(2S)-3-(4-hydroxy-2,3,6-trimethylphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid | 845622-93-7

• 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: (2S)-3-(4-hydroxy-2,3,6-trimethylphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 845622-93-7
• 化学式: C₁₇H₂₅NO₅
• 分子量: 323.389
• InChiKey: QCGRWKCNXOXWQG-ZDUSSCGKSA-N

物化性质

• 沸点：
  519.5±50.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 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：

  (2S)-3-(4-hydroxy-2,3,6-trimethylphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]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',3',6'-trimethyltyrosine)-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：

  4-iodo-2,3,5-trimethylphenol acetate 在 [Rh((R,R)-DIPAMP)(COD)]BF₄ 盐酸 、 palladium diacetate 、 TEA 、 氢气 、 三(邻甲基苯基)磷 作用下， 以 1,4-二氧六环 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 60.0 ℃ 、413.68 kPa 条件下， 反应 28.75h， 生成 (2S)-3-(4-hydroxy-2,3,6-trimethylphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
  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

文献信息

• 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
• US4599325A
  申请人：——

  公开号：US4599325A

  公开（公告）日：1986-07-08
• US4603121A
  申请人：——

  公开号：US4603121A

  公开（公告）日：1986-07-29