Patent RU-2617682-C2 (RU)
Inventor: LE-TIRAN Arno
IPC: A61P35/00
Filed: 2014-07-22
Granted: 2017-04-26
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention relates to a compound of formula (I), its enantiomers and pharmaceutically acceptable salts and compositions based thereon, which can be used in oncology:  
     
       
     
     where X and Y represent C or N, but cannot be identical, A 1  and A 2  together with atoms bearing them form heterocycle Het, selected from 5,6,7,8-tetrahydroindolizine or indolizine, or A 1  and A 2  represent H, (C 1 -C 6 )polyhaloalkyl or (C 1 -C 6 )alkyl, T represents H, (C 1 -C 6 )alkyl, optionally substituted with one-three halogen atoms, (C 1 -C 4 )alkyl-NR 1 R 2 , or (C 1 -C 4 )alkyl-OR 6 , R 1  and R 2  represent H or (C 1 -C 6 )alkyl, or R 1  and R 2  with a nitrogen atom bearing them form heterocycloalkyl, R 3  represents a cycloalkyl, heterocycloalkyl, aryl or heteroaryl, R 4  is phenyl, substituted in para-position with a group -OPO(OM)(OM'), -OPO(OM)(O - M 1   + ), -OPO(O - M 1   + )(O - M 2   + ), -OPO(O - )(O - )M 3   2+ , -OPO(OM)(O[CH 2 CH 2 O] n CH 3 ), or -OPO(O - M 1   + )(O[CH 2 CH 2 O] n CH 3 ), where M and M '  denote H, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, cycloalkyl or heterocycloalkyl from 5 or 6 members, while M 1   +  ,  M 2   +   and M 3   2+  represent pharmaceutically acceptable cations, n ranges from 1 to 5, wherein carbon atoms of previous groups or their possible substitutes can be deuterated, R 5  represents H or halogen, (C 1 -C 6 )alkyl or (C 1 -C 6 )alkoxy, R 6  represents H or (C 1 -C 6 )alkyl, R a , R b , R c  and R d  represents R 7 , halogen, (C 1 -C 6 )alkoxy, hydroxy, NR 7 R 7 '-CO-(C 0 -C 6 )alkyl-O-, or substitutes of pair (R b , R c ) together with carbon atoms, bearing them, form a ring of 5–7 members with 1 or 2 heteroatoms, selected from O and S, wherein one or more carbon atoms of ring can be deuterated or substituted with 1–3 groups, selected from halogen and (C 1 -C 6 )alkyl, R 7  and R 7 ' are H, (C 1 -C 6 )alkyl, or R 7  and R 7 ' together with a nitrogen atom, bearing them, form heterocycle, consisting of 5–7 members, "aryl" denotes phenyl, naphthyl, biphenyl or indenyl, "heteroaryl" denotes a mono- or bicyclic group, consisting of 5–10 members with at least one aromatic fragment and 1–4 heteroatoms, selected from O, S and N, "cycloalkyl" denotes a mono- or bicyclic, non-aromatic, carboxylic group consisting of 3–10 members, "heterocycloalkyl" denotes a mono-or bicyclic, non-aromatic, condensed or grouped from 3–10 ring members with 1–3 heteroatoms, selected from O, S, SO, SO 2  and N, aryl, heteroaryl, cycloalkyl and heterocycloalkyl groups, alkyl, alkenyl, alkynyl and alkoxy can be substituted with 1–3 groups, selected from (C 1 -C 6 )alkyl, (C 3 -C 6 )spiro, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S-, hydroxyl, oxo or N-oxide, nitro, cyano, -COOR', -OCOR', NR'Rʺ, (C 1 -C 6 )polyhaloalkyl, trifluoromethoxy, (C 1 -C 6 )alkylsulphonyl, halogen, aryl, heteroaryl, aryloxy, arylthio, cycloalkyl, heterocycloalkyl, optionally substituted with one or more halogens or alkyls, R' and Rʺ are H or (C 1 -C 6 )alkyl, Het group can be substituted with 1–3 groups, selected from (C 1 -C 6 )alkyl, hydroxy, (C 1 -C 6 )alkoxy, NR 1 'R 1 ʺ and halogen, wherein R 1 ' and R 1 ʺ assume values, defined for groups R' and Rʺ. 
     EFFECT: disclosed are novel effective anticancer agents and an efficient method for preparing them. 
     33 cl, 25 ex, 11 tbl