Patent ID: 6242494
Filing Date: 2001-06-05
Classification: C07C,C07D

Abstract:
A compound having the formula (I): ##STR4##or a pharmaceutically acceptable salt thereof, wherein the small numerals denote chrial centers in the compound;m is 1-3;R.sup.1 is selected from the group consisting of(1) hydrogen,(2) alkyl,(3) carboxaldehyde,(4) alkanoyl, where the alkanoyl can be optionally substituted with hydroxyl,and(5) --(CH.sub.2).sub.n CO.sub.2 R.sup.4, where n is 0-6, and R.sup.4 is selected from the group consisting of(a) hydrogen,(b) alkyl,(c) cycloalkyl,(d) (cycloalkyl)alkyl,(e) aryl,and(f) arylalkyl,where (c) and (d) can be optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of(i) alkyl,(ii) alkoxy,and(iii) aryl,andwhere (e) and (f) can be optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of(i) alkyl,(ii) alkanoyl,(iii) alkoxy,(iv) --CO.sub.2 R.sup.4,, where R.sup.4, is selected from the group consisting of,(a) hydrogen,(b) alkyl,(c) cycloalkyl,(d) (cycloalkyl)alkyl,(e) eryl,and(f) arylalkyl,(v) alkanoyloxy,(vi) carboxaldehyde,(vii) cycloalkyl,(viii) cycloalkenyl,(ix) halo,(x) nitro,(xi) perfluoroalkyl,(xii) perfluoroalkoxy,(xiii) arylsulfonylalkyl,(xiv) aryloylalkyloxycarbonylalkyl,(xv) --NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are independently selected from the group consisting of(1) hydrogen,(2) alkyl optionally substituted with alkoxy,(3) aryl,(4) arylalkyl,and(5') a nitrogen-protecting group,(xvi) --SO.sub.2 NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above,and(xvii) --C(O)NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above;R.sup.2 is selected from the group consisting of(1) alkyl,(2) cycloalkyl,(3) (cycloalkyl)alkyl,(4) --C(H)(SR.sup.15)(SR.sup.15'), where R.sup.15 and R.sup.15' are alkyl, or R.sup.15 and R.sup.15 ', together with the sulfurs to which they are attached, are a 1,3-dithiolane ring of a 1,3-dithiane ring,(5) aryl,(6) arylalkyl,and(7) --SR.sup.5, where R.sup.5 is selected from the group consisting of(a) alkyl,(b) cycloalkyl,(c) (cycloalkyl)alkyl,and(d) benzyl, where the benzyl can be optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of(i) alkyl,(ii) alkanoyl,(iii) alkoxy,(iv) --CO.sub.2 R.sup.4, where R.sup.4 is defined above,(v) alkanoyloxy,(vi) carboxaldehyde,(vii) cycloalkyl,(viii) cycloalkenyl,(ix) halo,(x) nitro,(xi) perfluoroalkyl,(xii) perfluoroalkoxy,(xiii) --NR.sup.6 R.sup.6,, where R.sup.6 and R.sup.6' are defined above,(xiv) --SO.sub.2 NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above,and(xv) --C(O)NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above;R.sup.3 is selected from the group consisting of(1) and aminoacyl group optionally capped with a carboxyl protecting group,(2) --N(R.sup.6)(CH.sub.2).sub.p R.sup.7, where p is 0-6, R.sup.6 is defined above, and R.sup.7 is selected from the group consisting of(a) hydrogen,(b) alkyl, where the alkyl can be optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of(i) oxo,(ii) thioxo,(iii) alkoxy,(iv) --CO.sub.2 R.sup.4, where R.sup.4 is defined above,(v) alkanoyloxy,(vi) carboxaldehyde,(vii) cycloalkyl,(viii) cycloalkenyl,(ix) halo,(x) nitro,(xi) perfluoroalkyl,(xii) perfluoroalkoxy,(xiii) --NR.sup.6 R.sup.6,, where R.sup.6 and R.sup.6' are defined above,(xiv) --SO.sub.2 NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above,(xv) --C(O)NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above,(xvi) aryl, and(xvii) hydroxy,(c) cycloalkyl, where the cycloalkyl can be optionally substituted with 1, 2, or 3 substituents indepdently selected from the group consisting of(i) alkyl,(ii) halo,(iii) oxo, and(iv) aryl,(d) aryl, where the aryl can be optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of(i) alkyl,(ii) alkanoyl,(iii) alkoxy,(iv) --CO.sub.2 R.sup.4, where R.sup.4 is defined above,(v) alkanoyloxy,(vi) carboxyaldehyde,(vii) cycloalkyl,(viii) cycloalkenyl,(ix) halo,(x) nitro,(xi) perfluoroalkyl,(xii) perfluoroalkoxy,(xiii) --NR.sup.6 R.sup.6,, where R.sup.6 and R.sup.6' are defined above,(xiv) --SO.sub.2 NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above,(xv) --C(O)NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above,(xvi) aryloxy,(xvii) arylalkoxy,(xvi) aryl, and(xvii) hydroxy,(e) --CO.sub.2 R.sup.4, where R.sup.4 is defined above,(f) --CONR.sup.6 R.sup.8, where R.sup.6 is defined above, and R.sup.8 is selected from the group consisting of(i) hydrogen(ii) alkyl, and(iii) aryl,where (ii) and (iii) can be optionally substituted with one, two, or three groups independently selected from the group consisting of(1') alkyl,(2') alkanoyl,(3') alkoxy,(4') --CO.sub.2 R.sup.4, where R.sup.4 is defined above,(5') alkanoyloxy,(6') carboxyaldehyde,(7') cycloalkyl,(8') cycloalkenyl,(9') halo,(10') nitro,(11') perfluoroalkyl,(12') perfluoroalkoxy,(13') --NR.sup.6 R.sup.6,, where R.sup.6 and R.sup.6' are defined above,(14') --SO.sub.2 NR.sup.6 N.sup.6', where R.sup.6 and R.sup.6' are defined above,(15') --C(O)NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above,(16') aryloxy,(17') arylalkoxy,(18') aryl, and(19') hydroxy,(g) --NR.sup.6 R.sup.8, where R.sup.6 and R.sup.8 are defined above, and(h) --N(R.sup.6)SO.sub.2 R.sup.12, where R.sup.6 is defined previously, and R.sup.12 is selected from the group consisting of(i) alkyl,(ii) aryl, and(iii) arylalkyl,where (ii) and (iii) can be optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of(1') alkyl,(2') alkanoyl,(3') alkoxy,(4') --CO.sub.2 R.sup.4, where R.sup.4 is defined above,(5') alkanoyloxy,(6') carboxaldehyde,(7') cycloalkyl,(8') cycloalkenyl,(9') halo,(10') nitro,(11') perfluoroalkyl,(12') perfluoroalkoxy,(13') --NR.sup.6 R.sup.6,, where R.sup.6 and R.sup.6' are defined above,(14') --SO.sub.2 NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above,(15') --C(O)NR.sup.6 R.sup.6', where R.sup.6 and R.sup.6' are defined above,(16') aryloxy,(17') arylalkoxy,(18') aryl, and(19') hydroxy,and(3) --O(CH.sub.2).sub.p R.sup.7 are defined above;with the proviso that at least one of R.sup.1, R.sup.2, or R.sup.3 has contained therein an aryl or cycloalkyl group;X is hydroxyl or sulfhydryl;andY is hydrogen;orX and Y, taken together with the carbon atom to which they are attached, form a carbonyl or thiocarbonyl;with the proviso that when X is hydroxyl; Y is hydrogen; R.sup.3 is --N(R.sup.6)(CH.sub.2).sub.p R.sup.7 wherein is hydrogen, p is 0-6, and R.sup.7 is alkyl, alkoxycarbonyl, carboxyl, or phenyl; and R.sup.2 is phenyl, m is not 1;andwith the proviso that when X and Y, together with the carbon atom to which they are attached, are carbonyl; R.sup.3 is --N(R.sup.6)(CH.sub.2).sub.p R.sup.7 wherein R.sup.6 is hydrogen, p is 0-6, and R.sup.7 is alkyl, alkoxycarbonyl, carboxyl, or phenyl; and R.sup.2 is phenyl, m is not 1.