Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-03-01
1997-11-11
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544371, 546176, 546199, 5483591, 5483595, A61K 4356
Patent
active
056864809
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB94/01935 filed Sep. 6, 1994.
This invention relates to a particular class of fused tricyclic heteroaromatic compounds based on a substituted pyrazole moiety. These compounds are ligands for dopamine receptor subtypes within the body and are therefore of use in the treatment and/or prevention of disorders of the dopamine system, including schizophrenia, depression, nausea, Parkinson's disease, tardive dyskinesias and extrapyramidal side-effects associated with treatment by conventional neuroleptic agents, neuroleptic malignant syndrome, and disorders of hypothalamic-pituitary function such as hyperprolactinaemia and amenorrhoea.
Upper gastrointestinal tract motility is believed to be under the control of the dopamine system. The compounds according to the present invention may thus be of use in the prevention and/or treatment of gastrointestinal disorders, and the facilitation of gastric emptying.
Dependence-inducing agents such as cocaine and amphetamine have been shown to interact with the dopamine system. Compounds capable of counteracting this effect, including the compounds in accordance with the present invention, may accordingly be of value in the prevention or reduction of dependence on a dependence-inducing agent.
Dopamine is known to be a peripheral vasodilator; for example, it has been shown to exert a dilatory effect on the renal vascular bed. This implies that the compounds of the present invention may be beneficial in controlling vascular blood flow.
The localisation of dopamine receptor mRNA in rat heart and large vessels has been noted. This suggests a role for dopamine receptor ligands in controlling cardiovascular function, either by affecting cardiac and smooth muscle contractility or by modulating the secretion of vasoactive substances. The compounds according to the present invention may therefore be of assistance in the prevention and/or treatment of such conditions as hypertension and congestive heart failure.
Molecular biological techniques have revealed the existence of several subtypes of the dopamine receptor. The dopamine D.sub.1 receptor subtype has been shown to occur in at least two discrete forms. Two forms of the D.sub.2 receptor subtype, and at least one form of the D.sub.3 receptor subtype, have also been discovered. More recently, the D.sub.4 (Van Tol et al., Nature (London), 1991, 350, 610) and D.sub.5 (Sunahara et al., Nature (London), 1991, 350, 614) receptor subtypes have been described.
In DE-A-2119977 there is described and claimed inter alia a class of their preparation. No utility is, however, ascribed in DE-A-2119977 to the compounds described therein.
U.S. Pat. Nos. 3,553,230 and 3,825,539 describe a range of No. 3,553,230 are stated to have utility as muscle relaxants and antidepressant agents, whilst those of U.S. Pat. No. 3,825,539 are stated to possess central nervous system depressant and anti-inflammatory activity. In addition, the compounds of both publications are alleged to be useful as intermediates in the preparation of pickling inhibitors, wood preservatives and moth proofing agents. In neither publication, however, is there any suggestion that the compounds described therein would be of any assistance in treating disorders of the dopamine system.
The compounds in accordance with the present invention, being ligands for dopamine receptor subtypes within the body, are accordingly of use in the treatment and/or prevention of disorders of the dopamine system.
The present invention accordingly provides a compound of formula I, or a salt thereof or a prodrug thereof: ##STR1## wherein the broken circle represents two non-adjacent double bonds whereby the five-membered ring containing X and Y is aromatic;
one of X and Y represents nitrogen, and the other of X and Y represents N--R.sup.2 ;
Z represents a chemical bond, an oxygen or sulphur atom, or a methylene group;
Q represents a substituted, or aryl-fused, five- or six-membered monocyclic heteroaliphatic ring containing one or two nitrogen atoms and optionally one oxygen
REFERENCES:
patent: 3553230 (1971-01-01), Freedman
patent: 3969527 (1976-07-01), Krapcho et al.
J. of Med. Chem., 27, 12, 1984, pp. 1607-1613, J. M. Jones et al.
J. H. Jones et al. `Synthesis of 4-Substituted of Medicinal Chemistry, vol. 27, No. 12, 1984 pp. 1607-1613.
G. Haeusler et al. `Pharmacological Basis For Hypertensive Therapy With A Novel Dopamine Agonist` Chemical Abstracts vol. 118, No. 9, Mar. 1, 1993 No 72912b.
Collins Ian James
Leeson Paul David
Rowley Michael
Bucknum Michael
Merck Sharp & Dohme Ltd.
North Robert J.
Shah Mukund J.
Winokur Melvin
LandOfFree
Fused tricyclic heteroaromatic derivatives as dopamine receptor does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Fused tricyclic heteroaromatic derivatives as dopamine receptor , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Fused tricyclic heteroaromatic derivatives as dopamine receptor will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1229554