US 2002/0161050 A1Published application

Benzene butyric acids and their derivatives as inhibitors of matrix metalloproteinases

AssigneeWarner-Lambert Company

InventorsClaude Forsey Purchase JR., Bruce David Roth, Andrew David White

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Abstract

Benzene butyric acid compounds and derivatives are described as well as methods for the preparation and pharmaceutical compositions of same, which are useful as inhibitors of matrix metalloproteinases, particularly gelatinase A, collagenase-3, and stromelysin-1 and for the treatment of multiple sclerosis, atherosclerotic plaque rupture, aortic aneurysm, heart failure, left ventricular dilation, restenosis, periodontal disease, corneal ulceration, treatment of bums, decubital ulcers, wound healing, cancer, inflammation, pain, arthritis, osteoporosis, renal disease, or other autoimmune or inflammatory disorders dependent upon tissue invasion by leukocytes or other activated migrating cells, acute and chronic neurodegenerative disorders including stroke, head trauma, spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, cerebral amyloid angiopathy, AIDS, Parkinson's disease, Huntington's disease, prion diseases, myasthenia gravis, and Duchenne's muscular dystrophy.

Claims56

Dependent claims

A compound of Formula I

69
wherein R1 is hydrogen,
alkyl,
cycloalkyl,
aryl,
arylalkyl,
heteroaryl,
heteroarylalkyl,
heterocycle, or
heterocyclealkyl;
R2, R2a, R3, and R3a are either the same or different and are each independently seledted from
hydrogen,
fluorine,
-(C1-10alkyl)n-R5 wherein n is zero or an integer of 1,
alkyl is unsubstituted or optionally substituted with 1 to 3 substituents selected from
—OR7 wherein R7 is hydrogen or alkyl,
—SR7 wherein R7 is as defined above,
—CH2—S—CO-alkyl,
70
wherein R7 is as defined above,
—CO-alkyl,
—CO2-alkyl,
—O—CO-alkyl,
—S—CO-alkyl,
71
wherein R7 is as defined above,
—SO-alkyl,
—SO2-alkyl,
—CN,
—CF3, or
—HN—SO2-alkyl and,
R5 is hydrogen,
aryl,
heteroaryl,
heterocycle,
N-phthalimido,
N-2,3-naphthylimido,
indol-3-yl,
imidazol-4-yl,
2-, 3-, or 4-pyridyl,
2,4-dioxo-1,5,5-trimethyl-imidazolidin-3-yl or a side chain of a naturally occurring or unnaturally occurring amino acid;
R4 is SH or
OR4a wherein R4a is hydrogen,
alkyl,
arylalkyl,
cycloalkyl,
acyloxymethyl or NHOR4a wherein R4a is as defined above;
X is
72
73
wherein R6 is hydrogen,
methyl or optionally R1 and R6 are taken together to form a ring containing from 4 to 7 carbons which may be unsubstituted or substituted with alkyl,
aryl,
arylalkyl,
heteroaryl,
heteroarylalkyl,
heterocycle, or
heterocyclealkyl,
74
wherein R6 is as defined above,
75
wherein R6 is as defined above,
76
wherein R6 is as defined above,
77
wherein R6 is as defined above,
78
wherein R6 and R6a are either the same or different and are each independently as defined above for R6,
79
wherein R6 is as defined above,
80
wherein R6 is as defined above,
81
wherein R6 is as defined above,
82
wherein R6 is as defined above, or
83
wherein R6 and R6a are as defined above;
Z is
84
85
wherein R7 is as defined above,
86
wherein R7 is as defined above,
87
F is fluorine;
and
m is zero or an integer of 1 to 4;
and corresponding isomers thereof;
or a pharmaceutically acceptable salt thereof.

87 more elements

The compound selected from the group consisting of:

4-[4-(4-Bromo-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-(4-Benzoylamino-phenyl)-4-oxo-butyric acid;
4-[4-(4-Chloro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2-Fluoro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(3-Fluoro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Fluoro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2-Iodo-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2,4-Dichloro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2,6-Dichloro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(3,4-Dichloro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2,4-Difluoro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-(4-Bromo-phenyl)-butyrylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-(4-Bromo-phenyl)-acetylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(3-Cyano-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(Benzo[1,3]dioxol-5-yl-carbonylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(Biphenyl-4-yl-carbonylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Cyano-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2-Methoxy-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(3-Methoxy-benzoylamino)-phenyl]-4oxo-butyric acid;
4-[4-(4-Methoxy-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2,4-Dimethoxy-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2,4-Dimethoxy-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2,5-Demethoxy-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2,6-Demethoxy-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(3,5-Dimethoxy-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-Oxo-4-[4-(3,4,5-trimethoxy-benzoylamino)-phenyl]-butyric acid;
4-[4-(4-Methyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Decyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Ethyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Tert-Butyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Butoxy-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(Cyclohexanecarbonyl-amino)-phenyl]-4-oxo-butyric acid;
4-[4-(Furan-2-yl-carbonyl-amino)-phenyl]-4-oxo-butyric acid;
4-Oxo-4-[4-(thiophen-2-yl-carbonyl-amino)-phenyl]-butyric acid;
4-[4-(3-Chlorobenzo[B]thiophen-2-yl-carbonyl-amino)-phenyl]-4-oxo-butyric acid;
4-Oxo-4-[4-(phenylacetyl-amino)-phenyl]-butyric acid;
4-Oxo-4-[4-(3-phenyl-propionyl-amino)-phenyl]-butyric acid;
4-[-4-(Dodecanoyl-amino)-phenyl]-4-oxo-butyric acid;
4-[-4-(Heptanoyl-amino)-phenyl]-4-oxo-butyric acid;
4-[4-(3-Carboxy-propionyl-amino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Carboxy-butyryl-amino)-phenyl]-4-oxo-butyric acid;
4-[4-(Carboxy-acetyl-amino)-phenyl]-4-oxo-butyric acid;
4-[4-(3-Nitro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Nitro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(Butyryl-amino)-phenyl]-4-oxo-butyric acid;
4-[-4-(Decanoyl-amino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Chloro-phenoxy-acetylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(3,4-Dimethoxy-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(3,4-Dimethoxy-phenylacetyl-amino)-phenyl]-4-oxo-butyric acid;
4-[4-(Napthyl-2-yl-carbonylamino)-phenyl]-4-oxo-butyric acid;
4-Oxo-4-[4-(pyridin-3-yl-carbonylamino)-phenyl]-butyric acid;
4-[4-(Adamantan-1-yl-carbonylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(Oleoyl-amino)-phenyl]-4-oxo-butyric acid;
4-[4-(Nonanoyl-amino)-phenyl]-4-oxo-butyric acid;
4-Oxo-4-[4-(propionylamino)-phenyl]-butyric acid;
4-[4-(2-Acetoxy-2,2-dimethyl-acetylamino)-phenyl]-4-oxo-butyric acid;
4-Oxo-4-[4-(phenoxy-acetylamino)-phenyl]-butyric acid;
4-[4-(Oxalamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Chloro-3-nitro-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-Oxo-4-[4-(phenylazo-benzoylamino)-phenyl]-butyric acid;
4-[4-(Cinnamoylamino)-phenyl]-4-oxo-butyric acid;
(±)-2-(Acetylthio)methyl-4-[4-(4-methyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
(±)-3-(Acetylthio)methyl-4-[4-(4-methyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
(±)-2-(2,4-Dioxo-1,5,5-trimethyl-imidazolidin-3-yl)methyl-4-[4-(4-methyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
(±)-2-(4-Benzyloxy-phenyl)methyl-4-[4-(4-methyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
(±)-4-[4-(4-Methyl-benzoylamino)-phenyl]-4-oxo-2-(3-phenyl-propyl)-butyric acid;
(±)-4-[4-(4-Methyl-benzoylamino)-phenyl]-4-oxo-2-(2-phthalimindo-ethyl)-butyric acid;
(±)-2-(4-Methyl-benzenesulfonyl)amino-4-[4-(4-methyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
(±)-4-[4-(4-Methyl-benzoylamino)-phenyl]-4-oxo-3-(pyridin-3-yl)methyl-butyric acid;
4-[4-(Octanoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Heptyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2-Naphthoylamino)-phenyl]-4-oxo-butyric acid;
4-Oxo-4-[4-(4-trifluoromethyl-benzoylamino)-phenyl]-butyric acid;
4-Oxo-4-[4-(2,3,4,5,6-pentafluoro-benzoylamino)-phenyl]-butyric acid;
4-[4-(2-Fluoro-4-trifluoromethyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(3-Fluoro-4-trifluoromethyl-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(4-Hexyloxy-benzoylamino)-phenyl]-4-oxo-butyric acid;
4-[4-(2-Benzo[b]thiophene-carbonylamino)-phenyl]-4-oxo-butyric acid;
4-Oxo-4-[4-(2-quinoxaloylamino)-phenyl-butyric acid;
4-[4-(4-Dipropylaminosulfonyl-benzoylamino)-phenyl-4-oxo-butyric acid;
4-Oxo-[4-(3-phenyl-ureido)-phenyl]-butyric acid;
{4-[3-(4-Chloro-phenyl)-ureido]-phenyl}-4-oxo-butyric acid;
{4-[3-(4-Bromo-phenyl)-ureido]-phenyl}-4-oxo-butyric acid;
{4-[3-(4-Fluoro-phenyl)-ureido]-phenyl}-4-oxo-butyric acid;
4-Oxo-{4-[3-(4-trifluoro-phenyl)-ureido]-phenyl}-butyric acid;
{4-[3-(4-Methoxy-phenyl)-ureido]-phenyl}-4-oxo-butyric acid;
{4-[3-(4-Methyl-phenyl)-ureido]-phenyl}-4-oxo-butyric acid;
4-Oxo-{4-[3-(thiophen-2-yl)-ureido]-phenyl} -butyric acid;
4-Oxo-4-[4-(phenoxycarbonylamino)-phenyl]-butyric acid;
4-{4-[(4-Chloro-phenoxy)-carbonylamino]-phenyl}-4-oxo-butyric acid;
4-{4-[(4-Bromo-phenoxy)-carbonylamino]-phenyl}-4-oxo-butyric acid;
4-{4-[(4-Fluoro-phenoxy)-carbonylamino]-phenyl}-4-oxo-butyric acid;
4-{4-[(4-Methoxy-phenoxy)-carbonylamino]-phenyl}-4-oxo-butyric acid;
4-{4-[(4-Methyl-phenoxy)-carbonylamino]-phenyl}-4-oxo-butyric acid;
4-Oxo-4-{4-[(4-trifluoromethyl-phenoxy)-carbonylamino]-phenyl}-butyric acid;
4-Oxo-{4-[4-(2-thiophenoxy)-carbonylamino]-phenyl}-butyric acid;
4-[4-(4-Bromo-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-(4-Benzoylamino-phenyl)-4-hydroxyimino-butyric acid;
4-[4-(4-Chloro-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(2-Fluoro-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(3-Fluoro-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(4-Fluoro-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-Hydroxyimino-4-[4-(2-iodo-benzoylamino)-phenyl]-butyric acid;
4-[4-(2,4-Dichloro-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(2,6-Dichloro-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(3,4-Dichloro-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(2,4-Difluoro-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(4-(4-Bromo-phenyl)-butyrylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(4-(4-Bromo-phenyl)-acetylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(3-Cyano-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(Benzo[1,3]dioxol-5-yl-carbonylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(Biphenyl-4-yl-carbonylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(4-Cyano-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-Hydroxyimino-4-[4-(2-methoxy-benzoylamino)-phenyl]-butyric acid;
4-Hydroxyimino-4-[4-(3-methoxy-benzoylamino)-phenyl]-butyric acid;
4-Hydroxyimino-4-[4-(4-methoxy-benzoylamino)-phenyl]-butyric acid;
4-[4-(2,4-Dimethoxy-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(2,5-Dimethoxy-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(2,6-Dimethoxy-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(3,5-Dimethoxy-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-Hydroxyimino-4-[4-(3 ,4,5-trimethoxy-benzoylamino)-phenyl]-butyric acid;
4-Hydroxyimino-4-[4-(4-Methyl-benzoylamino)-phenyl]-butyric acid;
4-[4-(4-Decyl-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(4-Ethyl-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(4-Tert-Butyl-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(4-Butoxy-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(Cyclohexanecarbonyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(Furan-2-yl-carbonyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-Hydroxyimino-4-[4-(thiophen-2-yl-carbonyl-amino)-phenyl]-butyric acid;
4-[4-(3-Chlorobenzo[B]thiophen-2-yl-carbonyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-Hydroxyimino-4-[4-(phenylacetyl-amino)-phenyl]-butyric acid;
4-Hydroxyimino-4-[4-(3-phenyl-propionyl-amino)-phenyl]-butyric acid;
4-[4-(2,2-Dimethyl-pentanoyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-[-4-(Dodecanoyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-[-4-(Heptanoyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(3-Carboxy-propionyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(4-Carboxy-butyryl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(Carboxy-acetyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-Hydroxyimino-4-[4-(3-nitro-benzoylamino)-phenyl]-butyric acid;
4-Hydroxyimino-4-[4-(4-nitro-benzoylamino)-phenyl]-butyric acid;
4-[4-(Butyryl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-[-4-(Decanoyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(Diphenylacetyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(4-Chloro-phenoxy-acetylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(3,4-Dimethoxy-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-[4-(3,4-Dimethoxy-phenylacetyl-amino)-phenyl]-4-hydroxyimino-butyric acid;
4-Hydroxyimino-4-[4-(napthyl-2-yl-carbonylamino)-phenyl]-butyric acid;
4-Hydroxyimino-4-[4-(pyridin-3-yl-carbonylamino)-phenyl]-butyric acid;
4-[4-(Adamantan-1-yl-carbonylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-Hydroxyimino-4-[4-(oleoyl-amino)-phenyl]-butyric acid;
4-Hydroxyimino-4-[4-(nonanoyl-amino)-phenyl]-butyric acid;
4-Hydroxyimino-4-[4-(propionylamino)-phenyl]-butyric acid;
4-[4-(2-Acetoxy-2,2-dimethyl-acetylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-Hydroxyimino-4-[4-(2-phenoxy-propionylamino)-phenyl]-butyric acid;
4-Hydroxyimino-4-[4-(phenoxy-acetylamino)-phenyl]-butyric acid;
4-Hydroxyimino-4-[4-(oxalamino)-phenyl]-butyric acid;
4-[4-(4-Chloro-3-nitro-benzoylamino)-phenyl]-4-hydroxyimino-butyric acid;
4-Hydroxyimino-4-[4-(phenylazo-benzoylamino)-phenyl]-butyric acid;
4-[4-(Cinnamoylamino)-phenyl]-4-hydroxyimino-butyric acid;
(±)-2-(Acetylthio)methyl-4-hydroxyimino-4-[4-(4-methyl-benzoylamino)-phenyl]-butyric acid;
(±)-3-(Acetylthio)methyl-4-hydroxyimino-4-[4-(4-methyl-benzoylamino)-phenyl]-butyric acid;
(±)-2-(2,4-Dioxo-1,5,5-trimethyl-imidazolidin-3-yl)methyl-4-hydroxyimino-4-[4-(4-methyl-benzoylamino)-phenyl]-butyric acid;
(±)-2-(4-Benzyloxy-phenyl)methyl-4-hydroxyimino-4-[4-(4-methyl-benzoylamino)-phenyl]-butyric acid;
(±)-4-Hydroxyimino-4-[4-(4-methyl-benzoylamino)-phenyl]-2-(3-phenyl-propyl)-butyric acid;
(±)-4-Hydroxyimino-4-[4-(4-methyl-benzoylamino)-phenyl]-2-(2-phthalimindo-ethyl)-butyric acid;
(±)-4-Hydroxyimino-2-(4-methyl-benzenesulfonyl)amino-4-[4-(4-methyl-benzoylamino)-phenyl]-butyric acid;
and
(±)-4-Hydroxyimino-4-[4-(4-methyl-benzoylamino)-phenyl]-3-(pyridin-3-yl)methyl-butyric acid;
and corresponding isomers thereof;
or a pharmaceutically acceptable salt thereof.

167 more elements

A method for preparing a compound of Formula Ia

118
wherein R1 is hydrogen,
alkyl,
cycloalkyl,
aryl,
arylalkyl,
heteroaryl,
heteroarylalkyl,
heterocycle, or
heterocyclealkyl;
R2, R2a, R3, and R3a are either the same or different and are each independently selected from
hydrogen,
fluorine,
-(C1-10alkyl)n-R5 wherein n is zero or an integer of 1,
alkyl is unsubstituted or optionally substituted with 1 to 3 substituents selected from
—OR7 wherein R7 is hydrogen or alkyl,
—SR7 wherein R7 is as defined above,
—CH2—S—CO-alkyl,
119
wherein R7 is as defined above,
—CO-alkyl,
—CO2-alkyl,
—O—CO-alkyl,
—S—CO-alkyl,
120
wherein R7 is as defined above,
—SO-alkyl,
—SO2-alkyl,
—CN,
—CF3, or
—NH—SO2-alkyl and,
R5 is hydrogen,
aryl,
heteroaryl,
heterocycle,
N-phthalimido,
N-2,3-naphthylimido,
indol-3-yl,
imidazol-4-yl,
2-, 3-, or 4-pyridyl,
2,4-dioxo-1,5,5-trimethyl-imidazolidin-3-yl or a side chain of a naturally occurring or unnaturally occurring amino acid;
X is
121
wherein R6 is hydrogen,
methyl or optionally R1 and R6 are taken together to form a ring containing from 4 to 7 carbons which may be unsubstituted or substituted with alkyl,
aryl,
arylalkyl,
heteroaryl,
heteroarylalkyl,
heterocycle, or
heterocyclealkyl,
122
wherein R6 is as defined above,
123
wherein R6 is as defined above,
124
wherein R6 is as defined above,
125
wherein R6 is as defined above,
126
eherein R6 and R6a are either the same or different and are each independently as defined above for R6,
127
wherein R6 is as defined above,
128
wherein R6 is as defined above,
129
wherein R6 is as defined above,
130
wherein R6 is as defined above, or
131
wherein R6 and R6a are as defined above;
F is fluorine;
m is zero or an integer of 1 to 4;
and R7 is hydrogen or alkyl;
and corresponding isomers thereof;
or a pharmaceutically acceptable salt thereof which comprises deprotection of a compound of Formula (A)
132 p1 wherein PG1 is selected from the group consisting of methyl, ethyl, tert-butyl, and benzyl, and X, F, m, R1, R2, R2a, R3, and R3a are as defined above using standard methodology followed by condensation with a compound of Formula (B)
H2NOR7 (B)
wherein R7 is as defined above to give a compound of Formula Ia and if desired, converting a compound of Formula Ia to a corresponding pharmaceutically acceptable salt by conventional means and, if so desired, converting the corresponding pharmaceutically acceptable salt to a compound of Formula Ia by conventional means.

76 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/023,288Filed 17 Dec 2001
Priority: 12 Jul 1999
Published: 31 Oct 2002
Term ends: Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07D 213/82
Amides; Imides: in position 3
C07C 233/54
With the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring:…
C07C 233/55
With the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring:…
C07C 233/63
Having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings: having the nitrogen atom of at…

Family

Application09/351,549Division · filed 12 Jul 1999
Application10/023,288Division · filed 17 Dec 2001
US 6,541,521 B1Related patent
US 6,624,196 B2Related patent
US 2002/0161050 A1This patent

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