3-[[[5-(4-Methylsulfonylphenyl)-3-pyridinyl]amino]methyl]phenol | 875147-71-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-[[[5-(4-Methylsulfonylphenyl)-3-pyridinyl]amino]methyl]phenol
• 英文别名: 3-[[[5-(4-methylsulfonylphenyl)pyridin-3-yl]amino]methyl]phenol
• CAS: 875147-71-0
• 化学式: C₁₉H₁₈N₂O₃S
• 分子量: 354.4
• InChiKey: IBOVRMYKUOUGQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  5

文献信息

• Pyrazines and Pyridines and Derivatives Thereof as Therapeutic Compounds
  申请人：Springer Joy Caroline

  公开号：US20080015191A1

  公开（公告）日：2008-01-17

  The present invention pertains to certain pyrazines and pyridines, and derivatives thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formulae: (I) wherein: Q is independently —N═ or —CH═; one of R P2 and R P3 is independently a group of the formula -J 1 -L 1 -Z; wherein: if Q is —N═, then -J 1 -L 1 -Z is independently: —NH-Z; —O-Z; or S-Z; if Q is —CH═, then -J 1 -L 1 -Z is independently: —NH—(CH 2 ) n -Z, wherein n is independently 0 or 1; —O-Z; or —S-Z; Z is independently: C 6-14 carboaryl, C 5-14 heteroaryl, C 3-12 carbocyclic, C 3-12 heterocyclic; and is independently unsubstituted or substituted; the other of R P2 and R P3 is independently —H, —NHR N1 , or —NHC(═O)R N2 ; wherein: R N1 , if present, is independently —H or aliphatic saturated C 1-4 alkyl; R N2 , if present, is independently —H or aliphatic saturated C 1-4 alkyl; one of R P5 and R P6 is independently a group of the formula —W—Y; wherein: W is independently: a covalent bond; —NR N4 —, —O—, —S—, —C(═O)—, —CH 2 —; —NR N4 —CH 2 —, —O—CH 2 —, —S—CH 2 —, —C(═O)—CH 2 —, —(CH 2 ) 2 —; —CH 2 —NR N4 —, —CH 2 —O—, —CH 2 —S—, or —CH 2 —C(═O)—; wherein R N4 , if present, is independently —H or aliphatic saturated C 1-4 alkyl; Y is independently: C 6-14 carboaryl, C 5-14 heteroaryl, C 3-12 carbocyclic, C 3-12 heterocyclic; and is independently unsubstituted or substituted; the other of R P5 and R P6 is independently —H; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, e.g., both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

  本发明涉及某些吡嗪和吡啶以及它们的衍生物，其中，它们在抑制RAF（例如B-RAF）活性、抑制细胞增殖、治疗癌症等方面发挥作用，更具体地涉及以下式的化合物：（I）其中：Q独立地为—N═或—CH═；RP2和RP3中的一个独立地为以下式的基团-J1-L1-Z；其中：如果Q为—N═，则-J1-L1-Z独立地为：—NH-Z；—O-Z；或S-Z；如果Q为—CH═，则-J1-L1-Z独立地为：—NH—（CH2）n-Z，其中n独立地为0或1；—O-Z；或—S-Z；Z独立地为：C6-14碳芳基，C5-14杂芳基，C3-12碳环烷基，C3-12杂环烷基；并且独立地未取代或取代；RP2和RP3中的另一个独立地为—H，—NHRN1或—NHC(═O)RN2；其中：如果存在RN1，则独立地为—H或脂肪饱和的C1-4烷基；如果存在RN2，则独立地为—H或脂肪饱和的C1-4烷基；RP5和RP6中的一个独立地为以下式的基团—W—Y；其中：W独立地为：共价键；—NRN4—，—O—，—S—，—C(═O)—，—CH2—；—NRN4—CH2—，—O—CH2—，—S—CH2—，—C(═O)—CH2—，—(CH2)2—；—CH2—NRN4—，—CH2—O—，—CH2—S—，或—CH2—C(═O)—；其中如果存在RN4，则独立地为—H或脂肪饱和的C1-4烷基；Y独立地为：C6-14碳芳基，C5-14杂芳基，C3-12碳环烷基，C3-12杂环烷基；并且独立地未取代或取代；RP5和RP6中的另一个独立地为—H；以及其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、N-氧化物、化学保护形式和前药。本发明还涉及包括这些化合物的药物组合物，以及使用这些化合物和组合物，例如在体内和体外，来抑制RAF（例如B-RAF）活性，抑制受体酪氨酸激酶（RTK）活性，抑制细胞增殖，并用于治疗因RAF、RTK等的抑制而得到改善的疾病和病况，如癌症（例如结直肠癌、黑色素瘤）等增生性疾病。
• Pyridinylamines
  申请人：Eickhoff Jan Elke

  公开号：US20090196912A1

  公开（公告）日：2009-08-06

  Described are pyridinylamines and pharmaceutically acceptable salts thereof, the use of these pyridinylamines for the prophylaxis and/or treatment of various diseases such as infectious diseases, including opportunistic infections, prion diseases immunological diseases, autoimmune diseases, bipolar and clinical disorders, cardiovascular diseases, cell proliferative diseases, diabetes, inflammation, transplant rejections, erectile dysfunction, neurodegenerative diseases and stroke, as well as pharmaceutical compositions containing at least one pyridinylamine and/or pharmaceutically acceptable salts thereof. Furthermore, reaction procedures for the synthesis of the pyridinylamines are disclosed.

  本文描述了吡啶基胺及其药用盐，以及这些吡啶基胺在预防和/或治疗各种疾病方面的用途，包括传染病，包括机会性感染，朊病，免疫性疾病，自身免疫性疾病，双相和临床障碍，心血管疾病，细胞增殖性疾病，糖尿病，炎症，移植排斥，勃起功能障碍，神经退行性疾病和中风，以及至少含有一种吡啶基胺和/或其药用盐的制药组合物。此外，还公开了合成吡啶基胺的反应程序。
• Compositions and methods to improve the therapeutic benefit of indirubin and analogs thereof, including meisoindigo
  申请人：Brown Dennis M.

  公开号：US10383847B2

  公开（公告）日：2019-08-20

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutically active agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to therapeutically active agents selected from the group consisting of: (i) indirubin; (ii) an analog of indirubin; (iii) a derivative of indirubin or of an analog of indirubin; and (iv) a pharmaceutical composition comprising indirubin, an analog of indirubin, or a derivative of indirubin or of an analog of indirubin, especially meisoindigo. In particular, the therapeutically active agents selected from the group consisting of: (i) indirubin; (ii) an analog of indirubin; (iii) a derivative of indirubin or of an analog of indirubin; and (iv) a pharmaceutical composition comprising indirubin, an analog of indirubin, or a derivative of indirubin or of an analog of indirubin, especially meisoindigo, are effective Nek9 inhibitors. The active agent, such as meisoindigo, can act as a Nek9 inhibitor. The active agent can be used together with Nek9 inhibitors or agents that inhibit the expression of Nek9.

  本发明描述了通过提高单一疗法的疗效或减少副作用来提高以前受次优治疗性能限制的治疗活性制剂的疗效的方法和组合物。这种方法和组合物特别适用于选自以下组别的治疗活性剂：(i) 靛红素；(ii) 靛红素的类似物；(iii) 靛红素或靛红素类似物的衍生物；(iv) 包含靛红素、靛红素类似物或靛红素或靛红素类似物衍生物的药物组合物，特别是甲异靛。特别是，选自以下组别的治疗活性剂是有效的 Nek9 抑制剂：(i) 靛红素；(ii) 靛红素的类似物；(iii) 靛红素的衍生物或靛红素的类似物；以及 (iv) 由靛红素、靛红素的类似物或靛红素的衍生物或靛红素的类似物，特别是 meisoindigo 组成的药物组合物。活性剂，如 meisoindigo，可作为 Nek9 抑制剂。活性剂可与 Nek9 抑制剂或抑制 Nek9 表达的制剂一起使用。
• PYRIDINYLAMINES
  申请人：GPC Biotech AG

  公开号：EP1789393A2

  公开（公告）日：2007-05-30
• PYRAZINES AND PYRIDINES AND DERIVATIVES THEREOF AS THERAPEUTIC COMPOUNDS
  申请人：The Wellcome Trust Limited

  公开号：EP1831184B1

  公开（公告）日：2011-02-09