Oxazole compound as multi-targeted inhibitor of IRAK4 and BTK
Provided are a class of multi-targeted inhibitors of IRAK4 and BTK, and the use thereof in preparing a drug for treating IRAK4- and BTK-related diseases. The present invention specifically relates to the compounds represented by formula (II), isomers thereof or pharmaceutically acceptable salts thereof.
1 . A compound represented by formula (II) or a pharmaceutically acceptable salt thereof,
wherein,
R 1 is selected from H, F, Cl, Br, I, OH, NH 2 , CN, C 1-6 alkyl, cyclopropyl and —C(═O)—NH 2 , wherein the C 1-6 alkyl, cyclopropyl and —C(═O)—NH 2 are optionally substituted by 1, 2 or 3 R a ;
R 2 is selected from thienyl, phenyl, pyridyl, cyclopropyl, cyclohexyl and
wherein the thienyl, phenyl, pyridyl, cyclopropyl, cyclohexyl and
are optionally substituted by 1, 2, 3, 4 or 5 R b ;
T 1 is selected from CH 2 , NH and O;
R 3 is selected from C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted by 1, 2 or 3 R c ;
R a is each independently selected from F, OH, NH 2 and CN;
R b is each independently selected from H, D, F, Cl, Br, I, OH, NH 2 , CN, C 1-3 alkyl, COOH, —C(═O)—C 1-3 alkyl, —C(═O)—O—C 1-3 alkyl and —C(═O)—NH 2 , wherein the OH, NH 2 , C 1-3 alkyl, COOH, —C(═O)—C 1-3 alkyl, —C(═O)—O—C 1-3 alkyl and —C(═O)—NH 2 are optionally substituted by 1, 2 or 3 R;
R c is each independently selected from F, OH, NH 2 , CN, CH 3 , COOH and —SO 2 CH 3 ;
R is each independently selected from F, OH, NH 2 and CH 3 .
2 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein, R 1 is selected from H, F, Cl, Br, I, OH, NH 2 , CN, C 1-3 alkyl, cyclopropyl and —C(═O)—NH 2 , wherein the C 1-3 alkyl, cyclopropyl and —C(═O)—NH 2 are optionally substituted by 1, 2 or 3 R a .
3 . The compound as defined in claim 2 , the isomer thereof or the pharmaceutically acceptable salt thereof, wherein, R 1 is selected from CN, CH 3 , CF 3 ,
and —C(═O)—NH 2 .
4 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein, R b is each independently selected from H, D, F, Cl, Br, I, OH, NH 2 , CN, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , COOH,
wherein the OH, NH 2 , CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 ,
are optionally substituted by 1, 2 or 3 R.
5 . The compound as defined in claim 4 or the pharmaceutically acceptable salt thereof, wherein, R b is each independently selected from H, D, F, Cl, OH, OCH 3 , CN, CH 3 , CH 2 OH, CH 2 NH 2 , COOH,
6 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein, R 2 is selected from thienyl, phenyl, cyclopropyl, cyclohexyl,
wherein the thienyl, phenyl, cyclopropyl, cyclohexyl,
are optionally substituted by 1, 2, 3, 4 or 5 R b .
7 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein, R 2 is selected from
8 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein, R 2 is selected from
9 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein, R 3 is selected from C 2-5 alkyl, wherein the C 2-5 alkyl is optionally substituted by 1, 2 or 3 R c .
10 . The compound as defined in claim 9 or the pharmaceutically acceptable salt thereof, wherein, R 3 is selected from CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 and CH 2 CH 2 CH(CH 3 ) 2 , wherein the CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 and CH 2 CH 2 CH(CH 3 ) 2 are optionally substituted by 1, 2 or 3 R c .
11 . The compound as defined in claim 10 or the pharmaceutically acceptable salt thereof, wherein, R 3 is selected from
12 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, the compound is selected from,
wherein, L 1 is selected from C 2-5 alkyl, and R 1 , R 3 and R b are as defined in claim 1 .
13 . A compound represented by the following formula or a pharmaceutically acceptable salt thereof,
14 . A pharmaceutical composition, comprising a therapeutically effective amount of the compound as defined in claim 1 or the pharmaceutically acceptable salt thereof as active ingredient and a pharmaceutically acceptable carrier.
15 . A method for treating diseases related to IRAK4 and BTK in a subject in need thereof, comprising administering an effective amount of the compound as defined in claim 1 or the pharmaceutically acceptable salt thereof to the subject.
16 . A method for treating diseases related to IRAK4 and BTK in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition as defined in claim 14 to the subject.
17 . A method for inhibiting IRAK4 and/or BTK in a subject in need thereof, comprising administering an effective amount of the compound as defined in claim 1 or the pharmaceutically acceptable salt thereof to the subject.
18 . A method for inhibiting IRAK4 and/or BTK in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition as defined in claim 14 to the subject.