Patent RU-2734261-C2 (RU)
Title: Optionally condensed heterocyclyl-substituted pyrimidine derivatives suitable for treating inflammatory, metabolic, oncological and autoimmune diseases
Inventor: SCHRODER GLAD SANNE
IPC: C07D405/14
Filed: 2015-07-31
Granted: 2020-10-13
Abstract: FIELD: pharmaceuticals. 
     SUBSTANCE: invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, where Y is NR; R is hydrogen or C 1-4 alkyl; R 1  denotes hydrogen, C 1-4 alkyl or C 1-4 alkyl substituted with halogen; R 2  is halogen; or R and R 2  are combined to form condensed 5-member heteroaryl ring, containing 1 nitrogen heteroatom; R 3  is selected from a group consisting of hydrogen, halogen, C 1-4 alkyl, C 1-4 alkyl substituted with halogen, C 1-4 alkoxy, C 1-4 alkoxy substituted with halogen, and oxo; R 4a  is selected from a group consisting of hydrogen, halogen, -OH, -CN, C 1-6 alkyl, C 1-6 alkyl substituted with -C(=O)NR 8 R 9 , C 1-6 alkyl substituted by halogen, C 1 -C 6 alkoxy, C 1 -C 6 alkoxy substituted with halogen, and 5–6-member heteroaryl containing 1–3 nitrogen heteroatoms; R 4b  is selected from a group, consisting of hydrogen, halogen, oxo, -OH, C 1-4 alkyl substituted with halogen, C 1-4 alkyl, C 1-4 alkoxy and C 1-4 alkoxy substituted with halogen; R 5  is -(CR 8 R 9 )p-CR 13 R 14 R 15 ; n, m and p are integers, independently selected from a group consisting of 0, 1 and 2; R 6a  is selected from a group consisting of hydrogen, C 1-6 alkyl and C 1-6 alkyl substituted with hydroxyl; R 6b  is hydrogen; each R 7  independently represents hydrogen or C 1-6 alkyl; R 8  and R 9  are independently selected from a group consisting of hydrogen, C 1-6 alkyl and C 1-6 alkyl substituted with hydroxyl, a group of di-C 1-6 alkylamino, -COOH, NH 2 , C 1-6  alkoxy or halogen; R 13  is absent or selected from the group consisting of hydrogen, -OH, -CN, halogen, C 1-6 alkyl, C 1-6 alkyl substituted with hydroxy, halogen, C 1-6 alkoxy or -NR 8 SO 2 R 7 , C 1-6 alkoxy, -(CR 8 R 9 )pC(=O)OR 7 , -(CR 8 R 9 )p-SO 2 R 7  and -(CR 8 R 9 )pC(=O)NR 8 R 9 ; R 14  and R 15  are combined to form a ring system selected from a group consisting of substituted or unsubstituted C 3-8 cycloalkyl, substituted or unsubstituted C 3-7 heteroalicylic, containing 1–2 heteroatoms, independently selected from a group consisting of oxygen, nitrogen and optionally oxidised sulfur, substituted or unsubstituted phenyl and substituted or unsubstituted 5–6 membered heteroaryl containing 1–4 heteroatoms, independently selected from nitrogen, oxygen and sulfur; where, when the ring system is substituted, the substituent is present once or twice and is -(CH 2 ) q (R 5a ), where R 5a  is independently selected from a group, consisting of -CH 2 COOR 20 , -COOR 20 , -CH 2 CONR 21 R 22 , -CN, -CH 2 -CN, C 1-6 alkyl, -C(=O)-C 1-6 alkyl, -OR 20  , -OH, -COR 20 , morpholinyl, -C(=O)-morpholinyl, -OCH 2 -tetrahydrofuryl, piperazinonyl, piperidinyl-CONR 21 R 22 , -CONR 21 R 22 , -CH 2 -triazolyl, -CF 3 , imidazolyl-2,4-dione, methyl-substituted imidazolyl-2,4-dione, tetrazolyl, CH 2 -tetrazolyl, piperidyl-CH 2 OR 20 , possibly methyl substituted pyrrolidonyl, -NR 21 SO 2 R 20 , -CH 2 OR 20 , -SO 3 R 20 , -SO 2 R 20 , -CH 2 -SO 2 R 20 , -CH 2 C(CH 3 ) 2 (OR 20 ), -CH 2 CH(CH 3 )(OR 20 ), -CH(OR 20 )CH 3 , -SO 2 NR 21 R 22 , -CH 2 -SO 2 NR 21 R 22 , -NR 21 SO 2 R 20 , optionally methyl substituted C 3-6 cycloalkyl and halogen, and q is an integer selected from 0, 1 and 2; R 20 , R 21  and R 22  are independently selected from a group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkyl, substituted with one to three halogens or C 1-6 alkoxy, -CN, and C 3-6 cycloalkyl; B is a ring system selected from a group, consisting of phenyl, naphthyl and 5–6-member heteroaryl containing 1–2 nitrogen atoms; C is a ring system selected from C 3-5 heteroalicyclyl, containing nitrogen heteroatom and optionally containing additional heteroatom nitrogen or oxygen, and 5-member heteroaryl, containing nitrogen heteroatom and optionally containing 1–2 additional heteroatoms independently selected from nitrogen and oxygen; where B is bonded to carbon atom adjacent to atom N of ring system C. Invention also relates to pharmaceutical composition, having the property of an inhibitor of activity of an orphan receptor, associated with a receptor of retinoic acid (ROR), based on said compounds. 
     
       
     
     formula (I) 
     EFFECT: technical result is obtaining novel compounds and a pharmaceutical composition based thereon, which can be used in medicine for treating inflammatory, metabolic, oncological and autoimmune diseases. 
     39 cl, 3 dwg, 5 tbl, 205 ex