1-氟-3-碘-5-甲氧基苯 | 1167056-58-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 1-氟-3-碘-5-甲氧基苯
• 英文名称: 1-fluoro-3-iodo-5-methoxybenzene
• CAS: 1167056-58-7
• 化学式: C₇H₆FIO
• 分子量: 252.027
• InChiKey: FLSYCEKFVMRKPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-氟-3-碘-5-甲氧基苯 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 以70%的产率得到3-氟-5-碘苯酚
  参考文献：
  名称：

  Efficient Discovery of Potent Anti-HIV Agents Targeting the Tyr181Cys Variant of HIV Reverse Transcriptase

  摘要：

  Non-nucleoside reverse transcriptase inhibitors (NNRTIs) that interfere with the replication of human immunodeficiency virus (HIV) are being pursued with guidance from molecular modeling including free-energy perturbation (FEP) calculations for protein inhibitor binding affinities. The previously reported pyrimidinylphenylamine 1 and its chloro analogue 2 are potent anti-HIV agents; they inhibit replication of wild-type HIV-1 in infected human T-cells with EC50 values of 2 and 10 nM, respectively. However, they show no activity against viral strains containing the Tyr181Cys (Y181C) mutation in HIV-RT. Modeling indicates that the problem is likely associated with extensive interaction between the dimethylallyloxy substituent and Tyr181. As an alternative, a phenoxy group is computed to be oriented in a manner diminishing the contact with Tyr181. However, this replacement leads to a roughly 1000-fold loss of activity for 3 (2.5 mu M). The present report details the efficient, computationally driven evolution of 3 to novel NNRTIs with sub-10 nM potency toward both wild-type HIV-1 and Y181C-containing variants. The critical contributors were FEP substituent scans for the phenoxy and pyrimidine rings and recognition of potential benefits of addition of a cyanovinyl group to the phenoxy ring.

  DOI：

  10.1021/ja2058583
• 作为产物：
  描述：

  3,5-二氟硝基苯 在 盐酸 、 铁粉 、 sodium hydride 、 氯化铵 、 sodium nitrite 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 水 为溶剂， 反应 7.75h， 生成 1-氟-3-碘-5-甲氧基苯
  参考文献：
  名称：

  Efficient Discovery of Potent Anti-HIV Agents Targeting the Tyr181Cys Variant of HIV Reverse Transcriptase

  摘要：

  Non-nucleoside reverse transcriptase inhibitors (NNRTIs) that interfere with the replication of human immunodeficiency virus (HIV) are being pursued with guidance from molecular modeling including free-energy perturbation (FEP) calculations for protein inhibitor binding affinities. The previously reported pyrimidinylphenylamine 1 and its chloro analogue 2 are potent anti-HIV agents; they inhibit replication of wild-type HIV-1 in infected human T-cells with EC50 values of 2 and 10 nM, respectively. However, they show no activity against viral strains containing the Tyr181Cys (Y181C) mutation in HIV-RT. Modeling indicates that the problem is likely associated with extensive interaction between the dimethylallyloxy substituent and Tyr181. As an alternative, a phenoxy group is computed to be oriented in a manner diminishing the contact with Tyr181. However, this replacement leads to a roughly 1000-fold loss of activity for 3 (2.5 mu M). The present report details the efficient, computationally driven evolution of 3 to novel NNRTIs with sub-10 nM potency toward both wild-type HIV-1 and Y181C-containing variants. The critical contributors were FEP substituent scans for the phenoxy and pyrimidine rings and recognition of potential benefits of addition of a cyanovinyl group to the phenoxy ring.

  DOI：

  10.1021/ja2058583

文献信息

• Development of a Highly Potent Transthyretin Amyloidogenesis Inhibitor: Design, Synthesis, and Evaluation
  作者：Francisca Pinheiro、Irantzu Pallarès、Francesca Peccati、Adrià Sánchez-Morales、Nathalia Varejão、Filipa Bezerra、David Ortega-Alarcon、Danilo Gonzalez、Marcelo Osorio、Susanna Navarro、Adrián Velázquez-Campoy、Maria Rosário Almeida、David Reverter、Félix Busqué、Ramon Alibés、Mariona Sodupe、Salvador Ventura

  DOI：10.1021/acs.jmedchem.2c01195

  日期：2022.11.10

  its dissociation and subsequent aggregation, is a therapeutic strategy for these pathologies. Departing from the crystal structure of TTR in complex with tolcapone, a potent binder in clinical trials for ATTR, we combined rational design and molecular dynamics (MD) simulations to generate a series of novel halogenated kinetic stabilizers. Among them, M-23 displays one of the highest affinities for TTR

  转甲状腺素蛋白淀粉样变性 (ATTR) 是一组以转甲状腺素蛋白 (TTR) 的错误折叠和淀粉样蛋白沉积为特征的致命性疾病。发现结合并稳定 TTR 四聚体、防止其解离和随后聚集的小分子是这些病症的治疗策略。从与托卡朋复合的 TTR 的晶体结构出发，托卡朋是 ATTR 临床试验中的一种有效粘合剂，我们结合合理设计和分子动力学 (MD) 模拟，生成了一系列新型卤代动力学稳定剂。其中，M-23显示出迄今为止描述的对 TTR 的最高亲和力之一。TTR/ M-23正如 MD 模拟预测的那样，晶体结构证实了前所未有的蛋白质-配体接触的形成，从而导致体外和全血清中的四聚体稳定性增强。我们证明了 TTR 配体的 MD 辅助设计构成了发现分子的新途径，这些分子与M-23一样，有可能成为治疗 ATTR 的高效药物。
• Tricyclic derivatives and their pharmaceutical use and compositions
  申请人：CEPHALON, INC.

  公开号：EP2792678A1

  公开（公告）日：2014-10-22

  This application relates to tricyclic compounds of Formula I: including all stereoisomeric forms, all mixtures of stereoisomeric forms, and salts of these compounds. This application also relates to compositions comprising compounds of Formula I, stereoisomeric forms, all mixtures of stereoisomeric forms, and salts thereof and uses therefor.

  本申请涉及式 I 的三环化合物： 包括所有立体异构体形式、立体异构体形式的所有混合物以及这些化合物的盐。本申请还涉及由式 I 化合物、立体异构体、立体异构体的所有混合物及其盐组成的组合物及其用途。
• Design, Synthesis and Discovery of Picomolar Selective α4β2 Nicotinic Acetylcholine Receptor Ligands
  作者：Venkata M. Yenugonda、Yingxian Xiao、Edward D. Levin、Amir H. Rezvani、Thao Tran、Nour Al-Muhtasib、Niaz Sahibzada、Teresa Xie、Corinne Wells、Susan Slade、Joshua E. Johnson、Sivanesan Dakshanamurthy、Hye-Sik Kong、York Tomita、Yong Liu、Mikell Paige、Kenneth J. Kellar、Milton L. Brown

  DOI：10.1021/jm4008455

  日期：2013.11.14

  Developing novel and selective compounds that desensitize alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs) could provide new effective treatments for nicotine addiction, as well as other disorders. Here we report a new class of nAChR ligands that display high selectivity and picomolar binding affinity for alpha 4 beta 2 nicotinic receptors. The novel compounds have K-i; values in the range of 0.031-0.26 nM and properties that should make them good candidates as drugs acting in the CNS. The selected lead compound 1 (VMY-2-95) binds with high affinity and potently desensitizes alpha 4 beta 2 nAChRs. At a dose of 3 mg/kg, compound 1 significantly reduced rat nicotine self-administration. The overall results support further characterizations of compound 1 and its analogues in preclinical models of nicotine addiction and perhaps other disorders involving nAChRs.
• PITB: A high affinity transthyretin aggregation inhibitor with optimal pharmacokinetic properties
  作者：Francisca Pinheiro、Nathalia Varejão、Adrià Sánchez-Morales、Filipa Bezerra、Susanna Navarro、Adrián Velázquez-Campoy、Félix Busqué、Maria Rosário Almeida、Ramon Alibés、David Reverter、Irantzu Pallarès、Salvador Ventura

  DOI：10.1016/j.ejmech.2023.115837

  日期：2023.12
• TRICYCLIC DERIVATIVES AND THEIR PHARMACEUTICAL USE AND COMPOSITIONS
  申请人：Cephalon, Inc.

  公开号：EP2516445B1

  公开（公告）日：2015-03-11