N-benzyloxycarbonyl-N-[4-(t-butoxycarbonylamino)butyl]thiourea | 714978-26-4

• 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: N-benzyloxycarbonyl-N-[4-(t-butoxycarbonylamino)butyl]thiourea
• 英文别名: benzyl N-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butylcarbamothioyl]carbamate
• CAS: 714978-26-4
• 化学式: C₁₈H₂₇N₃O₄S
• 分子量: 381.496
• InChiKey: YBVVTLNVIPHUGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyl-N-[4-(t-butoxycarbonylamino)butyl]thiourea 在 盐酸 、 三乙胺 、 mercury dichloride 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 benzyl N-[N'-(4-aminobutyl)-N-[(1S,2S,13R,21R)-22-(cyclopropylmethyl)-2,16-dihydroxy-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15,17,19(25)-heptaen-7-yl]carbamimidoyl]carbamate
  参考文献：
  名称：

  A Bivalent Ligand (KDN-21) Reveals Spinal δ and κ Opioid Receptors Are Organized as Heterodimers That Give Rise to δ₁ and κ₂ Phenotypes. Selective Targeting of δ−κ Heterodimers

  摘要：

  In view of recent pharmacological studies suggesting the existence of delta-kappa opioid receptor heterodimers/oligomers in the spinal cord, we have synthesized and evaluated (intrathecally in mice) a series of bivalent ligands (KDN series) containing kappa and delta antagonist pharmacophores. Pharmacological and binding data have provided evidence for the bridging of spinal delta-kappa receptor heterodimers by KDN-21 and for their identification as delta(1) and kappa(2). The selectivity profile of KDN-21 and the apparent absence of coupled delta(1)-kappa(2) phenotypes in the brain suggest a new approach for targeting receptors.

  DOI：

  10.1021/jm0342358
• 作为产物：
  描述：

  N-叔丁氧羰基-1,4-丁二胺 、 benzyloxycarbonyl isothiocyanate 以 二氯甲烷 为溶剂， 反应 2.0h， 以82%的产率得到N-benzyloxycarbonyl-N-[4-(t-butoxycarbonylamino)butyl]thiourea
  参考文献：
  名称：

  Discovery of N-(4-Aminobutyl)-N′-(2-methoxyethyl)guanidine as the First Selective, Nonamino Acid, Catalytic Site Inhibitor of Human Dimethylarginine Dimethylaminohydrolase-1 (hDDAH-1)

  摘要：

  N-(4-Aminobutyl)-N'-(2-methoxyethyl)guanidine (8a) is a potent inhibitor targeting the hDDAH-1 active site (K-i = 18 mu M) and derived from a series of guanidine- and amidine-based inhibitors. Its nonamino acid nature leads to high selectivities toward other enzymes of the nitric oxide-modulating system. Crystallographic data of 8a-bound hDDAH-1 illuminated a unique binding mode. Together with its developed N-hydroxyguanidine prodrug 11, 8a will serve as a most widely applicable, pharmacological tool to target DDAH-1-associated diseases.

  DOI：

  10.1021/acs.jmedchem.9b01230

文献信息

• A bivalent ligand (KMN-21) antagonist for μ/κ heterodimeric opioid receptors
  作者：Shijun Zhang、Ajay Yekkirala、Ye Tang、Philip S. Portoghese

  DOI：10.1016/j.bmcl.2009.10.045

  日期：2009.12

  In an effort to develop antagonists for kappa-mu opioid receptor heterodimers, a series of bivalent ligands 3-6 containing kappa- and mu-antagonist pharmacophores were designed and synthesized. Evaluation of the series in HEK-293 cells revealed 4 (KMN-21) to selectively antagonize the activation of kappa-mu heterodimers, suggesting possible bridging of receptors when the bivalent ligand spacer contains 21 atoms. Published by Elsevier Ltd.
• Discovery of <i>N</i>-(4-Aminobutyl)-<i>N</i>′-(2-methoxyethyl)guanidine as the First Selective, Nonamino Acid, Catalytic Site Inhibitor of Human Dimethylarginine Dimethylaminohydrolase-1 (<i>h</i>DDAH-1)
  作者：Ina Lunk、Felix-Alexander Litty、Sven Hennig、Ingrid R. Vetter、Jürke Kotthaus、Karin S. Altmann、Gudrun Ott、Antje Havemeyer、Carmen Carrillo García、Bernd Clement、Dennis Schade

  DOI：10.1021/acs.jmedchem.9b01230

  日期：2020.1.9

  N-(4-Aminobutyl)-N'-(2-methoxyethyl)guanidine (8a) is a potent inhibitor targeting the hDDAH-1 active site (K-i = 18 mu M) and derived from a series of guanidine- and amidine-based inhibitors. Its nonamino acid nature leads to high selectivities toward other enzymes of the nitric oxide-modulating system. Crystallographic data of 8a-bound hDDAH-1 illuminated a unique binding mode. Together with its developed N-hydroxyguanidine prodrug 11, 8a will serve as a most widely applicable, pharmacological tool to target DDAH-1-associated diseases.
• A Bivalent Ligand (KDN-21) Reveals Spinal δ and κ Opioid Receptors Are Organized as Heterodimers That Give Rise to δ₁ and <i>κ</i>₂ Phenotypes. Selective Targeting of δ−κ Heterodimers
  作者：Rashmi G. Bhushan、Shiv K. Sharma、Zhihua Xie、David J. Daniels、Philip S. Portoghese

  DOI：10.1021/jm0342358

  日期：2004.6.1

  In view of recent pharmacological studies suggesting the existence of delta-kappa opioid receptor heterodimers/oligomers in the spinal cord, we have synthesized and evaluated (intrathecally in mice) a series of bivalent ligands (KDN series) containing kappa and delta antagonist pharmacophores. Pharmacological and binding data have provided evidence for the bridging of spinal delta-kappa receptor heterodimers by KDN-21 and for their identification as delta(1) and kappa(2). The selectivity profile of KDN-21 and the apparent absence of coupled delta(1)-kappa(2) phenotypes in the brain suggest a new approach for targeting receptors.