(5,6-二甲氧基吡啶-2-基)甲醇 | 59081-38-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (5,6-二甲氧基吡啶-2-基)甲醇
• 英文名称: (5,6-dimethoxypyridin-2-yl)methanol
• CAS: 59081-38-8
• 化学式: C₈H₁₁NO₃
• mdl: MFCD11857655
• 分子量: 169.18
• InChiKey: FASQBELOVBMULV-UHFFFAOYSA-N

物化性质

• 熔点：
  34-35 °C
• 沸点：
  266.4±35.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.375
• 拓扑面积：
  51.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• WGK Germany：
  3
• 危险标志：
  GHS07
• 危险性描述：
  H302
• 海关编码：
  2933399090
• 危险性防范说明：
  P280,P305+P351+P338

反应信息

• 作为反应物：
  描述：

  (5,6-二甲氧基吡啶-2-基)甲醇 在 正丁基锂 、 四溴化碳 、 三苯基膦 作用下， 以 乙醚 、 二氯甲烷 、 Petroleum ether 为溶剂， 反应 3.83h， 生成 tert-butyl-[(2E,4R,5R,6E,8E,11E)-13-(5,6-dimethoxypyridin-2-yl)-3,5,7,11-tetramethyltrideca-2,6,8,11-tetraen-4-yl]oxy-dimethylsilane
  参考文献：
  名称：

  Piericidin A1 和 B1 以及关键类似物的全合成

  摘要：

  详细介绍了 piericidin A1 和 B1 的全合成及其对一系列关键类似物制备的扩展，包括 ent-piericidin A1 (ent-1)、4'-deshydroxypiericidin A1 (58)、5'-desmethylpiericidin A1 (73)、4'-deshydroxy-5'-desmethylpiericidin A1 (75) 和相应的类似物 51、59、76 和 77，带有简化的法呢基侧链。对这些关键类似物的评估以及从它们进一步功能化衍生的那些类似物，允许对关键结构特征进行扫描，从而提供对在吡啶基核和侧链中发现的取代基的作用的新见解。吡啶基核与完全精心设计的侧链的战略性后期杂苄基斯蒂勒交叉偶联反应允许容易地获得类似物，其中分子的每一半都可以被系统地和发散地修饰。吡啶基核通过 N-磺酰基-1-氮杂丁二烯的​​逆电子需求 Diels-Alder 反应组装而

  DOI：

  10.1021/ja0632862
• 作为产物：
  描述：

  ethyl 5,5,6,6-tetramethoxy-1-(methylsulfonyl)-1,4,5,6-tetrahydropyridine-2-carboxylate 在 三氟化硼乙醚 、 二异丁基氢化铝 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 1.0h， 生成 (5,6-二甲氧基吡啶-2-基)甲醇
  参考文献：
  名称：

  Piericidin A1 和 B1 以及关键类似物的全合成

  摘要：

  详细介绍了 piericidin A1 和 B1 的全合成及其对一系列关键类似物制备的扩展，包括 ent-piericidin A1 (ent-1)、4'-deshydroxypiericidin A1 (58)、5'-desmethylpiericidin A1 (73)、4'-deshydroxy-5'-desmethylpiericidin A1 (75) 和相应的类似物 51、59、76 和 77，带有简化的法呢基侧链。对这些关键类似物的评估以及从它们进一步功能化衍生的那些类似物，允许对关键结构特征进行扫描，从而提供对在吡啶基核和侧链中发现的取代基的作用的新见解。吡啶基核与完全精心设计的侧链的战略性后期杂苄基斯蒂勒交叉偶联反应允许容易地获得类似物，其中分子的每一半都可以被系统地和发散地修饰。吡啶基核通过 N-磺酰基-1-氮杂丁二烯的​​逆电子需求 Diels-Alder 反应组装而

  DOI：

  10.1021/ja0632862

文献信息

• [EN] TRICYCLIC PIPERIDINE COMPOUNDS<br/>[FR] COMPOSÉS PIPÉRIDINIQUES TRICYCLIQUES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2016177690A1

  公开（公告）日：2016-11-10

  The present invention relates to compounds of the formula (I) wherein R1a, R1b, R2, R3, (R4)n and ring (A) are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), to methods for the preparation of such compounds of formula (I), and especially to their use as TPH modulators.

  本发明涉及式(I)的化合物，其中R1a、R1b、R2、R3、(R4)n和环(A)如描述中所述，其制备方法，其药学上可接受的盐，以及作为药物的用途，含有一个或多个式(I)化合物的药物组合物，制备这种式(I)化合物的方法，特别是作为TPH调节剂的用途。
• [EN] SUBSTITUTED THIADIAZOLYL DERIVATIVES AS DNA POLYMERASE THETA INHIBITORS<br/>[FR] DÉRIVÉS SUBSTITUÉS DE THIADIAZOLYLE COMME INHIBITEURS DE L'ADN POLYMÉRASE THÊTA
  申请人：IDEAYA BIOSCIENCES INC

  公开号：WO2022118210A1

  公开（公告）日：2022-06-09

  Disclosed herein are certain thiadiazolyl derivatives of Formula (I), (II), (III), or (IV): (I), (II), (III), (IV) that inhibit DNA Polymerase Theta (Polθ) activity, in particular inhibit Polθ activity by inhibiting ATP dependent helicase domain activity of Polθ. Also, disclosed are pharmaceutical compositions comprising such compounds and methods of treating and/or preventing diseases treatable by inhibition of Polθ such as cancer, including homologous recombination (HR) deficient cancers.

  本文披露了某些Formula (I), (II), (III), 或 (IV)的噻二唑衍生物：(I), (II), (III), (IV)，它们抑制DNA聚合酶Theta (Polθ)的活性，特别是通过抑制Polθ的ATP依赖的解旋酶结构域活性来抑制Polθ的活性。此外，还披露了包含这些化合物的药物组合物以及治疗和/或预防通过抑制Polθ可治疗的疾病的方法，例如癌症，包括同源重组 (HR) 缺陷癌症。
• <i>N</i>-(2-Benzoylphenyl)-<scp>l</scp>-tyrosine PPARγ Agonists. 2. Structure−Activity Relationship and Optimization of the Phenyl Alkyl Ether Moiety
  作者：Jon L. Collins、Steven G. Blanchard、G. Evan Boswell、Paul S. Charifson、Jeff E. Cobb、Brad R. Henke、Emily A. Hull-Ryde、Wieslaw M. Kazmierski、Debra H. Lake、Lisa M. Leesnitzer、Jürgen Lehmann、James M. Lenhard、Lisa A. Orband-Miller、Yolanda Gray-Nunez、Derek J. Parks、Kelli D. Plunkett、Wei-Qin Tong

  DOI：10.1021/jm980413z

  日期：1998.12.1

  We previously reported the identification of (2S)-((2-benzoylphenyl)amino)-3-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}propanoic (2) (PPAR gamma pK(i) = 8.94, PPAR gamma, pEC(50) = 9.47) as a potent and selective PPAR gamma agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPAR gamma agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2-benzoylphenyl)amino)-3-4-[2-(5-methyl-2-pyridin-4-yloxazol-4-yl)ethoxy]phenyl}propionic acid (16) (PPAR gamma pK(i) = 8.85, PPAR gamma pEC(50) = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4-2-[5-methyl-2-(4-methylpiperazin-1-yl)thiazol-4-yl]ethoxy}pheynyl)propionic acid (24) (PPAR gamma pK(i) = 8.6, PPAR gamma pEC(50) = 8.89) provided two potent and selective PPAR gamma agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPAR gamma ligands (PPAR gamma pK(i)'s 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPAR gamma binding, functional activity, selectivity, and aqueous solubility.
• Ring-truncated deguelin derivatives as potent Hypoxia Inducible Factor-1α (HIF-1α) inhibitors
  作者：Ho Shin Kim、Mannkyu Hong、Su-Chan Lee、Ho-Young Lee、Young-Ger Suh、Dong-Chan Oh、Ji Hae Seo、Hoon Choi、Jun Yong Kim、Kyu-Won Kim、Jeong Hun Kim、Joohwan Kim、Young-Myeong Kim、So-Jung Park、Hyun-Ju Park、Jeewoo Lee

  DOI：10.1016/j.ejmech.2015.09.033

  日期：2015.11

  A series of fluorophenyl and pyridine analogues of 1 and 2 were synthesized as ring-truncated deguelin surrogates and evaluated for their HIF-1 alpha inhibition. Their structure-activity relationship was systematically investigated based on the variation of the linker B-region moiety. Among the inhibitors, compound 25 exhibited potent HIF-1 alpha inhibition in a dose-dependent manner and significant antitumor activity in H1299 with less toxicity than deguelin. It also inhibited in vitro hypoxia-mediated angiogenic processes in HRMECs. The docking study indicates that 25 occupied the C-terminal ATP-binding pocket of HSP90 in a similar mode as 1, which implies that the anticancer and antiangiogenic activities of 25 are derived from HIF-1 alpha destabilization by binding to the C-terminal ATP-binding site of hHSP90. (C) 2015 Elsevier Masson SAS. All rights reserved.
• TRICYCLIC PIPERIDINE COMPOUNDS
  申请人：Actelion Pharmaceuticals Ltd

  公开号：EP3292127A1

  公开（公告）日：2018-03-14