2-(2-hydroxyethyl)-5-methyl-1H-isoindole-1,3(2H)-dione | 223733-35-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(2-hydroxyethyl)-5-methyl-1H-isoindole-1,3(2H)-dione
• 英文别名: 2-(2-Hydroxyethyl)-5-methylisoindole-1,3-dione
• CAS: 223733-35-5
• 化学式: C₁₁H₁₁NO₃
• 分子量: 205.213
• InChiKey: QJVHJUXTPFPKSF-UHFFFAOYSA-N

物化性质

• 熔点：
  94-96 °C(Solv: ethyl ether (60-29-7); dichloromethane (75-09-2))
• 沸点：
  385.0±35.0 °C(Predicted)
• 密度：
  1.333±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-hydroxyethyl)-5-methyl-1H-isoindole-1,3(2H)-dione 、 4-碘异硫氰酸苯酯 在 sodium hydride 、 水 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 24.0h， 以37%的产率得到O-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl] 4-iodophenylthiocarbamate
  参考文献：
  名称：

  Novel modifications in the series of O-(2-phthalimidoethyl)-N-substituted thiocarbamates and their ring-opened congeners as non-nucleoside HIV-1 reverse transcriptase inhibitors

  摘要：

  The structure-activity relationships (SARs) of N-aryl-O-(2-phthalimidoethyl)thiocarbamates (C-TCs) and their imide ring-opened congeners (O-TCs) as non-nucleoside HIV-1 reverse transcriptase inhibitors were further investigated. The SAR strategy involved modifications of the N-phenyl ring followed by the hybridization of the most promising N-aryl and O-(2-phthalimidoethyl)substructures. The role of stereochemistry and tert-butyl substitution of the phthalimidoethyl moiety on activity was also investigated. Seventy-six analogues were prepared by parallel solution-phase synthesis. Twenty-two C-TCs displayed nanomolar activity against wild-type HIV-1 and a number of analogues were effective against the Y181C mutant. Compound 56 combined the highest activity so far identified against Y181C (EC50=1.3 mu M) with good potency against the K103R mutant (EC50=4.8 mu M). Docking simulations helped to rationalize the SARs. (c) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.09.024
• 作为产物：
  描述：

  4-甲基苯酐 、 C.I.酸性橙108 反应 2.0h， 以68%的产率得到2-(2-hydroxyethyl)-5-methyl-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  基于结构的设计，平行合成，结构活性关系和分子模型研究的硫代氨基甲酸酯，苯乙基噻唑基硫脲衍生物的新型有效的非核苷HIV-1逆转录酶抑制剂等排体。

  摘要：

  在本文中，我们描述了我们基于结构的配体设计，合成策略和结构与活性关系（SAR）的研究，这些研究导致了硫代氨基甲酸酯（TC）的鉴定，这是一类新型的非核苷类逆转录酶抑制剂（NNRTIs），等位基因苯乙基噻唑基硫脲（PETT）衍生物的制备。假设O- [2-（邻苯二甲酰亚胺基）乙基]苯基硫代氨基甲酸酯为先导化合物，前述酰基硫代氨基甲酸酯的前体之一（Ranise，A .;等人，J。Med。Chem。2003，46，768-781） ，通过平行合成制备了两个目标溶液相TC库。领先的优化策略导致对位取代的TC 31、33、34、39、40、41、44、45和50在纳摩尔浓度的基于MT-4的测定中对野生型HIV-1具有活性（ EC50范围：0.04-0.01 microM）。最有效的同类物50（EC50 = 0。01 microM）在邻苯二甲酰亚胺部分的第4位带有一个甲基，在N-苯环的对位带有一个硝基。大

  DOI：

  10.1021/jm049252r

文献信息

• Parallel synthesis, molecular modelling and further structure–activity relationship studies of new acylthiocarbamates as potent non-nucleoside HIV-1 reverse transcriptase inhibitors
  作者：Andrea Spallarossa、Sara Cesarini、Angelo Ranise、Silvia Schenone、Olga Bruno、Alberto Borassi、Paolo La Colla、Margherita Pezzullo、Giuseppina Sanna、Gabriella Collu

  DOI：10.1016/j.ejmech.2008.10.032

  日期：2009.5

  The structure–activity relationships (SARs) of acylthiocarbamates (ATCs), a new class of non-nucleoside HIV-1 reverse transcriptase inhibitors, have been expanded. Sixty-six new analogues were prepared by parallel solution-phase synthesis. In general, the potency of new ATCs was better than that of the first series and O-[2-phthalimidoethyl] 4-chlorophenyl(3-nitrobenzoyl) thiocarbamate turned out to

  新型的非核苷HIV-1逆转录酶抑制剂酰基硫代氨基甲酸酯（ATC）的结构-活性关系（SAR）已得到扩展。通过平行溶液相合成制备了六十六种新的类似物。总的来说，新ATC的效能比第一个ATC更好，O- [2-邻苯二甲酰亚胺基乙基] 4-氯苯基（3-硝基苯甲酰基）硫代氨基甲酸酯被证明是迄今为止合成的最有效的ATC（EC 50  = 1.5 nM ）。几种ATC在微摩尔浓度下对带有RT Y181C突变的HIV-1菌株具有活性，其中之一对K103R变体也具有中等活性。进行了对接模拟以合理化最相关的SAR。
• [EN] N-CYCLYL-3 - (CYCLYLCARBONYLAMINOMETHYL) BENZAMIDE DERIVATIVES AS RHO KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE N-CYCLYL-3-(CYCLYLCARBONYLAMINOMÉTHYL)BENZAMIDE EN TANT QU'INHIBITEURS DE LA RHO KINASE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012006203A1

  公开（公告）日：2012-01-12

  The present invention relates to compounds of formula (I) : and pharmaceutically acceptable salts thereof, wherein R1and R2 are various ring systems. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of Rho Kinase mediated diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及化合物的公式（I）及其药学上可接受的盐，其中R1和R2是不同的环系统。该发明还涉及包括这些化合物的药物组合物，使用这些化合物治疗Rho激酶介导的疾病和障碍的方法，制备这些化合物的方法以及在这些过程中有用的中间体。
• Parallel one-pot synthesis and structure–activity relationship study of symmetric formimidoester disulfides as a novel class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors
  作者：Sara Cesarini、Andrea Spallarossa、Angelo Ranise、Silvia Schenone、Olga Bruno、Paolo La Colla、Laura Casula、Gabriella Collu、Giuseppina Sanna、Roberta Loddo

  DOI：10.1016/j.bmc.2008.05.010

  日期：2008.6

  variation of the N-aryl portion (mono-, di- and trisubstitution of the phenyl ring and its replacement with a 1-naphthyl, cyclopropyl or benzyl group) and of the 2-phthalimidoethyl moiety (introduction of a methyl on the phthalimide substructure, replacement of the phthalimide moiety with a phenyl ring and elongation of the ethyl linker). Most DSs proved to inhibit the wild-type HIV-1 replication in

  非核苷逆转录酶抑制剂（NNRTI）O-（2-邻苯二甲酰亚胺基乙基）-N-芳基硫代氨基甲酸酯（C-TCs）的分子复制导致对称甲酰亚胺基二硫化物（DSs）鉴定为一类新型的有效NNRTIs。铅化合物1 [TC O-（2-邻苯二甲酰亚胺基乙基）-N-苯基硫代氨基甲酸酯的异硫代氨基甲酸酯形式的二聚体]可以防止EC-4值为EC（50）的MT-4细胞培养中的野生型HIV-1繁殖。 0.35微米 为了进行结构-活性关系（SAR）研究，我们通过空前的一锅法溶液相平行合成方法制备了1的40个类似物。SAR策略着重于N-芳基部分的变化（苯环的单，双和三取代，以及被1-萘基取代，环丙基或苄基）和2-邻苯二甲酰亚胺基乙基部分（在邻苯二甲酰亚胺亚结构上引入甲基，用苯环取代邻苯二甲酰亚胺部分，并延长乙基连接基）。在基于细胞的测定中，大多数DS被证明可抑制野生型HIV-1复制，其中15个在纳摩尔浓度下具有活性。最有效的同
• RHO KINASE INHIBITORS
  申请人：Cook Brian Nicholas

  公开号：US20120165322A1

  公开（公告）日：2012-06-28

  The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 and R 2 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及式(I)的化合物和其药学上可接受的盐，其中R1和R2的定义如本文所述。本发明还涉及包含这些化合物的药物组合物、使用这些化合物治疗各种疾病和障碍的方法、制备这些化合物的过程以及在这些过程中有用的中间体。
• Multimetallic Iridium-Tin (Ir-Sn₃) Catalyst in<i>N</i>-Acyliminium Ion Chemistry: Synthesis of 3-Substituted Isoindolinones<i>via</i>Intra- and Intermolecular Amidoalkylation Reaction
  作者：Arnab Kumar Maity、Sujit Roy

  DOI：10.1002/adsc.201400234

  日期：2014.8.11

  AbstractThe multimetallic iridium‐tritin (Ir‐Sn3) complex [Cp*Ir(SnCl3)2SnCl2(H2O)2}] (1) proved to be a highly effective catalyst towards COH bond activation of γ‐hydroxylactams, leading to a nucleophilic substitution reaction known as the α‐amidoalkylation reaction. Catalyst 1 can be easily synthesized from the reaction of (pentamethylcyclocyclopentadienyl)iridium dichloride dimer [Cp*IrCl2]2} and tin(II) dichloride (SnCl2). In terms of catalyst loading, reaction conditions and yields of the product formed, 1 is found to be superior compared to classical Lewis acid catalysts. Different carbon (arenes, heteroarenes, allyltrimethylsilane, 1,3‐dicarbonyls) and heteroatom (alcohols, thiols, amides and sulfonamides) nucleophiles have been successfully employed in the intramolecular and intermolecular alkylations, as well as in heterocyclization reactions. In the majority of cases good to excellent yields of 3‐substituted isoindolinones and 5‐substituted pyrrolidin‐2‐ones have been obtained. Besides, the reactions are also atom economical and salt free. It is proposed that the multimetallic Ir‐Sn3 catalyst behaves as a mild and selective Lewis acid to activate the γ‐hydroxylactam towards the formation of the N‐acyliminium ion; the latter being trapped by potent nucleophiles leading to the desired products.magnified image