3-甲酰基-5-硝基苯甲酸甲酯 | 172899-78-4

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 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: 3-甲酰基-5-硝基苯甲酸甲酯
• 中文别名: 甲基3-甲酰-5-硝基苯；甲基3-甲酰-5-硝基苯甲酸
• 英文名称: methyl 3-formyl-5-nitrobenzoate
• CAS: 172899-78-4
• 化学式: C₉H₇NO₅
• 分子量: 209.158
• InChiKey: VWRFFTKYHYLALS-UHFFFAOYSA-N

物化性质

• 沸点：
  354.2±32.0 °C(Predicted)
• 密度：
  1.386±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  89.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2918300090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  3-甲酰基-5-硝基苯甲酸甲酯 在 palladium on activated charcoal 氢氧化钾 、 polymer-bound carbodiimide 、 氢气 、 1-羟基苯并三唑 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 3-Amino-5-(1-{[4-(benzyloxycarbonylamino-imino-methyl)-benzylcarbamoyl]-methyl}-3-chloro-5-isopropylamino-6-oxo-1,6-dihydro-pyrazin-2-yl)-benzoic acid
  参考文献：
  名称：

  Structure-based drug design of pyrazinone antithrombotics as selective inhibitors of the tissue factor VIIa complex

  摘要：

  Structure-based drug design coupled with polymer-assisted solution-phase library synthesis was utilized to develop a series of pyrazinone inhibitors of the tissue factor/Factor Vila complex. The crystal structure of a tri-peptide ketothiazole complexed with TF/VIIa was utilized in a docking experiment that identified a benzyl-substituted pyrazinone as a P-2 surrogate for the tri-peptide. A 5-step PASP library synthesis of these aryl-substituted pyrazinones was developed. The sequence allows for attachment of a variety of P-1 and P-3 moieties, which led to synthesis pyrazinone 23. Compound 23 exhibited 16 nM IC50 against TF/VIIa with > 6250x selectivity versus Factor Xa and thrombin. This potent and highly selective inhibitor of TF/VIIa was chosen for preclinical intravenous proof-of-concept studies to demonstrate the separation between antithrombotic efficacy and bleeding side effects in a primate model of thrombosis. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00410-4
• 作为产物：
  描述：

  5-硝基间苯二甲酸单甲酯 在 吡啶 、 copper(l) iodide 、 草酰氯 、 lithium tri-t-butoxyaluminum hydride 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 1.17h， 生成 3-甲酰基-5-硝基苯甲酸甲酯
  参考文献：
  名称：

  Design and Synthesis of Benzoic Acid Derivatives as Influenza Neuraminidase Inhibitors Using Structure-Based Drug Design

  摘要：

  A series of 94 benzoic acid derivatives was synthesized and tested for its ability to inhibit influenza neuraminidase. The enzyme-inhibitor complex structure was determined by X-ray crystallographic analysis for compounds which inhibited the enzyme. The most potent compound tested in vitro, 5 (4-(acetylamino)-3-guanidinobenzoic acid), had an IC50 = 2.5 x 10(-6) M against N9 neuraminidase. Compound 5 was oriented in the active site of the neuraminidase ina manner that was not predicted from the reported active site binding of GANA (4) with neuraminidase. In a mouse model of influenza, 5 did not protect the mice from weight loss due to the influenza virus when dosed intranasally.

  DOI：

  10.1021/jm970479e

文献信息

• Substituted benzene derivatives useful as neuraminidase inhibitors
  申请人：BioCryst Pharmaceuticals, Inc.

  公开号：US05602277A1

  公开（公告）日：1997-02-11

  A compound of the Formula (I): ##STR1## or pharmaceutically-suitable salts or prodrug forms thereof, wherein: n is 0-1; m is 0; p is 0-1; R.sup.1 is --CO.sub.2 H; R.sup.2 is selected from the group consisting of H, --OH, and --NH.sub.2 ; R.sup.3 is H; R.sup.4 is --C(O)NHR.sup.8 ; R.sup.5 is --NHC(R.sup.6)NH.sub.2 R.sup.6 is selected from the group consisting of .dbd.NH, .dbd.NOH, .dbd.NCN, .dbd.O, and .dbd.S; and R.sup.8 is selected from the group consisting of C.sub.1 -C.sub.4 linear or branched alkyl substituted with 0-3 halogens on each carbon.

  化合物的化学式（I）：##STR1##或其药用盐或前药形式，其中：n为0-1；m为0；p为0-1；R.sup.1为--CO.sub.2 H；R.sup.2选自H、--OH和--NH.sub.2的组；R.sup.3为H；R.sup.4为--C（O）NHR.sup.8；R.sup.5为--NHC（R.sup.6）NH.sub.2 R.sup.6选自.dbd.NH、.dbd.NOH、.dbd.NCN、.dbd.O和.dbd.S的组；R.sup.8选自每个碳上取代有0-3卤素的C.sub.1-C.sub.4直链或支链烷基的组。
• 6-Membered unsaturated heterocyclic compounds useful for selective inhibition of the coagulation cascade
  申请人：Pharmacia Corporation

  公开号：US20040106626A1

  公开（公告）日：2004-06-03

  The present invention relates to compounds, and prodrugs thereof, composition and methods useful for preventing and treating thrombotic conditions in mammals. The compounds of the present invention, and prodrugs thereof, selectively inhibit certain proteases of the coagulation cascade.

  本发明涉及化合物及其前药、组合物和方法，用于预防和治疗哺乳动物的血栓病症。本发明的化合物及其前药，选择性地抑制凝血级联反应中的某些蛋白酶。
• 一类RBJ小分子抑制剂
  申请人：中国医学科学院基础医学研究所

  公开号：CN118439991A

  公开（公告）日：2024-08-06

  本发明涉及药物化学领域，具体涉及一类RBJ小分子抑制剂，更具体地涉及式I所示化合物，其药物组合物、制备方法和用途。本发明的化合物可以作为一种高度选择性和非常有效的RET抑制剂，此类化合物能够抑制RBJ表达和/或活性，对GTPase/MEK1蛋白相互作用具有优异的抑制活性。
• Design, Parallel Synthesis, and Crystal Structures of Pyrazinone Antithrombotics as Selective Inhibitors of the Tissue Factor VIIa Complex
  作者：John J. Parlow、Brenda L. Case、Thomas A. Dice、Ricky L. Fenton、Michael J. Hayes、Darin E. Jones、William L. Neumann、Rhonda S. Wood、Rhonda M. Lachance、Thomas J. Girard、Nancy S. Nicholson、Michael Clare、Roderick A. Stegeman、Anna M. Stevens、William C. Stallings、Ravi G. Kurumbail、Michael S. South

  DOI：10.1021/jm030131l

  日期：2003.9.1

  Structure-based drug design (SBDD) and polymer-assisted solution-phase (PASP) library synthesis were used to develop a series of pyrazinone inhibitors of the Tissue Factor/Factor Vlla (TF/VIIa) complex. The crystal structure of a tripeptide-alpha-ketothiazole complexed with TF/VIIa was utilized in a docking experiment to identify the pyrazinone core as a starting scaffold. The pyrazinone core could orient the substituents in the correct spatial arrangement to probe the S-1, S-2, and S-3 pockets of the enzyme. A multistep PASP library synthesis was designed to prepare the substituted pyrazinones varying the P-1, P-2, and P-3 moieties. Hundreds of pyrazinone TF/VIIa inhibitors were prepared and tested in several serine protease enzyme assays involved in the coagulation cascade. The inhibitors exhibited modest activity on TF/ VIIa with excellent selectivity over thrombin (Ha) and Factor Xa. The structure-activity relationship of the pyrazinone inhibitors will be discussed and X-ray crystal structures of selected compounds complexed with the TF/VIIa enzyme will be described. This study ultimately led to the synthesis of compound 34, which exhibited 16 nM (IC50) activity on TF/VIIa with >6250x selectivity vs Factor Xa and thrombin. This potent and highly selective inhibitor of TF/VIIa was chosen for preclinical, intravenous proof-of-concept studies to demonstrate the separation between antithrombotic efficacy and bleeding side effects in a nonhuman primate model of electrolytic-induced arterial thrombosis.
• 6-MEMBERED UNSATURATED HETEROCYCLIC COMPOUNDS USEFUL FOR SELECTIVE INHIBITION OFTHE COAGULATION CASCADE
  申请人：Pharmacia Corporation

  公开号：EP1448534A1

  公开（公告）日：2004-08-25