foundation, Inc.

  公开号：US11376248B2

  公开（公告）日：2022-07-05

  The present invention provides methods for detecting and/or treating a subject having an aneurysm or at risk for developing an aneurysm. It has been discovered that a key metabolite of the kynurenine (Kyn) pathway, a major route for the metabolism of essential amino acid tryptophan (Trp) into nicotinamide adenine dinucleotide (NAD+), plays a critical role in the formation of aneurysms, for example abdominal aortic aneurysms. In particular, it has been discovered that 3-Hydroxyanthranilic acid (3-HAA), a product of kynureninase (KYNU), plays a causative role in the formation of aneurysms by, for example exerting pro-inflammatory effects on vascular smooth muscle cells. It has further been discovered that elevated levels of 3-HAA are indicative of the presence and/or progression of an aneurysm, and 3-HAA levels correlate with the size (aortic diameter) of the aneurysm.

  本发明提供了检测和/或治疗患有动脉瘤或有罹患动脉瘤风险的受试者的方法。现已发现，犬尿氨酸（Kyn）途径的一种关键代谢物--将必需氨基酸色氨酸（Trp）代谢为烟酰胺腺嘌呤二核苷酸（NAD+）的主要途径--在动脉瘤（例如腹主动脉瘤）的形成中起着关键作用。特别是，研究发现，3-羟基氨基苯甲酸（3-HAA）是犬尿苷酶（KYNU）的产物，通过对血管平滑肌细胞产生促炎作用等方式，在动脉瘤的形成过程中起着致病作用。研究进一步发现，3-HAA 水平的升高表明动脉瘤的存在和/或发展，3-HAA 水平与动脉瘤的大小（主动脉直径）相关。
• EP0581907A4
  申请人：——

  公开号：EP0581907A4

  公开（公告）日：1994-04-06
• INHIBITORS OF KYNURENINASE
  申请人：THE UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：EP0581907A1

  公开（公告）日：1994-02-09
• TREATMENT OF ANEURYSMS
  申请人：Georgia State University Research Foundation, Inc.

  公开号：US20200138810A1

  公开（公告）日：2020-05-07

  The present invention provides methods for detecting and/or treating a subject having an aneurysm or at risk for developing an aneurysm. It has been discovered that a key metabolite of the kynurenine (Kyn) pathway, a major route for the metabolism of essential amino acid tryptophan (Trp) into nicotinamide adenine dinucleotide (NAD+), plays a critical role in the formation of aneurysms, for example abdominal aortic aneurysms. In particular, it has been discovered that 3-Hydroxyanthranilic acid (3-HAA), a product of kynureninase (KYNU), plays a causative role in the formation of aneurysms by, for example exerting pro-inflammatory effects on vascular smooth muscle cells. It has further been discovered that elevated levels of 3-HAA are indicative of the presence and/or progression of an aneurysm, and 3-HAA levels correlate with the size (aortic diameter) of the aneurysm.
• US5254725A
  申请人：——

  公开号：US5254725A

  公开（公告）日：1993-10-19