Patent RU-2333199-C2 (RU)
IPC: A61K31/397
Filed: 2003-07-01
Granted: 2008-09-10
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention concerns a compound of the formula (I)   , where A ring is selected out of phenyl or thienyl; X is selected out of -CR 2 R 3 -, -O- and -S(O) a -; where a is 0-2; Y is selected out of -CR 4 R 5 -, -O- and -S(O) a -; where a is 0-2; at least one -CR 2 R 3 - or -CR 4 R 5 - group is present; R 1  is independently selected out of halogeno, C 1-6 alkyl and C 1-6 ealkoxy; b is equal to 0-3; R 2  and R 3 , R 4  and R 5  are independently selected out of hydrogen, hydroxy, C 1-6 alkyl and C 1-6 alkoxy; or R 2  and R 3 , R 4  and R 5  together form oxogroup; R 6  is independently selected out of halogeno, C 1-6 alkyl and C 1-6 alkoxy; c is 0-5; R 7  is independently selected out of halogeno, trifluoromethyl, trifluoromethoxy, methyl, ethyl, methoxy and ethoxy; d is 0-4; R 9  is hydrogen or C 1-4 alkyl; R 10  is hydrogen or C 1-4 alkyl; R 11  and R 12  are independently selected out of hydrogen, C 1-4 alkyl or carbocyclyl; where R 11  and R 12  can possibly be independently substituted for carbon atom with one or more substitute selected out of R 25 ; R 13  is hydrogen, C 1-4 alkyl or carbocyclyl; where R 13  can possibly be substituted for carbon atom with one or more substitute selected out of R 27 ; R 14  is hydrogen, hydroxy, amino, carbamoyl, mercapto, sulfamoyl, etc; or R 14  is a group of the formula (IA)   , where Z is -N(R 35 )-; where R 35  is hydrogen or C 1-4 alkyl; R 15  is hydrogen or C 1-4 alkyl; R 16  and R 17  are independently selected out of hydrogen, hydroxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, C 1-6 alkyl, C 1-6 alkoxy, N-(C 1-6 alkyl)-amino etc; R 18  is selected out of hydroxy, amino, carbamoyl, mercapto, sulfamoyl, C 1-10 alkyl, C 1-10 alkoxy, N-(C 1-10 alkyl)amino, N,N-(C 1-10 alkyl) 2 amino, etc; p is 1-3; q is 0-1; r is 0-3; m is 0-2; n is 1-2; where R 1 , R 6 , R 7 , R 16 , R 17 , R 13 , R 9  can be equal or different; R 25 , R 27  and R 33  are independently selected out of hydroxy, amino, carbamoyl, mercapto, sulfamoyl, C 1-10 alkyl, C 1-10 alkoxy, C 1-10 alkoxycarbonyl, N-(C 1-10 alkyl)amino, etc; where carbocyclyl is a saturated, partially saturated or non-saturated monocyclic carbon ring including 3-6 atoms; or its pharmaceutically acceptable salt, solvate, or salt solvate. Compounds of the formula (I) or its pharmaceutically acceptable salts, solvates, or salt solvates are obtained by interaction of acid of the formula (IV)   or its activated derivative with amine of the formula (V)   . Compounds of the formula (I), where R 14  is a group of the formula (IA), are obtained by interaction of compound of the formula (VI)  , where R 14  is carboxy, or its activated derivative, with amine of the formula (VI). Compounds of the formula (I), where X or Y is -S(O) a -, and a is 1 or 2, is obtained by oxidation of compound of the formula (I), where X or Y is -S(O) a -, and a is 0 (for compounds of the formula (I), where a is 1 or 2), or a is 1 (for compounds of the formula (I), where a is 2). The invention concerns pharmaceutical composition with inhibition effect on cholesterol absorption containing effective quantity of compound of the formula (I) combined with pharmaceutically acceptable dilutant or carrier, and combination of compound of the formula (I) and hydroxymethylglutaryl-coenzyme A (HMG Co-A) reductase inhibitor. Compounds of the formula (I) are applied to produce inhibition effect on cholesterol absorption or in hyperlipidemic state treatment of haematothermal animals. 
     EFFECT: obtaining diphenylazetidinone derivatives with inhibition effect on cholesterol absorption. 
     38 cl, 54 ex