{3-[1-(2-Benzyloxycarbonylamino-ethyl)-3-chloro-2-oxo-propylcarbamoyl]-3-tert-butoxycarbonylamino-propyl}-carbamic acid benzyl ester | 693222-14-9

• 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: {3-[1-(2-Benzyloxycarbonylamino-ethyl)-3-chloro-2-oxo-propylcarbamoyl]-3-tert-butoxycarbonylamino-propyl}-carbamic acid benzyl ester
• 英文别名: Boc-DL-Dab(Cbz)-DL-Dab(Cbz)-CH2Cl；benzyl N-[5-chloro-3-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(phenylmethoxycarbonylamino)butanoyl]amino]-4-oxopentyl]carbamate
• CAS: 693222-14-9
• 化学式: C₃₀H₃₉ClN₄O₈
• 分子量: 619.115
• InChiKey: XGWHZEWCYKDRLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  43
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  {3-[1-(2-Benzyloxycarbonylamino-ethyl)-3-chloro-2-oxo-propylcarbamoyl]-3-tert-butoxycarbonylamino-propyl}-carbamic acid benzyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 [3-(2-Amino-4-benzyloxycarbonylamino-butyrylamino)-5-chloro-4-oxo-pentyl]-carbamic acid benzyl ester; hydrochloride
  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-[1-(2-Benzyloxycarbonylamino-ethyl)-3-chloro-2-oxo-propylcarbamoyl]-3-tert-butoxycarbonylamino-propyl}-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

• Immediate deamination from the aminomethyl group attached to 1,2-dihydropyrazin-2-one derivative during catalytic hydrogenation
  作者：Yoshio Okada、Yutaka Fujisawa、Akihisa Morishita、Kimitaka Shiotani、Anna Miyazaki、Yoshio Fujita、Tingyou Li、Yuko Tsuda、Toshio Yokoi、Sharon D. Bryant、Lawrence H. Lazarus

  DOI：10.1016/s0040-4039(02)01944-5

  日期：2002.11

  The catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one to remove benzyloxycarbonyl (Z) groups resulted ill a side reaction. Purification by reverse-phase HPLC and analysis by proton unclear magnetic resonance (H-1 NMR) spectroscopy identified the product as 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. It was determined through the synthesis of two 1,2-dihydropyrazin-2-one derivatives, composed of alanine and 2,3-diaminopropionic acid that deamination occurred specifically and easily (under atmospheric pressure and at the room temperature) Only in the case of 6-benzyloxycarbonylaminomethyl-3,5-dimethyl-1,2-dihydropyrazin-2-one. The catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one specifically yields the deaminated product, 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 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.