IBNalA | 1314879-45-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: IBNalA
• 英文别名: 17-allyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(3-iodo)benzamido]morphinan；N-[(4R,4aS,7R,7aR,12bS)-4a,9-dihydroxy-3-prop-2-enyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-iodobenzamide
• CAS: 1314879-45-2
• 化学式: C₂₆H₂₇IN₂O₄
• 分子量: 558.416
• InChiKey: OWOWCHRXILVEKL-HJUABUFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  82
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  纳洛酮 在 ammonium acetate 、 sodium cyanoborohydride 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.17h， 生成 IBNalA
  参考文献：
  名称：

  Generation of novel radiolabeled opiates through site-selective iodination

  摘要：

  Tritiated opioid radioligands have proven valuable in exploring opioid binding sites. However, tritium has many limitations. Its low specific activity and limited counting efficiency makes it difficult to examine low abundant, high affinity sites and its disposal is problematic due to the need to use organic scintillants and its relatively long half-life. To overcome these issues, we have synthesized both unlabeled and carrier-free radioiodinated iodobenzoyl derivatives of 6 beta-naltrexamine ((125)I-BNtxA, 18), 6 beta-naloxamine ((125)I-BNalA, 19) and 6 beta-oxymorphamine ((125)I-BOxyA, 20) with specific activities of 2100 Ci/mmol. To optimize the utility of the radioligand, we designed a synthesis in which the radiolabel is incorporated in the last synthetic step, which required the selective iodination of the benzoyl moiety without incorporation into the phenolic A ring. Competition studies demonstrated high affinity of the unlabelled compounds for opioid receptors in transfected cell lines, as did the direct binding of the (125)I-ligands to the opioid receptors. The radioligand displayed very high sensitivity, enabling a marked reduction in tissue, as well as excellent signal/noise characteristics. These new (125)I-radioligands should prove valuable in future studies of opioid binding sites. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.008

文献信息

• Synthesis and Evaluation of Aryl-Naloxamide Opiate Analgesics Targeting Truncated Exon 11-Associated μ Opioid Receptor (MOR-1) Splice Variants
  作者：Susruta Majumdar、Joan Subrath、Valerie Le Rouzic、Lisa Polikar、Maxim Burgman、Kuni Nagakura、Julie Ocampo、Nathan Haselton、Anna R. Pasternak、Steven Grinnell、Ying-Xian Pan、Gavril W. Pasternak

  DOI：10.1021/jm300305c

  日期：2012.7.26

  3-Iodobenzoylnaltrexamide 1 (IBNtxA) is a potent analgesic acting through a novel receptor target that lack many side-effects of traditional opiates composed, in part, of exon 11-associated truncated six transmembrane domain MOR-1 (6TM/E11) splice variants. To better understand the SAR of this drug target, a number of 4,5-epoxymorphinan analogues were synthesized. Results show the importance of a free 3-phenolic group, a phenyl ring at the 6 position, an iodine at the 3'or 4' position of the phenyl ring, and an N-allyl or c-propylmethyl group to maintain high 6TM/E11 affinity and activity. 3 Iodobenzoylnaloxamide 15 (IBNalA) with a N-allyl group displayed lower 5 opioid receptor affinity than its naltrexamine analogue, was 10-fold more potent an analgesic than morphine, elicited no respiratory depression or physical dependence, and only limited inhibition of gastrointestinal transit. Thus, the arylnaloxarnide scaffold can generate a potent analgesic acting through the 6TM/E11 sites with advantageous side-effect profile and greater selectivity.
• Generation of novel radiolabeled opiates through site-selective iodination
  作者：Susruta Majumdar、Maxim Burgman、Nathan Haselton、Steven Grinnell、Julia Ocampo、Anna Rose Pasternak、Gavril W Pasternak

  DOI：10.1016/j.bmcl.2011.05.008

  日期：2011.7

  Tritiated opioid radioligands have proven valuable in exploring opioid binding sites. However, tritium has many limitations. Its low specific activity and limited counting efficiency makes it difficult to examine low abundant, high affinity sites and its disposal is problematic due to the need to use organic scintillants and its relatively long half-life. To overcome these issues, we have synthesized both unlabeled and carrier-free radioiodinated iodobenzoyl derivatives of 6 beta-naltrexamine ((125)I-BNtxA, 18), 6 beta-naloxamine ((125)I-BNalA, 19) and 6 beta-oxymorphamine ((125)I-BOxyA, 20) with specific activities of 2100 Ci/mmol. To optimize the utility of the radioligand, we designed a synthesis in which the radiolabel is incorporated in the last synthetic step, which required the selective iodination of the benzoyl moiety without incorporation into the phenolic A ring. Competition studies demonstrated high affinity of the unlabelled compounds for opioid receptors in transfected cell lines, as did the direct binding of the (125)I-ligands to the opioid receptors. The radioligand displayed very high sensitivity, enabling a marked reduction in tissue, as well as excellent signal/noise characteristics. These new (125)I-radioligands should prove valuable in future studies of opioid binding sites. (C) 2011 Elsevier Ltd. All rights reserved.