β-naloxamine

• 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: β-naloxamine
• 英文别名: (4R,4aS,7R,7aR,12bS)-7-amino-3-prop-2-enyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol
• 化学式: C₁₉H₂₄N₂O₃
• 分子量: 328.411
• InChiKey: UBCLWVBUOUMVQE-UPQOXJCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  79
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-金刚烷甲酸 、 β-naloxamine 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 potassium carbonate 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 5.0h， 以76%的产率得到17-allyl-3,14β-dihydroxy-4,5α-epoxy-6β-[2-adamantylmethanamido]morphinan
  参考文献：
  名称：

  Synthesis and Evaluation of Aryl-Naloxamide Opiate Analgesics Targeting Truncated Exon 11-Associated μ Opioid Receptor (MOR-1) Splice Variants

  摘要：

  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.

  DOI：

  10.1021/jm300305c
• 作为产物：
  描述：

  纳洛酮 在 hydrazine hydrate 、 顺-2-戊烯醇 、 偶氮二甲酸二异丙酯 、 potassium tri-sec-butyl-borohydride 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 32.5h， 生成 β-naloxamine
  参考文献：
  名称：

  用于放射光亲和标记细胞系和小鼠脑中阿片受体的 IBNtxA 叠氮基芳基类似物的合成和表征。

  摘要：

  Mu 阿片受体 (MOR-1) 介导临床使用的阿片类药物（如吗啡、羟考酮和芬太尼）的生物学作用。μ 阿片受体基因 OPRM1 经历广泛的选择性剪接，产生多个剪接变体。一种类型的剪接变体是仅包含六个跨膜结构域 (6TM) 的截短变体，可介导新型阿片类药物（例如 3'-碘苯甲酰纳曲胺 (IBNtxA)）的镇痛作用。以前，我们已经证明 IBNtxA 是一种有效的镇痛剂，对一系列疼痛模型有效，但没有许多与传统阿片类药物相关的副作用。为了调查 IBNtxA 标记的目标，我们合成了 IBNtxA 的两种芳基叠氮基类似物，它们允许对转染细胞系中的小鼠 mu 阿片受体 (mMOR-1) 和可能包含小鼠大脑中 6TM 位点的 mMOR-1 蛋白复合物进行光标记。我们证明了 IBNtxA 的烯丙基和炔烃芳基叠氮基衍生物在细胞系和 MOR-1 蛋白复合物外源或内源性表达以及在小鼠大脑中发现的有效放射性光标记 m

  DOI：

  10.1007/s10571-020-00867-6

文献信息

• Stereoselective synthesis of β-naltrexol, β-naloxol β-naloxamine, β-naltrexamine and related compounds by the application of the mitsunobu reac
  作者：Csaba Simon、Sándor Hosztafi、Sándor Makleit

  DOI：10.1016/s0040-4020(01)85541-1

  日期：1994.1

  As a continuation of our work, aimed at adopting the Mitsunobu reaction in the morphine series, a few representatives of dihydroisocodeines and dihydroisomorphines and their 14 beta-hydroxy analogues were prepared. p-Nitrobenzoic acid was used as carboxylic acid and the prepared esters were cleaved to obtain the title compounds. Using phthalimide as acidic component several new 6 beta-phthalimidodihydromorphine and dihydrocodeine derivatives and their 14 beta-hydroxy analogues have been synthesized. Cleavage of the phthalimido derivatives with hydrazine hydrate afforded the corresponding 6 beta-amino derivatives.
• 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.
• COMPOSITIONS FOR AFFECTING WEIGHT LOSS
  申请人：Weber Eckard

  公开号：US20070270450A1

  公开（公告）日：2007-11-22

  Disclosed are compositions for affecting weight loss comprising a first compound and a second compound, where the first compound is an opioid antagonist and the second compound causes increased agonism of a melanocortin 3 receptor (MC3-R) or a melanocortin 4 receptor (MC4-R) compared to normal physiological conditions. Also disclosed are methods of affecting weight loss, increasing energy expenditure, increasing satiety in an individual, or suppressing the appetite of an individual, comprising identifying an individual in need thereof and treating that individual to antagonize opioid receptor activity and to enhance α-MSH activity.
• US7375111B2
  申请人：——

  公开号：US7375111B2

  公开（公告）日：2008-05-20
• US7462626B2
  申请人：——

  公开号：US7462626B2

  公开（公告）日：2008-12-09