Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1998-07-02
2000-01-18
Ramsuer, Robert W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514602, 544139, 544335, 5483147, 5483541, 548539, 564 91, A61K 3118, A61K 31535, C07D23326, C07D41312
Patent
active
060158123
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel N-(arylsulphonyl)amino acid derivatives, to their preparation and to pharmaceutical compositions containing them.
These compounds have affinity for bradykinin (BK) receptors. Bradykinin is a nonapeptide belonging, like the decapeptide kallidin, to the class of kinins and which shows physiological activity in the cardiovascular field and as a mediator in inflammation and pain. Several bradykinin receptors are distinguished: the B.sub.1 and B.sub.2 receptors (D. Regoli et al., Pharmacol. Rev., 1980, 32, 1-46). More precisely, the B.sub.2 receptors are the bradykinin and kallidin receptors: they are predominant and are normally found in most tissues; the B.sub.1 receptors are the receptors specific for [des-Arg.sup.9 ] bradykinin and for [des-Arg.sup.10 ] kallidin: they are induced during inflammatory processes.
Bradykinin receptors have been cloned for different species, in particular for the human species: B.sub.1 receptor: J. G. Menke et al., J. Biol. Chem., 1994, 269 (34) 21583-21586; B.sub.2 receptor: J. F. Hess, Biochem. Biophys. Res. Commun., 1992, 184, 260-268.
The reviews: Drug News and Perspectives, 1994, 7 (10), 603-611 and Exp. Opin. Ther. Patents, 1995, 5 (4), 331-340, give an account on bradykinin-receptor antagonists. Many antagonists described have peptide structures. As bradykinin-receptor antagonists, mention may be made in particular of HOE-140 (F. J. Hock, Brit. J. Pharmacol. 1991, 102, 769-773) for the B.sub.2 receptor and [des-Arg.sup.9, Leu.sup.8 ] bradykinin for the B.sub.1 receptor (M. N. Perkins et al., Pain, 1993, 53, 191-197). Recently, a B.sub.2 receptor antagonist of non-peptide structure, SR 173657, has been described in Archiv Pharmacol., 1996, Suppl. 1, 354 (4), R6.
According to the present invention, a novel family of compounds having affinity for the bradykinin receptors has now been found; these compounds are N-(arylsulphonyl)amino acid derivatives.
Among the N-(arylsulphonyl)amino acid derivatives, some are known and have various pharmacological activities. Thus, compounds with anti-thrombotic activity are described in the European, German and international patents or patent applications EP 558,961, EP 236,163, EP 236,164, DD 155,954, DE 4,115,468 and WO 92/16549. In this field of activity, NAPAP, derived from N-(naphthalenesulphonyl)glycine of formula: ##STR2## is described in Pharmazie, 1987, 42 (5), 346. ##STR3##
Furthermore, N-tosyl-.beta.-alanine derivatives of formula: attached, constitute a ring such as piperidine, pyrrolidine or morpholine, are described in Pharmazie, 1984, 39 (5), 315-317.
Similarly, N-(arylsulphonyl)proline derivatives have been cited as thrombin inhibitors in Pharmazie, 1986, 41 (4), 233-235 and Pharmazie, 1987, 42 (2), 114-116.
Moreover, patent application EP 614,911 describes compounds of formula: ##STR4## in which, in particular: Ar.sub.I is a naphthyl, a phenyl, a quinolyl or an isoquinolyl, which are optionally substituted; (C.sub.1 -C.sub.4)alkyl; and R'.sub.II form a double bond; -C.sub.3)alkylene; (C.sub.1 -C.sub.4)alkyl or form, together with the nitrogen atom to which they are attached, a (C.sub.5-C.sub.7)heterocycle; -C.sub.4)alkylamino, di(C.sub.1 -C.sub.4)alkylamino, pyrrolidinyl, piperidino, morpholino, piperazinyl, (C.sub.1 -C.sub.4)alkyl-4-piperazinyl, amidino, (C.sub.1 -C.sub.4)alkylamidino, guanidino, (C.sub.1 -C.sub.4)alkylguanidino, pyridyl, imidazolyl, pyrimidinyl, indolyl, hydroxyl, (C.sub.1 -C.sub.4)alkoxy, (C.sub.2 -C.sub.3)alkoxycarbonyl, amino(C.sub.1 -C.sub.4)alkyl-N-(C.sub.1 -C.sub.4)alkylamino, carbamoyl or phenyl, which is optionally substituted; to form a heterocycle and together are (C.sub.2 -C.sub.3)alkylene when Z.sub.1 is nothing, in the form of pure enantiomers or mixtures thereof in any proportion;
These compounds have affinity for the biological receptors of the neuropeptide Y.
According to the present invention, novel, compounds have now been found which have, unexpectedly, affinity for the bradykinin receptors.
The subject of the present invention is the compounds of
REFERENCES:
Wagner, Chemical Abstracts, vol. 107, No. 92532, 1987.
Robinson et al., Tetrahedron, 49(48), 1993, pp. 11329-11340.
Beilstein: Registry No. 6609829, 1995.
Beilstein: Registry No. 3458151, 1963.
Busson et al., J. Org. Chem., 43(23), 1978, pp. 4438-4441.
Beilstein: Registry No. 419229, 1993.
Carlson et al., J. Org. Chem., 31(7), 1966, pp. 2385-2386.
Beilstein: Registry No. 454128.
Burke et al., Exp. Opin. Ther. Patents, 5(4), 1995, pp. 331-339.
Ferrari Bernard
Gougat Jean
Muneaux Claude
Muneaux Yvette
Perreaut Pierre
Alexander Michael D.
Ramsuer Robert W.
Sanofi-Synthelabo
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