1-氯-6-甲氧基-9H-2,4,9-三氮杂芴 | 98792-03-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 中文名称: 1-氯-6-甲氧基-9H-2,4,9-三氮杂芴
• 中文别名: 4-氯-8-甲氧基-5H-嘧啶并[5,4-B]吲哚；4-氯-8-甲氧基-5H-嘧啶并[5,4-b]吲哚
• 英文名称: 1-chloro-6-methoxy-9H-2,4,9-triazafluorene
• 英文别名: 4-chloro-8-methoxy-5H-pyrimido[5,4-b]indole
• CAS: 98792-03-1
• 化学式: C₁₁H₈ClN₃O
• mdl: MFCD00753479
• 分子量: 233.657
• InChiKey: GFJIJJZNYCWNGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  1-氯-6-甲氧基-9H-2,4,9-三氮杂芴 在 sodium nitrate 、 硫酸 作用下， 以99%的产率得到1-chloro-6-nitro-9H-2,4,9-triazafluorene
  参考文献：
  名称：

  Design and Synthesis of New Templates Derived from Pyrrolopyrimidine as Selective Multidrug-Resistance-Associated Protein Inhibitors in Multidrug Resistance

  摘要：

  In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated.

  DOI：

  10.1021/jm0310129
• 作为产物：
  描述：

  5-methoxy-3-(dimethylamino-methyleneamino)-1H-indole-2-carboxylic acid ethyl ester 在 氨 、 2,3-二甲基苯胺 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 1-氯-6-甲氧基-9H-2,4,9-三氮杂芴
  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。
• [EN] SELECTIVE INHIBITORS OF GENOTOXIC STRESS-INDUCED IKK/NF-kB PATHWAYS<br/>[FR] INHIBITEURS SÉLECTIFS DE VOIES IKK/NF-KB INDUITES PAR LE STRESS GÉNOTOXIQUE
  申请人：MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN HELMHOLTZ GEMEINSCHAFT

  公开号：WO2018087389A1

  公开（公告）日：2018-05-17

  The invention relates to chemical compounds and their use as a medicament in the treatment of a disease associated with genotoxic stress-induced I KK/NF-κΒ (NF-kappaB) activation, preferably in the treatment of a subject suffering from cancer exhibiting genotoxic stress-induced I KK/NF-κΒ activation. The invention further relates to a pharmaceutical composition comprising a compound of the invention for the treatment of a subject afflicted by a disease associated with genotoxic stress-induced I KK/NF-κΒ activation.

  这项发明涉及化合物及其作为药物在治疗与基因毒性应激诱导的I KK/NF-κΒ（NF-kappaB）激活相关疾病中的用途，优选用于治疗患有展现基因毒性应激诱导的I KK/NF-κΒ激活的癌症患者。该发明还涉及一种包含该发明化合物的药物组合物，用于治疗患有与基因毒性应激诱导的I KK/NF-κΒ激活相关疾病的患者。
• Selective inhibitors of gentotoxic steress-induced IKK/NF-κB pathways
  申请人：Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft

  公开号：US11028084B2

  公开（公告）日：2021-06-08

  A method is for treatment of a disease associated with genotoxic stress-induced inhibitor of nuclear factor-κB kinase/nuclear factor kappa-light chain enhancer of activated B cells (IKK/NF-κB) signaling. The method can include administering a compound to a subject having a cancer exhibiting genotoxic stress induced IKK/NF-κB activation.

  一种方法用于治疗与基因毒性应激诱导的核因子-κB激酶/活化B细胞的核因子卡巴轻链增强子（IKK/NF-κB）信号转导抑制有关的疾病。该方法可包括向患有基因毒性应激诱导的IKK/NF-κB活化的癌症的受试者施用一种化合物。
• 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：——
• SELECTIVE INHIBITORS OF GENOTOXIC STRESS-INDUCED IKK/NF-kB PATHWAYS
  申请人：Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft

  公开号：EP3538529A1

  公开（公告）日：2019-09-18