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    • 31. 发明专利
    • AT213726T
    • 2002-03-15
    • AT95939677
    • 1995-11-15
    • SCHERING CORP
    • MCKITTRICK BRIAN ADUGAR SUNDEEPBURNETT DUANE A
    • A61K31/395A61K31/397A61K31/44A61K31/4427A61K31/4433A61P3/06A61P9/10C07D205/08C07D401/12C07D409/12
    • Sulfur-substituted azetidinone hypocholesterolemic agents of the formula I or a pharmaceutically acceptable salt thereof, wherein: Ar1 is aryl, R10-substituted aryl or heteroaryl; Ar2 is aryl or R4-substituted aryl; Ar3 is aryl or R5-substituted aryl; X and Y are -CH2-, -CH(lower alkyl)- or -C(dilower alkyl)-; R is -OR6, -O(CO)R6, -O(CO)OR9 or -O(CO)NR6R7; R1 is hydrogen, lower alkyl or aryl; or R and R1 together are =O; q is 0 or 1; r is 0, 1 or 2; m and n are 0-5; provided that the sum of m, n and q is 1-5; R4 is selected from lower alkyl, -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -(lower alkylene)-COOR6 and -CH=CH-COOR6; R5 is selected from -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -CF3, -CN, -NO2, halogen, -(lower alkylene)COOR6 and -CH=CH-COOR6; R6, R7 and R8 are H, lower alkyl, aryl or aryl-substituted lower alkyl; R9 is lower alkyl, aryl or aryl-substituted lower alkyl; and R10 is selected from lower alkyl, -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -CF3, -CN, -NO2 and halogen; are disclosed, as well as pharmaceutical compositions containing them, and a method of lowering serum cholesterol by administering said compounds, alone or in combination with a cholesterol biosynthesis inhibitor.
    • 34. 发明专利
    • ES2155849T3
    • 2001-06-01
    • ES94907200
    • 1994-01-19
    • SCHERING CORP
    • DUGAR SUNDEEPCLADER JOHN WBURNETT DUANE ABROWNE MARGARET EDAVIS HARRY R
    • A61K31/395A61K31/397A61K31/435A61K31/695A61P3/06A61P9/10C07D205/12C07D471/10C07F7/18
    • Novel compounds of the formula or a pharmaceutically acceptable salt thereof, wherein: R1 is R2 and R3 are independently selected from -CH2-, -CH(lower alkyl)-, -C(di-lower alkyl)-, -CH=CH- and -C(lower alkyl)=CH-; or R1 with R2, or R1 with R3, form -CH=CH- or -CH=C(lower alkyl)-; u and v are independently 0-3, provided both are not zero; R4 is B-(CH2)mC(O)-; m is 0-5; B-(CH2)q-; q is 0-6; B-(CH2)e-Z-(CH2)r; Z is -O-, -C(O)-, phenylene, -N(R8)- or -S(O)0-2-, e and r is 0-5; the sum of e and r is 0-6; B-(C2-C6 alkenylene)-; B'-(C4-C6 alkadienylene)-; B-(CH2)t-Z-(C2-C6 alkenylene)-; t is 0-3; the sum of t and the number of carbon atoms in the alkenylene chain is 2-6; B-(CH2)f-V-(CH2)g-; V is cycloalkylene, f is 1-5, g is 0-5; the sum of f and g is 1-6; B-(CH2)t-V-(C2-C6 alkenylene)- or B'-(C2-C6 alkenylene)-V-(CH2)t-; the sum of t and the number of carbon atoms in the alkenylene chain is 2-6, B-(CH2)a-Z-(CH2)b-V-(CH2)d-; a, b and d are 0-6; the sum of a, b and d is 0-6; T-(CH2)s-; T is cycloalkyl, s is 0-6; or R1 and R4 together form B is optionally-substituted phenyl, indanyl, indenyl, naphthyl, tetrahydronaphthyl or optionally substituted-heteroaryl; and R20 and R21 are independently optionally-substituted phenyl, optionally-substituted naphthyl, indanyl, indenyl, tetrahydronaphthyl, benzodioxolyl, optionally-substituted heteroaryl, optionally-substituted benzofused heteroaryl or cyclopropyl, pharmaceutical compositions, the use as hypocholesterolemic agents, processes for preparing, and the use in combination with cholesterol biosynthesis inhibitors to treat or prevent athersclerosis.
    • 36. 发明专利
    • Sulfur-substituted azetidinone compounds useful as hypocholesterolemic agents
    • AU698750B2
    • 1998-11-05
    • AU4140196
    • 1995-11-15
    • SCHERING CORP
    • MCKITTRICK BRIAN ADUGAR SUNDEEPBURNETT DUANE A
    • A61K31/395A61K31/397A61K31/44A61K31/4427A61K31/4433A61P3/06A61P9/10C07D205/08C07D401/12C07D409/12
    • Sulfur-substituted azetidinone hypocholesterolemic agents of the formula I or a pharmaceutically acceptable salt thereof, wherein: Ar1 is aryl, R10-substituted aryl or heteroaryl; Ar2 is aryl or R4-substituted aryl; Ar3 is aryl or R5-substituted aryl; X and Y are -CH2-, -CH(lower alkyl)- or -C(dilower alkyl)-; R is -OR6, -O(CO)R6, -O(CO)OR9 or -O(CO)NR6R7; R1 is hydrogen, lower alkyl or aryl; or R and R1 together are =O; q is 0 or 1; r is 0, 1 or 2; m and n are 0-5; provided that the sum of m, n and q is 1-5; R4 is selected from lower alkyl, -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -(lower alkylene)-COOR6 and -CH=CH-COOR6; R5 is selected from -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -CF3, -CN, -NO2, halogen, -(lower alkylene)COOR6 and -CH=CH-COOR6; R6, R7 and R8 are H, lower alkyl, aryl or aryl-substituted lower alkyl; R9 is lower alkyl, aryl or aryl-substituted lower alkyl; and R10 is selected from lower alkyl, -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -CF3, -CN, -NO2 and halogen; are disclosed, as well as pharmaceutical compositions containing them, and a method of lowering serum cholesterol by administering said compounds, alone or in combination with a cholesterol biosynthesis inhibitor.
    • 38. 发明专利
    • ES2107548T3
    • 1997-12-01
    • ES92916790
    • 1992-07-21
    • SCHERING CORP
    • BURNETT DUANE ACLADER JOHN WTHIRUVENGADAM TIRUVETTIPURAM KTANN CHOU-HONGLEE JUNNINGMC ALLISTER TIMOTHY
    • A61K31/397A61K31/40A61K31/415A61K31/44A61K31/4427A61K31/443A61K31/4433A61K31/47A61K31/395A61K31/495A61K31/535A61K31/695A61P3/06A61P9/10C07D205/08C07D205/085C07D401/04C07D403/04C07D405/04C07D405/10C07D409/04C07D413/10C07F7/08C07F7/10C07F7/18
    • Novel compounds of the formula wherein A is -CH=CH-B; -C IDENTICAL C-B; -(CH2)p-X-B, wherein p is 0-2 and X is a bond, -NH- or-S(O)0-2; optionally substituted heteroaryl or benzofused heteroaryl; -C(O)-B; or wherein k is 1-2; D is B'-(CH2)mC(O)-, wherein m is 1-5; B'-(CH2)q-, wherein q is 2-6; B'-(CH2)e-Z-(CH2)r-, wherein Z is -O-, -C(O)-, phenylene, -NR8- or -S(O)0-2-, e is 0-5 and r is 1-5, provided that the sum of e and r is 1-6; B'-(alkenylene)-; B'-(alkadienylene)-; B'-(CH2)t-Z-(alkenylene), wherein t is 0-3, provided that the sum of t and the number of carbon atoms in the alkenylene chain is 2-6; B'-(CH2)f-V-(CH2)g-, wherein V is cycloalkylene, f is 1-5 and g is 0-5, provided that the sum of f and g is 1-6; B'-(CH2)t-V-(alkenylene) or B'-(alkenylene)-V-(CH2)t-, provided that the sum of t and the number of carbon atoms in the alkenylene chain is 2-6; B'-(CH2)a-Z-(CH2)b-V-(CH2)d-, wherein a, b and d are 0-6, provided that the sum of a, b and d is 0-6; T(CH2)s-, wherein T is cycloalkyl and s is 1-6; naphthylmethyl or optionally substituted heteroarylmethyl; B is optionally substituted phenyl; B' is naphthyl, optionally substituted heteroaryl or optionally substituted phenyl; R is hydrogen, fluoro, alkyl, alkenyl, alkynyl, or B-(CH2)h-, wherein h is 0-3; R4 is optionally substituted phenyl, indanyl, benzofuranyl, tetrahydronaphthyl, pyridyl, pyrazinyl, pyrimidinyl or quinolyl; are disclosed, as well as their use as hypocholesterolemic agents; the method of using compounds of the formula II wherein R20 is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted heteroaryl, or optionally substituted benzofused heteroaryl, R21, R22 and R23 are independently selected from H or R20; E, F and G are independently a bond; cycloalkylene; alkylene; alkenylene; alkynylene; a substituted alkylene, alkenylene or alkynylene chain ; an interrupted alkylene, alkenylene or alkynylene chain ; or an interrupted alkylene, alkenylene or alkynylene chain substituted by one or more substituents; or one of R21-E and R22-F is selected from the group consisting of halogeno, OH, alkoxy, -OC(O)R5, -NR10R11, -SH or -S(alkyl); R5 is alkyl, phenyl, R14-phenyl, benzyl or R14-benzyl; R10 and R11 are independently selected from H and lower alkyl, or a pharmaceutically acceptable salt thereof, in a pharmaceutically aceptable carrier as hypocholesterolemic agents is also disclosed.
    • 39. 发明专利
    • NO972272L
    • 1997-05-16
    • NO972272
    • 1997-05-16
    • SCHERING CORP
    • MCKITTRICK BRIAN ADUGAR SUNDEEPBURNETT DUANE A
    • A61K31/395A61K31/397A61K31/44A61K31/4427A61K31/4433A61P3/06A61P9/10C07D205/08C07D401/12C07D409/12
    • Sulfur-substituted azetidinone hypocholesterolemic agents of the formula I or a pharmaceutically acceptable salt thereof, wherein: Ar1 is aryl, R10-substituted aryl or heteroaryl; Ar2 is aryl or R4-substituted aryl; Ar3 is aryl or R5-substituted aryl; X and Y are -CH2-, -CH(lower alkyl)- or -C(dilower alkyl)-; R is -OR6, -O(CO)R6, -O(CO)OR9 or -O(CO)NR6R7; R1 is hydrogen, lower alkyl or aryl; or R and R1 together are =O; q is 0 or 1; r is 0, 1 or 2; m and n are 0-5; provided that the sum of m, n and q is 1-5; R4 is selected from lower alkyl, -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -(lower alkylene)-COOR6 and -CH=CH-COOR6; R5 is selected from -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -CF3, -CN, -NO2, halogen, -(lower alkylene)COOR6 and -CH=CH-COOR6; R6, R7 and R8 are H, lower alkyl, aryl or aryl-substituted lower alkyl; R9 is lower alkyl, aryl or aryl-substituted lower alkyl; and R10 is selected from lower alkyl, -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -CF3, -CN, -NO2 and halogen; are disclosed, as well as pharmaceutical compositions containing them, and a method of lowering serum cholesterol by administering said compounds, alone or in combination with a cholesterol biosynthesis inhibitor.