4-(3H-imidazo[4,5-c]pyridin-2-yl)-fluoren-9-one | 915138-72-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 4-(3H-imidazo[4,5-c]pyridin-2-yl)-fluoren-9-one
• 英文别名: 4-(1h-Imidazo[4,5-C]pyridin-2-Yl)fluoren-9-One；4-(3H-imidazo[4,5-c]pyridin-2-yl)fluoren-9-one
• CAS: 915138-72-6
• 化学式: C₁₉H₁₁N₃O
• 分子量: 297.316
• InChiKey: MAPDUHHTXROZLC-UHFFFAOYSA-N

物化性质

• 沸点：
  612.9±57.0 °C(Predicted)
• 密度：
  1.422±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3H-imidazo[4,5-c]pyridin-2-yl)-fluoren-9-one 在 sodium tetrahydroborate 、 水 作用下， 以 甲醇 为溶剂， 反应 0.25h， 生成 4-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-fluoren-9(R,S)-ol
  参考文献：
  名称：

  Novel Fluorene Derivatives, Composition Containing Said Derivatives and the Use Thereof

  摘要：

  这项发明涉及4-(苯并咪唑-2-基)芴和4-(氮杂苯并咪唑-2-基)芴的衍生物，涉及包含这些衍生物的药物组合物，以及涉及治疗与Hsp90蛋白活性相关的疾病的方法，包括给予这些衍生物。

  公开号：

  US20080153837A1
• 作为产物：
  描述：

  3,4-二氨基吡啶 、 9-芴酮-4-甲酰氯 在 三乙胺 、 盐酸 、 三氟乙酸 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 4.33h， 以100%的产率得到4-(3H-imidazo[4,5-c]pyridin-2-yl)-fluoren-9-one
  参考文献：
  名称：

  Tricyclic Series of Heat Shock Protein 90 (Hsp90) Inhibitors Part I: Discovery of Tricyclic Imidazo[4,5-c]pyridines as Potent Inhibitors of the Hsp90 Molecular Chaperone

  摘要：

  A novel class of heat shock protein 90 (Hsp90) inhibitors was developed after a low throughput screen (LTS) of a focused library containing approximately 21K compounds selected by virtual screening. The initial [1-{3-H-imidazo[4,5-c]pyridin-2-yl}-3,4- dihydro-2H-pyrido[2,1-a]isoindole-6-one] (1) compound showed moderate activity (IC50 = 7.6 mu M on Hsp82, the yeast homologue of Hsp90). A high-resolution X-ray structure shows that compound 1 binds into an "induced" hydrophobic pocket, 10-15 angstrom away from the ATP/resorcinol binding site. Iterative cycles of structure-based drug design (SBDD) and chemical synthesis led to the design and preparation of analogues with improved affinity. These optimized molecules make productive interactions within the ATP binding site as reported by other Hsp90 inhibitors. This resulted in compound 8, which is a highly potent inhibitor in biochemical and cellular assays (K-d = 0.35 nM on Hsp90; IC50 = 30 nM on SKBr3 mammary carcinoma cells) and in an in vivo leukemia model.

  DOI：

  10.1021/jm200784m
• 作为试剂：
  描述：

  盐酸羟胺 、 sodium acetate 、 4-(3H-imidazo[4,5-c]pyridin-2-yl)-fluoren-9-one 在 水 、 oximes 、 4-(3H-imidazo[4,5-c]pyridin-2-yl)-fluoren-9-one 作用下， 以 乙醇 、 水 为溶剂， 反应 16.0h， 以In this way we obtain 18.6 g of equimolecular mixture of the Z and E oximes of 4-(3H-imidazo[4,5-c]pyridin-2-yl)-fluoren-9-one的产率得到4-(3H-imidazo[4,5-c]pyridin-2-yl)-fluoren-9-one oxime
  参考文献：
  名称：

  Fluorene derivatives, composition containing said derivatives and the use thereof

  摘要：

  本发明涉及4-(苯并咪唑-2-基)芴和4-(氮杂苯并咪唑-2-基)芴的衍生物，包括这些衍生物的制药组合物，以及治疗与Hsp90蛋白活性相关的疾病的方法，包括给予这些衍生物。

  公开号：

  US07674795B2

文献信息

• NOUVEAUX DERIVES DU FLUORENE, COMPOSITIONS LES CONTENANT ET UTILISATION
  申请人：Aventis Pharma S.A.

  公开号：EP1888579A2

  公开（公告）日：2008-02-20
• US7674795B2
  申请人：——

  公开号：US7674795B2

  公开（公告）日：2010-03-09
• [EN] NOVEL FLUORENE DERIVATIVES, COMPOSITION CONTAINING SAID DERIVATIVES AND THE USE THEREOF<br/>[FR] NOUVEAUX DERIVES DU FLUORENE, COMPOSITIONS LES CONTENANT ET UTILISATION
  申请人：AVENTIS PHARMA SA

  公开号：WO2006123061A2

  公开（公告）日：2006-11-23

  [EN] The invention relates to novel products of formula (1), wherein A1, A2, A3 and A4 are CRa or N, R1 and R1' are such that one represents H, Hal, C1C3-alkyl, C1C3-alkoxy, alkyl-OH, CF3, cyano, carboxy or carboxamido and the other represents Hal; CF3 ; OH ; SH; nitro; amino ; NH-OH ; NH-CO-H ; NH-CO-OH, NH-CO-O alkyl , NH-CO-NH2 ; carboxy ; CN ; CO-NH2 ; X-(CH2)m-alkyl; X-(CH2)m-cycloalkyl ; X-(CH2)m-heterocycloalkyl ; X-(CH2)m-aryl or X-(CH2)m-heteroaryl with X = simple bond, CH2, CH=CH, CH2-O, CH2-NH, CH2-C(O), CH2-C(O)-O, CH2-C(O)-NH, CH2-NH-(CO), CH2-NH-S(O), CH2-NH-S(O)2, O, S, NH, O-C(O), C(O)-NH, -NH-C(O), -NH-C(O)-C(O)-, -NH-C(O)-NH-, ; NH-CS, NH-S(O) or NH-S(O)2 ; m = 0, 1 or 2, or R1 and R'1 form with C to which they are bound either a radical =O ; =S ; =N-OH ; =N-NH2 ; =N-NH-CO-NH2, =CH-OH ; =Y1-(CH2)m-aryl or =Y1-(CH2)m heteroaryl, wherein Y1 represents CH, CH-CO-, CH-CO-NH, N, N-O or N-NH-, where m = 0, 1 or 2, or a cycle, R2 et R'2 represent H, halogen, CF3, nitro, cyano, alkyl, hydroxy, mercapto, amino, alkylamino, dialkylamino, alkoxy, alkylthio, free or esterified carboxy, carboxamide, CO-NH(alkyl) et CO N(alkyl)2, p= 1 à 3 et p'= 1 à 4; Ra represents H ; halogen ; CF3 ; hydroxy ; mercapto ; nitro ; amino ; NH-OH ; NH-CO-H ; NH-CO-NH2 ; carboxy ; CN ; CO-NH2 ; Y-(CH2)n-alkyl ; Y-(CH2)n-cycloalkyl, Y-(CH2)n-heterocycloalkyl, Y-(CH2)n-aryl or Y-(CH2)n-heteroaryl, with Y = O, S, NH, O-C(O), C(O)-NH, NH-C(O), NH-S(O) or NH-S(O)2, with n = 0, 1, 2 or 3, wherein all alkyl, alkoxy, alkylthio, cycloalkyl, heterocycloalkyl, aryl and heteroaryl radicals are optionally substituted and all products in any forms are tautomers and isomers and the salts, which are used in the form of drugs.
  [FR] L'invention concerne les nouveaux produits de formule (I) : dans laquelle A1, A2, A3 et A4 représentent CRa ou N ; R1 et R1' sont tels que l'un représente H, Hal, C1C3-alkyle, C1C3-alcoxy, alkyl-OH, CF3, cyano, carboxy ou carboxamido ; et l'autre représente H ; Hal; CF3 ; OH ; SH; nitro ; amino ; NH-OH ; NH-CO-H ; NH-CO-OH, NH-CO-Oalkyle , NH-CO-NH2 ; carboxy ; CN ; CO-NH2 ; X-(CH2)m-alkyle; X-(CH2)m-cycloalkyle ; X-(CH2)m-hétérocycloalkyle ; X-(CH2)m-aryle ou X-(CH2)m-hétéroaryle avec X = simple liaison, CH2, CH=CH, CH2-O, CH2-NH, CH2-C(O), CH2-C(O)-O, CH2-C(O)-NH, CH2-NH-(CO), CH2-NH-S(O), CH2-NH-S(O)2, O, S, NH, O-C(O), C(O)-NH, -NH-C(O), -NH-C(O)-C(O)-, -NH-C(O)-NH-, ; NH-CS, NH-S(O) ou NH-S(O)2 ; m = 0, 1 ou 2 ; soit R1 et R'1 forment avec C auquel ils sont liés soit un radical =O ; =S ; =N-OH ; =N-NH2 ; =N-NH-CO-NH2, =CH-OH ; =Y1-(CH2)m-aryle ou =Y1-(CH2)m -hétéroaryle, avec Y1 représente CH, CH-CO-, CH-CO-NH, N, N-O ou N-NH-, avec m = 0, 1 ou 2 , soit un cycle, R2 et R'2, représente H, halogène, CF3, nitro, cyano, alkyle, hydroxy, mercapto, amino, alkylamino, dialkylamino, alkoxy, alkylthio, carboxy libre ou estérifié, carboxamide, CO-NH(alkyl) et CO N(alkyl)2, p= 1 à 3 et p'= 1 à 4 ; Ra représente H ; halogène ; CF3 ; hydroxy ; mercapto ; nitro ; amino ; NH-OH ; NH-CO-H ; NH-CO-NH2 ; carboxy ; CN ; CO-NH2 ; Y-(CH2)n-alkyle ; Y-(CH2)n-cycloalkyle, Y-(CH2)n-hétérocycloalkyle, Y-(CH2)n-aryle ou Y-(CH2)n-hétéroaryle, avec Y = O, S, NH, O-C(O), C(O)-NH, NH-C(O), NH-S(O) ou NH-S(O)2, avec n = 0, 1, 2 ou 3, tous les radicaux alkyle, alcoxy, alkylthio, cycloalkyle, hétérocycloalkyle, aryle et hétéroaryle étant éventuellement substitués, ces produits étant sous toutes les formes tautomères et isomères et les sels, à titre de médicaments.
• Novel Fluorene Derivatives, Composition Containing Said Derivatives and the Use Thereof
  申请人：MAILLIET Patrick

  公开号：US20080153837A1

  公开（公告）日：2008-06-26

  This invention relates to derivatives of 4-(benzimidazol-2-yl)fluorene and 4-(azabenzimidazol-2-yl)fluorene, to pharmaceutical compositions comprising such derivatives, and to methods of treatment of disorders related to Hsp90 protein activity, comprising administering such derivatives.

  这项发明涉及4-(苯并咪唑-2-基)芴和4-(氮杂苯并咪唑-2-基)芴的衍生物，涉及包含这些衍生物的药物组合物，以及涉及治疗与Hsp90蛋白活性相关的疾病的方法，包括给予这些衍生物。
• Tricyclic Series of Heat Shock Protein 90 (Hsp90) Inhibitors Part I: Discovery of Tricyclic Imidazo[4,5-<i>c</i>]pyridines as Potent Inhibitors of the Hsp90 Molecular Chaperone
  作者：François Vallée、Chantal Carrez、Fabienne Pilorge、Alain Dupuy、Annick Parent、Luc Bertin、Fabienne Thompson、Paul Ferrari、Florence Fassy、Annabelle Lamberton、Anne Thomas、Rosalia Arrebola、Stéphane Guerif、Alexandre Rohaut、Victor Certal、Jean-Marie Ruxer、Cécile Delorme、Alain Jouanen、Jacques Dumas、Claudine Grépin、Cécile Combeau、Hélène Goulaouic、Norbert Dereu、Vincent Mikol、Patrick Mailliet、Hervé Minoux

  DOI：10.1021/jm200784m

  日期：2011.10.27

  A novel class of heat shock protein 90 (Hsp90) inhibitors was developed after a low throughput screen (LTS) of a focused library containing approximately 21K compounds selected by virtual screening. The initial [1-3-H-imidazo[4,5-c]pyridin-2-yl}-3,4- dihydro-2H-pyrido[2,1-a]isoindole-6-one] (1) compound showed moderate activity (IC50 = 7.6 mu M on Hsp82, the yeast homologue of Hsp90). A high-resolution X-ray structure shows that compound 1 binds into an "induced" hydrophobic pocket, 10-15 angstrom away from the ATP/resorcinol binding site. Iterative cycles of structure-based drug design (SBDD) and chemical synthesis led to the design and preparation of analogues with improved affinity. These optimized molecules make productive interactions within the ATP binding site as reported by other Hsp90 inhibitors. This resulted in compound 8, which is a highly potent inhibitor in biochemical and cellular assays (K-d = 0.35 nM on Hsp90; IC50 = 30 nM on SKBr3 mammary carcinoma cells) and in an in vivo leukemia model.