O-(4-iodobenzyl)hydroxylamine hydrochloride | 1446093-00-0

• 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: O-(4-iodobenzyl)hydroxylamine hydrochloride
• 英文别名: O-(4-Iodobenzyl)hydroxylamine Hydrochloride；O-[(4-iodophenyl)methyl]hydroxylamine;hydrochloride
• CAS: 1446093-00-0
• 化学式: C₇H₈INO*ClH
• 分子量: 285.512
• InChiKey: QKTGWFUBZHRJRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  35.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  O-(4-iodobenzyl)hydroxylamine hydrochloride 在 吡啶 、 磷酸三甲酯 、 1,8-双二甲氨基萘 、 三氯氧磷 作用下， 反应 2.84h， 生成
  参考文献：
  名称：

  4-Alkyloxyimino-cytosine nucleotides: tethering approaches to molecular probes for the P2Y6 receptor

  摘要：

  4-烷氧亚氨基嘧啶核苷酸衍生物作为某些G蛋白偶联P2Y受体（P2YRs）的激动剂显示出高度效力。为了对P2Y6R激动剂进行荧光标记，我们在两个位置（胞苷衍生物的N4位和γ-磷酸基团）上探查了包括炔烃在内的各种功能团，用于点击化学反应。在CDP的嘧啶核碱4位上进行扩展亚氨基取代，相比于CTP衍生物中的γ-磷酸酯形成，通常更好地保持了P2Y6R的效力。荧光染料Alexa Fluor 488的共轭物16激活了在1321N1人星形胶质瘤细胞中表达的人P2Y6R，其EC50为9 nM，并且对这种受体的选择性远高于其他由尿嘧啶核苷酸激活的P2Y受体。流式细胞术检测到16对表达P2Y6R的细胞有特异性标记，而对野生型1321N1细胞无标记。此外，共聚焦显微镜显示16被内化（半衰期18分钟）并有表面结合的荧光。已知的P2Y6R配体抑制标记。16与P2Y6R的同源模型的理论对接预测了荧光团与TM3的外部部分之间的静电相互作用。因此，我们确定了N4-苄氧基团作为合成功能化类似物的结构容许位点，从而得到用于研究P2Y6R的高亲和力分子探针。

  DOI：

  10.1039/c3md00132f
• 作为产物：
  描述：

  4-碘苄醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 甲基肼 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 3.0h， 生成 O-(4-iodobenzyl)hydroxylamine hydrochloride
  参考文献：
  名称：

  NOVEL VASCULAR LEAKAGEAGE INHIBITOR

  摘要：

  本公开涉及一种新型血管渗漏抑制剂。本发明的新型血管渗漏抑制剂抑制血管内皮细胞凋亡，抑制由VEGF诱导的肌动蛋白应激纤维的形成，并增强皮质肌动蛋白环结构，从而抑制血管渗漏。因此，本发明的血管渗漏抑制剂可以预防或治疗由血管渗漏引起的各种疾病。由于本发明的血管渗漏抑制剂是由商业可获得或易于合成的孕酮合成的，因此具有明显优越的商业合成可行性。

  公开号：

  US20140378399A1

文献信息

• Structure–Activity Relationship of 3-Methylcytidine-5′-α,β-methylenediphosphates as CD73 Inhibitors
  作者：Mirko Scortichini、Riham Mohammed Idris、Susanne Moschütz、Antje Keim、Veronica Salmaso、Clemens Dobelmann、Paola Oliva、Karolina Losenkova、Heikki Irjala、Samuli Vaittinen、Jouko Sandholm、Gennady G. Yegutkin、Norbert Sträter、Anna Junker、Christa E. Müller、Kenneth A. Jacobson

  DOI：10.1021/acs.jmedchem.1c01852

  日期：2022.2.10

  We recently reported N4-substituted 3-methylcytidine-5′-α,β-methylenediphosphates as CD73 inhibitors, potentially useful in cancer immunotherapy. We now expand the structure–activity relationship of pyrimidine nucleotides as human CD73 inhibitors. 4-Chloro (MRS4598 16; Ki = 0.673 nM) and 4-iodo (MRS4620 18; Ki = 0.436 nM) substitution of the N4-benzyloxy group decreased Ki by ∼20-fold. Primary alkylamine

  我们最近报道了N 4取代的 3-甲基胞苷-5'-α,β-亚甲基二磷酸作为 CD73 抑制剂，可能用于癌症免疫治疗。我们现在扩展了嘧啶核苷酸作为人类 CD73 抑制剂的结构-活性关系。 N 4 -苄氧基的4-氯（MRS4598 16 ； K i = 0.673 nM）和4-碘（MRS4620 18 ； K i = 0.436 nM）取代使K i降低约20倍。通过具有不同亚甲基链长度（ 24和25 ）的对氨基基团偶联的伯烷基胺衍生物是官能化同系物，用于随后与载体或报告基团缀合。具有两种抑制剂的 hCD73 的 X 射线结构表明核糖环构象适应，并且苄氧基亚氨基（ E构型）与腺嘌呤抑制剂中的N 4 -苄基结合到相同的区域（C 端和 N 端结构域之间） 。分子动力学确定了稳定的相互作用并预测了构象多样性。因此，通过N 4 -苄氧基取代，我们大大增强了抑制效力并增加了分子探针的功能。通过原位阻断肿瘤组织中的
• Phosphine-Catalyzed Ring-Opening Regioselective Addition of Cyclopropenones with Amides
  作者：Huamin Wang、Yibo Wei、Yongjun He、Tian-Juan He、Ying-Wu Lin

  DOI：10.1021/acs.joc.4c00941

  日期：2024.7.19

  A series of amides, including α-bromo hydroxamates, N-alkoxyamides, and N-aryloxyamides, were subjected to phosphine-catalyzed ring-opening O-selective addition with cyclopropenones, producing various special α,β-unsaturated esters containing oxime ether motif, in moderate to excellent yields, with high regioselectivity, and exclusive O-selectivity. The methodology is highly atom-economical, with simple

  一系列酰胺，包括α-溴异羟肟酸酯、 N-烷氧基酰胺和N-芳氧基酰胺，在膦催化下与环丙烯酮进行开环O-选择性加成，生成各种含有肟醚基序的特殊α,β-不饱和酯，产率中等至优异，具有高区域选择性和独特的O选择性。该方法具有高度原子经济性、操作步骤简单、底物范围广（超过44个例子）。
• O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1
  作者：William P. Malachowski、Maria Winters、James B. DuHadaway、Ariel Lewis-Ballester、Shorouk Badir、Jenny Wai、Maisha Rahman、Eesha Sheikh、Judith M. LaLonde、Syun-Ru Yeh、George C. Prendergast、Alexander J. Muller

  DOI：10.1016/j.ejmech.2015.12.028

  日期：2016.1

  Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a. potent sub-micromolar inhibitor of IDO1. Structure activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications. (C) 2015 Elsevier Masson SAS. All rights reserved.
• PURINE AND PYRIMIDINE NUCLEOTIDES AS ECTO-5'-NUCLEOTIDASE INHIBITORS
  申请人：The United States of America,as represented by the Secretary,Department of Health and Human Services

  公开号：US20210169911A1

  公开（公告）日：2021-06-10

  Disclosed is a compound of formula (I), wherein Q, U, T, A, a, b, c, and n are as defined herein. Also disclosed are methods of inhibiting ecto-5′-nucleotidase, inhibiting suppression of an antitumor immune response, inhibiting tumor growth of a cancerous tumor, inhibiting metastasis of cancer in a mammal afflicted with cancer, synergistically enhancing a response of a mammal afflicted with cancer undergoing treatment with an immunotherapeutic anti-cancer agent, potentiating an activity of an inhibitor of nicotinamide phosphoribosyltransferase in a mammal undergoing treatment of a mammal with the inhibitor, and treating preeclampsia in a mammal in need thereof, comprising administering to an animal an effective amount of a compound of formula (I).