公开(公告)号：US20110159017A1

公开(公告)日：2011-06-30

申请号：US12936576

申请日：2009-04-10

Applicant: Benoit Van Den Eynde ,  Luc Pilotte ,  Etienne De Plaen

Inventor： Benoit Van Den Eynde ,  Luc Pilotte ,  Etienne De Plaen

IPC: A61K39/395 ,  C12Q1/68 ,  G01N33/574 ,  A61K31/4439 ,  A61K31/192 ,  A61K31/40 ,  A61K31/225 ,  A61K31/198 ,  A61K35/12 ,  A61K31/353 ,  A61K31/405 ,  C12N5/09 ,  C12N5/0783 ,  A61P35/00

CPC classification number: C12Q1/6886 ,  C12Q2600/158

Abstract: The unexpected expression of tryptophan 2,3-dioxygenase (TDO2) in cancer cells and tumors has been established. Methods for diagnosing cancer based on the expression of TDO2 are provided, as are methods for treating cancer and inhibiting the growth of cancer cells by inhibiting TDO2, as well as pharmaceutical compositions.

Abstract translation: 已经建立了色氨酸2,3-双加氧酶（TDO2）在癌细胞和肿瘤中的意想不到的表达。 提供了基于TDO2的表达来诊断癌症的方法，以及通过抑制TDO 2以及药物组合物来治疗癌症并抑制癌细胞生长的方法。

公开(公告)号：US20110112282A1

公开(公告)日：2011-05-12

申请号：US12736526

申请日：2009-04-15

Applicant: Ute Roehrig ,  Loay Awad ,  Olivier Michelin ,  Benoit Van Den Eynde ,  Luc Pilotte ,  Vincent Stroobant ,  Pierre Larrieu

Inventor： Ute Roehrig ,  Loay Awad ,  Olivier Michelin ,  Benoit Van Den Eynde ,  Luc Pilotte ,  Vincent Stroobant ,  Pierre Larrieu

IPC: C07H7/04 ,  C07D209/48 ,  C07C211/58 ,  C07C211/63 ,  C07D215/38 ,  C07C237/20 ,  C07D207/16

CPC classification number: A61K31/136 ,  A61K31/05 ,  A61K31/085 ,  A61K31/12 ,  A61K31/167 ,  A61K31/4045 ,  A61K31/4192 ,  A61K31/428 ,  A61K31/4439 ,  A61K31/47 ,  C07C35/36 ,  C07C35/38 ,  C07C39/367 ,  C07C43/23 ,  C07C49/786 ,  C07C49/83 ,  C07C215/86 ,  C07C217/90 ,  C07C237/04 ,  C07C251/22 ,  C07C2602/10 ,  C07C2603/18 ,  C07D207/16 ,  C07D209/14 ,  C07D209/48 ,  C07D209/88 ,  C07D215/26 ,  C07D215/38 ,  C07D215/40 ,  C07D249/06 ,  C07D277/36 ,  C07D277/40 ,  C07D277/72 ,  C07D277/74 ,  C07D401/04

Abstract: Compounds of formula (I), and pharmaceutically acceptable salts thereof, in which each compound is adapted to occupy the binding site of human IDO, which comprises a large hydrophobic pocket A and a second, proximal hydrophobic pocket B, the compound comprising at least one of the following elements: (i) a large hydrophobic fragment to substantially fill pocket A in the binding site of human IDO; (ii) an atom that can coordinate to the heme iron of human IDO, (iii) a positively charged group that can form a salt-bridge with the heme 7-propionate of the human IDO; (iv) a negatively charged group that can form a salt-bridge with Arg231 of the human IDO; (v) a hydrophobic group that can form van der Waals interactions with pocket B; and (vi) one or more substituents that can hydrogen bond to Ser167 and to Gly262, and as IDO inhibitors and their therapeutic use, eg in the treatment of cancer.

Abstract translation: 其中每种化合物适于占据人IDO的结合位点的式（I）化合物及其药学上可接受的盐，其包含大的疏水性口袋A和第二近端疏水口袋B，所述化合物包含至少一种 的以下元素：（i）大的疏水性片段，以基本上填充人IDO的结合位点中的口袋A; （ii）可以配合人类IDO的血红素铁的原子，（iii）可以与人类IDO的7-丙酸血红素形成盐桥的带正电荷的基团; （iv）可以与人类IDO的Arg231形成盐桥的带负电荷的基团; （v）可与袋B形成范德华相互作用的疏水基团; 和（vi）可以与Ser167和Gly262氢键合的一个或多个取代基，以及作为IDO抑制剂及其治疗用途，例如用于治疗癌症。