Nguyen C H, Lavelle F, Riou J F, Bissery M C, Huel C, Bisagni E
URA 1387 CNRS, Synthèse Organique, Institut Curie, Orsay, France.
Anticancer Drug Des. 1992 Jun;7(3):235-51.
Using previously described techniques, various new 1-amino-substituted 5H-pyrido[4,3-b]indoles (gamma-carbolines, gamma-C) and 5H-benzo[e]pyrido[4,3-b]indoles (BPI) have been synthesized and evaluated. For known compounds containing a 1-[(dimethylamino)propyl] group, 1a and 1b in the gamma-C series and 2 in the BPI series are the most active. Studies with newly synthesized derivatives show that: (i) in the gamma-C series, the 4-unsubstituted-8-hydroxy-compound was inactive, whereas the 4-unsubstituted-9-hydroxy-5H-benzo[e]pyrido[4,3-b]indole is active; (ii) the 4-ethyl-8-hydroxy-5H-pyrido[4,3-b]indole derivative retains antitumor properties, but the 1-amino-substituted 4-ethyl-9-hydroxy-5H-benzo[e]pyrido[4,3-b]indole analog is devoid of biological activity; (iii) in the 5H-benzo[e]pyrido[4,3-b]indole series, the displacement of a hydroxyl group from the 9- to 10-position leads to inactive compounds. Based on the structural analogies, these results were unexpected because the same substituents on the 4-position lead to different biological properties in the two series.
利用先前描述的技术，已经合成并评估了各种新型的1-氨基取代的5H-吡啶并[4,3-b]吲哚（γ-咔啉，γ-C）和5H-苯并[e]吡啶并[4,3-b]吲哚（BPI）。对于已知含有1-[(二甲氨基)丙基]基团的化合物，γ-C系列中的1a和1b以及BPI系列中的2活性最高。对新合成衍生物的研究表明：（i）在γ-C系列中，4-未取代的-8-羟基化合物无活性，而4-未取代的-9-羟基-5H-苯并[e]吡啶并[4,3-b]吲哚有活性；（ii）4-乙基-8-羟基-5H-吡啶并[4,3-b]吲哚衍生物保留抗肿瘤特性，但1-氨基取代的4-乙基-9-羟基-5H-苯并[e]吡啶并[4,3-b]吲哚类似物没有生物活性；（iii）在5H-苯并[e]吡啶并[4,3-b]吲哚系列中，羟基从9位移至10位会导致化合物无活性。基于结构上的相似性，这些结果出乎意料，因为4位上相同的取代基在两个系列中导致了不同的生物学特性。
