Patent RU-2330019-C2 (RU)
Title: Derivatives of piperidine, method of obtaining them, pharmaceutical composition on their basis and method of treating chemokine mediated painful state with their use
Inventor: EHLKARAZ LILIAN
IPC: A61K31/4725
Filed: 2003-02-17
Granted: 2008-07-27
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention relates to the compounds of the formula (I)   where: X is O; Y represents a bond, CH 2 , NR 35 , CH 2 NH, CH 2 NHC(O), CH(OH), CH(NHC(O)R 33 ), CH(NHS(O) 2 R 34 ), CH 2 O or CH 2 S; Z is C(O), or if Y is a bond, then Z can also be S(O) 2 ; R 1  could be substituted with phenyl; R 4  is hydrogen, C 1-6 -alkyl (substituted possibly by C 3-6 -pilkoalkyl) or C 3-6 -cycloalkyl; R 2 , R 3 , R 5 , R 6 , R 7  and R 8  are independently hydrogen, C 1-6 -alkyl or C 3-6 -cycloalkyl; type independently indicate 0 or 1; R 9  could possibly be substituted with an aryl or heterocycle; R 10 , R 32  and R 35  are independently hydrogen, C 1-6 -alkyl or C 3-6 -cycloalkyl; R 33  and R 34  are C 1-6 -alkyl or C 3-6 -cycloalkyl; where the aforesaid aryl and heterocyclic groups, when possible, can be substitute with: halogen cyanogens, nitro, hydroxyl, oxo, S(O)Kr 12 , OC(O)NR 13 R 14 , NR 15 R 16 , NR 17 C(O)R 18 , NR 19 C(O)NR 20 R 21 , S(O) 2 NR 22 R 23 , NR 24 S(O) 2 R 25 , C(O)NR 26 R 27 , C(O)R 28 , CO 2 R 29 , NR 30 CO 2 R 31 , by C 1-6 -alkyl (which itself can be monosubstituted with NHC(O)phenyl), C 1-6 -halogenalkyl, C 1-6 -alkoxy(C 1-6 )alkyl, C 1-6 -alkoxy, C 1-6 -halogenaloxy, C 1-6 -alkoxy(C 1-6 )-alkoxy, C 1-6 -alkylthio, C 2-6 -alkenyl, C 2-6 -alkinil, C 3-10 -cycloalkyl, methylenedioxy, difluoromethylenedioxy, phenyl, phenyl(C 1-4 )alkyl, phenoxy, phenylthio, phenyl(C 1-4 )alkyl, morpholinyl, heteroaryl, heteroaryl(C 1-4 )alkyl, heteroarylhydroxy of heteroaryl(C 1-4 )alkoxy, where any of the said phenyl and heteroaryl groups can be substituted by halogen, hydroxyl, nitro, S(O) r (C 1-4 -alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4 -alkyl), S(O) 2 N(C 1- . 4 -alkyl) 2 , cyanogens, C 1-4 -alkyl, C 1-4 -alkoxy, C(O)NH 2 , C(O)NH(C 1-4 -alkyl), CO 2 H, CO 2 (C 1-4 -alkyl), NHC(O)( C 1-4 -alkyl), NHS(O) 2 (C 1-4 -alkyl), C(O)( C 1-4 -alkyl), CF 3  or OCF 3 ; k and r independently mean 0, 1 or 2; R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 26 , R 27 , R 29  and R 30  independently represent hydrogen, C 1-6 -alkyl (probably replaced by halogen, hydroxyl or C 3-10 -cycloalkyl), CH 2 (C 2-6 -alkenyl), C 3-6 -cycloalkyl, phenyl (itself probably replaced by halogen, hydroxyl, nitro, NH 2 , NH(C 1-4 -alkyl), NH(C 1-4 -alkyl) 2 , S(O) 2 (C 1-4 -alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4 -alkyl), S(O) 2 N(C 1-4 -alkyl) 2 , cyanogen, C 1-4 -alkyl, C 1-4 -alkoxy, C(O)NH 2 , C(O)NH(C 1-4 -alkyl), C(O)N(C 1-4 -alkyl) 2 , CO 2 H, CO 2 (C 1-4 -alkyl), NHC(O)(C 1-4 -alkyl), NHS(O) 2 (C 1-4 -alkyl), C(O)(C 1-4 -alkyl), CF 3  or OCF 3 ) or heterocyclyl (itself probably replaced by halogen, hydroxyl, nitro, NH 2 , NH(C 1-4 -alkyl), N(C 1-4 -alkyl) 2 , S(O) 2 )(C 1-4 -alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4 -alkyl), S(O) 2 N(C 1-4 -alkyl) 2 , cyanogen, C 1-4 -alkyl, C 1-4 -alkoxy, C(O)NH 2 , C(O)NH(C 1-4 -alkyl), C(O)N(C 1-4 -alkyl) 2 , CO 2 H 5  CO 2 (C 1-4 -alkyl), NHC(O)( C 1-4 -alkyl), NHS(O) 2 (C 1-4 -alkyl), C(O)( C 1-4 -alkyl), CF 3  or OCF 3 ); alternatively, NR 13 R 14 , NR 15 R 16 , NR 20 R 21 , NR 22 R 23 , NR 26 R 27  can independently form 4-7-member heterocyclic ring, selected from the group, which includes: azetidine (which can be substituted by hydroxyl or C 1-4 -alkyl), pyrrolidine, piperidine, azepine, 1,4-morpholine or 1,4-piperazine, the latter is probably substituted by C 1-4 -alkyl on the peripheral nitrogen; R 12 , R 25 , R 28  and R 31  are independently C 1-6 -alkyl (possibly substituted by halogen, hydroxyl or C 3-10 -cycloalkyl), CH 2 (C 2-6 -alkenyl), phenyl (itself probably replaced by halogen, hydroxyl, nitro, NH 2 , NH(C 1-4 - alkyl), N(C 1-4 -alkyl) 2 , (and these alkyl groups can connect to form a ring as described hereabove for R 13  and R 14 ), S(O) 2 (C 1-4 -alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4 -alkyl), S(O) 2 N(C 1-4 -alkyl) 2  (and these alkyl groups can connec to form a ring as described hereabove for R 13  and R 14 ), cyanogen, C 1-4 - alkyl, C 1-4 - alkoxy, C(O)NH 2 , C(O)NH(C 1-4 - alkyl), C(O)N(C 1-4 -alkyl) 2  (and these alkyl groups can connect to form a ring as described hereabove for R 13  and R 14 ), CO 2 H, CO 2 (C 1-4 -alkyl), NHC(O)(C 1-4 -alkyl), NHS(O) 2 (C 1-4 -alkyl), C(O)(C 1-4 -alkyl), NHC(O)(C 1-4 -alkyl), CF 3  or OCF 3 ) or heterocyclyl (itself probably replaced by halogen, hydroxyl, nitro, NH 2 , NH(C 1-4 -alkyl), N(C 1-4 -alkyl) 2 , (and these alkyl groups can connect to form a ring as described hereabove for R 13  and R 14 ), S(O) 2 (C 1-4 -alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4 -alkyl), S(O) 2 N(C 1-4 -alkyl) 2  (and these alkyl groups can connect to form a ring as described hereabove for R 13  and R 14 ), cyanogen, C 1-4 -alkyl, C 1-4 -alkoxy, C(O)NH 2 , C(O)NH(C 1-4 - alkyl), C(O)N(C 1-4 -alkyl) 2  (and these alkyl groups can connect to form a ring as described hereabove for R 13  and R 14 ), CO 2 H, CO 2 (C 1-4 -alkyl), NHC(O)(C 1-4 -alkyl), NHS(O) 2 (C 1-4 -alkyl), C(O)(C 1-4 -alkyl), CF 3  or OCF 3 ); or its N-oxide; or its pharmaceutically acceptable salt, solvate or solvate of its salt, which are modulators of activity of chemokines (especially CCR3); also described is the pharmaceutical composition on their basis and the method of treating the chemokines mediated painful condition. 
     EFFECT: obtaining new compounds possessing useful biological properties. 
     13 cl, 238 ex