3-碘-2-甲基喹啉-4-醇 | 64965-49-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 3-碘-2-甲基喹啉-4-醇
• 英文名称: 3-iodo-2-methylquinolin-4(1H)-one
• 英文别名: 4-Quinolinol, 3-iodo-2-methyl-；3-iodo-2-methyl-1H-quinolin-4-one
• CAS: 64965-49-7
• 化学式: C₁₀H₈INO
• 分子量: 285.084
• InChiKey: OTKAQDFXVUQKQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-碘-2-甲基喹啉-4-醇 在 sodium 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 21.0h， 生成 3-iodo-4-methoxy-2-methylquinoline
  参考文献：
  名称：

  Discovery, Synthesis, and Optimization of Antimalarial 4(1H)-Quinolone-3-Diarylethers

  摘要：

  The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by a novel chemical route and assessed for in vitro activity against multidrug resistant strains of Plasmodium falciparum and against malaria infections in mice. Here we describe the pathway to discovery of a potent class of orally active antimalarial 4(1H)-quinolone-3-diarylethers. The initial prototype, ELQ-233, exhibited low nanomolar IC50 values against all tested strains including clinical isolates harboring resistance to atovaquone. ELQ-271 represented the next critical step in the iterative optimization process, as it was stable to metabolism and highly effective in vivo. Continued analoging revealed that the substitution pattern on the benzenoid ring of the quinolone core significantly influenced reactivity with the host enzyme. This finding led to the rational design of highly selective ELQs with outstanding oral efficacy against murine malaria that is superior to established antimalarials chloroquine and atovaquone.

  DOI：

  10.1021/jm500147k
• 作为产物：
  描述：

  β-Anilino-crotonsaeureaethylester 在 dowtherm A 、 碘 、 正丁胺 、 potassium iodide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.33h， 生成 3-碘-2-甲基喹啉-4-醇
  参考文献：
  名称：

  Discovery, Synthesis, and Optimization of Antimalarial 4(1H)-Quinolone-3-Diarylethers

  摘要：

  The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by a novel chemical route and assessed for in vitro activity against multidrug resistant strains of Plasmodium falciparum and against malaria infections in mice. Here we describe the pathway to discovery of a potent class of orally active antimalarial 4(1H)-quinolone-3-diarylethers. The initial prototype, ELQ-233, exhibited low nanomolar IC50 values against all tested strains including clinical isolates harboring resistance to atovaquone. ELQ-271 represented the next critical step in the iterative optimization process, as it was stable to metabolism and highly effective in vivo. Continued analoging revealed that the substitution pattern on the benzenoid ring of the quinolone core significantly influenced reactivity with the host enzyme. This finding led to the rational design of highly selective ELQs with outstanding oral efficacy against murine malaria that is superior to established antimalarials chloroquine and atovaquone.

  DOI：

  10.1021/jm500147k

文献信息

• Concise and Practical Asymmetric Synthesis of a Challenging Atropisomeric HIV Integrase Inhibitor
  作者：Keith R. Fandrick、Wenjie Li、Yongda Zhang、Wenjun Tang、Joe Gao、Sonia Rodriguez、Nitinchandra D. Patel、Diana C. Reeves、Jiang-Ping Wu、Sanjit Sanyal、Nina Gonnella、Bo Qu、Nizar Haddad、Jon C. Lorenz、Kanwar Sidhu、June Wang、Shengli Ma、Nelu Grinberg、Heewon Lee、Youla Tsantrizos、Marc-André Poupart、Carl A. Busacca、Nathan K. Yee、Bruce Z. Lu、Chris H. Senanayake

  DOI：10.1002/anie.201501575

  日期：2015.6.8

  A practical and efficient synthesis of a complex chiral atropisomeric HIV integrase inhibitor has been accomplished. The combination of a copper‐catalyzed acylation along with the implementation of the BI‐DIME ligands for a ligand‐controlled Suzuki cross‐coupling and an unprecedented bis(trifluoromethane)sulfonamide‐catalyzed tert‐butylation renders the synthesis of this complex molecule robust, safe

  已经完成了一种实用有效的合成方法，用于合成复杂的手性阻转异构HIV整合酶抑制剂。铜催化的酰化与BI-DIME配体的结合使配体可控的Suzuki交叉偶联以及前所未有的双（三氟甲烷）磺酰胺催化的叔丁基化相结合，使该复杂分子的合成稳定，安全且经济。此外，相对于嵌入的阻转异构体，以不对称和非对映选择性的方式进行整体合成。
• [EN] PROCESS FOR THE PREPARATION OF AN HIV INTEGRASE INHIBITOR<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN INHIBITEUR DE L'INTÉGRASE DU VIH
  申请人：GILEAD SCIENCES INC

  公开号：WO2012138670A1

  公开（公告）日：2012-10-11

  The present invention is directed to an improved process for the preparation of Compounds of Formula (I) or salts thereof which are useful in the treatment of HIV infection. In particular, the present invention is directed to an improved process for the preparation of (2S)-2-tert-butoxy-2-(4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)- 2-methylquinolin-3-yl)acetic acid or salt thereof which is useful in the treatment of HIV infection. R4 is selected from the group consisting of (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (l), (m), (n) and (o); and R6 and R7 are each independently selected from H, halo and (C1-6) alkyl.

  本发明涉及一种改进的工艺，用于制备化合物的化合物（I）或其盐，该化合物在治疗HIV感染中有用。具体而言，本发明涉及一种改进的工艺，用于制备对治疗HIV感染有用的(2S)-2-叔丁氧基-2-(4-(2,3-二氢吡喃并[4,3,2-de]喹啉-7-基)-2-甲基喹啉-3-基)乙酸或其盐。其中R4从(a)、(b)、(c)、(d)、(e)、(f)、(g)、(h)、(i)、(j)、(k)、(l)、(m)、(n)和(o)组成的群中选择；R6和R7分别独立选择自H、卤素和（C1-6）烷基。
• 4(1H)-Quinolones Having Antimalarial Activity With Reduced Chemical Resistance
  申请人：Manetsch Roman

  公开号：US20130123258A1

  公开（公告）日：2013-05-16

  Provided are 4(1H)-quinolone derivatives effective in inhibiting or eliminating the viability of at least one of the stages in the life-cycle of the malarial parasite, and to show a reduced propensity to induce resistance to the compound by the target parasite. In particular, the compounds can be derivatives of phenoxyethoxy-quinolones, and including, but not only, 7-(2-phenoxyethoxy)quinolin derivatives. These compounds may be administered by themselves, with at least one other derivative compound, or with other antimalarial compounds, to an animal or human subject. The therapeutic compositions can be and formulated to reduce the extent of a Plasmodium infection in the recipient subject, or to reduce the likelihood of the onset or establishment of a Plasmodium infection if administered prior to the parasite contacting the subject. The therapeutic compositions can be formulated to provide an effective single dose amount of an antimalarial compound or multiple doses for administering over a period of time.

  提供了4(1H)-喹啉酮衍生物，能有效抑制或消除疟原虫生命周期中至少一个阶段的生存能力，并且显示出减少目标寄生虫对化合物产生抗药性的倾向。具体来说，这些化合物可以是苯氧乙氧基喹啉酮的衍生物，包括但不限于7-(2-苯氧乙氧基)喹啉衍生物。这些化合物可以单独或与至少另一种衍生物化合物或其他抗疟疾化合物一起，向动物或人类受试者施用。治疗组合物可以配制成减少受试者体内疟原虫感染程度的程度，或者在寄生虫接触受试者之前施用，以减少疟原虫感染的可能性。治疗组合物可以配制成提供有效的单剂量抗疟疾化合物或多剂量，以在一段时间内施用。
• Photoredox halogenation of quinolones: the dual role of halo-fluorescein dyes
  作者：Ritu、Sharvan Kumar、Parul Chauhan、Nidhi Jain

  DOI：10.1039/d1ob00538c

  日期：——

  An unprecedented visible light mediated regioselective C-3 halogenation of quinolones was achieved using halo-fluorescein dyes as a halogen source and air as an oxidant. This reaction has broad substrate scope and gives 3-halo quinolone derivatives.

  使用卤素荧光素染料作为卤素源和空气作为氧化剂，实现了对喹诺酮的前所未有的可见光介导的C-3卤代反应选择性。该反应具有广泛的底物范围，并产生3-卤代喹诺酮衍生物。
• Convenient and Efficient Microwave-Assisted Synthesis of a Methyl Derivative of the Fused Indoloquinoline Alkaloid Cryptosanguinolentine
  作者：Robert M. Gengan、Pitchai Pandian、Chandraprakash Kumarsamy、Palathurai S. Mohan

  DOI：10.3390/molecules15053171

  日期：——

  An efficient synthesis of a methyl derivative of the indoloquinoline alkaloid cryptosanguinolentine based on microwave-assisted reactions is described. The microwave-assisted synthesis of an intermediate 4-hydroxy-2-methylquinoline yielded 86% of the desired product and other intermediates prepared yielded high % of products in shorter reaction times, under optimum conditions, as compared to traditional methods.

  本研究介绍了一种基于微波辅助反应的吲哚喹啉生物碱隐鞘喹啉甲基衍生物的高效合成方法。与传统方法相比，微波辅助合成中间体 4-羟基-2-甲基喹啉可获得 86% 的所需产物，而且在最佳条件下，制备的其他中间体在较短的反应时间内也可获得较高的产物率。