Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are promising drug development targets due to their implications in pathologies such as cancer and neurodegenerative diseases. The search for IDO1 inhibitor has been intensely pursued but there is a paucity of potent TDO and IDO1/TDO dual inhibitors. Natural product tryptanthrin has been confirmed to bear IDO1 and/or TDO inhibitory activities. Herein, twelve novel tryptanthrin derivatives were synthesized and evaluated for the IDO1 and TDO inhibitory potency. All of the compounds were found to be IDO1/TDO dual inhibitors, in particular, compound 9a and 9b bore IDO1 inhibitory activity similar to that of INCB024360, and compound 5a and 9b had remarkable TDO inhibitory activity superior to that of the well-known TDO inhibitor LM10. This work enriches the collection of IDO1/TDO dual inhibitors and provides chemical molecules for potential development into drugs.

中文翻译：

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作为吲哚胺2，3-双加氧酶1和色氨酸2，3-双加氧酶的双重抑制剂的新型色胺酮衍生物的合成。

吲哚胺2,3-双加氧酶1（IDO1）和色氨酸2,3-双加氧酶（TDO）由于其在诸如癌症和神经退行性疾病等病理中的影响而成为有前途的药物开发目标。一直在努力寻找IDO1抑制剂，但缺乏有效的TDO和IDO1 / TDO双重抑制剂。天然产物色胺酮已被证实具有IDO1和/或TDO抑制活性。本文中，合成了十二种新颖的类胰蛋白酶，并评估了IDO1和TDO抑制能力。发现所有化合物都是IDO1 / TDO双重抑制剂，特别是化合物9a和9b具有与INCB024360相似的IDO1抑制活性，并且化合物5a和9b的TDO抑制活性明显优于众所周知的TDO。抑制剂LM10。