Salts of substituted nitrogenous heteroaromatic compounds, a pro

Details Salts of substituted nitrogenous heteroaromatic compounds, a pro Salts of substituted nitrogenous heteroaromatic compounds, a pro

1995-11-24

1997-09-09

Ivy, C. Warren

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

546301, 546312, 546337, C07D21338, C07D21336

Patent

active

056658869

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/FR95/00368, filed on 24 Mar. 1995, published as WO95/26339 Oct. 5, 1995.
The present invention relates to novel salts of substituted nitrogenous heteroaromatic compounds, a process for their preparation and pharmaceutical compositions containing them as active ingredients.
More particularly, the present invention concerns a novel class of salts of substituted nitrogenous heteroaromatic compounds for therapeutic use in pathological phenomena which involve the tachykinin system, non limiting and exclusive examples of which are: pain (D. Regoli et al., Life Sciences, 1987, 40, 109-117), allergy and inflammation (J. E. Morlay et al., Life Sciences, 1987, 41, 527-544), circulatory insufficiency (J. Losay et al., 1977, Substance P, Von Euler, I. S. and Pernow ed., 287-293, Raven Press, New York), gastrointestinal problems (D. Regoli et al., Trends Pharmacol. Sci., 1985, 4, 481-484), respiratory problems (J. Mizrahi et al., Pharmacology, 1982, 25, 39-50), neurological problems, neuropsychiatric problems (C. A. Maggi et al., J. Autonomic Pharmacol., 1993, 13, 23-93).
A number of studies have recently been carried out on tachykinins and their receptors. Tachykinins are distributed in both the central nervous system and in the peripheral nervous system. Receptors for tachykinins have been recognised and classified into three types: NK.sub.1, NK.sub.2, and NK.sub.3. Substance P (SP) is the endogenous ligand of NK.sub.1 receptors, neurokinin A (NK.sub.A) is that of NK.sub.2 receptors and neurokinin B (NK.sub.B) is that of NK.sub.3 receptors.
Receptors NK.sub.1, NK.sub.2 and NK.sub.3 have been shown to exist in different species. A review by C. A. Maggi et al. summarises this for tachykinins receptors and their antagonists and discusses pharmacological studies and applications to human therapeutics (J. Autonomic Pharmacol., 1993, 13, 23-93).
Among specific antagonists for receptor NK.sub.1 the following non peptide compounds may be cited: CP-96345 (J. Med. Chem., 1992, 35, 2591-2600), RP-68651 (Proc. Natl. Acad. Sci USA, 1991, 88, 10208-10212), SR 140333 (Curt. J. Pharmacol., 1993, 250, 403-413).
For receptor NK.sub.2, a selective non peptide antagonist, SR 48968, has been described in detail (Life Sci., 1992, 50, PL101-PL106).
Turning to receptor NK.sub.3, some non peptide compounds have been described as having an affinity for receptor NK.sub.3 in the rat and guinea pig-brain (FASEB J., 1993, 7(4), A710, 4104); a peptide antagonist [Trp.sup.7,.beta.Ala.sup.8 ]NK.sub.A, which is weakly specific for receptor NK.sub.3 in the rat brain, has also been described (J. Autonomic Pharmacol., 1993, 13, 23-93).
European patent application EP-A-0 336 230 describes peptide derivatives which are antagonists of substance P and neurokinin A and are suitable for the treatment and prevention of asthma.
International patent applications WO 90/05525, WO 90/05729, WO 91/09844, WO 91/08899 and European patent applications EP-A-0 436 334, EP-A-0 429 466 and EP-A-0 430 771 describe antagonists of substance P.
European applications EP-A-0 474 561, EP-A-0 512 901, EP-A-0 515 240, EP-A-0 559 538 and EP-A-0 591 040 also concern antagonists of neurokinin receptors.
Novel salts of substituted nitrogenous hetero-aromatic compounds which are antagonists for neurokinins have now been discovered.
In one aspect, therefore, the present invention concerns compounds of formula: ##STR2## where: Ar represents an aromatic or heteroaromatic mono-, di- or tricyclic group which may be substituted; -C.sub.4)alkoxymethylene group; a (C.sub.1 -C.sub.5)alkylene group; an oxygen atom; a --NR.sub.3 group; vinylene; or more times by a substituent selected from: a halogen atom, trifluoro-methyl, hydroxy, (C.sub.1 -C.sub.4)alkoxy, (C.sub.1 -C.sub.4)alkyl, said substituents being identical or different; thienyl; benzothienyl; naphthyl; indolyl which may be N-substituted by (C.sub.1 -C.sub.4)alkyl or benzyl; .omega.-hydroxy-(C.sub.2 -C.sub.4)alkylene; .omega.-(C.sub.1 -C.sub.4)alkoxy-(C.sub.2 -C.sub.4)alkylene; .omega.-benzyloxy-(C.sub.2 -

REFERENCES:
patent: 5340822 (1994-08-01), Emonds-Alt
Maggi et al., J. Auton. Pharmacol., vol. 13, 1993, pp. 23-93.

Affiliated with

Also associated with

Rating

Salts of substituted nitrogenous heteroaromatic compounds, a pro does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Salts of substituted nitrogenous heteroaromatic compounds, a pro, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Salts of substituted nitrogenous heteroaromatic compounds, a pro will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-71467