methyl 5-amino-4-iodo-2-methylbenzoate | 686342-80-3

• 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: methyl 5-amino-4-iodo-2-methylbenzoate
• CAS: 686342-80-3
• 化学式: C₉H₁₀INO₂
• 分子量: 291.088
• InChiKey: AHPLMUWQBFMNBX-UHFFFAOYSA-N

物化性质

• 沸点：
  346.1±42.0 °C(Predicted)
• 密度：
  1.733±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 5-amino-4-iodo-2-methylbenzoate 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 二(氰基苯)二氯化钯 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.25h， 生成 methyl 5-methyl-2-pentyl-3-2-methoxy-2-oxo-1-(2-(benzenesulfonyl)hydrazinyl)-1H-indole-6-carboxylate methyl ester
  参考文献：
  名称：

  一类吲哚衍生物及其制备方法和应用

  摘要：

  本发明公开了一类吲哚衍生物及其制备方法和应用，属于制药技术领域；所述吲哚衍生物为通式(Ⅰ)所代表的化合物：

  公开号：

  CN113717091B
• 作为产物：
  描述：

  5-氨基-2-甲基苯甲酸甲酯 在 N-碘代丁二酰亚胺 、 溶剂黄146 作用下， 反应 1.5h， 以49%的产率得到methyl 5-amino-4-iodo-2-methylbenzoate
  参考文献：
  名称：

  发现和SAR的第一个临床阶段蛋白激酶CK2抑制剂5-（3-氯苯基氨基）苯并[ c ] [2,6]萘吡啶-8-羧酸（CX-4945）

  摘要：

  本文中，我们对CX-4945（25n）的发现进行了编年史，CX-4945是蛋白激酶CK2的一流的，口服可生物利用的ATP竞争性抑制剂，在癌症的临床试验中得到了证实。CK2长期以来一直被认为是主要的癌症药物靶标，因为CK2的失调和过度表达在促进癌症的生存和抗凋亡途径中起着重要的作用。这些生物学特性以及CK2的小ATP结合位点对选择性抑制剂设计的适用性，使我们开发出了新型的癌症治疗剂。导致25n（K i = 0.38 nM）的最优化是通过分子建模指导的，这表明25n的强结合由疏水相互作用，与Lys68形成的离子桥以及与铰链区的氢键结合而成。发现25n具有高度选择性，可跨物种口服生物利用（20-51％），并且在异种移植模型中有效。25n的发现将首次使CK2在人类中具有治疗靶向性。

  DOI：

  10.1021/jm101251q

文献信息

• [EN] TRICYCLIC HETEROARYL COMPOUNDS USEFUL AS IRAK4 INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROARYLE TRICYCLIQUES UTILES EN TANT QU'INHIBITEURS D'IRAK4
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2021011724A1

  公开（公告）日：2021-01-21

  Disclosed are compounds of Formula (I) or a salt or prodrug thereof, wherein: X1 and X2 are independently C or N, provided that zero or one of X1 and X2 is N; Ring A represented by the structure is: or; and Q, R1, R2, R3, R4, R6, and p are define herein. Also disclosed are methods of using such compounds as modulators of IRAK4, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases, or in the treatment of cancer.

  披露了公式(I)的化合物或其盐或前药，其中：X1和X2独立地为C或N，条件是X1和X2中零个或一个是N；环A由以下结构表示：或；以及Q、R1、R2、R3、R4、R6和p在此定义。还披露了使用此类化合物作为IRAK4调节剂的方法，以及包含此类化合物的药物组合物。这些化合物可用于治疗、预防或减缓炎性和自身免疫疾病，或用于癌症治疗。
• Small molecule inhibition of a PDZ-domain interaction
  申请人：Guy Kiplin R.

  公开号：US20050043385A1

  公开（公告）日：2005-02-24

  Novel compounds that have been found effective in inhibiting PDZ domain interactions, and particularly interactions of PDZ domains in MAGIs with the oncogenic (tumor suppressor) protein PTEN and interactions between the PDZ domain in the Dishevelled (Dvl) protein and other proteins such as the Frizzled (Fz) protein, have the general formula The invention also includes combinatorial libraries, arrays and methods for screening and studying proteins using such compounds. Compounds of the invention have produced apoptosis in certain cell lines that overexpress the Dishevelled protein (Dvl); inhibiting Wnt signaling.

  已发现的新型化合物可有效抑制PDZ结构域相互作用，特别是MAGIs中的PDZ结构域与肿瘤抑制蛋白PTEN之间的相互作用，以及Dishevelled（Dvl）蛋白中的PDZ结构域与其他蛋白如Frizzled（Fz）蛋白之间的相互作用，其一般公式如下。该发明还包括用这些化合物进行筛选和研究蛋白的组合库、阵列和方法。该发明的化合物已在过度表达Dishevelled蛋白（Dvl）的某些细胞系中诱导细胞凋亡；抑制Wnt信号传导。
• PROTEIN KINASE MODULATORS
  申请人：CHUA Peter C.

  公开号：US20090239859A1

  公开（公告）日：2009-09-24

  The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate Pim kinase activity and/or FMS-like tyrosine kinase (Flt) activity. The invention also relates in part to methods for using such molecules.

  该发明部分涉及具有特定生物活性的分子，包括但不限于抑制细胞增殖、调节蛋白激酶活性和调节聚合酶活性。该发明的分子可以调节Pim激酶活性和/或FMS样酪氨酸激酶（Flt）活性。该发明还涉及使用这些分子的方法。
• Protein kinase modulators
  申请人：Cylene Pharmaceuticals, Inc.

  公开号：US08168651B2

  公开（公告）日：2012-05-01

  The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate Pim kinase activity and/or FMS-like tyrosine kinase (Flt) activity. The invention also relates in part to methods for using such molecules.

  本发明部分涉及具有特定生物活性的分子，包括但不限于抑制细胞增殖、调节蛋白激酶活性和调节聚合酶活性。本发明的分子可以调节Pim激酶活性和/或类FMS酪氨酸激酶(Flt)活性。本发明部分还涉及使用这些分子的方法。
• A Selective Irreversible Inhibitor Targeting a PDZ Protein Interaction Domain
  作者：Naoaki Fujii、Jose J. Haresco、Kathleen A. P. Novak、David Stokoe、Irwin D. Kuntz、R. Kiplin Guy

  DOI：10.1021/ja035540l

  日期：2003.10.1

  Irreversible inhibitors of proteases have proven themselves useful tools for determining which proteases are active under given conditions in tissues or cells and for studying the functional role that a protease plays in physiological processes. The application of such techniques to the study of the activity and function of protein-protein interactions has been hindered by the lack of guiding principles for the mechanistic design of irreversible inhibitors targeting the "active site" of a protein interaction. We report herein the first example of a mechanism-based irreversible inhibitor of a protein interaction that has been specifically targeted to one member of the PDZ family of protein interaction domains: the second PDZ domain of the membrane-associated guanylate kinase MAGI3. This inhibitor was designed using rationally directed computational evaluation to take advantage of a conserved histidine in the PDZ domain by introducing an ionizable group that will be held in close proximity to that nucleophile during binding. The novel compound exhibits all of the characteristics of an irreversible inhibitor of the interaction of the tumor suppressor PTEN with MAGI3 in in vitro models. In cells, the inhibitor can be shown to release PTEN from sequestration by MAGI3 and consequently upregulate the PKB signaling pathway.