US 5,843,941 AGranted

Ras farnesyl transferase inhibitors

AssigneesGenentech, Inc., Board of Regents, The University of Texas

InventorsJames C. Marsters, Jr., Michael S. Brown, Craig W. Crowley, Joseph L. Goldstein, Guy L. James, Robert S. McDowell, David Oare, Thomas E. Rawson, Mark Reynolds, Todd C. Somers

Life of this patent

Estimating the term…

Abstract

Benzodiazepine derivatives represented by the structure below are disclosed that act as potent inhibitors of ras farnesyl:protein transferase. Pharmaceutical compositions containing these benzodiazepines are provided for treatment of diseases foe which inhibition of the ras farnesyl:protein transferase as indicated. ##STR1##

Claims17

Dependent claims

A compound represented by structural formula (II):

##STR3539## where R.sup.1 is selected from the group ##STR3540## R and R' are independently selected from the group hydrogen,
halo(F, a, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkoxy,
hydroxy,
hydroxy-C.sub.1 -C.sub.6 alkyl,
C.sub.16 -C.sub.6 alkylcarbonyl, and
W' is selected from one to three substituents selected from the group
hydrogen,
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
R.sup.8 and
V;
R.sup.7 is selected from the group,
hydrogen, benzyl,
C.sub.1 -C.sub.4 alkyl and halo (F, CL, Br, L)C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.8 alkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.3 -C.sub.2 cycloalkyl-C.sub.1 -C.sub.3 aklyl,
C.sub.3 -C.sub.12 cycloalkyl,
C.sub.1 -C.sub.4 alkyl-Z--C.sub.1 -C.sub.4 alkyl, where Z is S or O,
C.sub.2 -C.sub.4 alkyl-NR--C.sub.2 -C.sub.4 alkyl,
C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 aryl,
C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 cycloalkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl,
C.sub.6 -C.sub.12 aryl-C.sub.2 -C.sub.4 alkynyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
where any aryl, alkyl, cycloalkyl or alkenyl moiety is optionally substituted with halo(F, Cl, Br, I), or --OR.sup.9 ;
R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a heterocyclic 5-, 6-, or 7-member ring containing 0, 1, or 2 additional heteroatoms selected from N, S, and O, optionally the heterocyclic ring is substituted with one or two groups selected from
oxo(.dbd.O),
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
R.sup.8 is selected from the group unsubstituted and substituted
C.sub.1 -C.sub.8 alkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.3 -C.sub.12 cycloalkyl-C.sub.1 -C.sub.4 alkyl,
C.sub.3 -C.sub.12 cycloalkyl
C.sub.1 -C.sub.4 alkyl-Z--C.sub.1 -C.sub.4 aklyl, where Z is S or O,
C.sub.2 -C.sub.4 alkyl-NR--C.sub.2 -C.sub.4 alkyl,
C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 aryl,
C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 cycloalkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.4 alkyl,
C.sub.6 -C.sub.12 aryl-C.sub.2 -C.sub.4 alkynyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-C.sub.1 -C.sub.3 alkyl,
where any aryl moiety is optionally substituted with halo(F, Cl, Br, I), --OR.sup.9 and V, and where any alkyl, cycloaLkyl or alkenyl group is optionally substituted with one to three groups selected from the group
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
NH--C(.dbd.NH)--NH.sub.2,
C(.dbd.O)NHOH,
C(.dbd.O)OR.sup.9,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28 and
V;
V is selected from the group
COR.sup.10,
SO.sub.3 R.sup.13,
NHSO.sub.2 CF.sub.3,
PO(OR.sup.13).sub.2,
SO.sub.2 NHR.sup.10,
CONHOR.sup.13,
C(OH)R.sup.10 PO(OR.sup.13).sub.2,
CN,
SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S, and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
CN,
C.sub.1 -C.sub.4 alky,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl)
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl),
N(C.sub.1 -C.sub.4 alkyl).sub.2,
CONHSO.sub.2 R.sup.15,
SO.sub.2 NHCOR.sup.15,
CONHSO.sub.2 R.sup.13,
CH.sub.2 CONHSO.sub.2 R.sup.15,
NHCONHSO.sub.2 R.sup.15,
NHSO.sub.2 NHCOR.sup.15,
CONHNHSO.sub.2 CF.sub.3,
CON(OH)R.sup.13,
CONHCOCF.sub.3,
CONHSO.sub.2 R.sup.10,
CONHSO.sub.2 R.sup.11,
CONHSO.sub.2 R.sup.13, ##STR3541## R.sup.9 is selected from the group hydrogen,
methyl,
ethyl,
isopropyl
phenyl, and
benzy
R.sup.10 is selected from the group
hydroxy,
C.sub.1 -C.sub.8 -alkoxy,
C.sub.3 -C.sub.12 -alkenoxy,
C.sub.6 -C.sub.12 -aryloxy,
C.sub.1 -C.sub.6 alkyl-C.sub.6 -C.sub.12 -aryloxy,
di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
acetylaminoethoxy,
nicotinoylaminoethoxy, and
succinamidoethoxy,
C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino,
hydroxy-C.sub.2 -C.sub.8 -alkoxy,
dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
NR.sup.11 R.sup.12 ;
R.sup.11 and R.sup.12 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from the group
nitro,
halo(F, a, Br, I), and
C.sub.1 -C.sub.4 -alkoxy;
R.sup.13 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl,
phenyl,
benzyl, and
CH.sub.2 --O--COCH.sub.3 ;
R.sup.15 is selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl, where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alky,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
C.sub.3 -C.sub.7 -cycloalkyl,
C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl as defined above,
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
C.sub.1 -C.sub.4 alkylthio,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
CO.sub.2 H,
CO.sub.2 -C.sub.1 -C.sub.4 -alkyl,
NH.sub.2,
N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
NH(C.sub.1 -C.sub.4)-alkyl!,
PO.sub.3 H,
PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
C.sub.1 -C.sub.4 -perfluoroalkl;
R.sup.16 is selected from the group
CN,
NO.sub.2,
COOR.sup.13,
C.sub.1 -C.sub.6 -perfluoroalkyl, and
CF.sub.3 ;
R.sup.19 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 -alkyl
C.sub.2 -C.sub.6 -alkenyl,
C.sub.1 -C.sub.6 -alkoxy,
C.sub.2 -C.sub.6 -alkoxyalkyl,
CH.sub.2 --O--COCH.sub.3, and
benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from the group
NO.sub.2,
NH.sub.2,
OH, and
OCH.sub.3 ;
X is selected from the group
NR.sup.24 --C(.dbd.O)--R.sup.25,
NR.sup.24 --C(.dbd.O)--R.sup.8,
NR.sup.24 --C(.dbd.O)--NR.sup.7 'R.sup.8,
NR.sup.24 --C(.dbd.O)O--R.sup.8,
NR.sup.24 --C(.dbd.O)S--R.sup.8,
(CH.sub.2).sub.1-4 --NR.sup.24 --C(.dbd.O)-R.sup.25,
NR.sup.24 --CH(OH)--R.sup.25,
NR.sup.24 --CH.sub.2 --R.sup.25,
NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0,1, or 2,
CHR.sup.24 --O--R.sup.25,
CHR.sup.24 --CH.sub.2 R.sup.25,
CHR.sup.24 --R.sup.25,
CR.sup.24 .dbd.CHR.sup.25 (E or Z),
(CH.sub.2).sub.1-4 --C(.dbd.O)--R.sup.25,
C.sub.6 -C.sub.10 aryl-R.sup.25,
heterocyle-R.sup.25,
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25,
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
R.sup.24 is selected from the group
hydrogen,
benzyl,
halo(F, a, Br, I)benzyl,
C.sub.1 -C.sub.6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
R.sup.25 is selected from R.sup.25, ##STR3542## R.sup.25 ' is selected from the group SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkylamine,
C.sub.2 -C.sub.6 alkenylamine, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
where any alkyl or alkenyl moiety is optionally substituted with one to three
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26, and
NR.sup.27 R.sup.28,
where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
R.sup.26 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
C.sub.1 -C.sub.6 alkanoyl;
R.sup.27 and R.sup.28 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
phenyl,
napthyl,
benzyl,
CH.sub.2 napthyl (.alpha. or .beta.)
C.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 cycloalkanoyl,
C.sub.6 -C.sub.10 aroyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkylsulfonyl,
C.sub.6 -C.sub.10 arylsulfonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
cinnamoyl,
heterocyclecarbonyl,
C.sub.1 -C.sub.6 alkoxycarbonyl,
C.sub.6 -C.sub.10 aryloxycarbonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
pyroglutamyl;
R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3543## and a cyclic imide represented by ##STR3544## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0, 1, or 2, and NR.sup.28 ;
J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl;
and
pharmaceutically acceptable salts thereof.

276 more elements

A compound represented by structural formula (II):

##STR3561## where R and R' are independently selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkoxy,
hydroxy,
hydroxy-C.sub.1 -C.sub.6 aLkyl,
C.sub.1 -C.sub.6 alkylcarbonyl, and
C.sub.1 -C.sub.6 alkyloxycarbonyl;
R.sup.1 and R.sup.2 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl, and ##STR3562## R.sup.1 and R.sup.2 taken together may form a covalent bond or fused benzene substituted with R and R';
R.sup.4 and R.sup.4 ' are independently selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
phenyl, and
benzyl;
R.sup.7 is selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 aLkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
W is selected from the group
C(.dbd.O)--NR.sup.7 'R.sup.8,
CH.sub.2 --C(.dbd.O)--NR.sup.7 'R.sup.8,
C(.dbd.O)--R.sup.8,
CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--CHR.sup.7 R.sup.8,
CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
C(.dbd.O)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--NR.sup.7 'R.sup.8,
CHR.sup.8 '--O--R.sup.8,
CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0, 1, or 2,
CR.sup.8 '.dbd.N--R.sup.8,
CHR.sup.8 '--R.sup.8,
W',
C.sub.1 -C.sub.3 alkyl-W',
C.sub.6 -C.sub.12 aryl-W',
C.sub.6 -C.sub.12 arYl-C.sub.1 -C.sub.3 alkyl-W',
heterocycde-W',
heterocycl-C.sub.1 -C.sub.3 alkyl-W',
C.sub.1 -C.sub.12 alkyl-C.sub.6 -C.sub.10 aryl-W', and
C.sub.1 -C.sub.2 alkyl-heterocyde-W',
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
W' is selected from one to three substituents selected from the group
hydrogen,
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
R.sup.8, and
V;
R.sup.7 ' is selected from the group
hydrogen,
benzyl,
C.sub.1 -C.sub.6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
R.sup.8 is selected from the group unsubstituted and substituted
C.sub.1 -C.sub.8 alkyl,
C.sub.1 -C.sub.4 alkyl-Z--C.sub.1 -C.sub.4 alkyl, where Z is S or O,
C.sub.2 -C.sub.4 alkyl-NR--C.sub.2 -C.sub.4 alkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.6 -C.sub.12 arylC.sub.1 -C.sub.3 alkyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol4-yl-C.sub.1 -C.sub.3 alkyl,
where any aryl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
NH--C(.dbd.NH)--NH.sub.2,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
V is selected from the group
COR.sup.10,
SO.sub.3 R.sup.13,
NHSO.sub.2 CF.sub.3,
PO(OR.sup.13).sub.2,
SO.sub.2 NHR.sup.10,
CONHOR.sup.13,
C(OH)R.sup.10 PO(OR.sup.13).sub.2,
halo(F, Cl, Br, I),
NO.sub.2,
CN,
SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO-(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
CONHSO.sub.2 R.sup.15,
SO.sub.2 NHCOR.sup.15,
CONHSO.sub.2 R.sup.13,
CH.sub.2 CONHSO.sub.2 R.sup.15,
NHCONHSO.sub.2 R.sup.15,
NHSO.sub.2 NHCOR.sup.15,
CONHNHSO.sub.2 CF.sub.3,
CON(OH)R.sup.13,
CONHCOCF.sub.3,
CONHS.sub.2 R.sup.10,
CONHSO.sub.2 R.sup.11,
CONHSO.sub.2 R.sup.13, ##STR3563## R.sup.9 is selected from the group hydrogen,
methyl,
ethyl,
isopropyl,
t-butyl,
phenyl, and
benzyl;
R.sup.10 is selected from the group
hydroxy,
C.sub.1 -C.sub.8 -alkoxy,
C.sub.3 -C.sub.12 -alkenoxy,
C.sub.6 -C.sub.12 -aryloxy,
C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 aryloxy,
di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
acetylaminoethoxy,
nicotinoylaminoethoxy, and
succinamidoethoxy, and
C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino,
hydroxy-C.sub.2 -C.sub.8 -alkoxy,
dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
NR.sup.11 R.sup.12 ;
R.sup.11 and R.sup.12 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alanoyl,
C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
nitro,
halo(F, Cl, Br, I), and
C.sub.1 -C.sub.4 -alkoxy;
R.sup.13 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
phenyl,
benzyl, and
CH.sub.2 --O--COCH.sub.3 ;
R.sup.15 is selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 aLkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
C.sub.3 -C.sub.7 -cycloalkyl,
C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl as defined above,
OH,
SH,
C.sub.1 -C.sub.4 -alkyl,
C.sub.1 -C.sub.4 -alkoxy,
C.sub.1 -C.sub.4 -alkylthio,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
CO.sub.2 H,
CO.sub.2 -(C.sub.1 -C.sub.4)-alkyl,
NH.sub.2,
N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
NH(C.sub.1 -C.sub.4)-alkyl!,
PO.sub.3 H,
PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
(C.sub.1 -C.sub.4)-perfluoroalkyl;
R.sup.16 is selected from the group
CN,
NO.sub.2,
COOR.sup.13,
C.sub.1 -C.sub.6 -perfluoroalkyl, and
CF.sub.3 ;
R.sup.19 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkoxy,
C.sub.2 -C.sub.6 alkoxyalkyl,
CH.sub.2 --O--COCH.sub.3, or
benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from
NO.sub.2,
NH.sub.2,
OH, or
OCH.sub.3 ;
X is selected from the group
NR.sup.24 --C(.dbd.O)--R.sup.25,
NR.sup.24 --C(.dbd.O)--R.sup.8,
NR.sup.24 --C(.dbd.O)NH--R.sup.8,
NR.sup.24 --C(.dbd.O)O--R.sup.8,
NR.sup.24 --C(.dbd.O)S--R.sup.8,
NR.sup.24 --CH(OH)--R.sup.25,
NR.sup.24 --CH.sub.2 --R.sup.25,
NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0, 1, or 2,
CHR.sup.24 --CH.sub.2 R.sup.25,
CHR.sup.24 --R.sup.25,
CR.sup.24 .dbd.CHR.sup.25 (E or Z),
C.sub.6 -C.sub.10 aryl-R.sup.25,
heterocycle-R.sup.25,
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
C.sub.1 -C.sub.2 alkyl-heterocyde-R.sup.25,
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
R.sup.24 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
R.sup.25 is selected from R.sup.25 ', ##STR3564## R.sup.25 ' is selected from the group SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkylamine,
C.sub.2 -C.sub.6 alkenylamine, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl
where any alkyl or alkenyl moiety is optionally substituted with
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26, and
NR.sup.27 R.sup.28, and
where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
R.sup.26 is selected from
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
C.sub.1 -C.sub.6 alkanoyl;
R.sup.27 and R.sup.28 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
phenyl,
napthyl,
benzyl,
CH.sub.2 napthyl (.alpha. or .beta.)
C.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 cycloaLkanoyl.
C6-C.sub.10 aroyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkylsulfonyl,
C.sub.6 -C.sub.10 arylsulfonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
cinnamoyl,
heterocydecarbonyl,
C.sub.1 -C.sub.6 alkoxycarbonyl,
C.sub.6 -C.sub.10 aryloxycarbonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
pyroglutamyl;
R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3565## a cyclic imide represented by ##STR3566## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28 ;
J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl;
and
pharmaceutically acceptable salts thereof.

293 more elements

A compound represented by structural formula (III):

##STR3567## where R and R' are independently selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkoxy,
hydroxy,
hydroxy-C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkylcarbonyl, and
C.sub.1 -C.sub.6 alkyloxycarbonyl;
R.sup.1 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and ##STR3568## R.sup.4 and R.sup.4 ' are independently selected from the group hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
phenyl, and
benzyl;
W is selected from the group
C(.dbd.O)--NR.sup.7 'R.sup.8,
CH.sub.2 --C(.dbd.O)--NRR.sup.8,
C(.dbd.O)--O--R.sup.8,
CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
CHR.sup.8 '-CHR.sup.7 R.sup.8,
CR.sup.8 '.dbd.--CR.sup.7 R.sup.8 (E or Z),
C(.dbd.O)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--NR.sup.7 'R.sup.8,
CHR.sup.8 '--O--R.sup.8
CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0, 1, or 2,
CR.sup.8 '.dbd.N--R.sup.8,
CHR.sup.8 --R.sup.8,
W',
C.sub.1 -C.sub.3 alkyl-W',
C.sub.6 -C.sub.12 aryl-W',
C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
heterocyde-W',
heterocycle-C.sub.1 -C.sub.3 alkyl-W',
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
C.sub.1 -C.sub.2 alkyl-heterocycle-W', and
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
W' is selected from one to three substituents selected from the group
hydrogen,
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
R.sup.8, and
V;
R.sup.7, each occurance, is independently selected from the group
hydrogen,
C.sub.1 -C.sub.4 alkyl,
halo(F, Cl, Br, I), and
halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
R.sup.7 ' is selected from the group
hydrogen,
C.sub.1 -C.sub.4 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
R.sup.8 is selected from the group unsubstituted and substituted
C.sub.1 -C.sub.8 alkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
where any aryl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
NH--C(.dbd.NH)--NH.sub.2,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
V is selected from the group
COR.sup.10,
SO.sub.3 R.sup.13,
NHSO.sub.2 CF.sub.3,
PO(OR.sup.13)2,
SO.sub.2 NHR.sup.10,
CONHOR.sup.13,
C(OH)R.sup.10 PO(OR.sup.13)2,
halo(F, Cl, Br, I),
NO.sub.2,
CN,
SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxyl,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
CONHSO.sub.2 R.sup.15,
SO.sub.2 NHCOR.sup.15,
CONHSO.sub.2 R.sup.13,
CH.sub.2 CONHSO.sub.2 R.sup.15,
NHCONHSO.sub.2 R.sup.15,
NHSO.sub.2 NHCOR.sup.15,
CONHNHSO.sub.2 CF.sub.3,
CON(OH)R.sup.13,
CONHCOCF.sub.3,
CONHSO.sub.2 R.sup.10,
CONHSO.sub.2 R.sup.11,
CONHSO.sub.2 R.sup.13, ##STR3569## R.sup.9 is selected from the group hydrogen,
methyl,
ethyl,
isopropyl,
t-butyl,
phenyl, and
benzyl;
R.sup.10 is selected from the group
hydroxy,
C.sub.1 -C.sub.8 -alkoxy,
C.sub.3 -C.sub.12 -alkenoxy,
C.sub.6 -C.sub.12 -aryloxy,
C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -aryloxy,
di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
acetylaminoethoxy,
nicotinoylaminoethoxy, and
succinamidoethoxy,
C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino,
hydroxy-C.sub.2 -C.sub.8 -alkoxy,
dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
NR.sup.11 R.sup.12 ;
R.sup.11 and R.sup.12 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
nitro,
halo(F, Cl, Br, I), and
C.sub.1 -C.sub.4 -alkoxy;
R.sup.13 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
phenyl,
benzyl, and
CH.sub.2 COCH.sub.3 ;
R.sup.15 is selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl, where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxyl,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
C.sub.3 -C.sub.7 -cyloalkyl,
C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl as defined above,
OH,
SH,
C.sub.1 -C.sub.4 -alkyl,
C.sub.1 -C.sub.4 -alkoxy,
C.sub.1 -C.sub.4 -alkylthio,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
CO.sub.2 H,
CO.sub.2 -(C.sub.1 -C.sub.4)-alkyl,
NH.sub.2,
N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
NH(C.sub.1 -C.sub.4)-alkyl!,
PO.sub.3 H, and
PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
(C.sub.1 -C.sub.4)-perfluoroalkyl;
R.sup.16 is selected from the group
CN,
NO.sub.2,
COOR.sup.13,
C.sub.1 -C.sub.6 -perfluoroalkyl, and
CF.sub.3 ;
R.sup.19 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkoxy,
C.sub.2 -C.sub.6 alkoxyalkyl,
CH.sub.2 --O--COCH.sub.3, and
benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from ##STR3570## R.sup.25 is selected from the group SR.sup.26 ,
SSR.sup.26,
OR.sup.26,
NOR.sup.26,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkylamine,
C.sub.2 -C6alkenylamine, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
where any alkyl or alkenyl moiety is optionally substituted with
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26, and
NR.sup.27 R.sup.28, and
where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
R.sup.26 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
C.sub.1 -C.sub.6 alkanoyl;
R.sup.27 and R.sup.28 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
phenyl,
napthyl,
benzyl,
CH.sub.2 napthyl (.alpha. or .beta.),
C.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 cycloalkanoyl,
C.sub.6 -C.sub.10 aroyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkylsulfonyl,
C.sub.6 -C.sub.10 arylsulfonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
cinnamoyl,
heterocyclecarbonyl,
C.sub.1 -C.sub.6 -alkoxycarbonyl,
C.sub.6 -C.sub.10 aryloxycarbonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
pyroglutamyl;
R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3571## and a cyclic imide represented by ##STR3572## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28 ;
J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl;
and
pharmaceutically acceptable salts thereof.

262 more elements

A compound represented by structural formula (IV):

##STR3573## where R and R' are independently selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 all,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkoxy,
hydroxy,
hydroxy-CC.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkylcarbonyl, and
C.sub.1 -C.sub.6 alkyloxycarbonyl;
R.sup.1 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl, and ##STR3574## R.sup.4 and R.sup.4 ' are independently selected from the group hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
phenyl, and
benzyl;
W is selected from the group
C(.dbd.O)-NR.sup.7 'R.sup.8,
CH.sub.2 --C(.dbd.O)-NR.sup.7 'R.sup.8,
C(.dbd.O)--O--R.sup.8,
CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--CHR.sup.7 R.sup.8,
CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
C(.dbd.O)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--NR.sup.7 'R.sup.8,
CHR.sup.8 '--O--R.sup.8,
CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0, 1, or 2,
CR.sup.8 '.dbd.N--R.sup.8,
CHR.sup.8 '--R.sup.8,
C.sub.1 -C.sub.3 alkyl-W',
C.sub.6 -C.sub.12 aryl-W',
C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
heterocyde-W',
heterocycle-C.sub.1 -C.sub.3 alkyl-W',
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
C.sub.1 -C.sub.2 alkyl-heterocyle-W', and
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
W' is selected from one to three substituents selected from the group
hydrogen,
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
R.sup.8, and
V;
R.sup.7, each occurance, is independently selected from the group
hydrogen,
C.sub.1-C.sub.4 alkyl,
halo(F, Cl, Br, I), and
halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
R.sup.7 ' is selected from the group
hydrogen,
C.sub.1 -C.sub.4 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
R.sup.8 is selected from the group unsubstituted and substituted
C.sub.1 -C.sub.8 alkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.6 -C.sub.12 arylC.sub.1 -C.sub.3 alkyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
where any aryl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
NH--C(.dbd.NH)--NH.sub.2,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
V is selected from the group
COR.sup.10,
SO.sub.3 R.sup.13,
NHSO.sub.2 CF.sub.3,
PO(OR.sup.13)2,
SO.sub.2 NHR.sup.10,
CONHOR.sup.13,
C(OH)R.sup.10 PO(OR.sup.13)2,
CN,
SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the
NO.sub.2,
NHO.sub.2,
OH, and
OCH.sub.3 ;
##STR3575## represents a heterocycle bonded to the benzodiazepine moiety through a spiro linkage, where the heterocycle is a 5- or 6-member saturated or unsaturated nitrogen containing ring having from 0 to 2 additional heteroatoms selected from O, N, and S, the ring optionally containing a keto --C(.dbd.O)--! group;
X' is selected from the group
C(.dbd.O)--R.sup.25,
CH(OH)--R.sup.25,
CHR.sup.24 --R.sup.25,
S(O).sub.u --R.sup.25 where u is 0, 1, or 2,
CHR.sup.24 --R.sup.25,
R.sup.25,
C.sub.6 -C.sub.10 aryl-R.sup.25,
heterocyle-R.sup.25,
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25,
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
R.sup.24 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
R.sup.25 is selected from R.sup.25, ##STR3576## heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C4alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
CONHSO.sub.2 R.sup.15,
SO.sub.2 NHCOR.sup.15,
CONHSO.sub.2 R.sup.13,
CH.sub.2 CONHSO.sub.2 R.sup.15,
NHCONHSO.sub.2 R.sup.15,
NHSO.sub.2 NHCOR.sup.15,
CONHNHSO.sub.2 CF.sub.3,
CON(OH)R.sup.13,
CONHCOCF.sub.3,
CONHSO.sub.2 R.sup.10,
CONHSO.sub.2 R.sup.11,
CONHSO.sub.2 R.sup.13, ##STR3577## R.sup.9 is selected from the group hydrogen,
methyl,
ethyl,
isopropyl,
t-bytyl,
phenyl, and
benzyl;
R.sup.10 is selected from the group
hydroxy,
C.sub.1 -C.sub.8 -alkoxy,
C.sub.3 -C.sub.12 -alkenoxy,
C.sub.6 -C.sub.12 -aryloxy,
C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -aryloxy,
di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
acetylaminoethoxy,
nicotinoylaminoethoxy, and
succinamidoethoxy,
C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino,
hydroxy-C.sub.2 -C.sub.8 -alkoxy,
dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
NR.sup.11 R.sup.12 ;
R.sup.11 and R.sup.12 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkanoyl,
C.sub.2 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
nitro,
halo(F, Cl, Br, I), and
C.sub.1 -C.sub.4 -alkoxy;
R.sup.13 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
phenyl,
benzyl, and
CH.sub.2 --O--COCH.sub.3 ;
R.sup.15 is selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl, where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
C.sub.3 -C.sub.7 -cycloalkyl,
C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl as defined above,
OH,
SH,
C.sub.1 -C.sub.4 -alkyl,
C.sub.1 -C.sub.4 -alkoxy,
C.sub.1 -C.sub.4 -alkylthio,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
CO.sub.2 H,
CO.sub.2 --(C.sub.1 -C.sub.4)--alkyl,
NH.sub.2,
N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
NH(C.sub.1 -C.sub.4)-alkyl!,
PO.sub.3 H, and
PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
(C.sub.1 -C4)-perfluoroalkyl;
R.sup.16 is selected from the group
CN,
NO.sub.2,
COOR.sup.13,
C.sub.1 -C.sub.6 -perfluoroalkyl, and
CF.sub.3 ;
R.sup.19 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkeny,
C.sub.1 -C.sub.6 alkoxy,
C.sub.2 -C.sub.6 aloxyalkyl,
CH.sub.2 --O--COCH.sub.3, and
benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from
NO.sub.2,
NH.sub.2,
OH, and
OCH.sub.3 ;
##STR3578## represents a heterocycle fused to the benzodiazepine moiety, where the heterocycle is a 5- or 6-member saturated or unsaturated di-nitrogen containing ring having from 0 to 1 additional heteroatom selected from O, N, and S, the ring optionally containing a keto --C(.dbd.O)--! group;
X' is selected from the group
C(.dbd.O)--R.sup.25,
CH(OH)--R.sup.25,
CHR.sup.24 --R.sup.25,
S(O).sub.u --R.sup.25 where u is 0,1, or 2,
CHR.sup.24 --R.sup.25,
R.sup.25,
C.sub.6 -C.sub.10 aryl--R.sup.25
heterocyle-R.sup.25,
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl--R.sup.25, and
C.sub.1 -C.sub.2 alkyl-heterocyle-R.sup.25,
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
R.sup.24 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
R.sup.25 is selected from R.sup.25 ', ##STR3579## R.sup.25 ' is selected from the group SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkylamine,
C.sub.2 -C.sub.6 alkenylamine, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
where any alkyl or alkenyl moiety is optionally substituted with
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26, and
NR.sup.27 R.sup.28, and
where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
R.sup.26 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
C.sub.1 -C.sub.6 akanoyl;
R.sup.27 and R.sup.28 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
phenyl,
napthyl,
benzyl,
CH.sub.2 napthyl (.alpha. or .beta.),
C.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 cycloalkanoyl,
C.sub.6 -C.sub.10 aroyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkylsulfonyl,
C.sub.6 -C.sub.10 arylsulfonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
cinnamoyl,
heterocyclecarbonyl,
C.sub.1 -C.sub.6 alkoxycarbonyl,
C.sub.6 -C.sub.10 aryloxycarbonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
pyroglutamyl;
R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3580## and a cyclic imide represented by ##STR3581## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0, 1, or 2, and NR.sup.28 ;
J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl;
and
pharmaceutically acceptable salt thereof.

303 more elements

A compound represented by structural formula (V):

##STR3582## where R and R' are independently selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkoxy,
hydroxy,
hydroxy-C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkylcarbonyl, and
C.sub.1 -C.sub.6 alkyloxycarbonyl;
R.sup.1 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl, and ##STR3583## R.sup.4 is selected from the group hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
phenyl, and
benzyl;
R.sup.7 is selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
A.sup.1 and A.sup.2 are independently selected from the group
CRR',
CR',
CRR.sup.8,
CR.sup.8,
N,
O, and
S, and
provided one of A.sup.1 and A.sup.2 is CRR.sup.8 or CR.sup.8 ;
represents a single or double bond;
R.sup.8 is selected from the group unsubstituted and substituted
C.sub.1 -C.sub.8 alkyl,
C.sub.2 -C.sub.8 alkenyl,
phenyl-C.sub.1 -C.sub.3 alkyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
where any phenyl moiety is optionally substituted with OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
NH--C(.dbd.NH)--NH.sub.2,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
V is selected from the group
COR.sup.10,
SO.sub.3 R.sup.3,
NHSO.sub.2 CF.sub.3,
PO(OR.sup.13).sub.2,
SO.sub.2 NHR.sup.10,
CONHOR.sup.13,
C(OH)R.sup.10 PO(OR.sup.13).sub.2,
CN,
SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2, and
CONHSO.sub.2 R.sup.15,
SO.sub.2 NHCOR.sup.15,
CONHSO.sub.2 R.sup.13,
CH.sub.2 CONHSO.sub.2 R.sub.15,
NHCONHSO.sub.2 R.sup.15,
NHSO.sub.2 NHCOR.sup.15,
CONHNHSO.sub.2 CF.sub.3,
CON(OH)R.sup.13,
CONHCOCF.sub.3,
CONHSO.sub.2 R.sup.10,
CONHSO.sub.2 R.sup.11,
CONHSO.sub.2 R.sup.13, ##STR3584## R.sup.9 is selected from the group hydrogen,
methyl,
ethyl,
isopropyl,
t-butyl,
phenyl, and
benzyl;
R.sup.10 is selected from the group
hydroxy,
C.sub.1 -C.sub.8 -alkoxy,
C.sub.3 -C.sub.12 -alkenoxy,
C.sub.6 -C.sub.12 -aryloxy,
C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.8 -alkoxy,
di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
acetylaminoethoxy,
nicotinoylaminoethoxy, and
succinamidoethoxy,
C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino,
hydroxy-C.sub.2 -C.sub.8 -alkoxy,
dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
NR.sup.11 R.sup.12 ;
R.sup.11 and R.sup.12 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from the group
nitro,
halo(F, Cl, Br, I), and
C.sub.1 -C.sub.4 -alkoxy;
R.sup.13 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
phenyl,
benzyl, and
CH.sub.2 --O--COCH.sub.3 ;
R.sup.15 is selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
C.sub.3 -C.sub.7 -cyloalkyl,
C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl as defined above,
OH,
SH,
C.sub.1 -C.sub.4 -alkyl,
C.sub.1 -C.sub.4 -alkoxy,
C.sub.1 -C.sub.4 -alkylthio,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
CO.sub.2 H,
CO.sub.2 (C.sub.1 -C.sub.4)alkyl,
NH.sub.2,
N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
NH(C.sub.1 -C.sub.4)-alkyl!,
PO.sub.3 H or
PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
(C.sub.1 -C.sub.4)-perfluoroalkyl;
R.sup.16 is selected from the group
CN,
NO.sub.2,
COOR.sup.13,
C.sub.1 -C.sub.6 -perfluoroalkyl, and
CF.sub.3 ;
R.sup.19 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkoxy,
C.sub.2 -C.sub.6 alkoxyalkyl,
CH.sub.2 --O--COCH.sub.3, and
benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from
NO.sub.2,
NH.sub.2,
OH, and
OCH.sub.3 ;
X is selected from the group
NR.sup.24 --C(.dbd.O)--R.sup.25,
NR.sup.24 --CH(OH)--R.sup.25,
NR.sup.24 --CH.sub.2 --R.sup.25,
NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0, 1, or 2,
CHR.sup.24 --CH.sub.2 R.sup.25,
CHR.sup.24 --R.sup.25,
CR.sup.24 .dbd.CHR.sup.25 (E or Z),
C.sub.6 -C.sub.10 aryl- R.sup.25,
heterocycle-R.sup.25,
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25, and
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
R.sup.24 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
R.sup.25 is selected from R.sup.25 ', ##STR3585## R.sup.25 ' is selected from the group SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkylamine,
C.sub.2 -C.sub.6 alkenylamine, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
where any alkyl or alkenyl moiety is optionally substituted with
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26 and
NR.sup.27 R.sup.28, and
where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
R.sup.26 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
C.sub.1 -C.sub.6 alkanoyl;
R.sup.27 and R.sup.28 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
phenyl,
napthyl,
benzyl,
CH.sub.2 napthyl (.alpha. or .beta.),
C.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 cycloalkanoyl,
C.sub.6 -C.sub.10 aroyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkylsulfonyl,
C.sub.6 -C.sub.10 arylsulfonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
cinnamoyl,
heterocyclecarbonyl,
C.sub.1 -C.sub.6 alkoxycarbonyl,
C.sub.6 -C.sub.10 aryloxycarbonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
pyroglutamyl;
R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3586## and a cyclic imide represented by ##STR3587## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28 ;
J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl;
and
pharmaceutically acceptable salts thereof.

246 more elements

A compound represented by structural formula (VI):

##STR3588## where R and R' are independently selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkoxy,
hydroxy,
hydroxy-C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkylcarbonyl, and
C.sub.1 -C.sub.6 alkyloxycarbonyl;
R.sup.1 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl, and ##STR3589## R.sup.4 and R.sup.4 ' are independently selected from the group hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
phenyl, and
benzyl;
W is selected from the group
C(.dbd.O)--NR.sup.7 '.sup.8,
CH.sub.2 --C(.dbd.O)--NR.sup.7 'R.sup.8,
C(.dbd.O)--O--R.sup.8,
CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--CHR.sup.7 R.sup.8,
CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
C(.dbd.O)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--NR7'R.sup.8,
CHR.sup.8 '--O--R.sup.8,
CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0,1, or 2,
CR.sup.8 '.dbd.N--R.sup.8,
CHR.sup.8 '--R.sup.8,
W',
C.sub.1 -C.sub.3 alkyl-W',
C.sub.6 -C.sub.12 aryl-W',
C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
heterocyde-W',
heterocycle-C.sub.1 -C.sub.3 alkyl-W',
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
C.sub.1 C.sub.2 alkyl-heterocyde-W',
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
W' is selected from one to three substituents selected from the group
hydrogen,
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
R.sup.8, and
V;
R.sup.7, each occurance, is independently selected from the group
hydrogen,
C.sub.1 -C.sub.4 alkyl, halo(F, Cl, Br, I), and
halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
R.sup.7 ' is selected from the group
hydrogen,
C.sub.1 -C.sub.4 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
R.sup.8 is selected from the group unsubstituted and substituted
C.sub.1 -C.sub.8 alkyl,
C.sub.2 -C.sub.8 alkenyl,
phenyl-C.sub.1 C.sub.3 alkyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
where any phenyl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
NH--C(.dbd.NH)--NH.sub.2,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
V is selected from the group
COR.sup.10,
SO.sub.3 R.sup.13,
NHSO.sub.2 CF.sub.3,
PO(OR.sup.13).sub.2,
SO.sub.2 NHR.sup.10,
CONHOR.sup.13,
C(OH)R.sup.10 PO(OR.sup.13).sub.2,
CN,
SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2, and
CONHSO.sub.2 R.sup.15,
SO.sub.2 NHCOR.sup.15,
CONHSO.sub.2 R.sup.13,
CH.sub.2 CONHSO.sub.2 R.sup.15,
NHCONHSO.sub.2 R.sup.15,
NHSO.sub.2 NHCOR.sup.15,
CONHNHSO.sub.2 CF.sub.3,
CON(OH)R.sup.13,
CONHCOCF.sub.3,
CONHSO.sub.2 R.sup.10,
CONHSO.sub.2 R.sup.11,
CONHSO.sub.2 R.sup.13, ##STR3590## R.sup.9 is selected from the group hydrogen,
methyl,
ethyl,
isopropyl,
t-butyl,
phenyl, and
benzyl;
R.sup.10 is selected from the group
hydroxy,
C.sub.1 -C.sub.8 -alkoxy,
C.sub.3 -C.sub.12 -alkenoxy,
C.sub.6 -C.sub.12 -aryloxy,
C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -aryloxy,
di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
acetylaminoethoxy,
nicotinoylaminoethoxy, and
succinamidoethoxy, and
C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
hydroxy-C.sub.2 -C.sub.8 -alkoxy,
dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
NR.sup.11 R.sup.12 ;
R.sup.11 and R.sup.12 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alanoyl substituted with from one to three groups selected from
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
nitro,
halo(F, Cl, Br, I), and
C.sub.1 -C.sub.4 -alkoxy;
R.sup.13 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl,
phenyl,
benzyl, and
CH.sub.2 --O--COCH.sub.3 ;
R.sup.15 is selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
C.sub.3 -C.sub.7 -cycloalkyl,
C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from
C.sub.6 -C.sub.14 aryl,
heteroaryl as defined above,
OH,
SH,
C.sub.1 -C.sub.4 -alkyl,
C.sub.1 C4-alkoxy,
C.sub.1 -C.sub.4 -alkylthio,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
CO.sub.2 H,
CO.sub.2 -(C.sub.1 -C.sub.4)-alkyl,
NH.sub.2,
N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
NH(C.sub.1 -C.sub.4)-alkyl!,
PO.sub.3 H, and
PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
(C.sub.1 -C.sub.4)-perfluoroalkyl;
R.sup.16 is selected from the group
CN,
NO.sub.2,
COOR.sup.13,
C.sub.1 -C.sub.6 -perfluoroalkyl, and
CF.sub.3 ;
R.sup.19 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkoxy,
(C.sub.2 -C.sub.6)-alkoxyalkyl,
CH.sub.2 --O--COCH.sub.3, and
benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from the group
NO.sub.2,
NH.sub.2,
OH, and
OCH.sub.3 ;
##STR3591## represents a heterocycle bonded to the benzodiazepine moiety through a ring nitrogen, where the heterocycle is a 5- or 6-member saturated or unsaturated nitrogen containing ring having from 0 to 2 additional heteroatoms selected from O, N, and S, the ring optionally containing a keto --C(.dbd.O)--! group;
R.sup.25 ' is selected from the group
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkylamine,
C.sub.2 -C.sub.6 alkenylamine, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
where any alkyl or alkenyl moiety is optionally substituted with
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26 and
NR.sup.27 R.sup.28, and
where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
R.sup.26 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
C.sub.1 -C.sub.6 alkanoyl;
R.sup.27 and R.sup.28 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
phenyl,
napthyl,
benzyl,
CH.sub.2 napthyl (.alpha. or .beta.)
C.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 cycloalkanoyl,
C.sub.6 -C.sub.10 aroyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkylsulfonyl,
C.sub.6 -C.sub.10 arylsulfonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkycarbamoyl,
cinnamoyl,
heterocyclecarbonyl,
C.sub.1 -C.sub.6 alkoxycarbonyl,
C.sub.6 -C.sub.10 aryloxycarbonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
pyroglutamyl;
R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3592## or a cyclic imide represented by ##STR3593## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28 ;
J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
and
pharmaceutically acceptable salts thereof.

265 more elements

A compound represented by structural formula (VII):

##STR3594## where R and R' are independently selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkoxy,
hydroxy,
hydroxy-C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkykarbonyl, and
C.sub.1 -C.sub.6 alkyloxycarbonyl;
R.sup.4 and R.sup.4 ' are independentl y selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
phenyl, and
benzyl;
R.sup.7 is selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
W is selected from the group the group
C(.dbd.O)--NR.sup.7 'R.sup.8,
CH.sub.2 --C(.dbd.O)--NR.sup.7 'R.sup.8,
C(.dbd.O)--O--R.sup.8,
CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--CHR.sup.7 R.sup.8,
CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
C(.dbd.O)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--NR.sup.7 'R.sup.8,
CHR.sup.8 '--O--R.sup.8,
CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0, 1, or 2,
CR.sup.8 '.dbd.N--R.sup.8,
CHR.sup.8 '--R.sup.8,
W',
C.sub.1 -C.sub.3 alkyl-W',
C.sub.6 -C.sub.12 aryl-W',
C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
heterocycle-W',
heterocyde-C.sub.1 -C.sub.3 alkyl-W',
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
C.sub.1 -C.sub.2 alkyl-heterocycle-W', and
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
W' is selected from one to three substituents selected from the group
hydrogen,
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
R.sup.8 and
V;
R.sup.7, each occurance, is independently selected from the group
hydrogen,
C.sub.1 C.sub.4 alkyl,
halo(F, Cl, Br, I), and
halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
R.sup.7 ' is selected from the group
hydrogen,
C.sub.1 -C.sub.4 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from the group
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
R.sup.8 is selected from the group unsubstituted and substituted
C.sub.1 -C.sub.8 alkyl,
C.sub.2 -C.sub.8 alkenyl,
phenyl-C.sub.1 -C.sub.3 alkyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
where any phenyl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
NH--C(.dbd.NH)--NH.sub.2,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
V is selected from the group
COR.sup.10,
SO.sub.3 R.sup.13,
NHSO.sub.2 CF.sub.3,
PO(OR.sup.13).sub.2,
SO.sub.2 NHR.sup.10,
CONHOR.sup.13,
C(OH)R.sup.10 PO(OR.sup.13).sub.2,
CN,
SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
CONHSO.sub.2 R.sup.15,
SO.sub.2 NHCOR.sup.15,
CONHSO.sub.2 R.sup.13,
CH.sub.2 CONHSO.sub.2 R.sup.15,
NHCONHSO.sub.2 R.sup.15,
NHSO.sub.2 NHCOR.sup.15,
CONHNSO.sub.2 CF.sub.3,
CON(OH)R.sup.13,
CONHCOCF.sub.3,
CONHSO.sub.2 R.sup.10,
CONHSO.sub.2 R.sup.11,
CONHSO.sub.2 R.sup.13, ##STR3595## R.sup.9 is selected from the group hydrogen,
methyl,
ethyl,
isopropyl,
t-butyl,
phenyl, and
benzyl;
R.sup.10 is selected from the group
hydroxy,
C.sub.1 -C.sub.8 -alkoxy,
C.sub.3 -C.sub.12 -alkenoxy,
C.sub.6 -C.sub.12 -aryloxy,
C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -aryloxy,
di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
acetylaminoethoxy,
nicotinoylaminoethoxy, and
succiamidoethoxy,
C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C4-alkoxy, and
amino,
hydroxy-C.sub.2 -C.sub.8 -alkoxy,
dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
NR.sup.11 R.sup.12 ;
R.sup.11 and R.sup.12 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
nitro,
halo(F, Cl, Br, I), and
C.sub.1 -C.sub.4 -alkoxy;
R.sup.13 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
phenyl,
benzyl, and
CH.sub.2 --O--COCH.sub.3 ;
R.sup.15 is selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2, and
C.sub.3 -C.sub.7 - cyloalkyl ,
C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl as defined above,
OH,
SH,
C.sub.1 -C.sub.4 -alkyl,
C.sub.1 -C.sub.4 -alkoxy,
C.sub.1 -C.sub.4 -alkylthio,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
CO.sub.2 H,
CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl,
NH.sub.2,
N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
NH(C.sub.1 -C.sub.4)-alkyl!,
PO.sub.3 H or
PO(OH)(C.sub.1 -C.sub.4 -alkoxy, and
(C.sub.1 -C.sub.4)-perfluoroalkyl;
R.sup.16 is selected from the group
CN,
NO,
COOR.sup.13,
C.sub.1 -C.sub.6 -perfluoroalkyl, and
CF.sub.3 ;
R.sup.19 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkoxy,
C.sub.2 -C.sub.6 alkoxyalkyl,
CH.sub.2 --O--COCH.sub.3, and
benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from
NO.sub.2,
NH.sub.2,
OH, and
OCH.sub.3 ;
X is selected from the group
NR.sup.24 --C(.dbd.O)--R.sup.25,
NR.sup.24 --CH(OH)--R.sup.25,
NR.sup.24 --CH.sub.2 --R.sup.25,
NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0, 1, or 2,
CHR.sup.24 --CH.sub.2 R.sup.25,
CHR.sup.24 --R.sup.25,
CR.sup.24 .dbd.CHR.sup.25 (E or Z),
C.sub.6 -C.sub.10 aryl-R.sup.25,
heterocycle-R.sup.25,
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25, and
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
R.sup.24 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
R.sup.25 is selected from R.sup.25 ', ##STR3596## R.sup.25 ' is selected from the group SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkylamine,
C.sub.2 -C.sub.6 alkenylamine, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
where any alkyl or alkenyl moiety is optionally substituted with
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26 and
NR.sup.27 R.sup.28, and
where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
R.sup.26 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl, halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
C.sub.1 -C.sub.6 alkanoyl;
R.sup.27 and R.sup.28 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
phenyl,
napthyl,
benzyl,
CH.sub.2 napthyl (.alpha. or .beta.)
C.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 cycloalkanoyl,
C.sub.6 -C.sub.10 aroyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alanoyl,
C.sub.1 -C.sub.6 alkylsulfonyl,
C.sub.6 -C.sub.10 arylsulfonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
cinnamoyl,
heterocyclecarbonyl,
C.sub.1 -C.sub.6 alkoxycarbonyl,
C.sub.6 -C.sub.10 aryloxycarbonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
pyroglutamyl;
R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3597## and a cyclic imide represented by ##STR3598## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0, 1, or 2, and NR.sup.28 ;
J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl;
and
pharmaceutically acceptable salts thereof.

284 more elements

A compound represented by structural formula (VIII):

##STR3599## where R.sup.1 is selected from the group
CF.sub.3 and ##STR3600## R and R' are independently selected from the group hydrogen,
halo (F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkoxy,
hydroxy,
hydroxy-C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkylcarbonyl, and
C.sub.1 -C.sub.6 alkyloxycarbonyl;
R.sup.4 and R.sup.4 ' are independently selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
phenyl, and
benzyl;
R.sup.7 is selected from the group
hydrogen
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
##STR3601## represents C.sub.6 -C.sub.10 aryl or a heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S, the C.sub.6 -C.sub.10 aryl or heteroaryl is optionally substituted with V and R.sup.8 ;
R.sup.8 is selected from the group unsubstituted and substituted
C.sub.1 -C.sub.8 alkyl,
phenyl-C.sub.1 -C.sub.3 alkyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
where any phenyl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
NH--C(.dbd.NH)--NH.sub.2,
C(.dbd.O)NHOH,
NHR.sub.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
V is selected from the group
COR.sup.10,
SO.sub.3 R.sup.13,
NHSO.sub.2 CF.sub.3,
PO(OR.sup.13).sub.2,
SO.sub.2 NHR.sup.10,
CONHOR.sup.13,
C(OH)R.sup.10 PO(OR.sup.13).sub.2,
CN,
SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
CONHSO.sub.2 R.sup.15,
SO.sub.2 NHCOR.sup.15,
CONHSO.sub.2 R.sup.13,
CH.sub.2 CONHSO.sub.2 R.sup.15,
NHCONHSO.sub.2 R.sup.15,
NHSO.sub.2 NHCOR.sup.15,
CONHNHSO.sub.2 CF.sub.3,
CON(OH)R.sup.13,
CONHCOCF.sub.3,
CONHSO.sub.2 R.sup.10,
CONHSO.sub.2 R.sup.11,
CONHSO.sub.2 R.sup.13, ##STR3602## R.sup.9 is selected from the group hydrogen,
methyl,
ethyl,
isopropyl,
phenyl, and
benzyl;
R.sup.10 is selected from the group
hydroxy,
C.sub.1 -C.sub.8 -alkoxy,
C.sub.3 -C.sub.12 -alkenoxy,
C.sub.6 -C.sub.12 -aryloxy,
C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.2 -aryloxy,
di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
acetylaminoethoxy,
nicotinoylaminoethoxy, and
succinamidoethoxy,
C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino,
hydroxy-C.sub.2 -C.sub.8 -alkoxy,
dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
NR.sup.11 R.sup.12 ;
R.sup.11 and R.sup.12 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
nitro,
halo(F, Cl, Br, I), and
C.sub.1 -C.sub.4 -alkoxy;
R.sup.13 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
phenyl,
benzyl, and
CH.sub.2 --O--COCH.sub.3 ;
R.sup.15 is selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
C.sub.3 -C.sub.7 -cydoalkyl,
C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl as defined above,
OH,
SH,
C.sub.1 -C.sub.4 -alkyl,
C.sub.1 -C.sub.4 -alkoxy,
C.sub.1 -C.sub.4 -alkylthio,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
CO.sub.2 H,
CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl,
NH.sub.2,
N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
NH(C.sub.1 -C.sub.4)-alkyl!,
PO.sub.3 H, and
PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
(C.sub.1 -C.sub.4)-perfluoroalkyl;
R.sup.16 is selected from the group
CN,
NO.sub.2,
COOR.sup.13,
C.sub.1 -C.sub.6 -perfluoroalkyl, and
CF.sub.3 ;
R.sup.19 is selected from the group
hydrogen,
(C.sub.1 -C.sub.6)-alkyl,
(C.sub.2 -C.sub.6)-alkenyl,
(C.sub.1 -C.sub.6)-alkoxy,
(C.sub.2 -C.sub.6)-alkoxyalkyl,
CH.sub.2 --O--COCH.sub.3, or
benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from
NO.sub.2,
NH.sub.2,
OH, or
OCH.sub.3 ;
X is selected from the group
NR.sup.24 --C(.dbd.O)--R.sup.25,
NR.sup.24 --CH(OH)--R.sup.25,
NR.sup.24 --CH.sub.2 --R.sup.25,
NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0,1, or 2,
CHR.sup.24 --CH.sub.2 R.sup.25,
CHR.sup.24 --R.sup.25,
CR.sup.24 .dbd.CHR.sup.25 (E or Z),
C.sub.6 -C.sub.10 aryl-R.sup.25,
heterocycle-R.sup.25,
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25,
C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25, and
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
R.sup.24 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 aLkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
R.sup.25 is selected from R.sup.25, ##STR3603## R.sup.25 ' is selected from the group SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkylamine,
C.sub.2 -C.sub.6 alkenylamine, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
where any alkyl or alkenyl moiety is optionally substituted with
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26 and
NR.sup.27 R.sup.28, and
where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
R.sup.26 is selected from
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
C.sub.1 -C.sub.6 alkanoyl;
R.sup.27 and R.sup.28 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
phenyl,
napthyl,
benzyl,
CH.sub.2 napthyl (.alpha. or .beta.)
C.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 cycloalkanoyl,
C.sub.6 -C.sub.10 aroyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkylsulfonyl,
C.sub.6 -C.sub.10 arylsulfonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
cinnamoyl,
heterocyclecarbonyl,
C.sub.1 -C.sub.6 alkoxycarbonyl,
C.sub.6 -C.sub.10 aryloxycarbonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
pyroglutamyl;
R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amime represented by ##STR3604## and a cyclic imide represented by ##STR3605## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28
J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl;
and
pharmaceutically acceptable salts thereof.

233 more elements

A compound represented by structural formula (IXa)-(IXd):

##STR3606## where R and R' are independently selected from the group
hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkoxy,
hydroxy,
hydroxy-C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkylcarbonyl, and
C.sub.1 -C.sub.6 alkyloxycarbonyl;
R.sup.1 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl, and ##STR3607## R.sup.4 and R.sup.4 ' are independently selected from the group hydrogen,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
phenyl, and
benzyl;
W is selected from the group
C(.dbd.O)--NR.sup.7 'R.sup.8,
CH.sub.2 --C(.dbd.O)NR.sup.7 'R.sup.8,
C(.dbd.O)--O--R.sup.8,
CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--CHR.sup.7 R.sup.8,
CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
C(.dbd.O)--CHR.sup.7 R.sup.8,
CHR.sup.8 '--NR.sup.7 'R.sup.8,
CHR.sup.8 '--O--R.sup.8,
CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0,1, or 2,
CR.sup.8 '.dbd.N--R.sup.8,
CHR.sup.8 '--R.sup.8,
W',
C.sub.l -C.sub.3 alkyl-W',
C.sub.6 -C.sub.12 aryl-W',
C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
heterocycle-W',
heterocyde-C.sub.1 -C.sub.3 alkyl-W',
C.sub.1 C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
C.sub.1 -C.sub.2 alkyl-heterocycle-W',
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
W' is selected from one to three substituents selected from the group
hydrogen,
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
R.sup.8, and
V;
R.sup.7, each occurance, is independently selected from the group
hydrogen,
C.sub.1 -C.sub.4 alkyl,
halo(F, Cl, Br, I), and
halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
R.sup.7 ' is selected from the group
hydrogen,
C.sub.1 -C.sub.4 alkyl, and
halo(F, CL Br, I)C.sub.1 -C.sub.4 alkyl;
R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
R.sup.8 is selected from the group unsubstituted and substituted
C.sub.1 -C.sub.8 alkyl,
C.sub.2 -C.sub.8 alkenyl,
phenyl-C.sub.1 -C.sub.3 alkyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
where any phenyl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
SR.sup.9,
SSR.sup.9,
SC(.dbd.P)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
NH--C(.dbd.NH)--NH.sub.2,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
V is selected from the group
COR.sup.10,
SO.sub.3 R.sup.13,
NHSO.sub.2 CF.sub.3,
PO(OR.sup.13).sub.2,
SO.sub.2 NHR.sup.10,
CONHOR.sup.13,
C(OH)R.sup.10 PO(OR.sup.13).sub.2,
CN,
SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
CONHSO.sub.2 R.sup.15,
SO.sub.2 NHCOR.sup.15,
CONHSO.sub.2 R.sup.13,
CH.sub.2 CONHSO.sub.2 R.sup.15,
NHCONHSO.sub.2 R.sup.15,
NHSO.sub.2 NHCOR.sup.15,
CONHNHSO.sub.2 CF.sub.3,
CON(OH)R.sup.13,
CONHCOCF.sub.3,
CONHSO.sub.2 R.sup.10,
CONHSO.sub.2 R.sup.11,
CONHSO.sub.2 R.sup.13, ##STR3608## R.sup.9 is selected from the group hydrogen,
methyl,
ethyl,
isopropyl,
t-butyl,
phenyl, and
benzyl;
R.sup.10 is selected from the group
hydroxy,
C.sub.1 -C.sub.8 -alkoxy,
C.sub.3 -C.sub.12 -alkenoxy,
C.sub.6 -C.sub.12 -arYloxy,
C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -ayloxy,
di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
acetylaninoethoxy,
nicotinoylaminoethoxy, and
succinamidoethoxy, and
C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and amino, and
hydroxy-C.sub.2 -C.sub.8 -alkoxy,
dihydroxy-C.sub.3 -C8-alkoxy, and
NR.sup.11 R.sup.12 ;
R.sup.1 land R.sup.12 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
nitro,
halo(F, Cl, Br, I),and
C.sub.1 -C.sub.4 -alkoxy;
R.sup.13 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
phenyl,
benzyl, and
CH.sub.2 --O--COCH.sub.3 ;
R.sup.15 is selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2, and
C.sub.3 -C.sub.7 -cycloalkyl,
C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from
C.sub.6 -C.sub.14 aryl,
heteroaryl as defined above,
OH,
SH,
C.sub.1 -C.sub.4 -alkyl,
C.sub.1 -C.sub.4 -alkoxy,
C.sub.1 -C.sub.4 -alkylthio,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
CO.sub.2 H,
CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl,
NH.sub.2,
N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
NH(C.sub.1 -C.sub.4)-alkyl!,
PO.sub.3 H, and
PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
(C.sub.1 -C.sub.4)-perfluoroalkyl;
R.sup.16 is selected from the group
CN,
NO.sub.2,
COOR.sup.13,
C.sub.1 -C.sub.6 -perfluoroalkyl, and
CF.sub.3 ;
R.sup.19 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkoxy,
(C.sub.2 -C.sub.6)-alkoxyalkyl,
CH.sub.2 --O--COCH.sub.3, and
benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from the group
NO.sub.2,
NH.sub.2,
OH, and
OCH.sub.3 ;
R25' is selected from the group
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C6alkylamine,
C.sub.2 -C.sub.6 alkenylamine, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
where any alkyl or alkenyl moiety is optionally substituted with
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26 and
NR.sup.27 R.sup.28, and
where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
R.sup.26 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
C.sub.1 -C.sub.6 alkanoyl;
R.sup.28 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
phenyl,
napthyl,
benzyl,
CH.sub.2 napthyl (.alpha. or .beta.)
C.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 cycloalkanoyl,
C.sub.6 -C.sub.10 aroyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alanoyl,
C.sub.1 -C.sub.6 alkylsulfonyl,
C.sub.6 -C.sub.10 arylsulfonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
cinnamoyl,
heterocyclecarbonyl,
C.sub.1 -C.sub.6 alkoxycarbonyl,
C.sub.6 -C.sub.10 aryloxycarbonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
pyroglutamyl;
and
pharmaceutically acceptable salts thereof.

262 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/313,068Filed 26 Sep 1994 · continuation in part
Priority: 14 May 1993
Granted: 1 Dec 1998
Term ends: Not estimatedThe source records don’t support an estimate.

Classification30 codes

C07D 223/16
Condensed with carbocyclic rings or ring systems: benzazepines; Hydrogenated benzazepines
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
A61P 35/00
Antineoplastic agents
C07D 243/10
Having the nitrogen atoms in positions 1 and 4: condensed with carbocyclic rings or ring systems

Family

Serial61,961Parent of this continuation-in-part · filed 14 May 1993
Serial82,202Parent of this continuation-in-part · filed 24 Jun 1993
US 5,843,941 AThis patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

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Abstract

A compound represented by structural formula (II):

##STR3539## where R.sup.1 is selected from the group ##STR3540## R and R' are independently selected from the group hydrogen,
halo(F, a, Br, I),
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
C.sub.1 -C.sub.6 alkoxy,
hydroxy,
hydroxy-C.sub.1 -C.sub.6 alkyl,
C.sub.16 -C.sub.6 alkylcarbonyl, and
W' is selected from one to three substituents selected from the group
hydrogen,
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
R.sup.8 and
V;
R.sup.7 is selected from the group,
hydrogen, benzyl,
C.sub.1 -C.sub.4 alkyl and halo (F, CL, Br, L)C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.8 alkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.3 -C.sub.2 cycloalkyl-C.sub.1 -C.sub.3 aklyl,
C.sub.3 -C.sub.12 cycloalkyl,
C.sub.1 -C.sub.4 alkyl-Z--C.sub.1 -C.sub.4 alkyl, where Z is S or O,
C.sub.2 -C.sub.4 alkyl-NR--C.sub.2 -C.sub.4 alkyl,
C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 aryl,
C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 cycloalkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl,
C.sub.6 -C.sub.12 aryl-C.sub.2 -C.sub.4 alkynyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
where any aryl, alkyl, cycloalkyl or alkenyl moiety is optionally substituted with halo(F, Cl, Br, I), or --OR.sup.9 ;
R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a heterocyclic 5-, 6-, or 7-member ring containing 0, 1, or 2 additional heteroatoms selected from N, S, and O, optionally the heterocyclic ring is substituted with one or two groups selected from
oxo(.dbd.O),
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.O)NHOH,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28, and
V;
R.sup.8 is selected from the group unsubstituted and substituted
C.sub.1 -C.sub.8 alkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.3 -C.sub.12 cycloalkyl-C.sub.1 -C.sub.4 alkyl,
C.sub.3 -C.sub.12 cycloalkyl
C.sub.1 -C.sub.4 alkyl-Z--C.sub.1 -C.sub.4 aklyl, where Z is S or O,
C.sub.2 -C.sub.4 alkyl-NR--C.sub.2 -C.sub.4 alkyl,
C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 aryl,
C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 cycloalkyl,
C.sub.2 -C.sub.8 alkenyl,
C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.4 alkyl,
C.sub.6 -C.sub.12 aryl-C.sub.2 -C.sub.4 alkynyl,
indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
imidazol-4-C.sub.1 -C.sub.3 alkyl,
where any aryl moiety is optionally substituted with halo(F, Cl, Br, I), --OR.sup.9 and V, and where any alkyl, cycloaLkyl or alkenyl group is optionally substituted with one to three groups selected from the group
SR.sup.9,
SSR.sup.9,
SC(.dbd.O)--R.sup.9,
OR.sup.9,
C(.dbd.NH)--NH.sub.2,
N.dbd.CH--NH.sub.2,
NH--CH.dbd.NH,
NH--C(.dbd.NH)--NH.sub.2,
C(.dbd.O)NHOH,
C(.dbd.O)OR.sup.9,
NHR.sup.9,
C(.dbd.O)NR.sup.27 R.sup.28 and
V;
V is selected from the group
COR.sup.10,
SO.sub.3 R.sup.13,
NHSO.sub.2 CF.sub.3,
PO(OR.sup.13).sub.2,
SO.sub.2 NHR.sup.10,
CONHOR.sup.13,
C(OH)R.sup.10 PO(OR.sup.13).sub.2,
CN,
SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S, and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
CN,
C.sub.1 -C.sub.4 alky,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl)
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl),
N(C.sub.1 -C.sub.4 alkyl).sub.2,
CONHSO.sub.2 R.sup.15,
SO.sub.2 NHCOR.sup.15,
CONHSO.sub.2 R.sup.13,
CH.sub.2 CONHSO.sub.2 R.sup.15,
NHCONHSO.sub.2 R.sup.15,
NHSO.sub.2 NHCOR.sup.15,
CONHNHSO.sub.2 CF.sub.3,
CON(OH)R.sup.13,
CONHCOCF.sub.3,
CONHSO.sub.2 R.sup.10,
CONHSO.sub.2 R.sup.11,
CONHSO.sub.2 R.sup.13, ##STR3541## R.sup.9 is selected from the group hydrogen,
methyl,
ethyl,
isopropyl
phenyl, and
benzy
R.sup.10 is selected from the group
hydroxy,
C.sub.1 -C.sub.8 -alkoxy,
C.sub.3 -C.sub.12 -alkenoxy,
C.sub.6 -C.sub.12 -aryloxy,
C.sub.1 -C.sub.6 alkyl-C.sub.6 -C.sub.12 -aryloxy,
di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
acetylaminoethoxy,
nicotinoylaminoethoxy, and
succinamidoethoxy,
C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino,
hydroxy-C.sub.2 -C.sub.8 -alkoxy,
dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
NR.sup.11 R.sup.12 ;
R.sup.11 and R.sup.12 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
nitro,
halo(F, Cl, Br, I),
C.sub.1 -C.sub.4 -alkoxy, and
amino, and
C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from the group
nitro,
halo(F, a, Br, I), and
C.sub.1 -C.sub.4 -alkoxy;
R.sup.13 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl,
phenyl,
benzyl, and
CH.sub.2 --O--COCH.sub.3 ;
R.sup.15 is selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl, where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
OH,
SH,
C.sub.1 -C.sub.4 alky,
C.sub.1 -C.sub.4 alkoxy,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
COOH,
COO--(C.sub.1 -C.sub.4 alkyl),
NH.sub.2,
NH(C.sub.1 -C.sub.4 alkyl), and
N(C.sub.1 -C.sub.4 alkyl).sub.2,
C.sub.3 -C.sub.7 -cycloalkyl,
C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
C.sub.6 -C.sub.14 aryl,
heteroaryl as defined above,
OH,
SH,
C.sub.1 -C.sub.4 alkyl,
C.sub.1 -C.sub.4 alkoxy,
C.sub.1 -C.sub.4 alkylthio,
CF.sub.3,
halo(F, Cl, Br, I),
NO.sub.2,
CO.sub.2 H,
CO.sub.2 -C.sub.1 -C.sub.4 -alkyl,
NH.sub.2,
N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
NH(C.sub.1 -C.sub.4)-alkyl!,
PO.sub.3 H,
PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
C.sub.1 -C.sub.4 -perfluoroalkl;
R.sup.16 is selected from the group
CN,
NO.sub.2,
COOR.sup.13,
C.sub.1 -C.sub.6 -perfluoroalkyl, and
CF.sub.3 ;
R.sup.19 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 -alkyl
C.sub.2 -C.sub.6 -alkenyl,
C.sub.1 -C.sub.6 -alkoxy,
C.sub.2 -C.sub.6 -alkoxyalkyl,
CH.sub.2 --O--COCH.sub.3, and
benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from the group
NO.sub.2,
NH.sub.2,
OH, and
OCH.sub.3 ;
X is selected from the group
NR.sup.24 --C(.dbd.O)--R.sup.25,
NR.sup.24 --C(.dbd.O)--R.sup.8,
NR.sup.24 --C(.dbd.O)--NR.sup.7 'R.sup.8,
NR.sup.24 --C(.dbd.O)O--R.sup.8,
NR.sup.24 --C(.dbd.O)S--R.sup.8,
(CH.sub.2).sub.1-4 --NR.sup.24 --C(.dbd.O)-R.sup.25,
NR.sup.24 --CH(OH)--R.sup.25,
NR.sup.24 --CH.sub.2 --R.sup.25,
NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0,1, or 2,
CHR.sup.24 --O--R.sup.25,
CHR.sup.24 --CH.sub.2 R.sup.25,
CHR.sup.24 --R.sup.25,
CR.sup.24 .dbd.CHR.sup.25 (E or Z),
(CH.sub.2).sub.1-4 --C(.dbd.O)--R.sup.25,
C.sub.6 -C.sub.10 aryl-R.sup.25,
heterocyle-R.sup.25,
C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25,
where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
R.sup.24 is selected from the group
hydrogen,
benzyl,
halo(F, a, Br, I)benzyl,
C.sub.1 -C.sub.6 alkyl, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
R.sup.25 is selected from R.sup.25, ##STR3542## R.sup.25 ' is selected from the group SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26,
C.sub.1 -C.sub.6 alkyl,
C.sub.2 -C.sub.6 alkenyl,
C.sub.1 -C.sub.6 alkylamine,
C.sub.2 -C.sub.6 alkenylamine, and
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
where any alkyl or alkenyl moiety is optionally substituted with one to three
SR.sup.26,
SSR.sup.26,
OR.sup.26,
NOR.sup.26, and
NR.sup.27 R.sup.28,
where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
R.sup.26 is selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
C.sub.1 -C.sub.6 alkanoyl;
R.sup.27 and R.sup.28 are independently selected from the group
hydrogen,
C.sub.1 -C.sub.6 alkyl,
phenyl,
napthyl,
benzyl,
CH.sub.2 napthyl (.alpha. or .beta.)
C.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 cycloalkanoyl,
C.sub.6 -C.sub.10 aroyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
C.sub.1 -C.sub.6 alkylsulfonyl,
C.sub.6 -C.sub.10 arylsulfonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
cinnamoyl,
heterocyclecarbonyl,
C.sub.1 -C.sub.6 alkoxycarbonyl,
C.sub.6 -C.sub.10 aryloxycarbonyl,
C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
pyroglutamyl;
R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3543## and a cyclic imide represented by ##STR3544## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0, 1, or 2, and NR.sup.28 ;
J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl;
and
pharmaceutically acceptable salts thereof.

276 more elements

Facts

Application

08/313,068Filed 26 Sep 1994 · continuation in part

Priority

14 May 1993

Granted

1 Dec 1998

Term ends

Not estimatedThe source records don’t support an estimate.

Classification30 codes

C07D 223/16
Condensed with carbocyclic rings or ring systems: benzazepines; Hydrogenated benzazepines
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
A61P 35/00
Antineoplastic agents
C07D 243/10
Having the nitrogen atoms in positions 1 and 4: condensed with carbocyclic rings or ring systems