Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-12-11
2002-12-10
Davis, Zinna Northington (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S416000, C546S146000, C548S465000
Reexamination Certificate
active
06492387
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to compounds useful as agents for the treatment of central nervous system disorders. More particularly, this invention relates to isoindolyl and isoquinolinyl aroyl pyrrole compounds useful as agents or modulators for the treatment of central nervous system disorders including, but not limited to, epilepsy and neuropathic pain and methods for the treatment thereof.
BACKGROUND OF THE INVENTION
The conditions grouped under the term “central nervous system disorder” constitute an area of continuing medical need. Such conditions include those disorders associated with convulsions, epilepsy, neuroprotective diseases, muscle tension and neuropathic pain.
Epilepsy continues to be an area of development for new drugs and therapies. The structures of newer anticonvulsants has been summarized in Drugs of the Future, 1991, (16) 317-320.However, the impact of such drugs and therapies have yet to be fully evaluated.
Neuropathic pain is defined as pain caused by aberrant somatosensory processing in the peripheral or central nervous system. Chronic or debilitating conditions, such as post-herpetic neuralgia and phantom limb syndrome, are categorized as neuropathic pain.
Central nervous system disorders are widespread and cause pain and suffering. Moreover, current methods of treating such disorders are often inadequate.
Anticonvulsants have been suggested for the treatment of neuropathic pain. Nadin Attal, et al., Effects of Gabapentin on the Different Components of Peripheral and Central Neuropathic Pain Syndromes: A Pilot Study,
Fr. Eur. Neurol.
1998, 40(4), 191-200 describes the anticonvulsant gabapentin having the following formula:
U.S. Pat. No. 5,760,007 describes other anticonvulsants useful in the treatment of neuropathic pain. More particularly, the reference describes the use of the anticonvulsant topiramate in treating neuropathic pain, wherein topiramate has the following general formula:
U.S. Pat. No. 5,332,736 (hereby incorporated by reference) describes substituted aroyl aminoacyl pyrrole compounds of the formula:
wherein,
A is simultaneously both
n is selected from 1 to 5;
R
1
is selected from the group consisting of H and C
1-4
alkyl;
R
2
and R
3
are selected from the group consisting of H and C
1-4
alkyl;
R
4
and R
5
are independently selected from the group consisting of H, and C
1-4
alkyl, phenyl C
1-4
alkyl and substituted phenyl C
1-4
alkyl where the substituent is on phenyl and selected from the group consisting of methyl and methoxy, or in the alternative, are fused and together with said nitrogen form a heterocyclic ring selected from the group consisting of:
wherein Y is S or O, x is 3 to 7 and R
7
is selected from the group consisting of methyl and hydroxymethyl; and R
6
is selected from the group consisting of halo, C
1-4
alkyl, C
1-4
alkoxy, hydroxy, nitro, amino, C
1-4
acylamino, cyano, trihaloC
1-4
alkyl, C
1-4
alkylsulfonyl, C
1-4
alkylsulfinyl and C
1-4
acyl, including pharmaceutically acceptable acid addition salts thereof as useful anticonvulsants.
U.S. patent application Ser. No. 09/505,916, filed on Feb. 17, 2000 (hereby incorporated by reference) describes aroyl aminoacyl pyrrole compounds of the formula:
wherein,
A is simultaneously both
n is an integer from 1 to 5;
R
1
is selected from the group consisting of H and C
1-4
alkyl;
R
2
and R
3
are selected from the group consisting of H and C
1-4
alkyl; R
4
and R
5
are independently selected from the group consisting of H, C
1-4
alkyl, phenyl C
1-4
alkyl and substituted phenyl C
1-4
alkyl where the substituent is on phenyl and selected from the group consisting of methyl and methoxy, or in the alternative, are fused and together with said nitrogen form a heterocyclic ring selected from the group consisting of 4-[bis(4-fluorophenyl)methylene]-piperidin-1-yl, 1,2,3,4-tetrahydro-6,7-dimethoxy-isoquinolin-2-yl,
wherein Y is S or O, x is 3 to 7 and R
7
is selected from the group consisting of methyl and hydroxymethyl; and R
6
is selected from the group consisting of halo, C
1-4
alkyl, C
1-4
alkoxy, hydroxy, nitro, amino, C
1-4
acylamino, cyano, trihaloC
1-4
alkyl, C
1-4
alkylsulfonyl, C
1-4
alkylsulfinyl and C
1-4
acyl, including pharmaceutically acceptable acid addition salts thereof as useful in the treatment of neuropathic pain.
U.S. patent application Ser. No. 60/215272, filed on Jun. 30, 2000 (hereby incorporated by reference) describes aroyl aminoacyl pyrrole compounds of Formula (I) and Formula (II):
wherein
A is a substituent selected from the group consisting of aryl and heteroaryl optionally substituted with one to two substituents selected from the group consisting of halogen, C
1-8
alkyl, C
1-8
alkyl, alkoxy, tri(halogen)C
1-8
alkyl and tri(halogen)C
1-8
alkoxy; n is an integer from 1 to 5; R
1
is C
1-8
alkyl optionally substituted with one to two substituents independently selected from the group consisting of hydroxy, C
1-8
alkoxy (optionally substituted with —SC
1-8
alkyl ), C
1-8
acyl, carboxy, carbonyl (further substituted with C
1-8
alkyl, C
1-8
alkoxy, amino or —SC
1-8
alkyl), oxy (further substituted with carbonylC
1-8
alkyl, carbonylC
1-8
alkoxy or carbonylamino), amino (optionally further substituted with one or two substituents independently selected from C
1-8
alkyl, C
1-8
acyl, carbonylC
1-8
alkyl, carbonylC
1-8
alkoxy, sulfinylC
1-8
alkyl or sulfonylC
1-8
alkyl), ureido (optionally further substituted with C
1-8
alkyl), thio (optionally further substituted with C
1-8
alkyl or amino), sulfinyl (optionally further substituted with C
1-8
alkyl or amino) and sulfonyl (optionally further substituted with C
1-8
alkyl or amino); R
2
and R
3
are substituents independently selected from the group consisting of hydrogen and C
1-8
alkyl; R
4
and R
5
are substituents independently selected from the group consisting of hydrogen, C
1-8
alkyl and arylC
1-8
alkyl; wherein aryl is optionally substituted with one to three substituents selected from the group consisting of C
1-8
alkyl, C
1-8
alkoxy, tri(halo)C
1-8
alkyl and tri(halo)C
1-8
alkoxy; or, in the alternative, R
4
and R
5
may be fused together with nitrogen to form a heterocyclic ring selected from the group consisting of:
—(heteroaryl)—(R
6
)
0-2
,
wherein x is an integer from 3 to 7 and Y is selected from the group consisting of N, S, S═O, SO
2
and O; and R
6
is a substituent selected from the group consisting of C
1-8
alkyl and hydroxyC
1-8
alkyl; and pharmaceutically acceptable acid addition salts thereof; with the proviso that, in the case of compound wherein n is an integer from 1 to 5; R
1
is selected from the group consisting of hydrogen and C
1-4
alkyl; R
2
and R
3
are selected from the group consisting of hydrogen and C
1-4
alkyl; R
4
and R
5
are independently selected from the group consisting of hydrogen, C
1-4
alkyl, phenylC
1-4
alkyl and substituted phenylC
1-4
alkyl where the substituent is on phenyl and selected from the group consisting of methyl and methoxy; or in the alternative, are fused and together with the nitrogen form a heterocyclic ring selected from the group consisting of: 4-[bis(4-fluorophenyl)methylene]-piperidin-1-yl, 1,2,3,4-tetrahydro-6,7-dimethoxy-isoquinolin-2-yl,
wherein Y is S or O and x is 3 to 7; and, R
6
is selected from the group consisting of methyl and hydroxymethyl; then, A cannot be substituted or unsubstituted phenyl as agents for the treatment of central nervous system disorders.
The isoindolyl and isoquinolinyl aroyl pyrrole compounds of the present invention have not been previously described as useful agents for the treatment of central nervous system disorders.
Accordingly, it is an object of the present invention to provide isoindolyl and isoquinolinyl aroyl pyrrole compounds useful as agents for the treatment of central nervous system disorders. It is also an object of the present invention to teach a method for the treatment of central nervous system disorders using the isoindolyl and isoquinolinyl aroyl pyrrole compounds of the present invention.
SUMMARY OF THE INVENTION
The pr
Carson John R.
Pitis Philip M.
Davis Zinna Northington
Harbour John W.
Ortho-McNeil Pharamaceutical, Inc.
LandOfFree
Isoindolyl and isoquinolinyl aroyl pyrrole compounds does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Isoindolyl and isoquinolinyl aroyl pyrrole compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Isoindolyl and isoquinolinyl aroyl pyrrole compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2992655