Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-12-17
2004-05-11
Rao, Deepak (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S210190, C514S210200, C514S210210, C544S335000, C546S172000, C546S268100, C548S314700, C548S518000, C548S953000
Reexamination Certificate
active
06734176
ABSTRACT:
SUMMARY OF THE INVENTION
The present invention relates to pharmaceutical compositions containing, as active ingredient, at least one compound of formula:
or one of its pharmaceutically acceptable salts, to the novel derivatives of formula (I), to their pharmaceutically acceptable salts and to their preparation as well as to their use in treating various disorders of the nervous system.
R
3
represent phenyl radicals, R
1
represents a radical —N(R
5
)—Y—R
6
, Y is SO
2
, R
5
represents a methyl radical and R
6
represents a phenyl radical is described as a synthesis intermediate in Patent WO 99/01451. The other compounds and their pharmaceutically acceptable salts are novel and as such form parts of the invention.
In formula (I)
R
1
represents a radical —NHCOR
4
or —N(R
5
)—Y—R
6
,
Y is CO or SO
2
,
R
2
and R
3
, which are identical or different, represent either an aromatic selected from phenyl, naphthyl and indenyl, these aromatics being unsubstituted or substituted with one or more halogen atoms or alkyl, alkoxy, formyl, hydroxyl, trifluoromethyl, trifluoro-methoxy, —CO-alk, cyano, —COOH, —COOalk, —CONR
7
R
8
, —CO—NH—NR
9
R
10
, alkylsulfanyl, alkylsulfinyl, alkyl-sulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkyl or -alk-NR
7
R
8
radicals; or a heteroaromatic selected from benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, pyrimidinyl, furyl, imidazolyl, isochromanyl, isoquinolyl, pyrrolyl, pyridyl, quinolyl, 1,2,3,4-tetrahydro-isoquinolyl, thiazolyl and thienyl rings, it being possible for these heteroaromatics to be unsubstituted or substituted with a halogen atom or an alkyl, alkoxy, hydroxyl, trifluoromethyl, trifluoromethoxy, cyano, —COOH, —COOalk, —CO—NH—NR
9
R
10
, —CONR
7
R
8
, -alk-NR
9
R
10
, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl or hydroxyalkyl radical,
R
4
represents a radical -alk-SO
2
—R
11
, -alk-SO
2
—CH═CH—R
11
, Het substituted with —SO
2
—R
11
or phenyl substituted with —SO
2
—R
11
or -alk-SO
2
—R
11
,
R
5
represents a hydrogen atom or an alkyl radical,
R
6
represents a phenylalkyl, Het or Ar radical,
R
7
and R
8
, which are identical or different, represent a hydrogen atom or an alkyl radical or alternatively R
7
and R
8
together form with the nitrogen atom to which they are attached a 3- to 10-membered saturated mono- or bicyclic heterocycle, optionally containing another heteroatom selected from oxygen, sulfur and nitrogen and being optionally substituted with one or more alkyl radicals,
R
9
and R
10
, which are identical or different, represent a hydrogen atom or an alkyl, —COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl radical or alternatively R
9
and R
10
together form with the nitrogen atom to which they are attached a 3- to 10-membered saturated or unsaturated mono- or bicyclic heterocycle, optionally containing another heteroatom selected from oxygen, sulfur and nitrogen and being optionally substituted with one or more alkyl, —COalk, —COOalk, —CO—NHalk, —CS—NHalk, oxo, hydroxyalkyl, -alk-O-alk or —CO—NH
2
radicals,
R
11
represents an alkyl, Ar or Het radical,
Ar represents a phenyl, naphthyl or indenyl radical, these radicals being optionally substituted with one or more halogen atoms or alkyl, alkoxy, cyano, —CO-alk, —COOH, —COOalk, —CONR
12
R
13
, —CO—NH—NR
14
R
15
, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, -alk-NR
14
R
15
, —NR
14
R
15
, alkylthioalkyl, formyl, hydroxyl, hydroxyalkyl, Het, —O-alk-NH-cycloalkyl, OCF
3
, CF
3
, —NH—CO-alk, —SO
2
NH
2
, —NH—COCH
3
, —NH—COOalk or Het radicals, or alternatively, on 2 adjacent carbon atoms, with a dioxymethylene,
Het represents a 3- to 10-membered unsaturated or saturated mono- or bicyclic heterocycle containing one or more heteroatoms selected from oxygen, sulfur and nitrogen optionally substituted with one or more halogen atoms or alkyl, alkoxy, vinyl, alkoxycarbonyl, oxo, hydroxyl, OCF
3
or CF
3
radicals, the nitrogen-containing heterocycles being optionally in their N-oxidized form,
R
12
and R
13
, which are identical or different, represent a hydrogen atom or an alkyl radical or alternatively R
12
and R
13
together form with the nitrogen atom to which they are attached a 3- to 10-membered saturated mono- or bicyclic heterocycle, optionally containing another heteroatom selected from oxygen, sulfur and nitrogen and being optionally substituted with one or more alkyl radicals,
R
14
and R
15
, which are identical or different, represent a hydrogen atom or an alkyl, —COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl radical or alternatively R
14
and R
15
together form with the nitrogen atom to which they are attached a 3- to 10-membered saturated or unsaturated mono- or bicyclic heterocycle, optionally containing another heteroatom selected from oxygen, sulfur and nitrogen and being optionally substituted with one or more alkyl, —COalk, —COOalk, —CO—NHalk, —CS—NHalk, oxo, hydroxyalkyl, -alk-O-alk or —CO—NH
2
radicals,
alk represents an alkyl or alkylene radical.
In the preceding definitions and in those which follow, unless otherwise stated, the alkyl and alkylene radicals and portions and the alkoxy radicals and portions are in the form of a straight or branched chain and contain 1 to 6 carbon atoms and the cycloalkyl radicals contain 3 to 10 carbon atoms.
Among the alkyl radicals, there may be mentioned the methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl and hexyl radicals. Among the alkoxy radicals, there may be mentioned the methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy and pentyloxy radicals.
Among the cycloalkyl radicals, there may be mentioned the cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl radicals.
The term halogen comprises chlorine, fluorine, bromine and iodine.
Among the heterocycles represented by Het, the following heterocycles may be mentioned: benzimidazole, benzoxazole, benzothiazole, benzothiophene, cinnoline, thiophene, quinazoline, quinoxaline, quinoline, pyrazole, pyrrole, pyridine, imidazole, indole, isoquinoline, pyrimidine, thiazole, thiadiazole, piperidine, piperazine, pyrrolidine, triazole, furan, tetrahydroisoquinoline, tetrahydroquinoline, these heterocycles being optionally substituted with one or more halogen atoms or alkyl, alkoxy, vinyl, alkoxycarbonyl, oxo, hydroxyl, OCF
3
or CF
3
radicals.
The compounds of formula (I) may be provided in the form of enantiomers and of diastereoisomers. These optical isomers and mixtures thereof also form part of the invention.
Preferably, the compounds of formula (I) are those for which
R
1
represents a radical —N(R
5
)—Y—R
6
,
Y is SO
2
,
R
2
represents either a phenyl which is unsubstituted or substituted with one or more halogen atoms or alkyl, alkoxy, trifluoromethyl, trifluoromethoxy, cyano, —CONR
7
R
8
, hydroxyalkyl or -alk-NR
7
R
8
radicals; or a heteroaromatic selected from the pyridyl, pyrimidyl, thiazolyl and thienyl rings, it being possible for these heteroaromatics to be unsubstituted or substituted with a halogen atom or an alkyl, alkoxy, hydroxyl, trifluoromethyl, trifluoromethoxy, —CONR
7
R
8
, -alk-NR
9
R
10
, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl or hydroxyalkyl radical,
R
3
represents either a phenyl which is unsubstituted or substituted with one or more halogen atoms or alkyl, alkoxy, trifluoromethyl, trifluoromethoxy, cyano, —CONR
7
R
8
, hydroxyalkyl or -alk-NR
7
R
8
radicals; or a heteroaromatic selected from the pyridyl, pyrimidyl, thiazolyl and thienyl rings, it being possible for these heteroaromatics to be unsubstituted or substituted with a halogen atom or an alkyl, alkoxy, hydroxyl, trifluoromethyl, trifluoromethoxy, —CONR
7
R
8
, -alk-NR
9
R
10
, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl or hydroxyalkyl radical,
R
5
represents a hydrogen atom or an alkyl radical,
R
6
represents a naphthyl, phenylalkyl, Het or phenyl radical optionally substituted with one or more halogen
Achard Daniel
Bouchard Herve
Bouquerel Jean
Filoche Bruno
Grisoni Serge
Aventis Pharma S.A.
Newman Irving
Rao Deepak
LandOfFree
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