(3-tert-Butoxycarbonylamino-5-chloro-4-oxo-pentyl)-carbamic acid benzyl ester | 693222-10-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3-tert-Butoxycarbonylamino-5-chloro-4-oxo-pentyl)-carbamic acid benzyl ester
• 英文别名: benzyl N-[5-chloro-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxopentyl]carbamate
• CAS: 693222-10-5
• 化学式: C₁₈H₂₅ClN₂O₅
• 分子量: 384.86
• InChiKey: TYZBHKWZTWHLDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-tert-Butoxycarbonylamino-5-chloro-4-oxo-pentyl)-carbamic acid benzyl ester 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢溴酸 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 tert-butyl N-[(2S)-3-(4-hydroxy-2,6-dimethylphenyl)-1-[(3S)-3-[2-[5-[2-[[(3S)-2-[(2S)-3-(4-hydroxy-2,6-dimethylphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]-3-methyl-6-oxo-1H-pyrazin-2-yl]ethylcarbamoyl]-3,4-dihydro-1H-isoquinolin-2-yl]-1-oxopropan-2-yl]carbamate
  参考文献：
  名称：

  Potent Dmt-Tic Pharmacophoric δ- and μ-Opioid Receptor Antagonists

  摘要：

  A series of dimeric Dmt-Tic (2',6'-dimethyl-L-tyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) analogues (8-14, 18-22) were covalently linked through diaminoalkane and symmetric or asymmetric 3,6-diaminoalkyl-2(1H)-pyrazinone moieties. All the compounds exhibited high affinity for both 6-opioid receptors K(6) = 0.06-1.53 nM] andy-opioid receptors [K-i(mu) = 1.375.72 nM], resulting in moderate delta-receptor selectivity [K-i(mu)/K-i(delta) = 3-46]. Regardless of the type of linker between the Dmt-Tic pharmacophores, delta-opioid-mediated antagonism was extraordinarily high in all analogues (pA(2) = 10.42-11.28), while in vitro agonism (MVD and GPI bioassays) was essentially absent (ca. 3 to > 10 mu M). While an unmodified N-terminus (9, 13, 18) revealed weaku-opioid antagonism (pA(2) = 6.78-6.99), N,N'-dimethylation (21, 22), which negatively impacts on mu-opioid-associated agonism (Balboni et al., Bioorg. Med. Chem. 2003, 11, 5435-5441), markedly enhanced mu-opioid antagonism (pA(2) = 8.34 and 7.71 for 21 and 22, respectively) without affecting 6-opioid activity. These data are the first evidence that a single dimeric opioid ligand containing the Dmt-Tic pharmacophore exhibits highly potent 6- andy-opioid antagonist activities.

  DOI：

  10.1021/jm050377l
• 作为产物：
  描述：

  4-benzyloxycarbonylamino-2-tert-butoxycarbonylamino-butyric acid 在 盐酸 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 12.42h， 生成 (3-tert-Butoxycarbonylamino-5-chloro-4-oxo-pentyl)-carbamic acid benzyl ester
  参考文献：
  名称：

  Potent Dmt-Tic Pharmacophoric δ- and μ-Opioid Receptor Antagonists

  摘要：

  A series of dimeric Dmt-Tic (2',6'-dimethyl-L-tyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) analogues (8-14, 18-22) were covalently linked through diaminoalkane and symmetric or asymmetric 3,6-diaminoalkyl-2(1H)-pyrazinone moieties. All the compounds exhibited high affinity for both 6-opioid receptors K(6) = 0.06-1.53 nM] andy-opioid receptors [K-i(mu) = 1.375.72 nM], resulting in moderate delta-receptor selectivity [K-i(mu)/K-i(delta) = 3-46]. Regardless of the type of linker between the Dmt-Tic pharmacophores, delta-opioid-mediated antagonism was extraordinarily high in all analogues (pA(2) = 10.42-11.28), while in vitro agonism (MVD and GPI bioassays) was essentially absent (ca. 3 to > 10 mu M). While an unmodified N-terminus (9, 13, 18) revealed weaku-opioid antagonism (pA(2) = 6.78-6.99), N,N'-dimethylation (21, 22), which negatively impacts on mu-opioid-associated agonism (Balboni et al., Bioorg. Med. Chem. 2003, 11, 5435-5441), markedly enhanced mu-opioid antagonism (pA(2) = 8.34 and 7.71 for 21 and 22, respectively) without affecting 6-opioid activity. These data are the first evidence that a single dimeric opioid ligand containing the Dmt-Tic pharmacophore exhibits highly potent 6- andy-opioid antagonist activities.

  DOI：

  10.1021/jm050377l

文献信息

• Potent Dmt-Tic Pharmacophoric δ- and μ-Opioid Receptor Antagonists
  作者：Tingyou Li、Yoshio Fujita、Kimitaka Shiotani、Anna Miyazaki、Yuko Tsuda、Akihiro Ambo、Yusuke Sasaki、Yunden Jinsmaa、Ewa Marczak、Sharon D. Bryant、Severo Salvadori、Lawrence H. Lazarus、Yoshio Okada

  DOI：10.1021/jm050377l

  日期：2005.12.1

  A series of dimeric Dmt-Tic (2',6'-dimethyl-L-tyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) analogues (8-14, 18-22) were covalently linked through diaminoalkane and symmetric or asymmetric 3,6-diaminoalkyl-2(1H)-pyrazinone moieties. All the compounds exhibited high affinity for both 6-opioid receptors K(6) = 0.06-1.53 nM] andy-opioid receptors [K-i(mu) = 1.375.72 nM], resulting in moderate delta-receptor selectivity [K-i(mu)/K-i(delta) = 3-46]. Regardless of the type of linker between the Dmt-Tic pharmacophores, delta-opioid-mediated antagonism was extraordinarily high in all analogues (pA(2) = 10.42-11.28), while in vitro agonism (MVD and GPI bioassays) was essentially absent (ca. 3 to > 10 mu M). While an unmodified N-terminus (9, 13, 18) revealed weaku-opioid antagonism (pA(2) = 6.78-6.99), N,N'-dimethylation (21, 22), which negatively impacts on mu-opioid-associated agonism (Balboni et al., Bioorg. Med. Chem. 2003, 11, 5435-5441), markedly enhanced mu-opioid antagonism (pA(2) = 8.34 and 7.71 for 21 and 22, respectively) without affecting 6-opioid activity. These data are the first evidence that a single dimeric opioid ligand containing the Dmt-Tic pharmacophore exhibits highly potent 6- andy-opioid antagonist activities.