Patent RU-2302414-C2 (RU)
Inventor: STARKE INGEMAR
IPC: C07K5/087
Filed: 2001-12-17
Granted: 2007-07-10
Abstract: FIELD: synthesis of biologically active compounds. 
     SUBSTANCE: invention provides 1,5-benzothiazepines of general formula I (formulae presented below), in which R v  and R w  are independently selected from hydrogen and C 1 -C 5 -alkyl; one of R x  and R y  represents hydrogen or C 1 -C 6 -alkyl and the other hydroxy or C 1 -C 6 -alkoxy; R z  is selected from halogen, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, C 1 -C 6 -alkyl, and other residues indicated in claim 1 of invention; v is a number from 0 to 5; one of R 4  and R 5  represents group of general formula IA; R 3  and R 6  and the second from R 4  and R 5  are independently selected from hydrogen, halogen, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, C 1 -C 6 -alkyl, and other residues indicated in claim 1; R 3  and R 6  and the second from R 4  and R 5  being optionally substituted by one or several R 16  groups at their carbon atoms; D represents -O-, -N(R a )-, -S(O) b - or -CH(R a )-, wherein R a  is hydrogen or C 1 -C 6 -alkyl; and b=0-2; ring A represents aryl or heteroaryl and is optionally substituted by one or several substituents selected from R 17 ; R 7  represents hydrogen, C 1 -C 4 -alkyl, carbocyclyl, or heterocyclyl and is optionally substituted by one or several substituents selected from R 18 ; R 8  represents hydrogen or C 1 -C 4 -alkyl; R 9  represents hydrogen or C 1 -C 4 -alkyl; R 10  represents hydrogen or C 1 -C 4 -alkyl, carbocyclyl, or heterocyclyl and is optionally substituted by one or several substituents selected from R 19 ; R 11  represents carboxy, sulfo, sulfino, phosphono, tetrazolyl, -P(O)(OR c )(OR d ), -P(O)(OH)(OR c ), -P(O)(OH)(R d ), or -(O)(OR c )(R d ), wherein R c  and R d  are independently selected from C 1 -C 6 -alkyl; or R 11  represents group of general formula IB, in which X is -N(R q )-, N(R q )C(O)-, -O-, or -S(O)a, wherein a=0-2; and R q  is hydrogen or C 1 -C 4 -alkyl; R 12  represents hydrogen or C 1 -C 4 -alkyl; R 13  and R 14  are independently selected from hydrogen, C 1 -C 4 -alkyl, carbocyclyl, heterocyclyl, or R 23 , of which C 1 -C 4 -alkyl, carbocyclyl, heterocyclyl, or R 23  can be optionally independently substituted by one or several substituents selected from R 20 ; R 15  represents carboxy, sulfo, sulfino, phosphono, tetrazolyl, -P(O)(OR e )(OR f ), -P(O)(OH)(OR e ), -P(O)(OH)(R e ), or -P(O)(OR e )(R f ), wherein R e  and R f  are independently selected from C 1 -C 6 -alkyl; or R 15  represents group of general formula IC, in which R 24  is selected from hydrogen and C 1 -C 4 -alkyl; R 24  is selected from hydrogen, C 1 -C 4 -alkyl carbocyclyl, heterocyclyl, and R 27 , of which C 1 -C 4 -alkyl, carbocyclyl, heterocyclyl, or R 27  can be optionally independently substituted by one or several substituents selected from R 28 ; R 26  is selected from carboxy, sulfo, sulfino, phosphono, tetrazolyl, -P(O)(OR g )(OR h ), -P(O)(OH)(OR g ), -P(O)(OH)(R g ), or -P(O)(OR g )(R h ), wherein R g  and R g  are independently selected from C 1 -C 6 -alkyl; p=1-3; wherein meanings for R 13  can be the same or different; q=0-1; r=0-3; wherein meanings for R 14  can be the same or different; m=0-2; wherein meanings for R 10  can be the same or different; n=1-3; wherein meanings for R 7  can be the same or different; z=0-3; wherein meanings for R 25  can be the same or different; R 16 , R 17 , and R 18  are independently selected from halogen, nitro, cyano, hydroxy, carbamoyl, mercapto, sulfamoyl, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkanoyl, C 1 -C 4 -alkanoyloxy, N-(C 1 -C 4 -alkyl)amino, N,N-(di-C 1 -C 4 -alkyl)amino, C 1 -C 4 -alkyl-S(O)a (wherein a=0-2), C 1 -C 4 -alkoxycarbonyl, N-(C 1 -C 4 -alkyl)sulfamoyl, and N,N-(di-C 1 -C 4 -alkyl)sulfamoyl; wherein R 16 , R 17 , and R 18  can be optionally independently substituted by one or several of R 21  at their carbon atoms; R 19 , R 20 , R 23 , R 27 , and R 28  are independently selected from halogen, nitro, cyano, hydroxy, carbamoyl, mercapto, sulfamoyl, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkanoyl, C 1 -C 4 -alkanoyloxy, N-(C 1 -C 4 -alkyl)amino, N.N-(di-C 1 -C 4 -alkyl)amino, C 1 -C 4 -alkanoylamino, N-(C 1 -C 4 -alkyl)carbamoyl, N,N-(di-C 1 -C 4 -alkyl)carbamoyl, C 1 -C 4 -alkyl-S(O)a (wherein a=0-2), C 1 -C 4 -alkoxycarbonyl, N-(C 1 -C 4 -alkyl)sulfamoyl, N,N-(di-C 1 -C 4 -alkyl)sulfamoyl, carbocyclyl, heterocyclyl, sulfo, sulfino, amidino, phosphono, -P(O)(OR a )(OR b ), -P(O)(OH)(OR a ), -P(O)(OH)(R a ), or -P(O)(OR a )(R b ), wherein R a  and R b  are independently selected from C 1 -C 6 -alkyl and wherein R 19 , R 20 , R 23 , R 27 , and R 28  can be optionally independently substituted by one or several of R 22  at their carbon atoms; R 21  and R 22  are independently selected from halogen, hydroxy, cyano, carbamoyl, mercapto, sulfamoyl, trifluoromethyl, trifluoromethoxy, methyl, ethyl, methoxy, ethoxy, vinyl, allyl, ethynyl, methoxycarbonyl, formyl, acetyl, formamido, acetylamino, acetoxy, methylamino, dimethylamino, N-methylcarbamoyl, N,N-dimethylcarbamoyl, methylthio, methylsulfinyl, mesyl, N-methylsulfamoyl, N,N-dimethylsulfamoyl; or pharmaceutically acceptable salt thereof, solvate, or salt solvate. Described are also method for preparing compounds of formula I, pharmaceutical compositions based on compounds I, and a method for achieving inhibiting effect relative to interscapular brown adipose tissue (IBAT), and intermediates.   (I),   (IA),   (IB),   (IC). 
     EFFECT: expanded synthetic possibilities in the 1,5-benzothiazepine series. 
     36 cl, 121 ex