7-hydroxy-4-methyl-1-(4-nitrophenyl)-2-oxo-1,2-dihydro-benzo[4,5]furo[3,2-b]-pyridine-3-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 7-hydroxy-4-methyl-1-(4-nitrophenyl)-2-oxo-1,2-dihydro-benzo[4,5]furo[3,2-b]-pyridine-3-carbonitrile
• 英文别名: 7-hydroxy-4-methyl-1-(4-nitrophenyl)-2-oxo-[1]benzofuro[3,2-b]pyridine-3-carbonitrile
• 化学式: C₁₉H₁₁N₃O₅
• 分子量: 361.313
• InChiKey: CVXXSLRRDWNFSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.53
• 重原子数：
  27.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  122.3
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  2-氟-4-甲氧基苯腈 在 1-羟基苯并三唑 吡啶 、 2-羟乙基甲砜 、 copper diacetate 、 三溴化硼 、 sodium hydride 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 potassium iodide 作用下， 以 甲醇 、 DMF (N,N-dimethyl-formamide) 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 70.0h， 生成 7-hydroxy-4-methyl-1-(4-nitrophenyl)-2-oxo-1,2-dihydro-benzo[4,5]furo[3,2-b]-pyridine-3-carbonitrile
  参考文献：
  名称：

  [EN] 4-SUBSTITUTED-1,5-DIHYDRO-PYRIDO[3,2-B]INDOL-2-ONES
  [FR] 1,5-DIHYDROPYRIDO[3,2-B]INDOL-2-ONES SUBSTITUEES EN POSITION 4

  摘要：

  公式（I）的4-取代1,5-二氢吡啶并[3,2-b]吲哚-2-酮：其N-氧化物，盐，立体异构体形式，消旋混合物，前药，酯和代谢物，其中n为1、2或3；R1为氢，氰基，卤素，取代羰基，甲基亚胺基，N-羟甲基亚胺基，单或双(C1-4烷基)甲基亚胺基，Het1或Het2；X为NR 2，O，S，SO，SO2；R2为氢，C1-10烷基，C2-10烯基，C3-7环烷基，可选择地取代；R2为取代为-COOR4的芳基；或R2为：(b-1)；(b-2)；-CpH2p-CH(OR14)-CqH2q-R15(b-3)；-CH2-CH2-(O-CH2-CH2)m-OR14(b-4)；-CH2-CH2-(O-CH2-CH2)m-NR5aR5b(b-5)；-a1=a2-a3=a4-为-CH=CH-CH=CH-；-N=CH-CH=CH-；-CH=N-CH=CH-；-CH=CH-N=CH-；-CH=CH-CH=N-；其中(c-1)-(c-5)中的氢原子可被某些基团取代；R3为可选择地取代的苯基或可以被取代的单环或双环芳香杂环系统；R21为卤素，羟基，氨基，羧基，C1-6烷基，C3-7环烷基，芳基C1-6烷基，甲酰基，C1-6烷基羰基，C1-6烷氧羰基，C1-6烷基羰氧基，-C(=O)-NR13R14；C1-6烷氧基，芳基C1-6烷氧基，多卤C1-6烷氧基，氨基，单或双(C1-6烷基)氨基，甲酰氨基，C1-6烷基羰胺基，C1-6烷基磺酰氨基，巯基，C1-6烷基硫基，芳基硫基，芳氧基，芳基C1-6烷基硫基，C1-6烷基烯基基，C1-6烷基磺基，芳基，芳胺基，Het1，Het2。

  公开号：

  WO2005111044A1

文献信息

• 4-SUBSTITUTED-1,5-DIHYDRO-PYRIDO[3,2-B]INDOL-2-ONES
  申请人：Kesteleyn Rudolf Romanie Bart

  公开号：US20070213320A1

  公开（公告）日：2007-09-13

  4-substituted 1,5-dihydro-pyrido[3,2-b]indol-2-ones of formula (I): the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein n is 1, 2 or 3; R 1 is hydrogen, cyano, halo, substituted carbonyl, methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C 1-4 alkyl)methanimidamidyl, Het 1 or Het 2 ; X is NR 2 , O, S, SO, SO 2 ; R 2 is hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 3-7 cycloalkyl, which are optionally substituted; R 2 is aryl substituted with —COOR 4 ; or R 2 is: —C p H 2p —CH(OR 14 )—C q H 2q —R 15 (b-3); —CH 2 —CH 2 —(O—CH 2 —CH 2 ) m —OR 14 (b-4); —CH 2 —CH 2 —(O—CH 2 —CH 2 ) m —NR 5a R 5b (b-5); -a 1 =a 2 -a 3 =a 4 - is —CH═CH—CH═CH—; —N═CH—CH═CH—; —CH═N—CH═CH—; —CH═CH—N═CH—; —CH═CH—CH═N—; wherein hydrogen atoms in (c-1)-(c-5) may be replaced by certain radicals; R 3 is optionally substituted phenyl or a monocyclic or bicyclic aromatic heterocyclic ring system that can be substituted; R 21 is halo, hydroxy, amino, carboxyl, C 1-6 alkyl, C 3-7 cycloalkyl, arylC 1-6 alkyl, formyl, C 1-6 alkylcarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylcarbonyloxy, —C(═O)—NR 13 R 14 ; C 1-6 alkyloxy, arylC 1-6 alkyloxy, polyhaloC 1-6 alkyloxy, amino, mono or di(C 1-6 alkyl)amino, formylamino, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, mercapto, C 1-6 alkylthio, arylthio, aryloxy, arylC 1-6 alkylthio, C 1-6 alkylsulfynyl, C 1-6 alkylsulfonyl, aryl, arylamino, Het 1 , Het 2 .
• Methods of Treating Mutated Hiv
  申请人：Jochmans Dirk Edward Desire

  公开号：US20090012046A1

  公开（公告）日：2009-01-08

  Nucleotide-competing reverse transcriptase inhibitors (NcRTI) bind to the active site of HIV reverse transcriptase (RT) in competition with the next incoming nucleotide. To further investigate the impact of RT inhibitor resistance mutations on the activity of NcRTIs, the susceptibility of >6000 recent clinical isolates for a prototype compound, NcRTI-1, was determined. Over 80% of the profiled clinical isolates remained susceptible for NcRTI-1 (FC<4). No cross-resistance was observed between NcRTI-1 and currently used RT inhibitors, apart from limited cross-resistance with 3TC/FTC. Analysis of the genotype of >1700 of these viruses showed that the combination of active site mutations M184V+Y115F correlated most with resistance to NcRTI-1 (FC=75). Analysis also indicated that the K65R mutation is associated with hypersusceptibility to NcRTI-1 and that it reverses the reduced susceptibility caused by M184V. These findings were confirmed in SDM strains. This reciprocity between the K65R and M184V mutation is unparalleled among RT inhibitors. When replicating wild-type HIV-1 in the presence of NcRTI-1, M184V+Y115F were selected. In the presence of both NcRTI-1 and tenofovir, NcRTI-1 prevents the selection of K65R.
• US7622582B2
  申请人：——

  公开号：US7622582B2

  公开（公告）日：2009-11-24
• [EN] 4-SUBSTITUTED-1,5-DIHYDRO-PYRIDO[3,2-B]INDOL-2-ONES<br/>[FR] 1,5-DIHYDROPYRIDO[3,2-B]INDOL-2-ONES SUBSTITUEES EN POSITION 4
  申请人：TIBOTEC PHARM LTD

  公开号：WO2005111044A1

  公开（公告）日：2005-11-24

  4-substituted 1,5-dihydro-pyrido[3,2-b]indol-2-ones of formula (I): the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein n is 1, 2 or 3; R1 is hydrogen, cyano, halo, substituted carbonyl, methanimidamidyl, N-hydroxymethanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; X is NR 2, O, S, SO, SO2; R2 is hydrogen, C 1-10alkyl, C2-10alkenyl, C 3-7cycloalkyl, which are optionally substituted; R2 is aryl substituted with -COOR4 ; or R2 is: (b-1); (b-2); -CpH2p-CH(OR14 )-CqH 2q-R15(b-3); -CH2-CH2-(O-CH2-CH2)m-OR14 (b-4); -CH2-CH2-(O-CH2-CH2)m-NR5aR5b(b-5); -a1=a2-a3=a4- is -CH=CH-CH=CH-; -N=CH-CH=CH-; -CH=N-CH=CH-; -CH=CH-N=CH-; -CH=CH-CH=N-; wherein hydrogen atoms in (c-1) - (c-5) may be replaced by certain radicals; R3 is obtionally substituted phenyl or a monocyclic or bicyclic aromatic heterocyclic ring system that can be substituted; R21 is halo, hydroxy, amino, carboxyl, C1-6alkyl, C3-7cycloalkyl, arylC1-6alkyl, formyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonylo xy, -C(=O)-NR13R14; C1-6alkyloxy, arylC1-6alkyloxy, polyhaloC1-6alkyloxy, amino, mono or di(C1-6alkyl)amino, formylamino, C1-6alkylcarbonylamino, C1-6alkylsulfo nylamino, mercapto, C1-6alkylthio, arylthio, aryloxy, arylC1-6alkylthio, C1-6alkylsulfynyl, C1-6alkylsulfo nyl, aryl, arylamino, Het1, Het2.

  公式（I）的4-取代1,5-二氢吡啶并[3,2-b]吲哚-2-酮：其N-氧化物，盐，立体异构体形式，消旋混合物，前药，酯和代谢物，其中n为1、2或3；R1为氢，氰基，卤素，取代羰基，甲基亚胺基，N-羟甲基亚胺基，单或双(C1-4烷基)甲基亚胺基，Het1或Het2；X为NR 2，O，S，SO，SO2；R2为氢，C1-10烷基，C2-10烯基，C3-7环烷基，可选择地取代；R2为取代为-COOR4的芳基；或R2为：(b-1)；(b-2)；-CpH2p-CH(OR14)-CqH2q-R15(b-3)；-CH2-CH2-(O-CH2-CH2)m-OR14(b-4)；-CH2-CH2-(O-CH2-CH2)m-NR5aR5b(b-5)；-a1=a2-a3=a4-为-CH=CH-CH=CH-；-N=CH-CH=CH-；-CH=N-CH=CH-；-CH=CH-N=CH-；-CH=CH-CH=N-；其中(c-1)-(c-5)中的氢原子可被某些基团取代；R3为可选择地取代的苯基或可以被取代的单环或双环芳香杂环系统；R21为卤素，羟基，氨基，羧基，C1-6烷基，C3-7环烷基，芳基C1-6烷基，甲酰基，C1-6烷基羰基，C1-6烷氧羰基，C1-6烷基羰氧基，-C(=O)-NR13R14；C1-6烷氧基，芳基C1-6烷氧基，多卤C1-6烷氧基，氨基，单或双(C1-6烷基)氨基，甲酰氨基，C1-6烷基羰胺基，C1-6烷基磺酰氨基，巯基，C1-6烷基硫基，芳基硫基，芳氧基，芳基C1-6烷基硫基，C1-6烷基烯基基，C1-6烷基磺基，芳基，芳胺基，Het1，Het2。