Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-11-23
2001-06-12
Huang, Evelyn Mei (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C546S122000
Reexamination Certificate
active
06245778
ABSTRACT:
This invention relates to novel compounds, to processes for preparing them, and to their use as therapeutic agents.
EP-A-0556008 (Shionogi) discloses condensed imidazopyridine derivatives with psychotropic activity, including the compound 1,6naphthyridine-6(5H)-carboxylic acid, 4-azido-3-[[(1,1-dimethylethoxy) carbonyl]amino]-7,8-dihydro, ethyl ester.
It has now been surprisingly found that carboxamide compounds of formula (I) below possess anti-convulsant activity and are therefore believed to be useful in the treatment and/or prevention of anxiety, mania, depression, panic disorders and/or aggression, disorders associated with a subarachnoid haemorrhage or neural shock, the effects associated with withdrawal from substances of abuse such as cocaine, nicotine, alcohol and benzodiazepines, disorders treatable and/or preventable with anti-convulsive agents, such as epilepsy including post-traumatic epilepsy, Parkinson's disease, psychosis, migraine, cerebral ischaemia, Alzheimer's disease and other degenerative diseases such as Huntingdon's chorea, schizophrenia, obsessive compulsive disorders (OCD), neurological deficits associated with AIDS, sleep disorders (including circadian rhythm disorders, insomnia & narcolepsy), tics (e.g. Giles de la Tourette's syndrome), traumatic brain injury, tinnitus, neuralgia, especially trigeminal neuralgia, neuropathic pain, dental pain, cancer pain, inappropriate neuronal activity resulting in neurodysthesias in diseases such as diabetes, MS and motor neurone disease, amyotrophic lateral sclerosis, ataxias, muscular rigidity (spasticity) and temporomandibular joint dysfunction.
Accordingly, the present invention provides a compound of formula (I) or pharmaceutically acceptable salt thereof:
where
R
1
is hydrogen, C
1-6
alkyl optionally substituted by hydroxy or C
1-4
alkoxy, or C
1-6
alkylphenyl;
R
2
is hydrogen or up to three substituents selected from halogen, NO
2
, CN, N
3
, C
1-6
alkylO-, C
1-6
alkylS-, C
1-6
alkyl, C
3-6
cycloalkyl,
C
3-6
cycloalkyl-C
1-4
alkyl-, C
1-6
alkenyl, C
1-6
alkynyl, CF
3
, CF
3
O, CF
3
CO—, C
1-6
alkylCO-, C
3-6
cycloalkylCO-,
C
3-6
cycloalkyl-C
1-4
alkylCO-, phenyl, phenoxy, benzyloxy, benzoyl, phenyl-C 14alkyl-,
or —NR
3
R
4
where
R
3
is hydrogen or C
1-4
alkyl, and
R
4
is hydrogen, C
1-4
alkyl, —CHO,
—CO
2
C
1-4
alkyl or —COC
1-4
alkyl;
or two R
2
groups form a saturated carbocyclic ring optionally interrupted by oxygen;
and X is selected from hydrogen, halogen, cyano, alkyl and alkoxy.
The compounds of this invention are typically naphthyridin-3-yl-benzamides.
In the formula (I), alkyl groups, including alkyl groups that are part of another moiety, may be straight chain or branched. Aromatic rings, especially phenyl groups, (including rings that are part of another moiety), may optionally be substituted with one or more independently selected halogen or C
1-6
alkyl, C
3-6
cycloalkyl, C
1-6
alkoxy or C
1-6
alkylcarbonyl.
Suitable C
3-6
cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
Suitable halo substituents include fluoro, chloro, iodo and bromo.
A suitable group of compounds of formula (I) have
R
1
as hydrogen, methyl or benzyl
R
2
as hydrogen, methoxy, ethoxy, iso-propyloxy, methyl, ethyl, iso-propyl, tert-butyl, pivaloyl, trifluoromethyl, chloro, bromo, or nitro.
Examples of compounds of formula (I) are:
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-methoxybenzamide and its monohydrochloride
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-benzamide
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-2-methoxy-4-t-butylbenzamide and its monohydrochloride
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-iso-propoxybenzamide and its monohydrochloride
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-ethoxybenzamide and its monohydrochloride
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-2-methoxy-5-pivaloylbenzamide and its monohydrochloride
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-trifluoromethyl benzarnide and its monohydrochloride
N-(6-benzyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-methoxybenzamide
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-methoxy-3-trifluoromethylbenzamide and its monohydrochloride
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-t-butylbenzamide and its monohydrochloride
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-ethoxybenzamide and its monohydrochloride
N-(6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-iso-propyloxybenzatnide and its monohydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-chloro-4-methoxybenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-ethyl benzamide
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-cyclohexylbenzarnide
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-benzoylbenzamide
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-2,3-dihydrobenzofuran-5-ylcarboxamide
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-t-butyl-3-trifluoromethylbenzamide
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-iso-propylbenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-ethoxy-3-nitrobenzamide hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-t-butylbenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-ethylbenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-cyano-4-methoxybenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-n-propyl-oxybenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3,5-dichloro-4-methoxybenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-iso-propylbenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-n-propyloxy-3-trifluoromethylbenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-iodo-4-methoxybenzamide hydrochloride N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-iso-propyl-3-trifluoromethylbenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-cyano-4-n-propyloxybenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-cyano-4-ethoxybenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-chloro-4-ethoxybenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-chloro-4-iso-propyloxybenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro [1,6]naphthyridin-3-yl)-3-fluoro-4-methoxybenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl]-4-ethyl-3-trifluoromethylbenzamide
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-iso-propyloxy-3-trifluoromethylbenzamide, hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-iodo-4-methylbenzamide hydrochloride
N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-azido-3-iodo-benzamide
N-(2-Bromo-6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-ethoxybenzamide
N-(2-Bromo-6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-methoxy-3-trifluoromethylbenzamide, hydrochloride
N-(2,6-Dimethyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-ethoxy-benzamide
N-(2,6-Dimethyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-methoxy-3-trifluoromethylbenzamide
N-(2-Cyano-6-methyl-5,6,7,8-tetrahydro[1 ,6]naphthyridin-3-yl)-4-methoxy-3-trifluoromethylbenzamide
N-(2-Chloro-6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-3-bromo-4-ethoxybenzamide
N-(2-Chloro-6-
Hadley Michael Stewart
Harling John David
Harrington Frank Peter
Thompson Mervyn
Ward Robert William
Hall Linda E.
Huang Evelyn Mei
King William T.
Kinzig Charles M.
SmithKline Beecham p.l.c.
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