(S)-2-((tert-butoxycarbonyl)amino)-3-(4-hydroxy-2-methylphenyl)propanoic acid | 137378-58-6

• 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: (S)-2-((tert-butoxycarbonyl)amino)-3-(4-hydroxy-2-methylphenyl)propanoic acid
• 英文别名: BOC-(L)-2-methyltyrosine；Boc-2-methyl-L-tyrosine；N-Boc-2-methyl-L-tyrosine；(2S)-3-(4-hydroxy-2-methylphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 137378-58-6
• 化学式: C₁₅H₂₁NO₅
• 分子量: 295.335
• InChiKey: YNNUYNGLAGTLKL-LBPRGKRZSA-N

物化性质

• 沸点：
  498.8±45.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-((tert-butoxycarbonyl)amino)-3-(4-hydroxy-2-methylphenyl)propanoic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 苯甲醚 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 H-(2'-monomethyltyrosine)-Pro-Phe-Phe-NH2*TFA
  参考文献：
  名称：

  Development of Potent μ-Opioid Receptor Ligands Using Unique Tyrosine Analogues of Endomorphin-2

  摘要：

  Six analogues of tyrosine, which contained alkyl groups at positions 2', 3', and 6', either singly or in combination on the tyramine ring, were investigated for their effect on the opioid activity of [Xaa(1)]endomorphin-2 (EM-2). The opioid analogues displayed the following characteristics: (i) high mu-opioid receptor affinity [K-i(mu) = 0.063-2.29 nM] with selectivity [K-i(delta)/Ki(mu)] ranging from 46 to 5347; (ii) potent functional mu-opioid agonism [GPI assay (IC50 = 0.623-0.924 nM)1 and with a correlation between delta-opioid receptor affinities and functional bioactivity using MVD; (iii) intracerebroventricular administration of [Dmt(1)]- (14) and [Det(1)]EM-2 (10) produced a dose-response antinociception in mice, with the former analogue more active than the latter; and (iv) a marked shift occurred from the trans-orientation at the Tyr(1)-Pro(2) bond to a cis-conformer compared to that observed previously with [Dmt(1)]EM-2 (14) (Okada et al. Bioorg. Med. Chem. 2003, 11, 1983-1984) except [Mmt(1)]EM-2 (7). The active profile of the [Xaa(1)]EM-2 analogues indicated that significant modifications on the tyramine ring are possible while high biological activity is maintained.

  DOI：

  10.1021/jm049384k
• 作为产物：
  描述：

  Boc-L-丝氨酸甲酯 在 2-双环己基膦-2',6'-二甲氧基联苯 、 咪唑 、 tris-(dibenzylideneacetone)dipalladium(0) 、 碘 、 三苯基膦 、 lithium hydroxide 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 (S)-2-((tert-butoxycarbonyl)amino)-3-(4-hydroxy-2-methylphenyl)propanoic acid
  参考文献：
  名称：

  Rapid Synthesis of Boc-2′,6′-dimethyl-l-tyrosine and Derivatives and Incorporation into Opioid Peptidomimetics

  摘要：

  The unnatural amino acid 2',6'-dimethyl-L-tyrosine has found widespread use in the development of synthetic opioid ligands. Opioids featuring this residue at the N-terminus often display superior potency at one or more of the opioid receptor types, but the availability of the compound is hampered by its cost and difficult synthesis. We report here a short, three-step synthesis of Boc-2',6'-dimethyl-L-tyrosine (3a) utilizing a microwave-assisted Negishi coupling for the key carbon-carbon bond forming step, and employ this chemistry for the expedient synthesis of other unnatural tyrosine derivatives. Three of these derivatives (3c, 3d, 30 have not previously been examined as Tyr(1) replacements in opioid ligands. We describe the incorporation of these tyrosine derivatives in a series of opioid peptidomimetics employing our previously reported tetrahydroquinoline (THQ) scaffold, and the binding and relative efficacy of each of the analogues at the three opioid receptor subtypes: mu (MOR), delta (DOR), and kappa (KOR).

  DOI：

  10.1021/acsmedchemlett.5b00344

文献信息

• Non-heterocyclic .beta.-phenyl-.alpha.-aminopropionic acid n-phenyl
  申请人：G. D. Searle & Co.

  公开号：US06114381A1

  公开（公告）日：2000-09-05

  Compounds, compositions and methods of treatment are described to control brain damage associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of a .beta.-phenyl-.alpha.-aminopropionic acid N phenyl amide compound as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of the formula ##STR1## wherein each of R.sup.1 and R.sup.5 is independently selected from hydrido, fluoro, chloro, bromo, methyl and ethyl; wherein R.sup.3 is selected from hydroxy, methoxy, ethoxy, methoxycarbonyloxy, ethoxycarbonyloxy, (2-methylpropoxy)carbonyloxy and (2-propenyloxy) carbonyloxy; wherein each of R.sup.6, R.sup.7 and R.sup.8 is hydrido; wherein each of R.sup.9 and R.sup.10 is independently selected from hydrido, methyl and ethyl; wherein R.sup.11 is one or more groups independently selected from hydrido, fluoro, chloro, hydroxy, methoxy, methyl and ethyl; or a tautomer or enantiomer therefor, or a pharmaceutically-acceptable salt or ester thereof.

  描述了用于控制与缺氧或缺血相关的脑损伤的化合物、组合物和治疗方法，通常在中风、心脏骤停或围产期窒息后发生。治疗包括给予β-苯基-α-氨基丙酸N苯胺类化合物作为拮抗剂，以抑制主要神经元兴奋性氨基酸受体位点的兴奋毒性作用。最感兴趣的化合物是具有以下结构的化合物：其中R.sup.1和R.sup.5中的每一个独立选择自氢、氟、氯、溴、甲基和乙基；其中R.sup.3选择自羟基、甲氧基、乙氧基、甲氧羰氧基、乙氧羰氧基、(2-甲基丙氧基)羰氧基和(2-丙烯氧基)羰氧基；其中R.sup.6、R.sup.7和R.sup.8中的每一个是氢；其中R.sup.9和R.sup.10中的每一个独立选择自氢、甲基和乙基；其中R.sup.11是一个或多个独立选择自氢、氟、氯、羟基、甲氧基、甲基和乙基的基团；或其互变异构体或对映体，或其药用可接受的盐或酯。
• [EN] EFFLUX PUMP INHIBITORS<br/>[FR] INHIBITEURS DE POMPE D'ECOULEMENT
  申请人：MICROCIDE PHARMACEUTICALS, INC.

  公开号：WO1999037667A1

  公开（公告）日：1999-07-29

  (EN) Compounds are described which have efflux pump inhibitor activity. Also described are methods of using such efflux pump inhibitor compounds and pharmaceutical compositions which include such compounds.(FR) L'invention concerne des composés présentant une activité d'inhibiteur de pompe d'écoulement. L'invention concerne également des méthodes d'utilisation de ces composés inhibiteurs et des compositions pharmaceutiques renfermant de tels composés.

  （中文翻译）描述了具有外排泵抑制剂活性的化合物。还描述了使用这种外排泵抑制剂化合物的方法和包括这种化合物的药物组合物。
• Enkephalin analogs
  申请人：G.D. Searle & Co.

  公开号：EP0136720A2

  公开（公告）日：1985-04-10

  The invention relates to novel enkephalin analogs of the formula: which are useful as analgesic agents.

  本发明涉及式如下的新型脑啡肽类似物： 可用作镇痛剂。
• Substituted tyrosil alanine dipeptide amides
  申请人：G.D. Searle & Co.

  公开号：EP0154234A2

  公开（公告）日：1985-09-11

  The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula: and the pharmaceutically acceptable acid addition salts thereof wherein R, represents straight or branched lower alkyl having 1 to 4 carbons; R2 represent hydrogen, hydroxy, -OCO2R1 substituent or lower alkyl having 1 to 4 carbons; R3 represents a hydrogen or lower alkyl having 1 to 6 carbons; R4 and R5 may be the same or different and represent hydrogen or lower alkyl having 1 to 6 carbons; n is 1 to 6; X represents a hydrogen, hydroxy or OCO2R1 substituent; A represents a cyclohexyl, phenyl or phenyl substituted with one or more lower alkyls containing 1 to 6 carbons, one or more amino, hydroxy, halogen, nitro or lower alkoxy substituent having 1 to 6 carbons; V represents the asymmetric carbon that may be racemic or have the D or L configuration; W represents the asymmetric carbon when R4 and R5 are not the same that may optionally be racemic or have the D or L configuration. These compounds are useful as analgesic and/or antihypertensive agents.

  本发明涉及式如下的新型取代酪氨丙氨酸二肽酰胺： 及其药学上可接受的酸加成盐 其中 R，代表具有 1 至 4 个碳原子的直链或支链低级烷基； R2 代表氢、羟基、-OCO2R1 取代基或具有 1 至 4 个碳原子的低级烷基； R3 代表氢或具有 1 至 6 个碳原子的低级烷基； R4 和 R5 可以相同或不同，代表氢或含 1 至 6 个碳原子的低级烷基； n 为 1 至 6； X 代表氢、羟基或 OCO2R1 取代基； A 代表环己基、苯基或被一个或多个含 1 至 6 个碳原子的低级烷基、一个或多个氨基、羟基、卤素、硝基或 1 至 6 个碳原子的低级烷氧基取代的苯基； V 代表不对称碳，可以是外消旋的，或具有 D 或 L 构型； W 代表 R4 和 R5 不相同时的不对称碳，可选择外消旋或具有 D 或 L 构型。这些化合物可用作镇痛剂和/或抗高血压剂。
• US4495178A
  申请人：——

  公开号：US4495178A

  公开（公告）日：1985-01-22