Benzene-sulphonamide derivatives and their uses

Details Benzene-sulphonamide derivatives and their uses Benzene-sulphonamide derivatives and their uses

2001-10-16

2004-11-16

Coleman, Brenda (Department: 1624)

Organic compounds -- part of the class 532-570 series

Organic compounds

Unsubstituted hydrocarbyl chain between the ring and the -c-...

C514S217120, C514S238200, C514S471000, C514S485000, C514S508000, C514S584000, C514S592000, C514S604000, C544S160000, C549S493000, C558S008000, C558S234000, C560S012000, C564S023000, C564S042000, C564S091000

Reexamination Certificate

active

06818765

ABSTRACT:

TECHNICAL DOMAIN
This invention relates to new benzene-sulphonamide derivatives and to their non-toxic salts as well as to their therapeutic uses.
DISCLOSURE OF THE INVENTION
The new benzene-sulphonamide derivatives, according to the invention, are represented by the general formula (I):
in which:
X represents a nitro, cyano, halogen group, eventually radioactive.
Y
1
represents a secondary or tertiary amino group, a sulphur or an oxygen;
Y
2
represents a nitrogen, an oxygen or a —NH group;
Z represents oxygen, sulphur, —N—CN or —CH—NO
2
; and
R
1
and R
2
, which can be identical or different, represent each independently a linear or ramified alkyl group, saturated or unsaturated wit 2 to 12 carbon atoms, an alicyclic group, saturated or unsaturated with 3 to 12 carbon atoms, eventually radioactive, an aryl group, substituted or not by one or several alkyl groups in C
1
-C
4
, nitro, cyano, trifluoromethyl, carboxy and halogen, or an arylalkyl group,
or R
1
and/or R
2
form with Y
1
and/or Y
2
a 5 to 7 membered heterocyclic group, saturated or unsaturated chains. with the exception of derivatives for which X is a nitro group,. Y
1
represents a secondary amine group (—NH—), Y
2
represents a —NH group, Z an oxygen, R
2
an isopropyl and R
1
an element selected in the group comprising (m-toluyl, phenyl and cyclooctyl) and with the exception of N-[(2-cyclooctylamino-5-cyanobenzene)sulfonyl]N′-isopropyl urea.
This invention refers also to optical isomers of benzene-sulphonamide derivatives covered by the formula (I) or to salts pharmacologically acceptable of these derivatives
This invention refers also to salts of these derivatives, covered by the formula (I), by addition of non-toxic basis, for example to sodium and potassic salts, to salts with an organic acid, as an amino acid such as the lysine, the arginine, for example.
When, in the general formula (I), one has an asymmetrical carbon atom (as for example when R
1
and/or R
2
represent an arylalkyl group), the invention refers as well as to pure optical isomers than to the racemic mixture.
Preferred classes of compounds according to the formula (I) are, especially, those in which the X represents a nitro, cyano, bromo or iodo group, Y
1
represents a —NH group, Y
2
represents a —NH group or an oxygen atom and R
1
and R
2
represent each independently an ethyl, butyl, tert-butyl propyl, isopropyl, pentyl, hexyl, heptyl, octyl, decyl, amyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclododecyl, 2-cyclohexenyl, m-toluyl, o-toluyl, p-toluyl, phenyl, allyl, adamantyl, norbornyl, caproyl, 3-carboxyphenyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, furfuryl, benzyl or 1-phenylethyl group.
Another preferred class of these compounds is that in which R
2
and Y
2
form a homopiperidin group and that in which R
1
and Y
1
form a morpholin or homopiperidin group.
Still another particularly interesting class is that made by radioactive derivatives of the invention, and especially the derivatives in which X represents radioactive iodine, such that the
126
I and its radioactive isotopes
125
I and
131
I, and those in which R
1
represents a saturated alicyclic group or unsaturated group with a tritium hydrogen in positions 2 and/or 3 of the cycle.
As one will see hereinafter in a more detailed way, the derivatives complying with the formula (I) are very useful in the prevention and/or treatment of illnesses involving the thromboxan A
2
at different levels, and especially in the cardiovascular and blood domains, pulmonary domain, reproduction domain and renal domain. They constitute also an excellent radiolabelled pharmacological tool of the thromboxan A2 receptors.
The present invention concerns, therefore, also the use of these benzene-sulphonamide derivatives and their salts for drug manufacture for the treatment and/or the prevention of the illnesses involving the thromboxan A2 as well as as radiolabelled pharmacological tools of the thromboxan A2 receptors and of the pharmaceutical compositions containing these derivatives, these latter or their salts being used alone or in combination with excipients and/or other therapeutic agents having a similar or different activity.
The active compounds of the invention can be administered, according to the invention, under the form of a pharmaceutical composition, in association with different pharmaceutical excipients and this by oral, parenteral, rectal and topical way.
For the oral administration, one will use pills, granules, tablets, capsules, solutions, syrups, emulsions and suspensions containing classic excipients or additives in clinical pharmacy.
By parenteral way, the salts of active products could be administered in aqueous solution for example.
For the rectal administration, one will use suppositories and, by topical way, lotions, unguents, pomades, aerosols or nebulizers.
The active products can be used alone or in combination with other active products having a similar or different activity.
Among the compounds which give, in pharmaceutical use, very interesting results, we have to consider those in the formula (I), in which X represents a NO
2
or iodine group,
Y
1
represents a secondary amino group,
Y
2
represents a —NH group,
Z represents an oxygen group, sulphur group or —N—CN group, and R
1
represents a cyclohexyl group, cycloheptyl group or cychlohexen-2-yl group, and
R
2
an isopropyl group, tert-butyl group, pentyl group or homopiperidin group,
and particularly considering the following compounds:
N-[(2-cyclohexylamin-5-nitrobenzene)sulfonyl]N′-tert-butyl urea,
N-cyano-N′-[(2-metatoluylamin-5-nitrobenzene)sulfonyl]homopiperidinoamidine,
N-[(2-cycloheptylamin-5-nitrobenzene)sulfonyl]N′-cyclohexyl thiourea, and
N-[(cyclohexen-2-yl)-5-iodobenzene)sulfonyl]N′-pentyl urea.


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M. Wittner et al., “Analogues of Torasemide—Structure Function Relationships—Experiments in the Thick Ascending Limb of the Loop of Henle of Rabbit Nephron”, European Journal of Physiology, vol. 408, No. 1, (1987), pp. 54-62.
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XP-002114294, Nov. 1972, Abstract.

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