α-Methyl-3-hydroxyphenylalanine | 831-74-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: α-Methyl-3-hydroxyphenylalanine
• 英文别名: α methyl meta tyrosine；α methyl m tyrosine；a-methyl-meta-tyrosine；(2S)-2-azaniumyl-3-(3-hydroxyphenyl)-2-methylpropanoate
• CAS: 831-74-3
• 化学式: C₁₀H₁₃NO₃
• 分子量: 195.218
• InChiKey: CAHPJJJZLQXPKS-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  α-Methyl-3-hydroxyphenylalanine 在 盐酸 作用下， 反应 0.75h， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of two analogues of (S)-α-methyl-3-carboxyphenylalanine

  摘要：

  Two analogues 2, 3 of (S)-alpha-methyl-3-carboxylphenylalanine 1 were synthesized to test their activity for metabotropic glutamate receptors (mGluRs). Both compounds 2 and 3 were inactive as antagonist for mGluRs, but 2 showed weak agonistic activity for GluR6 in contrast to that reported by Kemp and co-workers.

  DOI：

  10.1016/s0960-894x(98)00409-0
• 作为产物：
  描述：

  3-苯甲氧基苯甲醇 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 氢气 、 三溴化磷 、 lithium hexamethyldisilazane 作用下， 以 甲醇 、 乙醇 、 甲苯 为溶剂， 反应 30.92h， 生成 α-Methyl-3-hydroxyphenylalanine
  参考文献：
  名称：

  Synthesis and biological evaluation of two analogues of (S)-α-methyl-3-carboxyphenylalanine

  摘要：

  Two analogues 2, 3 of (S)-alpha-methyl-3-carboxylphenylalanine 1 were synthesized to test their activity for metabotropic glutamate receptors (mGluRs). Both compounds 2 and 3 were inactive as antagonist for mGluRs, but 2 showed weak agonistic activity for GluR6 in contrast to that reported by Kemp and co-workers.

  DOI：

  10.1016/s0960-894x(98)00409-0

文献信息

• SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITOR
  申请人：DREYFUS Nicolas Jacques Francois

  公开号：US20100261762A1

  公开（公告）日：2010-10-14

  A serotonin and norepinephrine reuptake inhibitor of the formula: its uses, and methods for its preparation are described.

  一种谷胺酸和去甲肾上腺素的再摄取抑制剂的配方：描述了其用途和制备方法。
• Renal-selective prodrugs for control of renal sympathetic nerve activity in the treatment of hypertension
  申请人：G.D. Searle & Co.

  公开号：US20030220521A1

  公开（公告）日：2003-11-27

  Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine-&bgr;-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kidney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension. Conjugates of particular interest are glutamyl derivatives of dopamine-&bgr;-hydroxylase inhibitors, of which N-acetyl-&ggr;-glutamyl fusaric acid hydrazide (shown below) is preferred. 1

  本文描述了一种肾选择性的前药，其在肾脏中优先转化为能够抑制参与肾交感神经活动的儿茶酚型神经递质合成的化合物。本文所描述的前药来源于能够抑制儿茶酚合成中的一个或多个酶的抑制剂化合物，这些化合物可分类为酪氨酸羟化酶抑制剂，多巴脱羧酶抑制剂或多巴胺-&bgr;-羟化酶抑制剂。这些抑制剂化合物通过可被肾脏中大量存在的酶选择性识别的可裂解键与化学基团（如谷氨酸衍生物）连接。释放的抑制剂化合物然后可在肾脏中用于抑制儿茶酚合成中的一个或多个酶。抑制肾脏儿茶酚合成可抑制与钠潴留相关的疾病（如高血压）相关的增强肾脏神经活动。特别感兴趣的共轭物是多巴胺-&bgr;-羟化酶抑制剂的谷氨酰衍生物，其中N-乙酰-&ggr;-谷氨酰富萨酸肼（如下图所示）是首选。1
• A pharmaceutical composition for oral administration for treating hypertension
  申请人：Merck & Co., Inc.

  公开号：EP0003353A1

  公开（公告）日：1979-08-08

  A pharmaceutical composition for treating hypertension containing L-a-methyl-p-tyrosine and a D,L- or L-hydrazino-phenyl propionic acid decarboxylase inhibitor.

  一种治疗高血压的药物组合物，包含L-a-甲基-p-酪氨酸和D，L-或L-肼基苯丙酸脱羧酶抑制剂。
• [EN] ARYLCYCLOBUTYL DERIVATIVES FOR TREATMENT OF PARKINSON'S DISEASE
  申请人：THE BOOTS COMPANY PLC

  公开号：WO1988006444A1

  公开（公告）日：1988-09-07

  (EN) Compounds of formula (I) in which Ar is optionally substituted phenyl, R1 is an optionally substituted aliphatic group and R2 and R3 are H or optionally substituted alkyl groups or R2 and R3 together with the nitrogen atom to which they are attached complete a heterocylic ring, are used in the treatment of Parkinson's disease. The compounds of formula (I) may be administered with a dopamine precursor such as levodopa and/or a dopa decarboxylase inhibitor such as carbidopa or benserazide. A preferred compound of formula (I) is $i(N),$i(N)-dimethyl-1-[1-(4-chlorophenyl)-cyclobutyl]-3-methylbutylamine hydrochloride monohydrate.(FR) Les composés décrits sont représentés par la formule (I), où Ar représente un phényle éventuellement substitué, R1 représente un groupe aliphatique éventuellement substitué et R2 et R3 représentent H ou des groupes alkyles éventuellement substitués ou R2 et R3 complètent, avec l'atome d'azote auquel ils sont liés, un anneau hétérocyclique. Lesdits composés sont utilisés dans le traitement de la maladie de Parkinson. Les composés de la formule (I) peuvent être administrés avec un précurseur de dopamine, tel que la lévodopa, et/ou avec un inhibiteur de décarboxylase de dopa, tel que la carbidopa ou un bensérazide. Un composé préféré de la formule (I) est constitué par un monohydrate d'hydrochlorure de $i(N),$i(N)-diméthyl-1-[1-(4-chlorophényl)-cyclobutyl]-3-méthylbutylamine.

  化合物的化学式为(I)，其中Ar为可选取代的苯基，R1为可选取代的脂肪基，R2和R3为H或可选取代的烷基，或者R2和R3与它们所连接的氮原子一起形成杂环环。这些化合物用于治疗帕金森病。化合物(I)可以与多巴胺前体如左旋多巴和/或多巴脱羧酶抑制剂如卡比多巴或苯磺酸倍他善一起使用。化合物(I)的首选化合物是$ i（N），$ i（N）-二甲基-1-[1-（4-氯苯基）-环丁基]-3-甲基丁胺盐酸单水合物。
• Renal-selective prodrugs for control of renal smpathetic nerve activity in the treatment of hypertension
  申请人：G.D. Searle & Co.

  公开号：US20040101523A1

  公开（公告）日：2004-05-27

  Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine-&bgr;-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kidney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension. Conjugates of particular interest are glutamyl derivatives of dopamine-&bgr;-hydroxylase inhibitors, of which N-acetyl-&ggr;-glutamyl fusaric acid hydrazide (shown below) is preferred. 1

  本文描述了肾脏选择性前药，这些前药被优先转化为能够抑制与肾脏交感神经活动相关的儿茶酚类神经递质合成的化合物。所述前药源自能够抑制儿茶酚类合成中涉及的一个或多个酶的抑制剂化合物，这些化合物可分类为酪氨酸羟化酶抑制剂，或多巴脱羧酶抑制剂，或是多巴胺-β-羟化酶抑制剂。这些抑制剂化合物与化学基团（例如谷氨酸衍生物）通过可被肾脏内的酶特异性识别的可切断键连接。被释放的抑制剂化合物随后可在肾脏中抑制一个或多个涉及儿茶酚类合成的酶。抑制肾脏儿茶酚类合成可以抑制与钠潴留相关的疾病（如高血压）所伴随的过度肾脏神经活动。特别感兴趣的结合物是多巴胺-β-羟化酶抑制剂的谷氨酰衍生物，其中N-乙酰-γ-谷氨酰菌核酸酸肼（如下图所示）是首选。1