Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-05-19
2000-02-22
Chang, Ceila
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514278, 514341, 514406, 546 16, 546211, 5483741, A61K 31445, C07D40112
Patent
active
060280840
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel pyrazole derivatives and their salts, to a method of preparing them and to pharmaceutical compositions containing them.
Numerous pyrazole derivatives have been described in the literature; more particularly, EP-A-268 554 and DE-A-3 910 248 claim pyrazoles possessing herbicidal properties, EP-A-430 186 and JP-A-3 031 840 claim compounds useful for photography, and EP-A-418 845 claims pyrazoles possessing anti-inflammatory, analgesic and antithrombotic activity.
Patent applications EP-A-576 357 and EP-A-658 546 describe pyrazole derivatives which have an affinity for the cannabinoid receptors. More particularly, patent application EP-A-656 354 claims N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3- carboxamide, or SR 141 716, and its pharmaceutically acceptable salts, which have a very good affinity for the central cannabinoid receptors.
Novel pyrazole-3-carboxamide derivatives have now been found which possess a very good affinity for the central cannabinoid receptors and are useful in the therapeutic areas in which cannabis is known to be involved.
These compounds can also be used as pharmacological tools, in animals or humans, for detecting and labeling the central cannabinoid receptors.
.DELTA..sup.9 -THC is the main active constituent extracted from Cannabis sativa (Tuner, 1985; in Marijuana, 84, Ed. Harvey, DY, IRL Press, Oxford).
The effects of cannabinoids are due to an interaction with high affinity specific receptors present in the central nervous system (Devane et al., Molecular Pharmacology, 1988, 34, 605-613) and in the peripheral nervous system (Nye et al., The Journal of Pharmacology and Experimental Therapeutics, 1985, 234, 784-791; Kaminski et al., 1992, Molecular Pharmacology, 42, 736-742; Munro et al., Nature, 1993, 365, 61-65).
Characterization of the receptors of the central nervous system has been made possible by the development of synthetic ligands for the cannabinoid receptors, such as the agonists WIN 55212-2 (J. Pharmacol. Exp. Ther., 1993, 264, 1352-1363) or CP 55,940 (J. Pharmacol. Exp. Ther., 1988, 247, 1046-1051).
According to one of its aspects, the present invention relates to the compounds of the formula ##STR2## in which: R.sub.1 is a fluorine, a hydroxyl, a (C.sub.1 -C.sub.5)alkoxy, a (C.sub.1 -C.sub.5)alkylthio, a hydroxy(C.sub.1 -C.sub.5)alkoxy, a group --NR.sub.10 R.sub.11, a cyano, a (C.sub.1 -C.sub.5)alkylsulfonyl or a (C.sub.1 -C.sub.5)alkylsulfinyl; nitrogen atom to which they are bonded, form a 5- to 10-membered, saturated or unsaturated heterocyclic radical which is unsubstituted or monosubstituted or polysubstituted by a (C.sub.1 -C.sub.3)alkyl or by a (C.sub.1 -C.sub.3)alkoxy; independently hydrogen, a halogen or a trifluoromethyl, and if R.sub.1 is a fluorine, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and/or R.sub.9 can also be a fluoromethyl, with the proviso that at least one of the substituents R.sub.4 or R.sub.7 is other than hydrogen; and -C.sub.5)alkyl, or R.sub.10 and R.sub.11, together with the nitrogen atom to which they are bonded, form a heterocyclic radical selected from pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl and piperazin-1-yl, which is unsubstituted or substituted by a (C.sub.1 -C.sub.4)alkyl;
(C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.5)alkyl, (C.sub.1 -C.sub.5)alkoxy and (C.sub.1 -C.sub.5)alkylthio are understood as meaning linear or branched C.sub.1 -C.sub.3 or C.sub.1 -C.sub.5 alkyl radicals or, respectively, alkoxy or alkylthio radicals.
Halogen is understood as meaning chlorine, fluorine, bromine or iodine, preferably chlorine.
5- or 10-membered, saturated or unsaturated heterocyclic radical is understood as meaning a fused or bridged, mono-, di- or tri-cyclic, non-aromatic heterocyclic radical. These radicals include the following in particular: pyrrolidin-1-yl, piperidin-1-yl, hexahydroazepin-1-yl, 2-azabicyclo[2.2.2]oct-5-en-2-yl, 2-azaadamant-2-yl, 1,2,3,6-tetrahydropyridin-1azabicyclo[2.2.1 ]heptan-2-yl and 2-azabicyclo[2.2.2]octan-2-yl.
The salts of the compound
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Barth Francis
Congy Christian
Martinez Serge
Rinaldi Murielle
Alexander Michael D.
Chang Ceila
Sanofi-Synthelabo
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