N-hydroxy-L-phenylalanine | 14668-24-7

• 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: N-hydroxy-L-phenylalanine
• 英文别名: L-N-Hydroxyphenylalanin；(2S)-2-(hydroxyamino)-3-phenylpropanoic acid
• CAS: 14668-24-7
• 化学式: C₉H₁₁NO₃
• 分子量: 181.191
• InChiKey: VTPJSQTVPKSYCB-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  L-苯丙氨酸甲酯盐酸盐 生成 N-hydroxy-L-phenylalanine
  参考文献：
  名称：

  Polonski,T.; Chimiak,A., Bulletin de l'Academie Polonaise des Sciences, Serie des Sciences Chimiques, 1979, vol. 27, p. 459 - 464

  摘要：

  DOI：

文献信息

• [EN] NEW CATECHOLAMINE PRODRUGS FOR USE IN THE TREATMENT OF PARKINSON'S DISEASE<br/>[FR] NOUVEAUX PROMÉDICAMENTS DE CATÉCHOLAMINE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE LA MALADIE DE PARKINSON
  申请人：H LUNDBECK AS

  公开号：WO2019101917A1

  公开（公告）日：2019-05-31

  The present invention provides compounds of formula (I) that are prodrugs of catecholamine for use in treatment of neurodegenerative diseases and disorders. The present invention also provides pharmaceutical compositions comprising compounds of the invention and methods of treating neurodegenerative or neuropsychiatric diseases and disorders using the compounds of the invention, in particular Parkinson's disease. Accordingly, the present invention relates to compounds of formula (Id) wherein R1 is H and R2 is selected from one of the substituents (i) and (ii) below; or R1 is selected from one of the substituents (i) and (ii) below and R2 is H; or R1 and R2 are both represented by substituent (i) below; or R1 and R2 are both represented by substituent (ii) below; or R1 is substituent (i) and R2 is substituent (ii); or R1 is substituent (ii) and R2 is substituent (i); (i) (ii) wherein * indicates the attachment point; and wherein the carbon atom at the attachment point on substituent (i) is in the S-configuration; or a pharmaceutically acceptable salt thereof.

  本发明提供了化合物(I)的中间体，用于治疗神经退行性疾病和紊乱。本发明还提供了包括本发明化合物的药物组合物，以及使用本发明化合物治疗神经退行性或神经精神疾病和紊乱的方法，特别是帕金森病。因此，本发明涉及化合物(I d)的公式，其中R1为H，R2从下面的取代基(i)和(ii)中选择一个；或R1从下面的取代基(i)和(ii)中选择一个，R2为H；或R1和R2都由下面的取代基(i)表示；或R1和R2都由下面的取代基(ii)表示；或R1为取代基(i)，R2为取代基(ii)；或R1为取代基(ii)，R2为取代基(i)；(i) (ii) 其中*表示连接点；取代基(i)上连接点的碳原子处于S构型；或其药用可接受盐。
• CONFORMATIONALLY CONSTRAINED, FULLY SYNTHETIC MACROCYCLIC COMPOUNDS
  申请人：Obrecht Daniel

  公开号：US20120270881A1

  公开（公告）日：2012-10-25

  Conformationally restricted, spatially defined 12-30 membered macrocyclic ring systems of formulae Ia and Ib are constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. These macrocycles Ia and Ib are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being the agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), ion channels and signal transduction pathways. In particular, these macrocycles act as antagonists of the motilin receptor, the FP receptor and the purinergic receptors P2Y 1 , as modulators of the serotonin receptor of subtype 5-HT 2B , as blockers of the voltage-gated potassium channel K v 1.3 and as inhibitors of the β-catenin-dependent “canonical” Wnt pathway. Thus they are showing great potential as medicaments for a variety of diseases.

  具有结构限制的、空间定义的12-30环的大环系统Ia和Ib由三个不同的分子部分构成：模板A、构象调节剂B和桥C。这些大环Ia和Ib可以通过并行合成或溶液中或固相上的组合化学来轻松制备。它们被设计用于与各种特定的生物靶标类相互作用，例如对G蛋白偶联受体（GPCRs）、离子通道和信号转导途径的激动或拮抗活性。特别地，这些大环作为莫蒂林受体的拮抗剂、FP受体和嘌呤受体P2Y1的调节剂、5-HT2B亚型的5-羟色胺受体的调节剂、电压门控钾通道Kv1.3的阻断剂以及β-连环蛋白依赖的“经典”Wnt途径的抑制剂。因此，它们显示出作为各种疾病药物的巨大潜力。
• [EN] PEPTIDOMIMETIC AGENTS, SYNTHESIS AND USES THEREOF<br/>[FR] AGENTS PEPTIDOMIMÉTIQUES, SYNTHÈSE ET UTILISATIONS DE CEUX-CI
  申请人：FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH

  公开号：WO2020227588A1

  公开（公告）日：2020-11-12

  Compounds for use in synthesis of peptidomimetic agents; synthesis of peptidomimetic agents; peptidomimetic diagnostic and therapeutic agents; and uses of the compounds and peptidomimetic agents in drug discovery, diagnosis, prevention and treatment of diseases are described.

  描述了用于合成肽类模拟药物的化合物；合成肽类模拟药物；肽类模拟诊断和治疗剂；以及化合物和肽类模拟药物在药物发现、诊断、预防和治疗疾病中的用途。
• [EN] TRIAZOLE-CROSSLINKED AND THIOETHER-CROSSLINKED PEPTIDOMIMETIC MACROCYCLES<br/>[FR] MACROCYCLES PEPTIDOMIMÉTIQUES RÉTICULÉS PAR TRIAZOLE ET PAR THIOÉTHER
  申请人：AILERON THERAPEUTICS INC

  公开号：WO2013123267A1

  公开（公告）日：2013-08-22

  Provided herein are peptidomimetic macrocycles and methods of using such macrocycles for the treatment of disease.

  本文提供了肽类模拟大环和使用这种大环治疗疾病的方法。
• [EN] ADMINISTRATION OF CATECHOLAMINE PRODRUGS IN COMBINATION WITH A 5-HT2B ANTAGONIST<br/>[FR] ADMINISTRATION DE PROMÉDICAMENTS DE CATÉCHOLAMINE EN COMBINAISON AVEC UN ANTAGONISTE DE 5-HT2B
  申请人：H LUNDBECK AS

  公开号：WO2020070099A1

  公开（公告）日：2020-04-09

  The present invention provides combinations comprising treatment with compounds that are prodrugs of the dopamine agonist (4aR,10aR)-1-n-Propyl-1,2,3,4,4a,5,10,10a- octahydro-benzo[g]quinoline-6,7-diol, in particular compounds of formula (Ia) below or a pharmaceutically acceptable salt thereof, together with a 5-HT2B antagonist. R1 and R2 are selected independently from the group consisting of H, C1-6 alkyl and saturated monocyclic C3-6 cycloalkyl, or one of R1 and R2 is H and the other is phenyl, or R1 and R2 are connected to form a saturated monocyclic 3-6 cycloalkyl.Especially, the invention is directed to the combined use of said compounds in the treatment of Parkinson's disease and/or other conditions for which treatment with a dopamine agonist is therapeutically beneficial. The present invention also provides pharmaceutical compositions comprising said compounds and a 5-HT2B antagonist. In a separate aspect, the invention relates to new compounds that are prodrugs of (4aR,10aR)-1-n-Propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinoline-6,7-diol wherein R1 and R2 are individually selected from the group consisting of H, C1-6 alkyl and saturated monocyclic C3-6 cycloalkyl; or a pharmaceutically acceptable salt thereof; with the proviso that both R1 and R2 cannot be H at the same time.

  本发明提供了包括与多巴胺激动剂(4aR,10aR)-1-丙基-1,2,3,4,4a,5,10,10a-辛氢-苯并[g]喹啉-6,7-二酚的前药一起治疗的组合物，特别是下面的式(Ia)化合物或其药学上可接受的盐，以及5-HT2B拮抗剂。R1和R2分别从H、C1-6烷基和饱和单环C3-6环烷基组成的群体中选择，或者R1和R2中的一个是H，另一个是苯基，或者R1和R2连接形成饱和的单环3-6环烷基。特别地，本发明针对上述化合物在帕金森病的治疗中的联合使用以及治疗多巴胺激动剂具有治疗益处的其他疾病。本发明还提供了包括上述化合物和5-HT2B拮抗剂的药物组合物。在另一个方面，本发明涉及新的化合物，这些化合物是(4aR,10aR)-1-丙基-1,2,3,4,4a,5,10,10a-辛氢-苯并[g]喹啉-6,7-二酚的前药，其中R1和R2分别从H、C1-6烷基和饱和单环C3-6环烷基组成的群体中选择；或者其药学上可接受的盐；但R1和R2不能同时为H。