Patent RU-2330841-C2 (RU)
Inventor: MAMMEN MATAJ
IPC: G01N33/94
Filed: 2004-02-13
Granted: 2008-08-10
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention concerns new compounds of the formula I:   , where: a is 0 or whole number of 1 to 3; each R 1  is selected independently out of the halogens; b is 0 or whole number of 1 to 3; each R 2  is selected independently out of the halogens; W is linked in 3 or 4 position against the nitrogen atom in piperidine ring and is O; c is 0 or whole number of 1 to 4; each R 3  is selected independently out of (1-4C)alkyls; or two groups of R 3  are linked together forming (1-3C)alkylene or oxyrane-2,3-diyl; R 4  is a bivalent group of the formula: -(R 4a ) d -(A 1 ) e -(R 4b ) t -Q-(R 4c ) g -(A 2 ) h -(R 4d ) i -, where each of d, e, f, g, h and i is selected independently out of 0 or 1; each of R 4a , R 4b , R 4c  and R 4d  is selected independently out of (1-10C)alkylene, where each alkylene group is unsubstituted or substituted by 1-5 substitutes selected independently out of (1-4C)alkyl, fluorine and hydroxy-; each of A 1  and A 2  is selected independently out of (3-7C)cycloalkylene, (6-10C)arylene, -O-(6-10C)arylene, (6-10C)arylene-O-, (2-9C)heteroarylene and (3-6C)heterocyclene where each cycloalkylene is unsubstituted or substituted by 1-4 substitutes selected independently out of (1-4C)alkyl, and each arylene, heteroarylene or heterocyclene group is unsubstituted or substituted by 1-4 substitutes selected independently out of halogens, (1-4C)alkyl, (1-4C)alkoxy-, -S(O) 2 -(1-4C)alkyl, hydroxy-, nitro- and trifluormethoxy; Q is selected out of -O-, -S(O) 2 -, -N(Q a )C(O)-, -C(O)N(Q b )-; -N(Q C )S(O) 2 -, -S(O) 2 N(Q d )-, -N(Q e )C(O)N(Q f )- and -N(Q k ) links; each of Q a , Q b , Q c , Q d , Q e , Q f  and Q k  is selected independently out of hydrogen, (1-6C)alkyl and A 3 , where alkyl group is unsubstituted or substituted by 1-3 substitutes selected independently out of fluorine, hydroxy- and (1-4C)alkoxy-; or together with nitrogen atom and R 4b  or R 4c  group to which they are linked they form 4-6-membered azacycloalkylene group; A 3  is selected independently out of (3-6C)cycloalkyl, (6-10C)aryl, (2-9C)heteroalkyl and (3-6C)heterocyclyl, where each cycloalkyl is unsubstituted or substituted by 1-4 substitutes selected independently out of (1-4C)alkyl, and each aryl, heteroaryl or heterocyclyl group is unsubstituted or substituted by 1-4 substitutes selected independently out of halogen, (1-4C)alkyl and (1-4C)alkoxy-, if the number of adjacent atoms in the shortest chain between two nitrogen atoms, to which R 4  is linked, lies within 4 to 16; R 5  is hydrogen or (1-4C)alkyl; R 6  is -NR 6a CR 6b (O), and R 7  is hydrogen; either R 6  and R 7  together form -NR 7a C(O)-CR 7b =CR 7c -; each of R 6a  and R 6b  is hydrogen or (1-4C)alkyl independently; and each of R 7a , R 7b  and R 7c  is hydrogen or (1-4C)alkyl independently; or the pharmaceutically acceptable salts, solvates or stereoisomers of the claimed compounds. The invention also concerns compounds of the formula I, 1-[2-(2-chlor-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinoline-5-yl)ethylamino]methyl}-5-methoxuphenylcarbamoyl)ethyl] piperidine-4-yl ether of biphenyl-2-ylcarbamine acid or its pharmaceutically acceptable salt or solvate, pharmaceutical composition, method of pulmonary disease treatment, method of bronchial lumen dilation for a patient, method of treatment of chronic obstructive pulmonary disease or asthma, method of obtaining the compound of the formula I, medicine based on it, and application of compounds described in any of the paragraphs 1, 13, 14, 24, 25, 26, 27 or 28. 
     EFFECT: obtaining of new biologically active compounds with high activity rate of both antagonist of muscarine receptors and β 2  agonist of adrenergic receptors. 
     42 cl, 186 ex