Patent RU-2658912-C1 (RU)
Inventor: GUAN Khojpin
IPC: C07D491/147
Filed: 2015-06-16
Granted: 2018-06-26
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention relates to a new compound of formula (I) or its pharmaceutically acceptable salt possessing the properties of inhibitor mTOR/PI3K. Action of the double inhibitor allows simultaneously blocking multiple signal transduction sites and more efficient prevention of signal transduction, thereby overcoming or delaying the drug resistance, and has a longer and more effective effect in the cancer treatment. In the compound of formula (I)   structural unit   can be replaced by   or   ; E is selected from the group consisting of C 3-6  cycloalkyl or C 1-6  alkyl substituted with R 3 , and number R 3  is 0, 1, 2 or 3, or E is selected from the group consisting of     and   , or E is selected from the group consisting of   and   optionally substituted with 1, 2 or 3 R 3 ; where zero, one, two or three of G 1~5  are selected from N, and the remaining ones are selected from C(R 3 ); G 6  is selected from the group consisting of -C(R 3 )(R 3 )-, -C(=O)N(R 3 )-, -N(R 3 )-, -C(=NR 3 )-, -S(=O) 2 N(R 3 )-, -S(=O)N(R 3 )-, -O-, -S-, -C(=O)O-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O) 2 - and -N(R 3 )C(=O)N(R 3 )-; zero, one or two of G 7~9  are selected from N, and the remaining ones are selected from C(R 3 ); zero, one, two, three or four of G 10~16  are selected from N, and the remaining ones are selected from C(R 3 ); G 17  is selected from N or C(R 3 ); zero, one, two or three of G 18~22  are selected from the group consisting of -C(=O)N(R 3 )-, -N(R 3 )-, -C(=NR 3 )-, -S(=O) 2 N(R 3 )-, -S(=O)N(R 3 )-, -O-, -S-, -C(=O)O-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O) 2 - and -N(R 3 )C(=O)N(R 3 )-, and the remaining ones are selected from -C(R 3 )(R 3 )-; one of L and Q is -S(=O) 2 NH- and the other is a single bond; or one of L and Q is -S(=O) 2 - and the other is CH 2 ; A and T are independently selected from N or CH; one of X and Y is selected from N and the other is selected from C(R 3 ); and Z is selected from CH, or X and Y is selected from C(R 3 ) and Z is selected from CH; B is selected from the group consisting of -N(R a )-; heteroatom or heteroatom group are independently selected from the group consisting of -C(=O)N(R a )-, -N(R a )-, -C(=NR a )-, -S(=O) 2 N(R a )-, -S(=O)N(R a )-, -O-, -S-, -C(=O)O-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O) 2 - and -N(R a )C(=O)N(R a )-; each m 1  is independently selected from 0, 1, 2 or 3; R 1  is independently selected from the group consisting of H, F, Cl, Br, I, OR a , N(R b )(R c ), C 1-3  alkyl,   R 2  and R 3  are independently selected from the group consisting of H, F, Cl, Br, I, CN, OR a , N(R b )(R c ), C 1-3  alkyl optionally substituted with R d ,     D 1  is selected from the group consisting of a single bond, -C(R e )(R e )-, -C(=O)N(R a )-, -N(R a )-, -C(=NR a )-, -S(=O) 2 N(R a )-, -S(=O)N(R a )-, -O- and -S-; D 2  is selected from -C(R a )(R a )-; n is selected from 1, 2, 3, 4, 5 or 6; R a , R b  and R c  are independently selected from the group consisting of H, C 3-6  cycloalkyl or C 1-6  alkyl optionally substituted with R d ; R e  is selected from the group consisting of H, C 1-6  alkyl or alkoxy optionally substituted with R d , C 3-6  cycloalkyl optionally substituted with R d ; R d  is selected from the group consisting of F, Cl, Br, I, CN, OH, CHO, COOH, CH 3 , CF 3 , CH 3 O and CH 3 CH 2 O, and number R d  is selected from 0, 1, 2, or 3; optionally, R a  and R a  in the same D 2 , two D 2 , or R a  and one D 2  together with the same carbon atom or oxygen atom, to which they are both attached, form one 3-, 4-, 5- or 6-membered carbocyclic ring or an oxygen-containing heterocyclic ring, wherein the number of oxygen atoms is 1 or 2. 
     EFFECT: compounds can be used for treating cancer. 
     8 cl, 3 dwg, 4 tbl, 241 ex