| 摘要 |
FIELD: organic chemistry, medicine, pharmacy. ^ SUBSTANCE: invention relates to substituted derivatives of imidazolidine of the formula (I): ^ wherein W means R1-A-C(R13) or compound of the formula: ^ ^ wherein ring system can be substituted with 1, 2 or 3 similar or different substituents R13; L means C(R13); m1 and m2 means independently of one another 0, 1, 2, 3 or 4 and sum m1 + m2 = 3 or 4; Y means carbonyl group; A means a direct bond or bivalent phenylene residue; B means bivalent (C1-C6)-alkylene residue wherein (C1-C6)-alkylene residue is unsubstituted or substituted with one or some similar or different residues taken among (C1-C8)-alkyl and (C3-C10)-cycloalkyl-(C1-C6)-alkyl; E means R10CO, HCO or R8O-CH2; R means hydrogen atom (H) or (C-C8)-alkyl, (C3-C12)-cycloalkyl-(C1-C8)-alkyl or, if necessary, substituted (C6-C14)-aryl wherein all R residues are not dependent of one another and can be similar or different; R1 means hydrogen atom (H), (C1-C10)-alkyl that, if necessary, can be substituted one or many times with fluorine atom or residue X-NH-C(=NH)-R20 wherein X means hydrogen atom (H); R2 means hydrogen atom (H) or (C1-C8)-alkyl; R3 means hydrogen atom (H), (C1-C10)-alkyl that can be one or many times substituted, if necessary, with fluorine atom, if necessary substituted (C6-C14)-aryl, if necessary substituted heteroaryl, (C6-C12)-bicycloalkyl, R11NH, COOR21, CONHR4 or CONHR15; R4 means (C1-C10)-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-[(C1-C10)-alkyl]-aminocarbonyl, (C1-C8)-alkoxycarbonyl, R5, R6-CO wherein R5 means, if necessary, substituted (C6-C14)-aryl; R6 means residue of natural or non-natural amino acid; R8 means hydrogen atom (H) or (C1-C10)-alkyl wherein R8 can be similar or different being independent of one another; R10 means hydroxy-group, (C1-C10)-alkoxy-group, (C1-C8)-alkylcarbonyloxy-(C1-C6)-alkoxy-group, (C1-C8)-alkoxycarbonyloxy-(C1-C6)-alkoxy-group, amino-group, mono- or di-[(C1-C10)-alkyl]-amino-group or R8R8N-CO-(C1-C6)-alkoxy-group wherein R8 residues can be similar or different being independently of one another; R11 means R12a-O-CO or R12a-S(O)2 wherein R12a means (C1-C10)-alkyl, if necessary substituted (C6-C14)-aryl, if necessary (C6-C14)-aryl-(C1-C4)-alkyl substituted by aryl residue or R15; R13 means hydrogen atom (H) or (C1-C6)-alkyl that can be substituted, if necessary, one or many times with fluorine atom; R15 means R16-(C1-C6)-alkyl or R16 wherein R16 means form 6-membered to 24-membered bicyclic or tricyclic residue; R20 means a direct bond or (C1-C6)-alkylene; R21 means hydrogen atom (H) or (C1-C8)-alkyl; R30 means one of residues R32(R)N-CO-N(R)R31 or R32(R)N-CS-N(R)R31; R32-CO-N(R)-R31 or R12a-O-CO-N(R)-R31 being R30 can't mean R32-CO-N(R)R31 if W means simultaneously R1-A-C(R13); A means a direct bond; R1 and R13 mean hydrogen atom (H); R31 means bivalent residue -R33-R34-R5-R36 wherein R36 is bound with nitrogen atom in imidazoline ring of the formula (I); R32 means (C1-C8)-alkyl that, if necessary, can be substituted one or many times with fluorine atom, (C3-C12)-cycloalkyl, if necessary substituted (C6-C14)-aryl, (C6-C14)-aryl-(C1-C8)-alkyl substituted in aryl group if necessary, substituted heteroaryl; R33 means a direct bond; R34 means bivalent residue among order (C1-C8)-alkylene, if necessary substituted (C6-C14)-arylene; R35 means a direct bond or bivalent (C1-C8)-alkylene residue; R36 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
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