[EN] 4H-IMIDAZO[1,5-A]INDOLE DERIVATIVES AND THEIR USE AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) AND/OR TRYPTOPHAN 2,3-DIOXYGENASE (TD02) MODULATORS<br/>[FR] DÉRIVÉS DE 4H-IMIDAZO[1,5-A]INDOLE ET LEUR UTILISATION EN TANT QUE MODULATEURS DE L'INDOLÉAMINE 2,3-DIOXYGÉNASE (IDO) ET/OU DE LA TRYPTOPHANE 2,3-DIOXYGÉNASE (TDO2)
申请人:REDX PHARMA PLC
公开号:WO2016051181A1
公开(公告)日:2016-04-07
This invention relates to novel compounds of formula (I) wherein wherein Ά' is a 5 or 6 membered aryl or heteroaryl group, unsubstituted or substituted with 1, 2 or 3 groups as defined in claim 1; X is a bond or -(CRA1R81)n- (wherein n is selected from 1, 2, 3 and 4); Y is selected from: a bond, -O-, -NRF, -S-, -C(O)-, -C(NRF)-, -C(ORF)Rc-, -C(NRFRG)RC-, -C(O)NRF-, -NRFC(O) -NRFC(O)NRG-, -NRFSO2NRG-, - SO2-, -SO2NRF-, -NRFSO2-, -OC(O)- and -C(O)O-; Z is a bond; R1 is H or a 3 to 16 membered fully saturated, partially unsaturated or aromatic mono-, di- or tri-cyc!ic moiety, which optionally may include 1, 2 or 3 heteroatoms selected from O, N and S, and which is unsubstituted or substituted with 1 to 5 substituents as defined in claim 1; R2 is selected from: H, halo, C1-4alkyl, C1-4haloalkyl, -ORA4 and C1-4alkyl substituted with -ORA4; and R3 and R4 are each independently selected from: H, halo, C1-4halkyl, C1-4haloalkyl, C3-6cycloalkyl, -ORA5, -NRA5RB4, -CN, -SRA5 and C1-4alkyl substituted with -ORA5; and pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as indoieamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxynase (TDO2) modulators (e.g. IDO1, IDO2 and/or TDO2 inhibitors).
本发明涉及公式(I)的新颖化合物,其中Ά'是一个5或6成员芳基或杂环芳基,未取代或取代为定义在权利要求1中的1、2或3个基团;X是一个键或者-(CRA1R81)n-(其中n选择自1、2、3和4);Y选择自:一个键,-O-,-NRF,-S-,-C(O)-,-C(NRF)-,-C(ORF)Rc-,-C(NRFRG)RC-,-C(O)NRF-,-NRFC(O)-,-NRFC(O)NRG-,-NRFSO2NRG-,-SO2-,-SO2NRF-,-NRFSO2-,-OC(O)-和-C(O)O-;Z是一个键;R1是H或者一个3到16成员完全饱和、部分不饱和或芳香的单、双或三环!化合物,可选地可能包括1、2或3个来自O、N和S的杂原子,未取代或取代为定义在权利要求1中的1到5个取代基;R2选择自:H,卤素,C1-4烷基,C1-4卤代烷基,-ORA4和C1-4烷基取代的-ORA4;R3和R4各自独立选择自:H,卤素,C1-4烷基,C1-4卤代烷基,C3-6环烷基,-ORA5,-NRA5RB4,-CN,-SRA5和C1-4烷基取代的-ORA5;以及包括这些新型化合物的药物组合物。更具体地,本发明涉及作为印度吲哌啶2,3-双氧酶(IDO)和/或色氨酸2,3-双氧酶(TDO2)调节剂(例如IDO1、IDO2和/或TDO2抑制剂)有用的化合物。