Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-01-10
2001-11-13
Shah, Mukund J. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S253060, C514S253090, C514S255030, C544S363000, C544S373000, C544S395000
Reexamination Certificate
active
06316450
ABSTRACT:
This invention relates to novel compounds having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of CNS disorders.
EPA 0 021 580 and EPA 0 076 072 describe sulphonamide derivatives which are disclosed as having antiarrhythmic activity. A structurally distinct class of compounds has now been discovered, which have been found to have 5HT
6
receptor antagonist activity. 5HT
6
receptor antagonists are believed to be of potential use in the treatment of certain CNS disorders such as anxiety, depression, epilepsy, obsessive compulsive disorders, migraine, Alzheimers disease, sleep disorders (including disturbances of Circadian rhythym), feeding disorders such as anorexia and bulimia, panic attacks, withdrawal from drug abuse such as cocaine, ethanol, nicotine and benzodiazepines, schizophrenia, and also disorders associated with spinal trauma and/or head injury such as hydrocephalus. Compounds of the invention are also expected to be of utility for cognitive memory enhancement. Compounds of the invention are also expected to be of use in the treatment of certain GI (gastrointestinal) disorders such as IBS (Irritable Bowel Syndrome).
The present invention therefore provides, in a first aspect, a compound of formula (I) or a salt thereof
wherein:
P is phenyl, naphthyl, anthracenyl, a bicyclic heterocyclic ring, a tricyclic heteroaromatic ring or is a 5 to 7-membered heterocyclic ring each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulphur;
A is a single bond, a C
1-6
alkylene or a C
1-6
alkenylene group;
B is SO
2
;
R
1
is halogen, C
1-6
alkyl optionally substituted by one or more fluorine atoms, C
3-6
cycloalkyl, C
2-6
alkenyl, C
1-6
alkynyl, C
1-6
alkanoyl, C
1-6
alkoxy, OCF
3
, hydroxy, hydroxyC
1-6
alkyl, hydroxyC
1-6
alkoxy, C
1-6
alkoxyC
1-6
alkoxy, nitro, cyano, NR
10
R
11
where R
10
and R
11
are independently hydrogen, C
1-6
alkyl or optionally substituted phenyl, SR
11
where R
11
is as defined above or R
1
is optionally substituted phenyl, naphthyl, a bicyclic heterocyclic ring, or is a 5 to 7-membered heterocyclic ring each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulphur, or R
1
together with a second R
1
substituent forms a group —O—CH
2
—O—, OCH
2
CH
2
O—, —CH
2
CH
2
CH— or —CH
2
CH
2
CH
2
CH
2
—,
n is 0, 1, 2, 3, 4, 5 or 6;
R
2
is hydrogen, C
1-6
alkyl, arylC
1-6
alkyl or together with group P form a 5 to 8 membered ring optionally substituted with one or more C
1-6
alkyl groups;
R
3
is hydrogen, halogen, C
1-6
alkyl, C
3-6
cycloalkyl, C
1-6
alkanoyl, C
1-6
alkoxy optionally substituted with one or more fluorine atoms, hydroxy, hydroxyC
1-6
alkyl, hydroxyC
1-6
alkoxy, C
1-6
alkoxyC
1-6
alkoxy, nitro, trifluoromethyl, cyano or aryl or together with the group R
5
forms a group (CH
2
)
2
O or (CH
2
)
3
O optionally substituted with 1 or more C
1-6
alkyl groups;
R
4
is —X(CH
2
)p-R
6
where X is a single bond, CH
2
, O, NH or N-alkyl and p is 0 to 6 and R
6
is an optionally substituted 4- to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from nitrogen, sulphur or oxygen, or R
6
is NR
7
R
8
where R
7
and R
8
are independently hydrogen, C
1-6
alkyl or aryl C
1-6
alkyl; and
R
5
is a group R
3
or together with R
3
forms a group (CH
2
)
2
O or (CH
2
)
3
O optionally substituted with 1 or more C
1-6
alkyl groups.
C
1-6
Alkyl groups, whether alone or as part of another group, may be straight chain or branched. As used herein the term aryl includes phenyl and naphthyl. When a group is defined as “optionally substituted”, unless otherwise stated, suitable substituents include halogen, C
1-6
alkyl, C
3-6
cycloalkyl, C
1-6
alkanoyl, C
1-6
alkoxy optionally substituted with one or more fluorine atoms, hydroxy, hydroxyC
1-6
alkyl, hydroxyC
1-6
alkoxy, C
1-6
alkoxyC
1-6
alkoxy, nitro, trifluoromethyl, or cyano.
When P is a bicyclic heterocyclic ring, suitable examples include benzothiophene, indole, quinoline or isoquinoline. Bicyclic heterocyclic rings can also be partially saturated. When P is a tricyclic heteroaromatic ring suitable examples include dibenzofuran. Suitable 5 to 7-membered heterocyclic rings include thienyl, furyl, pyrrolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pyridyl, pyrimidyl, pyrrolidinyl and pyrazinyl. The heterocyclic rings can be linked to the remainder of the molecule via any suitable carbon atom or, when present, a nitrogen atom. Preferably P is phenyl or naphthyl.
Suitably A is a single bond, a methylene or ethylene group or a —CH═CH-group. Preferably A is a single bond or methylene.
When R
1
is a a bicyclic heterocyclic ring or a 5 to 7 membered heterocyclic ring suitable examples include those listed in the definition of P.
It will be appreciated that when R
1
combines with a second R
1
substituent the two substituents must be attached to adjacent atoms on the ring P. Thus, when P is phenyl, groups such as methylenedioxyphenyl, ethylenedioxyphenyl, indane and tetrahydronapthalene are within the scope of this invention.
Suitably R
1
is hydrogen, halogen, phenyl, C
1-6
alkoxy most preferably OMe, SR
11
most preferably SMe or C
1-6
alkyl optionally substituted by one or more fluorine atoms, for example methyl or trifluoromethyl. Preferably R
1
is halogen. Preferably n is 0, 1, 2, 3 or 4.
Suitably R
2
is hydrogen, methyl or together with group P form a 5 or 6-membered ring. It will be appreciated that when groups P and R
2
are linked together the latter must be attached to the adjacent carbon atom on the ring P i.e. with an ortho relationship with respect to group A.
It will be appreciated that when R
3
/R
5
groups are linked together the two groups must be attached to adjacent carbon atoms of the phenyl ring. Preferably R
3
is a group R
5
, in particular hydrogen.
Preferably R
4
is meta with respect to the substituent B. Preferably X is a bond, p is 0 and R
6
is an optionally substituted 5- to 7-membered heterocyclic ring. The heterocyclic rings can be linked to the remainder of the molecule via a carbon atom or, when present, a nitrogen atom. Optional substituents for these rings, which can be present on carbon and/or nitrogen atoms, include C
1-6
alkyl, in particular methyl or NR
9
R
10
where R
9
and R
10
are independently hydrogen or C
1-6
alkyl. More preferably R
4
is an optionally substituted piperazine. Most preferably R
4
is N-methyl piperazine or NH-piperazine.
Preferably R
5
is para with respect to the substituent B. Suitably R
5
is C
1-6
alkoxy. Preferably R
5
is methoxy.
Particular compounds of the invention include:
4-Methoxy-3-(4-methylpiperazin-1-yl)-N-naphthalen-1-ylbenzenesulfonamide, N-(4-Chloronaphthalen-1-yl)-4-methoxy-3-(4-methylpiperazin-1-yl)benzene sulfonamide,
N-(3-Bromophenyl)-4-methoxy-3-(4-methylpiperazin-1-yl)benzene sulfonamide,
N-(3,4-Dichlorobenzyl)-4-methoxy-3-(4-methylpiperazin-1-yl)benzene sulfonamide,
6-Chloro-2-[4-methoxy-3-(4-methylpiperazin-1-yl)-benzenesulfonyl]-1,2,3,4-tetrahydroisoquinoline,
1-[4-Methoxy-3-(4-methyl-piperazin-1-yl)-benzene-sulfonyl]-6-trifluoromethyl-2,3 -dihydro-1H-indole,
N-(3-Chlorophenyl)-4-methoxy-N-methyl-3-(4-methylpiperazin-1-yl)-benzenesulfonamide,
1-[4-Methoxy-3-(4-methylpiperazin-1-yl)-benzenesulfonyl]-7-trifluoromethyl-1,2,3,4-tetrahydroquinoline,
N-(3-Iodo-4-methylphenyl)-4-methoxy-3-(4-methylpiperazin-1-yl)-benzenesulfonamide,
N-(5-Iodo-2-methylphenyl)-4-methoxy-3-(4-methylpiperazin-1-yl)-benzenesulfonamide,
N-(3,4-Methylenedioxyphenyl)-4-methoxy-3-(4-methylpiperazin-1-yl)benzenesulfonamide,
6-Chloro-1-[4-methoxy-3-(4-methylpiperazin-1-yl)benzenesulfonyl]-5-methyl-2,3-dihydro-1H-indole,
7,8-Dichloro-2-[4-methoxy-3-(4-methylpiperazin-1-yl)-benzenesulfonyl]-1,2,3,4-tetrahydroisoquinoline,
7,8-Dimethoxy-2-[4-methoxy-3-(4-methylpiperazin-1-yl)-benzenesulfonyl]-1,2,3,4-tetrahydroisoquinoline,
5-Bromo-2-[4-methoxy-3-(4-methylpiperazin-1-yl)-benzenesulfonyl]-1,2,3,4-tetrahydro
Bromidge Steven Mark
Moss Stephen Frederick
King William T.
Kinzig Charles M.
McKenzie Thomas C
Shah Mukund J.
Simon Soma G.
LandOfFree
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 Compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2593393