(3-hydroxy-5-(1H-indol-4-yl)phenyl)(pyridin-3-yl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3-hydroxy-5-(1H-indol-4-yl)phenyl)(pyridin-3-yl)methanone
• 英文别名: [3-hydroxy-5-(1H-indol-4-yl)-phenyl]-pyridin-3-yl-methanone；[3-hydroxy-5-(1H-indol-4-yl)phenyl]-pyridin-3-ylmethanone
• 化学式: C₂₀H₁₄N₂O₂
• 分子量: 314.343
• InChiKey: KCIVNSHCPGXDSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1,3-二溴-5-硝基苯 在 potassium phosphate 、 正丁基锂 、 2’-(dimethylamino)-2-biphenylylpalladium(II) chloride dinorbornylphosphine complex 、 二甲基硫 、 四丁基溴化铵 、 氧气 、 三氟乙酸 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 乙醚 、 正己烷 、 二氯甲烷 、 水 、 1,1,3,3-四甲基脲 为溶剂， 反应 4.83h， 生成 (3-hydroxy-5-(1H-indol-4-yl)phenyl)(pyridin-3-yl)methanone
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of N-(3-(1H-Indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a Potent Antimitotic Agent

  摘要：

  The synthesis and optimization of a series of orally bioavailable 1-(1H-indol-4-yl)-3,5-disubstituted benzene analogues as antimitotic agents are described A functionalized dibromobenzene intermediate was used as a key scaffold, which when modified by sequential Suzuki coupling and Buchwald-Hartwig amination provided a flexible entry to 1,3,5-trisubstituted phenyl compounds A 1H-indol-4-yl moiety at the 1-position was determined to be a critical feature for optimal potency The compounds have been shown to induce cell cycle arrest at the G2/M phase and demonstrate efficacy in both cell viability and cell proliferation assays The primary site of action for these agents is revealed by their colchicine competitive inhibition of tubulin polymerization, and a computational model has been developed for the association of these compounds to tubulin An optimized lead LP-261 significantly inhibits growth of a human non-small-cell lung tumor (NCI-H522) in a mouse xenograft model

  DOI：

  10.1021/jm100659v

文献信息

• Anti-cancer agents and uses thereof
  申请人：Kelly Martha

  公开号：US20060270686A1

  公开（公告）日：2006-11-30

  The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A 1 is N or CR 1 ; A 3 is N or CR 3 ; A 5 is N or CR 5 ; R 1 , R 3 —R 6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, non-small cell lung and colon.

  本发明涉及新化合物及其盐，它们的合成以及它们作为抗癌剂的用途。这些化合物包括式I的化合物： 和其溶剂化物、水合物和药用可接受盐，其中A 1 为N或CR 1 ；A 3 为N或CR 3 ；A 5 为N或CR 5 ；R 1 ，R 3 —R 6 和L在说明书中有定义；n为0或1；X为在环部分具有6-10个碳的可选择取代芳基，在环部分具有1-3个氮原子的可选择取代的6元杂芳基，在环部分具有0-4个氮原子且可选择具有1个硫原子或1个氧原子的可选择取代的5元杂芳基，或者在其中6元环与5元环或6元环融合的可选择取代的杂芳基，其中在每种情况下1、2、3或4个环原子是从氮、氧和硫中独立选择的杂原子。它们对广泛范围的癌症，特别是白血病、非小细胞肺癌和结肠癌有效。
• ANTI-CANCER AGENTS AND USES THEREOF
  申请人：KELLY Martha

  公开号：US20090093479A1

  公开（公告）日：2009-04-09

  The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A 1 is N or CR 1 ; A 3 is N or CR 3 ; A 5 is N or CR 5 ; R 1 , R 3 -R 6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, non-small cell lung and colon.

  本发明涉及新化合物及其盐，它们的合成方法以及它们作为抗癌剂的用途。这些化合物包括式I的化合物及其溶剂化物、水化物和药学上可接受的盐，其中A1为N或CR1；A3为N或CR3；A5为N或CR5；R1、R3-R6和L在规范中有定义；n为0或1；X是一个具有6-10个碳原子的环部分可选取代的芳基基团，一个具有1-3个氮原子的环部分可选取代的6元杂芳基基团，一个具有0-4个氮原子并可选地在环部分含有1个硫原子或1个氧原子的5元杂芳基基团，或者一个6元环与一个5元环或6元环融合的可选取代的杂芳基基团，在每种情况下，1、2、3或4个环原子是独立选择的氮、氧和硫杂原子。它们对广泛的癌症，尤其是白血病、非小细胞肺癌和结肠癌都有良好的治疗效果。
• WO2008/8059
  申请人：——

  公开号：——

  公开（公告）日：——
• US7504401B2
  申请人：——

  公开号：US7504401B2

  公开（公告）日：2009-03-17
• [EN] ANTI-CANCER AGENTS ANS USES THEREOF<br/>[FR] AGENTS ANTI-CANCER ET LEURS UTILISATIONS
  申请人：LOCUS PHARMACEUTICALS INC

  公开号：WO2008008059A1

  公开（公告）日：2008-01-17

  [EN] The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula (I): and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A¹ is N or CR¹; A³ is N or CR³; A⁵ is N or CR⁵; R¹, R³ R⁶ and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6- 10 carbons in the ring portion, an optionally-substituted 6- membered heteroaryl group having 1- 3 nitrogen atoms in the ring portion, an optionally-substituted 5- membered heteroaryl group having 0- 4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6- membered ring is fused either to a 5- membered ring or to a 6- membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, prostate, non-small cell lung and colon. They are additionally useful in the treatment of proliferative retinopathies such as diabetic neuropathy and macular degeneration.
  [FR] La présente invention concerne le domaine des nouveaux composés et de leurs sels, leurs synthèses et leur utilisation comme agents anti-cancer. Les composés comprennent des composés représentés par la formule (I) : et des solvates, des hydrates et des sels pharmaceutiquement acceptables de ces composés, où A¹ est N ou CR¹ ; A³ est N ou CR³ ; A⁵ est N ou CR⁵ ; R¹, R³, R⁶ et L sont définis dans la description ; n est 0 ou 1 ; et X est un groupe aryle facultativement substitué, ayant 6-10 carbones dans la partie cyclique, un groupe hétéroaryle à 6 chaînons, facultativement substitué, ayant 1-3 atomes d'azote dans la partie cyclique, un groupe hétéroaryle à 5 chaînons facultativement substitué, ayant 0-4 atomes d'azote dans la partie cyclique et ayant facultativement 1 atome de soufre ou 1 atome d'oxygène dans la partie cyclique, ou un groupe hétéroaryle facultativement substitué dans lequel un cycle à 6 chaînons est fusionné soit à un cycle à 5 chaînons, soit à un cycle à 6 chaînons, où, dans chaque cas, 1, 2, 3 ou 4 atomes de cycle sont des hétéroatomes indépendamment choisis parmi l'azote, l'oxygène et le soufre. Ils sont efficaces contre plusieurs types de cancers, notamment la leucémie, le cancer de la prostate, le cancer du poumon non à petites cellules et le cancer du côlon. Ils sont en outre utiles dans le traitement des rétinopathies prolifératives, telles que la neuropathie diabétique et la dégénérescence maculaire.