5-methoxy-6-nitro-4-azaindan | 161030-00-8

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 5-methoxy-6-nitro-4-azaindan
• 英文别名: 2-methoxy-3-nitro-6,7-dihydro-5H-cyclopenta[b]pyridine
• CAS: 161030-00-8
• 化学式: C₉H₁₀N₂O₃
• 分子量: 194.19
• InChiKey: AOJFILUZOOGEKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-methoxy-6-nitro-4-azaindan 在 镍 盐酸 、 manganese(IV) oxide 、 正丁基锂 、 四甲基乙二胺 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 20.0 ℃ 、202.65 kPa 条件下， 反应 11.0h， 生成 3-Amino-4-(3-methylbenzoyl)-1,5,6,7-tetrahydrocyclopenta[b]pyridin-2-one
  参考文献：
  名称：

  4-Benzyl and 4-Benzoyl-3-dimethylaminopyridin-2(1H)-ones:  In Vitro Evaluation of New C-3-Amino-Substituted and C-5,6-Alkyl-Substituted Analogues against Clinically Important HIV Mutant Strains

  摘要：

  In a program to optimize the anti-HIV activity of the 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 9 and 10, lead compounds in a new class of highly potent non-nucleoside type inhibitors of HIV-1 reverse transcriptase, modification of the alkyl substitutents at the C-5 and C-6 positions on the pyridinone ring and of the substitutents on the C-3 amino group has been studied. Of the 17 new 5/6-modified analogues prepared, compounds 31b and 32b substituted at C-5 by an extended nonpolar chain containing an ether function and a C-6 methyl group and compound 35 bearing a C-5 ethyl/C-6 hydroxymethyl substituent pattern were selected on the basis of their in vitro activity against wild-type HIV and the three principle mutant strains, K103N, Y181C, and Y188L. When tested further, it was shown that these molecules, and in particular compound 35, are globally more active than 9, 10, and efavirenz against an additional eight single [L100I, K101E, V106A, E138K, V179E, G190A/S, and F227C] and four double HIV mutant strains [L1001 + K103N, K101E + K103N, K103N + Y181C, and F227L + V106A] which are clinically relevant. Concerning modulation of the N-3 substituent, 36 new analogues were prepared. Of these, the N-methyl-N-(2-methoxyethyl)-substituted compounds 40, 42, and 62, as well as the doubly modified compounds 77a and 77b, were selected from the initial screen and were subsequently shown to be active at sub-micromolar concentrations (IC50'S) against all the other mutant strains except K103N + Y181C and F227L + V106A. Two possible, but distinct, modes of binding of these analogues in RT were suggested from molecular modeling studies. The preferred mode of binding for compound 62, corresponding to the predicted "orientation 1", was revealed in the X-ray crystal structure of the compound 62-RT complex.

  DOI：

  10.1021/jm0408621
• 作为产物：
  描述：

  methyl 6-methyl-3-nitro-2-pyridinecarboxylate 生成 5-methoxy-6-nitro-4-azaindan
  参考文献：
  名称：

  Tohda Yasuo, Kawahara Tohru, Eiraku Miyuki, Tani Keita, Nisiwaki Nagatosh+, Bull. Chem. Soc. Jap, 67 (1994) N 8, S 2176-2186

  摘要：

  DOI：

文献信息

• Nucleophilic Reaction upon Electron-Deficient Pyridone Derivatives. XIII. Regioselective Synthesis of 2-Substituted 3-Nitropyridines by One-Pot Reaction of Either 4- or 6-Substituted 1-Methyl-3,5-dinitro-2-pyridones with Ketones and Ammonia
  作者：Yasuo Tohda、Tohru Kawahara、Miyuki Eiraku、Keita Tani、Nagatoshi Nisiwaki、Masahiro Ariga

  DOI：10.1246/bcsj.67.2176

  日期：1994.8

  A one-pot synthesis of 2-substituted 3-nitropyridines was developed by a ring transformation of 6- or 4-substituted 1-methyl-3,5-dinitro-2-pyridones (2 or 3) with ammonia and enamines derived from ketones. Some intermediates having a 2,6-diazabicyclo[3.3.1]nonane skeleton were isolated from reactions of 3. The ring transformation proceeds via an addition-addition-elimination-elimination mechanism.

  2-取代 3-硝基吡啶的一锅合成是通过 6-或 4-取代的 1-甲基-3,5-二硝基-2-吡啶酮（2 或 3）与氨和酮衍生的烯胺的环转化而开发的. 一些具有2,6-二氮杂双环[3.3.1]壬烷骨架的中间体从3的反应中分离出来。环转化通过加成-加成-消除-消除机制进行。形成了很少的竞争性异构副产物，即 4-取代的 3-硝基吡啶和 4-硝基苯胺。2 种底物均表现出良好的反应性，但具有吸电子取代基的 3 种底物反应性和选择性较差。1,4,6-三甲基-3,5-二硝基-2-吡啶酮没有得到任何产物。
• Tohda Yasuo, Kawahara Tohru, Eiraku Miyuki, Tani Keita, Nisiwaki Nagatosh+, Bull. Chem. Soc. Jap, 67 (1994) N 8, S 2176-2186
  作者：Tohda Yasuo, Kawahara Tohru, Eiraku Miyuki, Tani Keita, Nisiwaki Nagatosh+

  DOI：——

  日期：——
• 4-Benzyl and 4-Benzoyl-3-dimethylaminopyridin-2(1<i>H</i>)-ones:  In Vitro Evaluation of New C-3-Amino-Substituted and C-5,6-Alkyl-Substituted Analogues against Clinically Important HIV Mutant Strains
  作者：Abdellah Benjahad、Martine Croisy、Claude Monneret、Emile Bisagni、Dominique Mabire、Sophie Coupa、Alain Poncelet、Imre Csoka、Jérôme Guillemont、Christophe Meyer、Koen Andries、Rudi Pauwels、Marie-Pierre de Béthune、Daniel M. Himmel、Kalyan Das、Eddy Arnold、Chi Hung Nguyen、David S. Grierson

  DOI：10.1021/jm0408621

  日期：2005.3.1

  In a program to optimize the anti-HIV activity of the 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 9 and 10, lead compounds in a new class of highly potent non-nucleoside type inhibitors of HIV-1 reverse transcriptase, modification of the alkyl substitutents at the C-5 and C-6 positions on the pyridinone ring and of the substitutents on the C-3 amino group has been studied. Of the 17 new 5/6-modified analogues prepared, compounds 31b and 32b substituted at C-5 by an extended nonpolar chain containing an ether function and a C-6 methyl group and compound 35 bearing a C-5 ethyl/C-6 hydroxymethyl substituent pattern were selected on the basis of their in vitro activity against wild-type HIV and the three principle mutant strains, K103N, Y181C, and Y188L. When tested further, it was shown that these molecules, and in particular compound 35, are globally more active than 9, 10, and efavirenz against an additional eight single [L100I, K101E, V106A, E138K, V179E, G190A/S, and F227C] and four double HIV mutant strains [L1001 + K103N, K101E + K103N, K103N + Y181C, and F227L + V106A] which are clinically relevant. Concerning modulation of the N-3 substituent, 36 new analogues were prepared. Of these, the N-methyl-N-(2-methoxyethyl)-substituted compounds 40, 42, and 62, as well as the doubly modified compounds 77a and 77b, were selected from the initial screen and were subsequently shown to be active at sub-micromolar concentrations (IC50'S) against all the other mutant strains except K103N + Y181C and F227L + V106A. Two possible, but distinct, modes of binding of these analogues in RT were suggested from molecular modeling studies. The preferred mode of binding for compound 62, corresponding to the predicted "orientation 1", was revealed in the X-ray crystal structure of the compound 62-RT complex.