2-[N-(tert-Butyloxycarbonyl)amino]-5-iodobenzoic acid | 445479-86-7

• 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: 2-[N-(tert-Butyloxycarbonyl)amino]-5-iodobenzoic acid
• 英文别名: 2-(tert-butoxycarbonylamino)-5-iodo-benzoic acid；2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-iodobenzoic acid；Boc-2-amino-5-iodobenzoic acid；5-iodo-2-[(2-methylpropan-2-yl)oxycarbonylamino]benzoic acid
• CAS: 445479-86-7
• 化学式: C₁₂H₁₄INO₄
• 分子量: 363.152
• InChiKey: NZVOASTYHQSAJJ-UHFFFAOYSA-N

物化性质

• 沸点：
  385.6±37.0 °C(Predicted)
• 密度：
  1.704±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 储存条件：
  存储温度应保持在2-8°C，并请避免光线直射。

反应信息

• 作为反应物：
  描述：

  2-[N-(tert-Butyloxycarbonyl)amino]-5-iodobenzoic acid 在 盐酸 、 乙酰氯 作用下， 以 甲醇 为溶剂， 反应 36.5h， 生成 7-iodo-4-(prop-2-yn-1-yl)-3-(4-(trifluoromethyl)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione
  参考文献：
  名称：

  Fully Functionalized Small-Molecule Probes for Integrated Phenotypic Screening and Target Identification

  摘要：

  Phenotypic screening offers a powerful approach to identify small molecules that perturb complex biological processes in cells and organisms. The tendency of small molecules, however, to interact with multiple protein targets, often with moderate to weak affinities, along with the lack of straightforward technologies to characterize these interactions in living systems, has hindered efforts to understand the mechanistic basis for pharmacological activity. Here we address this challenge by creating a fully functionalized small-molecule library whose membership is endowed with: (1) one or more diversity elements to promote interactions with different protein targets in cells, (2) a photoreactive group for UV light-induced covalent cross-linking to interacting proteins, and (3) an alkyne handle for reporter tag conjugation to visualize and identify cross-linked proteins. A library member was found to inhibit cancer cell proliferation selectively under nutrient-limiting (low glucose) conditions. Quantitative chemoproteomics identified MT-ND1, an integral membrane subunit of the similar to 1 MDa NADH:ubiquinone oxidoreductase (complex 1) involved in oxidative phosphorylation, as a specific target of the active probe. We further demonstrated that the active probe inhibits complex 1 activity in vitro (IC50 = 720 nM), an effect that is known to induce cell death in low-glucose conditions. Based on this proof of principle study, we anticipate that the generation and integration of fully functionalized compound libraries into phenotypic screening programs should facilitate the discovery of bioactive probes that are amenable to accelerated target identification and mechanistic characterization using advanced chemoproteomic technologies.

  DOI：

  10.1021/ja304213w
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 2-氨基-5-碘苯甲酸 在 sodium hydroxide 、 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 22.5h， 以89.5%的产率得到2-[N-(tert-Butyloxycarbonyl)amino]-5-iodobenzoic acid
  参考文献：
  名称：

  WO2007/45861

  摘要：

  公开号：

文献信息

• 3-(Tributylstannyl)allyl Alcohols: Useful Building Blocks for Solid-Phase Synthesis of Skipped Dienes and Trienes
  作者：Miroslav Havránek、Dalimil Dvořák

  DOI：10.1135/cccc20000434

  日期：——

  Repeated Stille coupling of 3-substituted 3-(tributylstannyl)allyl alcohols 2 on a solid support was used to synthesize a 21 × 21 library of skipped dienes and a 21 × 21 × 21 library of skipped trienes. Starting 3-(tributylstannyl)allyl alcohols were prepared by Pd-catalyzed hydrostannation of substituted prop-2-yn-1-ols, by hydroalumination by LiAlH₄ followed with transmetallation to tin using tributyltin methoxide, or by substitution of chlorine in (Z)-6-chloro-3-(tributylstannyl)hex-2-en-1-ol with appropriate nucleophile. Synthesized libraries were tested for the activity to endorphin receptors, but with negative results.

  使用固相支持上的3-取代3-(三丁基锡基)烯丙醇2的重复Stille偶联反应，合成了一个21×21的跳跃二烯库和一个21×21×21的跳跃三烯库。起始的3-(三丁基锡基)烯丙醇通过Pd催化的取代丙炔-1-醇的氢化锡化反应制备，或者通过氢铝化反应再经过转金属化到锡使用三丁基锡甲氧基，或者通过适当亲核试剂取代(Z)-6-氯-3-(三丁基锡基)己-2-烯-1-醇中的氯原子而得到。合成的库被测试其对内啡肽受体的活性，但结果为阴性。
• Enantiomerically pure 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists
  作者：Juan Jose Marugan、Kristi Leonard、Pierre Raboisson、Joan M. Gushue、Raul Calvo、Holly K. Koblish、Jennifer Lattanze、Shuyuan Zhao、Maxwell D. Cummings、Mark R. Player、Carsten Schubert、Anna C. Maroney、Tianbao Lu

  DOI：10.1016/j.bmcl.2006.03.067

  日期：2006.6

  The 1,4-benzodiazepine-2,5-dione is a suitable template to disrupt the interaction between p53 and Hdm2. The development of an enantioselective synthesis disclosed the stereochemistry of the active enantiomer. An in vitro p53 peptide displacement assay identified active compounds. These activities were confirmed in several cell-based assays including induction of the p53 regulated gene (PIG-3) and

  1,4-苯并二氮杂-2,5-二酮是合适的模板，可破坏p53与Hdm2之间的相互作用。对映选择性合成的发展揭示了活性对映异构体的立体化学。体外p53肽置换试验确定了活性化合物。这些活性在几种基于细胞的测定中得到证实，包括诱导p53调控基因（PIG-3）和胱天蛋白酶的活性。
• Discovery of the first Mycobacterium tuberculosis MabA (FabG1) inhibitors through a fragment-based screening
  作者：Léo Faïon、Kamel Djaout、Rosangela Frita、Catalin Pintiala、Francois-Xavier Cantrelle、Martin Moune、Alexandre Vandeputte、Kevin Bourbiaux、Catherine Piveteau、Adrien Herledan、Alexandre Biela、Florence Leroux、Laurent Kremer、Mickael Blaise、Abdalkarim Tanina、René Wintjens、Xavier Hanoulle、Benoit Déprez、Nicolas Willand、Alain R. Baulard、Marion Flipo

  DOI：10.1016/j.ejmech.2020.112440

  日期：2020.8

  Mycobacterium tuberculosis (M.tb), the etiologic agent of tuberculosis, remains the leading cause of death from a single infectious agent worldwide. The emergence of drug-resistant M.tb strains stresses the need for drugs acting on new targets. Mycolic acids are very long chain fatty acids playing an essential role in the architecture and permeability of the mycobacterial cell wall. Their biosynthesis

  结核分枝杆菌（M.tb）是结核病的病原体，仍然是全球单一传染病致死的主要原因。耐药性结核分枝杆菌的出现菌株强调需要药物作用于新靶标。分枝杆菌酸是很长的链脂肪酸，在分枝杆菌细胞壁的结构和渗透性中起着至关重要的作用。它们的生物合成涉及两个脂肪酸合酶（FAS）系统。在FAS-II周期的四种酶（MabA，HadAB / BC，InhA和KasA / B）中，MabA（FabG1）仍然是唯一尚未报道特异性抑制剂的酶。新的基于LC-MS / MS的酶促测定方法的开发，可以筛选1280个片段文库，并导致发现了第一个抑制MabA活性的小分子。将邻氨基苯甲酸系列的片段优化为更有效的抑制剂，并通过19 F配体观察的NMR实验证实了它们与MabA的结合。
• Novel 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists with improved cellular activity
  作者：Kristi Leonard、Juan Jose Marugan、Pierre Raboisson、Raul Calvo、Joan M. Gushue、Holly K. Koblish、Jennifer Lattanze、Shuyuan Zhao、Maxwell D. Cummings、Mark R. Player、Anna C. Maroney、Tianbao Lu

  DOI：10.1016/j.bmcl.2006.04.009

  日期：2006.7

  apoptosis. We have identified the 1,4-benzodiazepine-2,5-dione scaffold as a suitable template for inhibiting this interaction by binding to the Hdm2 protein. Several compounds have been made with improved potency, solubility, and cell-based activities.

  p53-Hdm2蛋白质-蛋白质相互作用的破坏诱导细胞生长停滞和凋亡。我们已经确定了1,4-苯并二氮杂-2,5-二酮支架是通过与Hdm2蛋白结合来抑制这种相互作用的合适模板。已经制备了具有增强的效力，溶解性和基于细胞的活性的几种化合物。
• Substituted 1,4-diazepines and uses thereof
  申请人：——

  公开号：US20040220179A1

  公开（公告）日：2004-11-04

  The present invention is directed to novel 1,4-diazepines, pharmaceutical compositions thereof, and the use thereof as inhibitors of HDM2-p53 interactions. Compounds have Formula I: 1 or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein: R 1 , R 2 , R 9 , R 10 , R a , R d and M are defined herein; X is a bivalent radical of: an alkane, a cycloalkane, an optionally-substituted arene, an optionally-substituted heteroarene, an optionally-substituted arylalkane or an optionally-substituted heteroarylalkane; and R 3 is —CO 2 R d , —CO 2 M, —OH, —NHR d , —SO 2 R d , —NHCONHR d , optionally-substituted amidino or optionally-substituted guanidino; or R 3 —X— is hydrogen or an electron pair; R 4 is oxygen or —NR 9 R 10 ; R 5 is cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; and R 6 , R 7 and R 8 are independently hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, a saturated or partially unsaturated heterocycle, cycloalkylalkyl, aralkyl or heteroarylalkyl, each of which is optionally substituted; or R 6 and R 7 , together with the carbon atom to which they are attached form a 3- to 7-membered carbocyclic ring optionally substituted 1 to 3 times with R a .

  本发明涉及新型1,4-二氮杂环烷化合物，其药物组成物，以及其作为HDM2-p53相互作用抑制剂的用途。化合物具有以下结构式I：1或其溶剂化合物、水合物或药用可接受盐；其中：R1、R2、R9、R10、Ra、Rd和M在此处定义；X是以下结构的双价基团：烷烃、环烷烃、可选取代芳烃、可选取代杂芳烃、可选取代芳基烷烃或可选取代杂芳基烷烃；而R3为—CO2Rd、—CO2M、—OH、—NHRd、—SO2Rd、—NHCONHRd、可选取代酰胺基或可选取代胍基；或者R3—X—为氢或电子对；R4为氧或—NR9R10；R5为环烷基、芳基、杂芳基、环烷基烷基、芳基烷基、杂芳基烷基，或饱和或部分不饱和的杂环，每种均可选取代；而R6、R7和R8独立地为氢、烷基、环烷基、芳基、杂芳基、饱和或部分不饱和的杂环、环烷基烷基、芳基烷基、杂芳基烷基，每种均可选取代；或者R6和R7，与它们相连的碳原子共同形成一个3至7成员的碳环，可选取代1至3次以Ra。