6'-nitro-3',4'-dihydro-1'H-spiro[imidazolidine-4,2'-naphthalene]-2,5-dione | 151152-93-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6'-nitro-3',4'-dihydro-1'H-spiro[imidazolidine-4,2'-naphthalene]-2,5-dione
• CAS: 151152-93-1
• 化学式: C₁₂H₁₁N₃O₄
• 分子量: 261.237
• InChiKey: AILQXIHPUACYSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.66
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  101.34
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  6'-nitro-3',4'-dihydro-1'H-spiro[imidazolidine-4,2'-naphthalene]-2,5-dione 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 生成 (+/-)-6'-amino-3',4'-dihydro-1'H-spiro[imidazolidine-4,2'-naphthalene]-2,5-dione
  参考文献：
  名称：

  Identification of novel, orally bioavailable spirohydantoin CGRP receptor antagonists

  摘要：

  A rapid analogue approach to identification of spirohydantoin-based CGRP antagonists provided novel, low molecular weight leads. Modification of these leads afforded a series of nanomolar benzimidazolinone-based CGRP receptor antagonists. The oral bioavailability of these antagonists was inversely correlated with polar surface area, suggesting that membrane permeability was a key limitation to absorption. Optimization provided compound 12, a potent CGRP receptor antagonist (K-i = 21 nM) with good oral bioavailability in three species. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.045
• 作为产物：
  描述：

  替群妥英 在 硝酸 作用下， 生成 6'-nitro-3',4'-dihydro-1'H-spiro[imidazolidine-4,2'-naphthalene]-2,5-dione
  参考文献：
  名称：

  Identification of novel, orally bioavailable spirohydantoin CGRP receptor antagonists

  摘要：

  A rapid analogue approach to identification of spirohydantoin-based CGRP antagonists provided novel, low molecular weight leads. Modification of these leads afforded a series of nanomolar benzimidazolinone-based CGRP receptor antagonists. The oral bioavailability of these antagonists was inversely correlated with polar surface area, suggesting that membrane permeability was a key limitation to absorption. Optimization provided compound 12, a potent CGRP receptor antagonist (K-i = 21 nM) with good oral bioavailability in three species. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.045

文献信息

• Regiospecific and conformationally restrained analogs of melphalan and dl-2-NAM-7 and their affinities for the large neutral amino acid transporter (system LAT1) of the blood–brain barrier
  作者：Jyothi Matharu、Jun Oki、David R. Worthen、Quentin R. Smith、Peter A. Crooks

  DOI：10.1016/j.bmcl.2010.04.086

  日期：2010.6

  Regiospecific and conformationally restrained analogs of melphalan and DL-2-NAM-7 have been synthesized and their affinities for the large neutral amino acid transporter (LAT1) of the blood-brain barrier have been determined to assess their potential for accessing the CNS via facilitated transport. Several analogs had K-i values in the range 2.1-8.5 mu M with greater affinities than that of either L-phenylalanine (K-i = 11 mu M) or melphalan (K-i = 55 mu M), but lower than DL-2-NAM-7 (K-i = 0.08 mu M). The results indicate that regiospecific positioning of the mustard moiety on the aromatic ring in these analogs is very important for optimal affinity for the large neutral amino acid transporter, and that conformational restriction of the DL-2-NAM-7 molecule in benzonorbornane and indane analogs leads to 25- to 60-fold loss, respectively, in affinity. (C) 2010 Elsevier Ltd. All rights reserved.