Patent RU-2228335-C2 (RU)
Inventor: PEJMAN ANUSHIRVAN
IPC: C07D403/12
Filed: 1997-12-19
Granted: 2004-05-10
Abstract: FIELD: organic chemistry, heterocyclic compounds, chemical technology, medicine, pharmacy. SUBSTANCE: invention relates to new compounds of formulas (I)   and (Ia)   in their all stereoisomeric forms or their mixtures in all ratios, and their pharmaceutically acceptable salts eliciting antagonistic activity with respect to vitronectin receptors. Compounds can be used as inhibitors of osseous resorption by osteoclasts, tumor growth or tumor metastatic spreading and so on. Invention relates also to methods for preparing compounds of formulas (I) and (Ia) and to pharmaceutical composition based on thereof. There are following values in compounds of formulas (I) and (Ia): X means hydrogen atom, NR 6 R 6′ , fluorine, chlorine, bromine atom, OR 6 , SR 6 , hydroxy-(C 1 -C 6 )-alkyl-NH, [hydroxy-(C 1 -C 6 )-alkyl] 2 N,, amino-(C 1 -C 6 )-alkyl-NH, [amino-(C 1 -C 6 )-alkyl] 2 N,, hydroxy-(C 1 -C 6 )-alkyl-O, hydroxy-(C 1 -C 6 )-alkyl-S or NH-CO-R 6 ; Y means hydrogen atom; G means a residue of the formula (II): (CR 1 R 2 ) n -A-(CR 1 R 2 ) m -(CR 1 R 3 ) i -(CR 1 R 2 ) q -R 4  (II); W means a residue of the formula (III): -B-(CR 1 R 2 ) r -A′-(CR 1 R 2 ) s -(CR 1 R 2 ) k -(CR 1 R 2 ) t -D-E (III); G a  means a residue of the formula (IIa): -(CR 1 R 2 ) r -A′-(CR 1 R 2 ) s -(CR 1 R 2 ) k -(CR 1 R 2 ) t -D-E (IIa); W a  means a residue of the formula (IIIa): -B-(CR 1 R 2 ) n -A-(CR 1 R 2 ) m -(CR 1 R 3 ) i -(CR 1 R 2 ) q -R 4  (IIIa); A, A′ mean independently of one another a single bond, -C(O)NH- or NH-; R 1 , R 2  mean independently of one another hydrogen, fluorine, chlorine atoms, cyano-group, nitro-group, (C 1 -C 10 )-alkyl, (C 3 -C 14 )-cycloalkyl, (C 3 -C 14 )-cycloalkyl-(C 1 -C 8 )-alkyl, (C 5 -C 14 )-aryl, (C 1 -C 8 )-aryl-(C 1 -C 8 )-alkyl,   or R 6 R 6′ N-R 7 ; R 3  means independently of one another hydrogen, fluorine, chlorine atom, cyano-group, nitro-group, (C 1 -C 18 )-alkyl, (C 3 -C 14 )-cycloalkyl, (C 3 -C 14 )-cycloalkyl-(C 1 -C 8 )-alkyl,(C 5 -C 14 )-aryl,(C 5 -C 14 )-aryl-(C 1 -C 8 )-alkyl,   or R 6 N(R 6′ )S(O) p R 7  being alkyl can be mono- or multi-unsaturated and alkyl or aryl can be mono- or multi-substituted with fluorine, chlorine, bromine atom, cyano-group, R 6 R 6′ N-R 7 , nitro-group,   or R 6 -O-R 7 ; R 4  means C(O)R 8 ; R 6 , R 6′ , R 5  mean independently of one another hydrogen atom (C 1 -C 10 )-alkyl, (C 3 -C 14 )-cycloalkyl, (C 3 -C 14 )-cycloalkyl-(C 1 -C 8 )-alkyl, (C 5 -C 14 )-aryl, (C 5 -C 14 )-aryl-(C 1 -C 8 )-alkyl; R 7  means independently of one another (C 1 -C 4 )-alkylene or a single bond; R 8  means hydroxy-group, (C 1 -C 8 )-alkoxy-group, (C 5 -C 14 )-aryl- -alkoxy-group, (C 5 -C 14 )-aryloxy-group, (C 1 -C 8 )-alkylcarbonyloxy-(C 1 -C 4 )-alkoxy-group, (C 5 -C 14 )-aryl- -(C 1 -C 8 )-alkylcarbonyloxy-(C 1 -C 8 )-alkoxy- group, NR 6 R 6′ , (di-((C 1 -C 8 )-alkyl)amino)-carbonylmethyloxy-group,(di-((C 5 -C 14 )-aryl-(C 1 -C 8 )-alkyl)amino)carbonylmethyloxy- group; B means an ordinary bond, NH, CONH, piperidinyl, sulfur atom or imidazole; D means a single bond,   or -R 6 C=N-, or -R 6 C=N-NR 6 -, being bivalent residues meaning D through a free bond on the right side are bound with the group E wherein E means hydrogen atom, -NH- -CH(=NH), -C(=NH)-NH 2  or 5,6-membered aromatic or non-aromatic residue comprising optionally 1 or 2 nitrogen atoms and possibly substituted with oxo-group,, residue R 5  or R 3  or possibly condensed with phenyl group as benzimidazole residue; n = 0, 1, 2, 3, 4 or 5; m = 0, 1, 2, 3, 4 or 5; i = 0 or 1; p means independently of one another 0, 1 or 2; q = 0, 1 or 2; r = 0, 1, 2, 3, 4, 5 or 6; s = 0, 1, 2, 3, 4 or 5; t = 0, 1, 2, 3, 4 or 5; k = 0 or 1; u = 0 or 2; in their all stereoisomeric forms or their mixtures in all ratios and their pharmaceutically acceptable salts. EFFECT: improved preparing methods, valuable biological and medicinal properties of compounds. 12 cl, 1 tbl, 29 ex