1-phenyl-1H-benzo[g]indazole-3-carboxylic acid | 665020-20-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-phenyl-1H-benzo[g]indazole-3-carboxylic acid
• 英文别名: 1-Phenylbenzo[g]indazole-3-carboxylic acid
• CAS: 665020-20-2
• 化学式: C₁₈H₁₂N₂O₂
• 分子量: 288.305
• InChiKey: OLIRTZDCNODEAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-phenyl-1H-benzo[g]indazole-3-carboxylic acid 以 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 N3-{2-[{2-[(1-phenyl-1H-benzo[g]indazole-3-yl-carbonyl)amino]ethyl}(methyl)amino]ethyl}-1-phenyl-1H-benzo[g]indazole-3-carboxamide
  参考文献：
  名称：

  Chromophore-modified bis-benzo[g]indole carboxamides: synthesis and antiproliferative activity of bis-benzo[g]indazole-3-carboxamides and related dimers

  摘要：

  Tricyclic pyrazole dimers that comprise two kinds of CONH-(CH(2))(n)-N(CH(3))-(CH(2))(n)-NHCO bridges to which are linked potential DNA-intercalating groups such as 1H-benzo[g]indazole, 2H-benzo[g]indazole and 1,4-dihydroindeno[1,2-c]pyrazole were designed, synthesized and some of them evaluated in vitro by NCI (Bethesda, USA) against nine types of cancer cells. Compounds 2a, 2f-i and 2o-r demonstrated significant antiproliferative activity, all with GI(50) values in the low micromolar range. Preliminary analysis of the structure-activity relationship for dimers 2 indicated that: (i) in the ground terms (2a and 2k) antitumor activities were strongly related to the type of chromophore, (ii) in contrast, either 1H-benzo[g]indazole- or 1,4-dihydroindeno[1,2-c]pyrazole-dimers when bore a N(1)-aryl group (2g, 2h, 2i, 2o, 2p, 2q and 2r) generally showed a good level of antitumor potency and (iii) for the most representative compounds (pairs of compounds: 2g,2h; 2o,2p and 2q,2r) the length of the bridges did not significantly contribute to the variations in cytotoxicity. Two members of this series, 2f and 2q, were selected and tested in the hollow fiber cell assay to evaluate in a preliminary fashion their in vivo antitumor activity. Finally, viscosity measurement of 2f with poly(dA-dT)(2), confirmed that these promising compounds behaved as typical DNA-intercalating agents.

  DOI：

  10.1016/s0014-827x(03)00131-9
• 作为产物：
  描述：

  ethyl 1-phenyl-1H-benzo[g]indazole-3-carboxylate 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 以98%的产率得到1-phenyl-1H-benzo[g]indazole-3-carboxylic acid
  参考文献：
  名称：

  Chromophore-modified bis-benzo[g]indole carboxamides: synthesis and antiproliferative activity of bis-benzo[g]indazole-3-carboxamides and related dimers

  摘要：

  Tricyclic pyrazole dimers that comprise two kinds of CONH-(CH(2))(n)-N(CH(3))-(CH(2))(n)-NHCO bridges to which are linked potential DNA-intercalating groups such as 1H-benzo[g]indazole, 2H-benzo[g]indazole and 1,4-dihydroindeno[1,2-c]pyrazole were designed, synthesized and some of them evaluated in vitro by NCI (Bethesda, USA) against nine types of cancer cells. Compounds 2a, 2f-i and 2o-r demonstrated significant antiproliferative activity, all with GI(50) values in the low micromolar range. Preliminary analysis of the structure-activity relationship for dimers 2 indicated that: (i) in the ground terms (2a and 2k) antitumor activities were strongly related to the type of chromophore, (ii) in contrast, either 1H-benzo[g]indazole- or 1,4-dihydroindeno[1,2-c]pyrazole-dimers when bore a N(1)-aryl group (2g, 2h, 2i, 2o, 2p, 2q and 2r) generally showed a good level of antitumor potency and (iii) for the most representative compounds (pairs of compounds: 2g,2h; 2o,2p and 2q,2r) the length of the bridges did not significantly contribute to the variations in cytotoxicity. Two members of this series, 2f and 2q, were selected and tested in the hollow fiber cell assay to evaluate in a preliminary fashion their in vivo antitumor activity. Finally, viscosity measurement of 2f with poly(dA-dT)(2), confirmed that these promising compounds behaved as typical DNA-intercalating agents.

  DOI：

  10.1016/s0014-827x(03)00131-9

文献信息

• TRICYCLIC 3-OXO-PROPANENITRILE COMPOUNDS
  申请人：PHARMACIA & UPJOHN S.p.A.

  公开号：EP1019380A2

  公开（公告）日：2000-07-19
• [EN] TRICYCLIC 3-OXO-PROPANENITRILE COMPOUNDS<br/>[FR] COMPOSES 3-OXO-PROPANENITRILE TRICYCLIQUES
  申请人：——

  公开号：WO1999016753A2

  公开（公告）日：1999-04-08

  [EN] Tricyclic 3-oxo-propanenitrile compounds of formula (I), wherein Y represents a nitrogen atom or a CH or N-oxide group; X represents an oxygen atom or NR2 wherein R2 represents C1-C6 alkyl, benzyl, pyridyl or phenyl, the phenyl being unsubstituted or substituted by one or two substituents chosen independently from halogen, trifluoromethyl, C1-C6 alkyl, C1-C6 alkoxy, nitro, amino, formylamino and C2-C8 alkanoylamino; each of R and R1 is independently hydrogen, halogen, CF3, C1-C6 alkyl, hydroxy, C1-C6 alkoxy, C3-C4 alkenyloxy, nitro, amino, formylamino, C2-C8 alkanoylamino or C2-C8 alkanoyloxy; m is zero or an integer of 1 to 6; Q is C1-C14 alkyl, phenyl or unsaturated pentatomic heteromonocylic ring containing two or three heteroatoms chosen from oxygen, sulphur and nitrogen, wherein the phenyl ring and the heteromonocylic ring are unsubstituted or substituted by one or two substituents chosen independently from halogen, CF3, C1-C6 alkyl, hydroxy, C1-C6 alkoxy, nitro, amino, formylamino, C2-C8 alkanoylamino or C2-C8 alkanoyloxy; and W represents a -CONH- or -SO2- or -CO- group; and pharmaceutically acceptable salt thereof having kynurenine-3-hydroxylase enzyme inhibitor activity are provided.
  [FR] L'invention concerne des composés 3-oxo-propanenitrile tricycliques correspondant à la formule (I), ainsi qu'un sel de ceux-ci, acceptable sur le plan pharmacologique. Dans cette formule Y représente un atome d'azote ou un groupe CH ou N-oxyde, X représente un atome d'oxygène ou NR2 dans lequel R2 représente alkyle C1-C6, benzyle, pyridyle ou phényle, phényle n'étant pas substitué ou l'étant par un ou deux substituants choisis indépendamment dans le groupe constitué par halogène, trifluorométhyle, alkyle C1-C6, alcoxy C1-C6, nitro, amino, formylamino et alcanoylamino C2-C8, R et R1 représentent chacun indépendamment hydrogène, halogène, CF3, alkyle C1-C6, hydroxy, alcoxy C1-C6, alcényloxy C3-C4, nitro, amino, formylamino, alcanoylamino C2-C8, ou alcanoyloxy C2-C8, m vaut zéro ou est un nombre entier compris entre 1 et 6, Q représente alkyle C1-C14, un noyau phényle ou un noyau hétéromonocyclique pentatomique insaturé contenant deux ou trois hétéroatomes choisis parmi oxygène, soufre et azote, le noyau phényle et le noyau hétéromonocyclique n'étant pas substitués ou l'étant pas un ou deux substituants choisis indépendamment dans le groupe constitué par halogène, CF3, alkyle C1-C6, hydroxy, alcoxy C1-C6, nitro, amino, formylamino, alcanoylamino C2-C8 ou alcanoyloxy C2- C8, et W représente un groupe -CONH- ou -SO2- ou -CO-. Ces composés et leur sel possèdent une activité inhibitrice de l'enzyme kynurénine-3-hydroxylase.
• Chromophore-modified bis-benzo[g]indole carboxamides: synthesis and antiproliferative activity of bis-benzo[g]indazole-3-carboxamides and related dimers
  作者：Gérard A Pinna、Maria A Pirisi、Jean-Mario Mussinu、Gabriele Murineddu、Giovanni Loriga、Amedeo Pau、Giuseppe E Grella

  DOI：10.1016/s0014-827x(03)00131-9

  日期：2003.9

  Tricyclic pyrazole dimers that comprise two kinds of CONH-(CH(2))(n)-N(CH(3))-(CH(2))(n)-NHCO bridges to which are linked potential DNA-intercalating groups such as 1H-benzo[g]indazole, 2H-benzo[g]indazole and 1,4-dihydroindeno[1,2-c]pyrazole were designed, synthesized and some of them evaluated in vitro by NCI (Bethesda, USA) against nine types of cancer cells. Compounds 2a, 2f-i and 2o-r demonstrated significant antiproliferative activity, all with GI(50) values in the low micromolar range. Preliminary analysis of the structure-activity relationship for dimers 2 indicated that: (i) in the ground terms (2a and 2k) antitumor activities were strongly related to the type of chromophore, (ii) in contrast, either 1H-benzo[g]indazole- or 1,4-dihydroindeno[1,2-c]pyrazole-dimers when bore a N(1)-aryl group (2g, 2h, 2i, 2o, 2p, 2q and 2r) generally showed a good level of antitumor potency and (iii) for the most representative compounds (pairs of compounds: 2g,2h; 2o,2p and 2q,2r) the length of the bridges did not significantly contribute to the variations in cytotoxicity. Two members of this series, 2f and 2q, were selected and tested in the hollow fiber cell assay to evaluate in a preliminary fashion their in vivo antitumor activity. Finally, viscosity measurement of 2f with poly(dA-dT)(2), confirmed that these promising compounds behaved as typical DNA-intercalating agents.