3-methyl-2,9-dihydro-2,4,9-triaza-fluoren-1-one | 98791-96-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 3-methyl-2,9-dihydro-2,4,9-triaza-fluoren-1-one
• 英文别名: 2-methyl-3H-pyrimido[5,4-b]indol-4(5H)-one；2-Methyl-3,5-dihydropyrimido[5,4-b]indol-4-one；2-methyl-3,5-dihydropyrimido[5,4-b]indol-4-one
• CAS: 98791-96-9
• 化学式: C₁₁H₉N₃O
• 分子量: 199.212
• InChiKey: IQHHQKIAYWULJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  57.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-methyl-2,9-dihydro-2,4,9-triaza-fluoren-1-one 在 2,3-二甲基苯胺 、 三氯氧磷 作用下， 反应 2.0h， 以53%的产率得到1-chloro-3-methyl-9H-2,4,9-triaza-fluorene
  参考文献：
  名称：

  Synthesis and some properties of 4-oxo-3,4-dihydro- and 2,4-dioxo-1,2,3,4-tetrahydropyrimido[5,4-b]indoles

  摘要：

  DOI：

  10.1007/bf00506067
• 作为产物：
  描述：

  3-[1-Dimethylamino-eth-(E)-ylideneamino]-1H-indole-2-carboxylic acid ethyl ester 在 氨 作用下， 以 乙醇 为溶剂， 反应 13.0h， 以76%的产率得到3-methyl-2,9-dihydro-2,4,9-triaza-fluoren-1-one
  参考文献：
  名称：

  Synthesis and some properties of 4-oxo-3,4-dihydro- and 2,4-dioxo-1,2,3,4-tetrahydropyrimido[5,4-b]indoles

  摘要：

  DOI：

  10.1007/bf00506067

文献信息

• [EN] PYRROLOPYRIMIDINE DERIVATIVES AS MODULATORS OF MULTI-DRUG RESISTANCE (MDR)<br/>[FR] DERIVES PYRROLOPYRIMIDINIQUES CONVENANT COMME MODULATEURS DE LA MULTIRESISTANCE AUX MEDICAMENTS
  申请人：XENOVA LTD

  公开号：WO2004111052A1

  公开（公告）日：2004-12-23

  A compound which is a pyrrolopyrimidine of formula (I) wherein R1 is selected from H, Cl-C6 alkyl which is unsubstituted or substituted, (CH2)nAr1, (CH2)pNR4R5, halogen and (CH2)pX; R2 is CH2)pArl; R3 is selected from H, Cl -C6 alkyl which is unsubstituted or substituted, (CH2)pZ and (CH2)pArl; P is an unsaturated 5, 6, or 7 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted; R4 and R5 which are the same or different are selected from H, Cl -C6 alkyl which is unsubstituted or substituted, (CH2)nC3-C10 cycloalkyl, (CH2)nAr1 , and (CH2)nOR6, or R4 and R5 together with the nitrogen atom to which they are attached, form a saturated five or six membered nitrogen containing heterocyclic ring which may contain one extra heteroatom selected from 0, N and S and which is unsubstituted or substituted; R6 is selected from H, Cl -C6 alkyl which is unsubstituted or substituted, C3-C10 cycloalkyl, (CH2)nOC1-C6alkyl which is unsubstituted or substituted, (CH2)nO(CH2)nAr1 , (CH2)nCO2C1-C6,alkyl which is unsubstituted or substituted and (CH2)nAr1; X is selected from CN, azide, (CH2)nNHSO2R6 and (CH2)nNHCOR6; Z is selected from CN, CO2R6 and CONR4R5; Ar1 is the same or different when more than one is present within a given substituent group and is an unsaturated C6-C10 membered carbocylic group or an unsaturated 5-11 membered heterocycle, either of which is unsubstituted or substituted; p is an integer of 1 to 6; n is the same or different when more than one is present within a given substituent group and is 0 or an integer of 1 to 6; with the proviso that the pyrrolepyrimidine compound of formula (I) is other than 1-(4-benzyl-piperazin-1-yl)-9H-2,4,9-triaza-fluorene; and the pharmaceutically acceptable salts thereof, have activity as inhibitors of MRP (multidrug resistant protein) and may thus be used to modulate multidrug resistance, for instance in potentiating the cytotoxicity of a chemotherapeutic agent.

  化合物是一种公式为（I）的吡咯吡嘧啶，其中R1从H、未取代或取代的Cl-C6烷基、（CH2）nAr1、（CH2）pNR4R5、卤素和（CH2）pX中选择；R2为（CH2）pArl；R3从H、未取代或取代的Cl-C6烷基、（CH2）pZ和（CH2）pArl中选择；P为未取代或取代的不饱和5、6或7成员碳环或杂环；R4和R5相同或不同，从H、未取代或取代的Cl-C6烷基、（CH2）nC3-C10环烷基、（CH2）nAr1和（CH2）nOR6中选择，或者R4和R5与它们连接的氮原子一起形成饱和的含氮五元或六元杂环，可能含有一个额外的杂原子，选择自O、N和S，未取代或取代；R6从H、未取代或取代的Cl-C6烷基、C3-C10环烷基、（CH2）nOC1-C6烷基、未取代或取代的（CH2）nO（CH2）nAr1、未取代或取代的（CH2）nCO2C1-C6烷基和（CH2）nAr1中选择；X从CN、叠氮、（CH2）nNHSO2R6和（CH2）nNHCOR6中选择；Z从CN、CO2R6和CONR4R5中选择；Ar1当多个存在于给定的取代基组内时相同或不同，为未取代或取代的不饱和C6-C10成员碳环或未取代或取代的不饱和5-11成员杂环；p为1至6的整数；n当多个存在于给定的取代基组内时相同或不同，为0或1至6的整数；但是，公式（I）的吡咯吡嘧啶化合物不是1-（4-苄基哌嗪-1-基）-9H-2,4,9-三氮杂萘；其药学上可接受的盐具有作为MRP（多药耐药蛋白）抑制剂的活性，因此可用于调节多药耐药性，例如在增强化疗药物的细胞毒性方面。
• Bicyclic and tricyclic pyrimidine tyrosine kinase inhibitors with antitubulin activity and methods of treating a patient
  申请人：Duquesne University of the Holy Spirit

  公开号：US10385064B2

  公开（公告）日：2019-08-20

  Bicyclic and tricyclic pyrimidine tyrosine kinase inhibitors with antitubulin activity are provided in the present invention. The compositions of the present invention possess dual activity in a single agent of potent vascular endothelial growth factor receptor inhibitory activity as well as antitubulin activity. Water soluble salts of these compositions are also described. Methods of treating a patient having cancer, macular degeneration, and arthritis with the compositions and salts thereof of the present invention are disclosed.

  本发明提供了具有抗微管蛋白活性的双环和三环嘧啶酪氨酸激酶抑制剂。本发明的组合物在单一制剂中具有双重活性，即强效血管内皮生长因子受体抑制活性和抗微管蛋白活性。本发明还描述了这些组合物的水溶性盐。公开了用本发明的组合物及其盐治疗癌症、黄斑变性和关节炎患者的方法。
• [EN] BICYCLIC AND TRICYCLIC PYRIMIDINE TYROSINE KINASE INHIBITORS WITH ANTITUBULIN ACTIVITY AND METHODS OF TREATING A PATIENT<br/>[FR] INHIBITEURS PYRIMIDINES BICYCLIQUES ET TRICYCLIQUES DE TYROSINE KINASE AYANT UNE ACTIVITÉ ANTITUBULINE, ET MÉTHODES DE TRAITEMENT D'UN PATIENT
  申请人：UNIV HOLY GHOST DUQUESNE

  公开号：WO2012106522A3

  公开（公告）日：2012-11-01
• SIMAKOV, S. V.;VELEZHEVA, V. S.;DVORKIN, V. V.;SUVOROV, N. N., XIMIYA GETEROTSIKL. SOEDIN., 1985, N 5, 635-639
  作者：SIMAKOV, S. V.、VELEZHEVA, V. S.、DVORKIN, V. V.、SUVOROV, N. N.

  DOI：——

  日期：——
• BICYCLIC AND TRICYCLIC PYRIMIDINE TYROSINE KINASE INHIBITORS WITH ANTITUBULIN ACTIVITY AND METHODS OF TREATING A PATIENT
  申请人：Duquesne University of The Holy Spirit

  公开号：EP2670244B1

  公开（公告）日：2018-04-11