Benzenesulphonamide compounds

Details Benzenesulphonamide compounds Benzenesulphonamide compounds

2002-07-12

2003-04-01

Ramsuer, Robert W. (Department: 1626)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C544S159000, C544S368000, C544S399000, C546S198000, C548S575000, C562S430000

Reexamination Certificate

active

06541471

ABSTRACT:

SUMMARY OF THE INVENTION
The present invention relates to new benzenesulphonamide compounds, and to pharmaceutical compositions containing them.
The compounds of the present invention have a novel structure giving them a TXA
2
receptor antagonist and 5HT
2
serotoninergic receptor antagonist character.
DESCRIPTION OF THE PRIOR ART
Compounds having a benzenesulphonamide chain have been described in Application EP 864 561 in relation to their NO-yielding character and their thromboxane A
2
(TXA
2
) receptor antagonist character, as well as in Applications EP 648 741 or WO 9406761 solely in relation to their TXA
2
receptor antagonist properties.
BACKGROUND OF THE INVENTION
Platelet aggregation and vasospasms play an essential role in the aetiology and development of atherothrombotic cardiovascular diseases. TXA
2
, an arachidonic acid metabolite, and serotonin (5HT), a neurotransmitter, are both powerful vasoconstrictor agents, and are able to induce or reinforce platelet activation, resulting in the aggregation thereof The vasoconstrictor and pro-aggregation actions of TXA
2
are effected through the intermediary of membrane receptors called TP receptors (Medicinal Research Reviews, 1991, 11 5, p. 503) while those of serotonin are effected through the intermediary of 5HT
1
or 5HT
2
receptors (T.I.P.S., 1991, 121, p. 223). Research strategies pursued with the aim of finding agents that block the production and/or activation of TXA
2
have led to the development of selective TP receptor antagonists, of TXA
2
-synthase inhibitors, or of mixed agents that exhibit both properties (Medicinal Research Reviews, ibid., T.I.P.S., 1991, 121, 158). Like TXA
2
, serotonin acts by stimulating platelets and vascular constriction and its activity is found to be increased in atherothrombotic diseases.
The idea of compounds that oppose both the process that causes thromboxane to become active and the process that causes serotonin to become active is extremely useful for the clinician. Such products have the advantage of offering more complete protection both against the activation of platelets and against vasospasms. It will thus be possible for such products to be used in the treatment of pathologies associated with increased activity of TXA
2
and 5-HT especially in the treatment of atherothrombotic cardiovascular diseases, such as myocardial infarction, angina pectoris, cerebral vascular accidents, Raynaud's disease, and also asthma and bronchospasms, as well as migraine and venous diseases.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to the compounds of formula (I):
wherein:
G represents a group such as:
wherein R
1
and R
2
independently represent a hydrogen atom, or an alkyl, cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl group, or
R
1
and R
2
together with the nitrogen atom form a heterocycloalkyl group of formula
having from 5 to 7 ring members, wherein Y represents a nitrogen atom, an oxygen atom or a CH
2
group and R
6
represents a hydrogen atom or an alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted arylcarbonyl, optionally substituted arylcarbonylalkyl, optionally substituted diarylalkyl, optionally substituted diarylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylcarbonyl or optionally substituted heteroarylcarbonylalkyl group,
R
3
represents a hydrogen atom or an alkyl or optionally substituted phenyl group,
R
a
represents a hydroxy, alkoxy, optionally substituted aryloxy, optionally substituted arylalkyloxy, amino, alkylamino, dialkylamino, optionally substituted arylamino or optionally substituted arylalkylamino group,
R
b
and R
c
, which may be identical or different, each represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a hydroxy group or a trihaloalkyl group,
m is an integer of from 0 to 1 inclusive,
n and q are identical or different integers of from 0 to 6 inclusive,
p and r are identical or different integers of from 1 to 6 inclusive,
to their enantiomers and diastereoisomers, and also to addition salts thereof with a pharmaceutically acceptable acid or base,
wherein:
the term “alkyl” denotes a linear or branched chain having from 1 to 6 carbon atoms,
the term “alkoxy” denotes a linear or branched alkyl-oxy group having from 1 to 6 carbon atoms,
the term “trihaloalkyl” denotes a carbon chain having from 1 to 3 carbon atoms and from 1 to 3 identical or different halogen atoms,
the term “alkenyl” denotes a chain having from 2 to 6 carbon atoms and containing from 1 to 3 double bonds,
the term “cycloalkyl” denotes a saturated cyclic group having from 3 to 8 carbon atoms,
the term “aryl” denotes a phenyl or naphthyl group,
the term “heteroaryl” denotes an aromatic monocyclic group, or a bicyclic group in which at least one of the rings is aromatic, having from 5 to 11 ring members and from 1 to 5 hetero atoms selected from nitrogen, oxygen and sulphur,
the terms “diarylalkyl” and “diarylalkenyl” denote, respectively, alkyl and alkenyl groups as defined hereinbefore, substituted by two identical or different aryl groups as defined hereinbefore,
the term “substituted” relating to phenyl, aryl, arylalkyl, arylcarbonyl, arylcarbonylalkyl, diarylalkyl, diarylalkenyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heteroarylcarbonylalkyl, arylamino and arylalkylamino denotes that the groups in question are substituted in the aromatic moiety by one or two identical or different substituents selected from halogen atoms and alkyl groups, alkoxy groups, hydroxy groups, cyano groups, nitro groups, amino groups (optionally substituted by one or two alkyl groups) and groups C(O)R
d
, R
d
representing a group selected from hydroxy, alkoxy and amino, wherein the heteroaryl and heteroarylalkyl groups may also be substituted by an oxo group in the non-aromatic moiety of the heteroaryl.
Amongst the pharmaceutically acceptable acids there may be mentioned, without implying any limitation, hydrochloric, hydrobromic, sulphuric, phosphonic, acetic, trifluoroacetic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, tartaric, maleic, citric, ascorbic, methanesulphonic, camphoric acid, etc.
Amongst the pharmaceutically acceptable bases there may be mentioned, without implying any limitation, sodium hydroxide, potassium hydroxide, triethylamine, tert-butylamine etc.
Preferred compounds of formula (I) are those wherein, taken together or separately, the value of p is 2, the value of q is 2, the substituent R
3
represents a hydrogen atom, the substituent R
a
represents a hydroxy group, the substituent R
b
represents a halogen atom and the substituent R
c
represents a hydrogen atom.
An especially advantageous embodiment of the invention relates to compounds of formula (I) wherein p and q are each 2, R
a
represents a hydroxy group, R
3
and R
c
each represents a hydrogen atom, R
b
represents a halogen atom and G represents an amino, dialkylamino or arylalkylamino group or a heterocycloalkyl group of formula:
wherein Y represents a nitrogen atom, an oxygen atom or a CH
2
group and R
6
is selected from a hydrogen atom and the groups optionally substituted aryl and optionally substituted heteroaryl.
In preferred compounds of formula (I), G represents a dialkylamino group.
Other preferred compounds of formula I are those wherein G represents a substituted heterocycloalkyl group
wherein:
represents a group having 5 or 6 ring members, such as: pyrrolyl, morpholino, piperidyl or piperazinyl,
and R
6
substituted on a carbon or nitrogen atom of the heterocycloalkyl represents a hydrogen atom, a phenyl substituent optionally substituted by a halogen atom, or a heteroaryl group having 9 ring members that contains one or two hetero atoms selected from nitrogen, oxygen and sulphur and is optionally substituted by a halogen atom.
Preferred compounds of formula

Affiliated with

Also associated with

Rating

Benzenesulphonamide 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 Benzenesulphonamide compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Benzenesulphonamide compounds will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3098383