Patent RU-2298003-C2 (RU)
Inventor: KHOFMAJSTER ARMIN
IPC: A61K31/4725
Filed: 2002-11-20
Granted: 2007-04-27
Abstract: FIELD: organic chemistry, medicine, pharmacy. 
     SUBSTANCE: invention relates to novel substituted derivatives of 4-phenyltetrahydroisoquinoline of the general formula (I):   wherein R1, R2, R3 and R4 mean independently of one another hydrogen (H), fluorine (F), chloride (Cl), bromine (Br) atoms, C a H 2a+1  wherein one or more atoms H are substituted with F, -NR11R12 or -SO j -R15 wherein a = 1-8; R11 and R12 mean independently of one another H, C e H 2e+1  or C rr H 2rr-1  wherein e = 1-4; rr = 3, 4, or in common with nitrogen atom to which they are bound form a cycle chosen from group consisting of pyrrolidinyl, piperidinyl, N-methylpiperazinyl, piperazinyl or morpholine; j = 1 or 2; R15 means C k H 2k+1  wherein k = 1-8; R5 means C p H 2p+1  or C ss H 2ss-1 ; p = 1-8; ss = 3-8; R6 means H; R7, R8 and R9 mean independently of one another mean -SO w R23, -NR32COR30, NR32CSR30, -NR32SO bb R30, H, F, Cl, Br, -OH, -NH 2 , C ee H 2ee+1 , -NR40R41, -CONR40R41 or -COOR42 wherein w = 0, 1 or 2; bb = 2 or 3; R23 means NR25R26 wherein R25 and R26 mean independently of one another H or C z H 2z+1 , C zz H 2zz-1  wherein z = 1-8; zz = 3-8 wherein in C z H 2z+1  and C zz H 2zz-1  one or more H atoms are substituted with fluorine atom and one or more CH 2 -groups are substituted with -C(=O) or NR27 wherein R27 means H or C aa H 2aa+1  wherein aa = 1-4; or R25 and R26 in common with nitrogen atom to which they are bound form 5-, 6- or 7-membered cycle; R30 means H, C cc H 2cc+1 , C yy H 2yy-1 , pyrrolydinyl, piperidinyl wherein in their cycles CH 2 -group can be substituted with oxygen atom (O) or -NR33; R32 and R33 mean independently of one another H or C h H 2h+1  wherein cc = 1-8; yy = 3-8; h = 1-8 wherein in the group C h H 2h+1  one or more hydrogen atoms are substituted with fluorine atom, and in the groups C cc H 2cc+1  and C yy H 2yy-1  one or more hydrogen atoms can be substituted with fluorine atom, and CH 2 -group can be substituted with O or -NR31 wherein NR31 means H, methyl, ethyl, acetyl or -SO 2 CH 3 ; or R30 means 6-membered heteroaryl with 1-4 nitrogen atoms, 0 or 1, S-atoms or 0, or 1 O-atom that represents unsubstituted or substituted with up to three substitutes chosen from group consisting of F, Cl, Br, J, C oo H 2oo+1  wherein one or more hydrogen atoms can be substituted with fluorine atom, -NO 2  or -NR70R71 wherein oo = 1-8; R70 and R71 mean independently of one another H, C uu H 2uu+1  or -COR72 wherein uu = 1-8; R72 means H, C vv H 2vv+1  wherein vv = 1-8; ee = 1-8; R40 and R41 mean independently of one another H, C tt H 2tt+1  or -C(NH)NH 2  wherein tt = 1-8 and wherein in the group C tt H 2tt+1  one or more CH 2 -groups can be substituted with NR44 wherein R44 means C gg H 2gg+1  wherein gg = 1-8; R42 means H or C hh H 2hh+1  wherein hh = 1-8 being, however, two substitutes from group R7, R8 and R9 can't mean -OH simultaneously, and at least one residue from R7, R8 and R9 must be chosen from group consisting of -CONR40R41, -O v SO w R23, -NR32COR30, -NR32CSR30 and -NR32SO bb R30. Also, invention relates to using above given compounds for preparing a medicinal agent. Also, invention considers a medicinal agent representing inhibitor of sodium-proton exchange of subtype III (NHE3) based on proposed compounds. Invention provides synthesis of novel compounds, a medicinal agent based on thereof for aims of treatment of such diseases as nervous system ischemia, insult and brain edema, in treatment of snore, shock, impaired respiratory impulse, as purgative agents, as agents against extoparasites, for prophylaxis of gall stones formation, as anti-atherosclerotic agents, agents against diabetes mellitus later complications, cancer diseases, fibrous diseases, endothelial dysfunction, hypertrophies and hyperplasia of organs and others. 
     EFFECT: valuable medicinal properties of compounds and medicinal agents. 
     21 cl, 15 tbl, 221 ex