4-肼基苯甲酰胺盐酸盐 | 74885-67-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-肼基苯甲酰胺盐酸盐
• 英文名称: 4-hydrazinobenzamide
• 英文别名: 4-Hydrazinylbenzamide
• CAS: 74885-67-9
• 化学式: C₇H₉N₃O
• 分子量: 151.168
• InChiKey: URSUOMZVWOFEST-UHFFFAOYSA-N

物化性质

• 沸点：
  389.0±25.0 °C(Predicted)
• 密度：
  1.317±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  81.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-肼基苯甲酰胺盐酸盐 在 溶剂黄146 、 二乙胺 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 4-[4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzamide
  参考文献：
  名称：

  Virtual Ligand Screening of the p300/CBP Histone Acetyltransferase: Identification of a Selective Small Molecule Inhibitor

  摘要：

  The histone acetyltransferase (HAT) p300/CBP is a transcriptional coactivator implicated in many gene regulatory pathways and protein acetylation events. Although p300 inhibitors have been reported, a potent, selective, and readily available active-site-directed small molecule inhibitor is not yet known. Here we use a structure-based, in silico screening approach to identify a commercially available pyrazolone-containing small molecule p300 HAT inhibitor, C646. C646 is a competitive p300 inhibitor with a K-i of 400 nM and is selective versus other acetyltransferases. Studies on site-directed p300 HAT mutants and synthetic modifications of C646 confirm the importance of predicted interactions in conferring potency. Inhibition of histone acetylation and cell growth by C646 in cells validate its utility as a pharmacologic probe and suggest that p300/CBP HAT is a worthy anticancer target.

  DOI：

  10.1016/j.chembiol.2010.03.006
• 作为产物：
  描述：

  对氨基苯甲酰胺 在 盐酸 、 sodium nitrite 、 tin(II) chloride dihdyrate 作用下， 生成 4-肼基苯甲酰胺盐酸盐
  参考文献：
  名称：

  Virtual Ligand Screening of the p300/CBP Histone Acetyltransferase: Identification of a Selective Small Molecule Inhibitor

  摘要：

  The histone acetyltransferase (HAT) p300/CBP is a transcriptional coactivator implicated in many gene regulatory pathways and protein acetylation events. Although p300 inhibitors have been reported, a potent, selective, and readily available active-site-directed small molecule inhibitor is not yet known. Here we use a structure-based, in silico screening approach to identify a commercially available pyrazolone-containing small molecule p300 HAT inhibitor, C646. C646 is a competitive p300 inhibitor with a K-i of 400 nM and is selective versus other acetyltransferases. Studies on site-directed p300 HAT mutants and synthetic modifications of C646 confirm the importance of predicted interactions in conferring potency. Inhibition of histone acetylation and cell growth by C646 in cells validate its utility as a pharmacologic probe and suggest that p300/CBP HAT is a worthy anticancer target.

  DOI：

  10.1016/j.chembiol.2010.03.006

文献信息

• Indole compounds and use thereof
  申请人：Glaxo Group Limited

  公开号：US04252803A1

  公开（公告）日：1981-02-24

  Compounds are disclosed of general formula (I): ##STR1## wherein R.sub.1 and R.sub.2 each independently represents a hydrogen atom, or an aryl, aralkyl, cycloalkyl, fluoroalkyl or alkyl group, which alkyl group is optionally substituted by an alkenyl group or by a group -OR.sub.7 or by ##STR2## where R.sub.7 and R.sub.8 each independently represents a hydrogen atom, an alkyl, aryl or aralkyl group; or R.sub.1 and R.sub.2 together with the nitrogen atom to which they are attached form a saturated monocyclic 5 to 7 membered ring which may contain a further hetero function (viz--O--, --NH or ##STR3## R.sub.3 and R.sub.4 have the same meanings as R.sub.1 and R.sub.2 and may together form an aralkylidene group; R.sub.5 represents a hydrogen atom or an alkyl or aralkyl group; R.sub.6 represents a hydrogen atom or an aryl or C.sub.1 -C.sub.3 alkyl group; Alk represents an C.sub.1 -C.sub.4 alkylene group optionally substituted at one or more of its carbon atoms by one to three C.sub.1 -C.sub.3 alkyl groups; and X represents an oxygen or sulphur atom, and its physiologically acceptable salts, hydrates and bioprecursors. The indoles (I) may be prepared by combinations of reactions to introduce the desired substituents into suitable intermediates either before or after cyclization to form the indole nucleus. The compounds have selective actions on blood vessels and, in particular exhibit antihypertensive properties. They may be formulated in conventional manner as pharmaceutical compositions.

  化合物的通用结构式（I）已披露如下：##STR1## 其中，R.sub.1和R.sub.2各自独立地代表氢原子，或芳基、芳基烷基、环烷基、氟烷基或烷基基团，该烷基基团可选择地被烯基基团或基团-OR.sub.7或##STR2##所取代，其中R.sub.7和R.sub.8各自独立地代表氢原子、烷基、芳基或芳基烷基；或者R.sub.1和R.sub.2与它们连接的氮原子一起形成饱和的单环5到7成员环，该环可能包含进一步的杂原子功能（即-O-，-NH或##STR3## R.sub.3和R.sub.4的含义与R.sub.1和R.sub.2相同，它们可以一起形成芳基烷基亚甲基基团；R.sub.5代表氢原子或烷基或芳基烷基基团；R.sub.6代表氢原子或芳基或C.sub.1 -C.sub.3烷基基团；Alk代表一个C.sub.1 -C.sub.4烷基基团，该烷基基团在其一个或多个碳原子上可以被一个到三个C.sub.1 -C.sub.3烷基基团取代；X代表氧原子或硫原子，以及其生理上可接受的盐、水合物和生物前体。这些吲哚（I）可以通过反应的组合制备，将所需的取代基引入适当的中间体，无论是在环化形成吲哚核之前还是之后。这些化合物对血管具有选择性作用，特别表现出降压性能。它们可以按照传统方式制备成药物组合物。
• [EN] A PROCESS FOR THE PREPARATION OF FROVATRIPTAN AND FROVATRIPTAN SUCCINATE AND THEIR SYNTHETIC INTERMEDIATES<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE FROVATRIPTAN ET DE SUCCINATE DE FROVATRIPTAN ET DE LEURS PRODUITS INTERMÉDIAIRES DE SYNTHÈSE
  申请人：GENERICS UK LTD

  公开号：WO2010122343A1

  公开（公告）日：2010-10-28

  The present invention relates to the active pharmaceutical ingredient frovatriptan and pharmaceutically acceptable salts thereof. In particular, it relates to efficient processes for the preparation of frovatriptan and its synthetic intermediates, which are amenable to large scale commercial production and provide the required products with improved yield and purity.

  本发明涉及活性药物成分frovatriptan及其药用可接受的盐。具体而言，涉及制备frovatriptan及其合成中间体的高效过程，这些过程适用于大规模商业生产，并提供具有改善产量和纯度的所需产品。
• Discovery of 4-[3-(<i>trans</i>-3-Dimethylaminocyclobutyl)-1<i>H</i>-indol-5-ylmethyl]- (4<i>S</i>)-oxazolidin-2-one (4991W93), a 5HT_1B/1D Receptor Partial Agonist and a Potent Inhibitor of Electrically Induced Plasma Extravasation
  作者：Karamjit Singh Jandu、Vikki Barrett、Michael Brockwell、David Cambridge、Duncan R. Farrant、Christopher Foster、Heather Giles、Robert C. Glen、Alan P. Hill、Heather Hobbs、Andrew Honey、Graeme R. Martin、John Salmon、Donna Smith、Patrick Woollard、David L. Selwood

  DOI：10.1021/jm000956k

  日期：2001.3.1

  pharmacophoric model of binding of 3-(2-aminoethyl)indoles to 5HT(1B/1D) receptors, we identified the 3-aminocyclobutyl group as a potential ethylamine isostere. A novel multidimensional chemometric approach was used to predict the intrinsic activity (degree of agonism) at the receptor. A qualitative model for pharmacokinetic properties was then used to guide the synthesis toward molecules likely to have

  利用3-（2-氨基乙基）吲哚与5HT（1B / 1D）受体结合的药效学模型，我们确定了3-氨基环丁基为潜在的乙胺等排体。一种新颖的多维化学计量学方法用于预测受体的内在活性（激动程度）。然后使用药代动力学性质的定性模型来指导合成向可能在人体中具有口服生物利用度的分子发展。开发了合成3-（3-二甲基氨基环丁基）吲哚的新途径。类似物显示，在5HT（1B / 1D）受体处的内在活性通常低于其乙胺对应物。4- [3-（反式-3-二甲基氨基环丁基）-1H-吲哚-5-基甲基]-（4S）-恶唑烷丁二酮（4991W93，1）被确定为对5HT（1B / 1D）受体的部分激动剂，内在活性低。该分子还具有针对5HT（1F）受体的显着活性，但对其他5HT受体具有选择性。另外，发现该化合物是电诱导血浆外渗的异常有效抑制剂。化合物1可用于治疗和预防偏头痛。
• LABELING AGENT FOR ANALYZING POST-TRANSLATIONAL MODIFICATIONS OF SERINE AND THREONINE
  申请人：Shinohara Yasuro

  公开号：US20140024124A1

  公开（公告）日：2014-01-23

  A glycoprotein and/or a glycopeptide which are a test substance is heated in the presence of a pyrazolone derivative, an isoxazolone derivative, a hydantoin derivative, a rhodanine derivative, a maleimide derivative, or the like under a basic condition to cleave and label a post-translational modification group for analysis, thereby enabling analysis of a post-translational modification of a serine residue and/or a threonine residue.

  一种糖蛋白和/或糖肽作为测试物质，在碱性条件下加热，同时加入吡唑酮衍生物、异恶唑酮衍生物、海因托因衍生物、罗丹明衍生物、马来酰亚胺衍生物等试剂，以切割和标记后翻译修饰基团，从而使丝氨酸残基和/或苏氨酸残基的后翻译修饰得以分析。
• Novel NQO1 substrates bearing two nitrogen redox centers: Design, synthesis, molecular dynamics simulations, and antitumor evaluation
  作者：Qijie Gong、Pengfei Wang、Tian Li、Zhan Yu、Le Yang、Chenyang Wu、Jiabao Hu、Fulai Yang、Xiaojin Zhang、Xiang Li

  DOI：10.1016/j.bioorg.2023.106480

  日期：2023.5

  skeleton bearing two nitrogen redox centers were designed by introducing amines or hydrazines to fit with the novel binding region of NQO1. Compound 24 with a (4-fluorophenyl)hydrazine substituent was identified as the most efficient substrate for NQO1 with the reduction rate and catalytic efficiency of 1972 ± 82 μmol NADPH/min/μmol NQO1 and 6.4 ± 0.4 × 106 M-1s-1, respectively. Molecular dynamics (MD) simulation

  通过分析 NQO1 的晶体结构，发现了配体的额外结合区域。在这项研究中，通过引入胺或肼设计了一系列具有带有两个氮氧化还原中心的新型骨架的衍生物，以适应 NQO1 的新型结合区域。具有(4-氟苯基) 肼取代基的化合物24被确定为 NQO1 最有效的底物，还原率和催化效率分别为 1972 ± 82 μmol NADPH/min/μmol NQO1 和 6.4 ± 0.4 × 10 6 M -1 s - 1，分别。分子动力学 (MD) 模拟显示氧化还原中心的氮原子与关键的 Tyr128 和 Tyr126 残基之间的距离为 3.5 Å (N 1-Tyr128) 和 3.4 Å (N 2 -Tyr126)。化合物24（IC 50 /A549 = 0.69 ± 0.09 μM）通过 NQO1 介导的氧化还原循环产生 ROS，在体外和体内对 A549 细胞显示出有效的抗肿瘤活性，从而成为有前途的 NQO1