5-methyl-1-(4-nitrophenyl)-3-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)-1,5-dihydro-pyrido[3,2-b]indol-2-one | 698396-95-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-methyl-1-(4-nitrophenyl)-3-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)-1,5-dihydro-pyrido[3,2-b]indol-2-one
• 英文别名: 5-Methyl-1-(4-nitrophenyl)-3-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]pyrido[3,2-b]indol-2-one
• CAS: 698396-95-1
• 化学式: C₂₁H₁₂F₃N₅O₄
• 分子量: 455.353
• InChiKey: DCYHHYFVJUPENV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  33
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-[(4-硝基苯基)氨基]-1H-吲哚-2-甲醛 在 羟胺 、 potassium carbonate 、 三乙胺 作用下， 以 吡啶 、 DMF (N,N-dimethyl-formamide) 、 乙醇 、 乙二醇 、 异丙醇 为溶剂， 反应 42.0h， 生成 5-methyl-1-(4-nitrophenyl)-3-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)-1,5-dihydro-pyrido[3,2-b]indol-2-one
  参考文献：
  名称：

  [EN] COMBINATIONS OF SUBSTITUTED 1-PHENYL-1,5-DIHYDRO-PYRIDO- [3,2-B] INDOL-2-ONES AND OTHER HIV INHIBITORS
  [FR] COMBINAISON DE SUBSTITUE 1-PHENYL-1,5-DIHYDRO-PYRIDO- [3,2-B] INDOL-2-ONES ET AUTRES INHIBITEURS DU VIH

  摘要：

  本发明涉及包含式(I)化合物的组合物；其N-氧化物、盐、立体异构体形式、消旋混合物、前药、酯或其代谢物，其中n为1、2或3；R1为H、CN、卤素、氨基C(=O)、C(=O)OH、C1-4烷氧基C(=O)、C1-4烷基C(=O)、单或双(C1-4烷基)氨基C(=O)、芳基氨基C(=O)、N-(芳基)-N-(C1-4烷基)氨基C(=O)、甲基亚胺基、N-羟基-甲基亚胺基、单或双(C1-4烷基)甲基亚胺基、Het1或Het2；R2为H、C1-10烷基、C2-10烯基、C3-7环烷基，其中所述的C1-10烷基、C2-10烯基和C3-7环烷基可以选择性地被取代；R3为硝基、氰基、氨基、卤素、羟基、C1-4烷氧基、羟基C(=O)、氨基C(=O)、C1-4烷氧基C(=O)、单或双(C1-4烷基)氨基C(=O)、C1-4烷基C(=O)、甲基亚胺基、单或双(C1-4烷基)甲基亚胺基、N-羟基-甲基亚胺基或Het1；以及另一种HIV抑制剂。该发明还涉及包含式(I)化合物和另一种HIV抑制剂的产品，作为用于同时、分开或顺序使用的联合制剂，用于治疗逆转录病毒感染，如HIV感染，特别是用于治疗多药耐药逆转录病毒感染。

  公开号：

  WO2005110411A1

文献信息

• [EN] SUBSTITUTED INDOLEPYRIDINIUM AS ANTI-INFECTIVE COMPOUNDS<br/>[FR] INDOLEPYRIDINIUM SUBSTITUE UTILISE COMME COMPOSES ANTI-INFECTION
  申请人：TIBOTEC PHARM LTD

  公开号：WO2004046143A1

  公开（公告）日：2004-06-03

  The present invention concerns the compounds of formula (1) (R3)n P(I) N O R1 R2 their N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites, wherein n is 1, 2 or 3; R1 is H, CN, halo, aminoC(=O), C(=O)OH, C1-4-alkyloxyC(=O), C1-4alkylC(='O), mono- or di(C1-4alkyl)aminoC(=O), arylaminoC(=O), N-(aryl)-N-(C1-4alkyl)aminoC(=O), methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; R2 is H, C1-10alkyl, C2-10allkenyl, C3-7cycloalkyl, wherein said C1-10alkyl,C2-10alkenyl and C3-7cycloalkyl may be optionally substituted; R3 is nitro, cyano, amino, halo, hydroxy,C1-4alkyloxy, hydroxyC(=O), aminoC(=O), C1-4alkyloxyC(=O), mono- or di(C1-4-alkyl)aminoC(=O), C1-4alkylC(=O), methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, N-hydroxy methanimidamidyl or Het1; for use as a medicine. The invention further relates to a novel subgroup of the compounds of formula (I), and to compositions comprising compounds of formula (I).

  本发明涉及式（1）的化合物（R3）n P(I) N O R1 R2及其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H、CN、卤素、氨基C(=O)、C(=O)OH、C1-4-烷氧基C(=O)、C1-4烷基C(='O)、单取代或双取代(C1-4烷基)氨基C(=O)、芳基氨基C(=O)、N-(芳基)-N-(C1-4烷基)氨基C(=O)、甲基亚胺基、N-羟基-甲基亚胺基、单取代或双取代(C1-4烷基)甲基亚胺基、Het1或Het2；R2为H、C1-10烷基、C2-10烯基、C3-7环烷基，其中所述的C1-10烷基、C2-10烯基和C3-7环烷基可以选择性地取代；R3为硝基、氰基、氨基、卤素、羟基、C1-4烷氧基、羟基C(=O)、氨基C(=O)、C1-4烷氧基C(=O)、单取代或双取代(C1-4-烷基)氨基C(=O)、C1-4烷基C(=O)、甲基亚胺基、单取代或双取代(C1-4烷基)甲基亚胺基、N-羟基甲基亚胺基或Het1；用作药物。本发明还涉及式(I)的化合物的新亚组，以及包含式(I)化合物的组合物。
• Substituted indolepyridinium as anti-infective compounds
  申请人：Kesteleyn Rudolf Romanie Bart

  公开号：US20060173000A1

  公开（公告）日：2006-08-03

  The present invention concerns the compounds of formula (I) their N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites, wherein n is 1, 2 or 3; R 1 is H, CN, halo, aminoC(═O), C(═O)OH, C 1-4 alkyloxyC(═O), C 1-4 alkylC(═O), mono- or di(C 1-4 alkyl)aminoC(═O), arylaminoC(═O), N-(aryl)-N—(C 1-4 alkyl)aminoC(═O), methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C 1-4 alkyl)methanimidamidyl, Het, or Het 2 ; R 2 is H, C 1-10 alkyl, C 2-10 alkenyl, C 3-7 cycloalkyl, wherein said C 1-10 alkyl, C 2-10 alkenyl and C 3-7 cycloalkyl may be optionally substituted; R 3 is nitro, cyano, amino, halo, hydroxy, C 1-4 alkyloxy, hydroxyC(═O), aminoC(═O), C 1-4 alkyloxyC(═O), mono- or di(C 1-4 alkyl)aminoC(═O), C 1-4 alkylC(═O), methanimidamidyl, mono- or di(C 1-4 alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het 1 ; for use as a medicine. The invention further relates to a novel subgroup of the compounds of formula (I), and to compositions comprising compounds of formula (I).

  本发明涉及式（I）化合物及其N-氧化物、盐、立体异构体、外消旋混合物、前药、酯和代谢物，其中n为1、2或3；R1为H、CN、卤、氨基C（═O）、C（═O）OH、C1-4烷氧基C（═O）、C1-4烷基C（═O）、单烷基或双烷基C（═O）氨基、芳基氨基C（═O）、N-(芳基)-N-(C1-4烷基)氨基C（═O）、甲基亚胺基、N-羟基-甲基亚胺基、单烷基或双烷基甲基亚胺基、Het或Het2；R2为H、C1-10烷基、C2-10烯基、C3-7环烷基，其中所述的C1-10烷基、C2-10烯基和C3-7环烷基可以选择性地被取代；R3为硝基、氰基、氨基、卤、羟基、C1-4烷氧基、羟基C（═O）、氨基C（═O）、C1-4烷氧基C（═O）、单烷基或双烷基C（═O）氨基、C1-4烷基C（═O）、甲基亚胺基、单烷基或双烷基甲基亚胺基、N-羟基-甲基亚胺基或Het1；用作药物。本发明还涉及式（I）化合物的新亚组，以及包含式（I）化合物的组合物。
• 4-Substituted-1,5-Dihydro-Pyrido[3,2-B]Indol-2-Ones
  申请人：Kesteleyn Rudolf Romanie Bart

  公开号：US20070249655A1

  公开（公告）日：2007-10-25

  The present invention concerns combinations comprising a compound of formula (I) the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters or metabolites thereof, wherein n is 1, 2 or 3; R 1 is H, CN, halo, aminoC(═O), C(═O)OH, C 1-4 alkyloxyC(═O), C 1-4 alkylC(═O), mono- or di(C 1-4 alkyl)aminoC(═O), arylaminoC(═O), N-(aryl)-N-(C 1-4 alkyl)aminoC(═O), methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C 1-4 alkyl)methanimidamidyl, Het 1 or Het 2 ; R 2 is H, C 1-4 alkyl, C 2-10 alkenyl, C 3-7 cycloalkyl, wherein said C 1-10 alkyl, C 2-10 alkenyl and C 3-7 cycloalkyl may be optionally substituted; R 3 is nitro, cyano, amino, halo, hydroxy, C 1-4 alkyloxy, hydroxyC(═O), aminoC(═O), C 1-4 alkyloxyC(═O), mono- or di(C 1-4 alkyl)aminoC(═O), C 1-4 alkylC(═O), methanimidamidyl, mono- or di(C 1-4 alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het 1 ; and another HIV inhibitor. The invention also concerns products comprising a compound of formula (I) and another HIV inhibitor, as a combined preparation for simultaneous, separate or sequential use in treatment of retroviral infections such as HIV infection, in particular, in the treatment of infections with multi-drug resistant retroviruses.

  本发明涉及一种组合物，包括式（I）化合物的N-氧化物、盐、立体异构体形式、混合物、前药、酯或其代谢物，其中n为1、2或3；R1为H、CN、卤素、氨基C（═O）、C（═O）OH、C1-4烷氧基C（═O）、C1-4烷基C（═O）、单烷基或二烷基氨基C（═O）、芳基氨基C（═O）、N-(芳基)-N-(C1-4烷基)氨基C（═O）、甲基亚胺基、N-羟基甲基亚胺基、单烷基或二烷基甲基亚胺基、Het1或Het2；R2为H、C1-4烷基、C2-10烯基、C3-7环烷基，其中所述的C1-10烷基、C2-10烯基和C3-7环烷基可以选择性地被取代；R3为硝基、氰基、氨基、卤素、羟基、C1-4烷氧基、羟基C（═O）、氨基C（═O）、C1-4烷氧基C（═O）、单烷基或二烷基氨基C（═O）、C1-4烷基C（═O）、甲基亚胺基、单烷基或二烷基甲基亚胺基、N-羟基甲基亚胺基或Het1；以及另一种HIV抑制剂。本发明还涉及包含式（I）化合物和另一种HIV抑制剂的产品，作为联合制剂，用于同时、分离或顺序治疗逆转录病毒感染，例如HIV感染，特别是治疗多药耐药逆转录病毒感染。
• SUBSTITUTED INDOLEPYRIDINIUM AS ANTI-INFECTIVE COMPOUNDS
  申请人：KESTELEYN Bart Rudolf Romanie

  公开号：US20100048563A1

  公开（公告）日：2010-02-25

  The present invention concerns the compounds of formula (I) their N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites, wherein n is 1, 2 or 3; R 1 is H, CN, halo, aminoC(═O), C(═O)OH, C 1-4 alkyloxyC(═O), C 1-4 alkylC(═O), mono- or di(C 1-4 alkyl)aminoC(═O), arylaminoC(═O), N-(aryl)-N—(C 1-4 alkyl)aminoC(═O), methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C 1-4 alkyl)methanimidamidyl, Het 1 or Het 2 ; R 2 is H, C 1-10 alkyl, C 2-10 alkenyl, C 3-7 cycloalkyl, wherein said C 1-10 alkyl, C 2-10 alkenyl and C 3-7 cycloalkyl may be optionally substituted; R 3 is nitro, cyano, amino, halo, hydroxy, C 1-4 alkyloxy, hydroxyC(═O), aminoC(═O), C 1-4 alkyloxyC(═O), mono- or di(C 1-4 alkyl)aminoC(═O), C 1-4 alkylC(═O), methanimidamidyl, mono- or di(C 1-4 alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het 1 ; for use as a medicine. The invention further relates to a novel subgroup of the compounds of formula (I), and to compositions comprising compounds of formula (I).

  本发明涉及式(I)化合物及其N-氧化物、盐、立体异构体、外消旋混合物、前药、酯和代谢物，其中n为1、2或3；R1为H、CN、卤素、氨基C(═O)、C(═O)OH、C1-4烷氧基C(═O)、C1-4烷基C(═O)、单取代或双取代(C1-4烷基)氨基C(═O)、芳基氨基C(═O)、N-(芳基)-N-(C1-4烷基)氨基C(═O)、甲基亚胺基、N-羟基甲基亚胺基、单取代或双取代(C1-4烷基)甲基亚胺基、Het1或Het2；R2为H、C1-10烷基、C2-10烯基、C3-7环烷基，其中所述的C1-10烷基、C2-10烯基和C3-7环烷基可以选择性地被取代；R3为硝基、氰基、氨基、卤素、羟基、C1-4烷氧基、羟基C(═O)、氨基C(═O)、C1-4烷氧基C(═O)、单取代或双取代(C1-4烷基)氨基C(═O)、C1-4烷基C(═O)、甲基亚胺基、单取代或双取代(C1-4烷基)甲基亚胺基、N-羟基甲基亚胺基或Het1；用作药物。本发明还涉及式(I)化合物的新亚组，以及包含式(I)化合物的组合物。
• 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.