Patent RU-2239641-C2 (RU)
Inventor: VENER FOL KMAR
IPC: C07K5/117
Filed: 1998-11-18
Granted: 2004-11-10
Abstract: FIELD: organic chemistry, medicine, pharmacy. 
     SUBSTANCE: invention relates to substituted derivatives of imidazolidine of the formula (I):    
     wherein W means R 1 -A-C(R 13 ) or compound of the formula: 
     
       
     
     wherein ring system can be substituted with 1, 2 or 3 similar or different substituents R 13 ; L means C(R 13 ); m 1  and m 2  means independently of one another 0, 1, 2, 3 or 4 and sum m 1  + m 2  = 3 or 4; Y means carbonyl group; A means a direct bond or bivalent phenylene residue; B means bivalent (C 1 -C 6 )-alkylene residue wherein (C 1 -C 6 )-alkylene residue is unsubstituted or substituted with one or some similar or different residues taken among (C 1 -C 8 )-alkyl and (C 3 -C 10 )-cycloalkyl-(C 1 -C 6 )-alkyl; E means R 10 CO, HCO or R 8 O-CH 2 ; R means hydrogen atom (H) or (C-C 8 )-alkyl, (C 3 -C 12 )-cycloalkyl-(C 1 -C 8 )-alkyl or, if necessary, substituted (C 6 -C 14 )-aryl wherein all R residues are not dependent of one another and can be similar or different; R 1  means hydrogen atom (H), (C 1 -C 10 )-alkyl that, if necessary, can be substituted one or many times with fluorine atom or residue X-NH-C(=NH)-R 20  wherein X means hydrogen atom (H); R 2  means hydrogen atom (H) or (C 1 -C 8 )-alkyl; R 3  means hydrogen atom (H), (C 1 -C 10 )-alkyl that can be one or many times substituted, if necessary, with fluorine atom, if necessary substituted (C 6 -C 14 )-aryl, if necessary substituted heteroaryl, (C 6 -C 12 )-bicycloalkyl, R 11 NH, COOR 21 , CONHR 4  or CONHR 15 ; R 4  means (C 1 -C 10 )-alkyl that is unsubstituted or substituted once or many times with similar or different residues taken among of the order: hydroxycarbonyl, aminocarbonyl, mono- or di-[(C 1 -C 10 )-alkyl]-aminocarbonyl, (C 1 -C 8 )-alkoxycarbonyl, R 5 , R 6 -CO wherein R 5  means, if necessary, substituted (C 6 -C 14 )-aryl; R 6  means residue of natural or non-natural amino acid; R 8  means hydrogen atom (H) or (C 1 -C 10 )-alkyl wherein R 8  can be similar or different being independent of one another; R 10  means hydroxy-group, (C 1 -C 10 )-alkoxy-group, (C 1 -C 8 )-alkylcarbonyloxy-(C 1 -C 6 )-alkoxy-group, (C 1 -C 8 )-alkoxycarbonyloxy-(C 1 -C 6 )-alkoxy-group, amino-group, mono- or di-[(C 1 -C 10 )-alkyl]-amino-group or R 8 R 8 N-CO-(C 1 -C 6 )-alkoxy-group wherein R 8  residues can be similar or different being independently of one another; R 11  means R 12a -O-CO or R 12a -S(O) 2  wherein R 12a  means (C 1 -C 10 )-alkyl, if necessary substituted (C 6 -C 14 )-aryl, if necessary (C 6 -C 14 )-aryl-(C 1 -C 4 )-alkyl substituted by aryl residue or R 15 ; R 13  means hydrogen atom (H) or (C 1 -C 6 )-alkyl that can be substituted, if necessary, one or many times with fluorine atom; R 15  means R 16 -(C 1 -C 6 )-alkyl or R 16  wherein R 16  means form 6-membered to 24-membered bicyclic or tricyclic residue; R 20  means a direct bond or (C 1 -C 6 )-alkylene; R 21  means hydrogen atom (H) or (C 1 -C 8 )-alkyl; R 30  means one of residues R 32 (R)N-CO-N(R)R 31  or R 32 (R)N-CS-N(R)R 31 ; R 32 -CO-N(R)-R 31  or R 12a -O-CO-N(R)-R 31  being R 30  can't mean R 32 -CO-N(R)R 31  if W means simultaneously R 1 -A-C(R 13 ); A means a direct bond; R 1  and R 13  mean hydrogen atom (H); R 31  means bivalent residue -R 33 -R 34 -R 5 -R 36  wherein R 36  is bound with nitrogen atom in imidazoline ring of the formula (I); R 32  means (C 1 -C 8 )-alkyl that, if necessary, can be substituted one or many times with fluorine atom, (C 3 -C 12 )-cycloalkyl, if necessary substituted (C 6 -C 14 )-aryl, (C 6 -C 14 )-aryl-(C 1 -C 8 )-alkyl substituted in aryl group if necessary, substituted heteroaryl; R 33  means a direct bond; R 34  means bivalent residue among order (C 1 -C 8 )-alkylene, if necessary substituted (C 6 -C 14 )-arylene; R 35  means a direct bond or bivalent (C 1 -C 8 )-alkylene residue; R 36  means a direct bond; e and h mean independently of one another 0 or 1; in all their steroisomeric forms and mixtures and in all ratios, and their physiologically acceptable salt. Also, invention relates to a method for preparing compounds of the formula (I) and pharmaceutical preparation eliciting ability to inhibit adhesion and/or migration of leukocytes and/or VLA-4-receptors. 
     EFFECT: improved preparing method, valuable medicinal properties of preparation. 
     23 cl, 13 tbl, 221 ex