Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-01-29
1998-12-01
Gerstl, Robert
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548703, A61K 31425, C07D41706
Patent
active
058439714
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to novel heterocyclic compounds having therapeutic activity, processes and intermediates for their preparation, pharmaceutical formulations containing said compounds and the medicinal use of said compounds.
BACKGROUND OF THE INVENTION
There exists a large group of acute and chronic neuropsychiatric disorders for which safe and clinically effective treatments are not currently available. This diverse group of disorders encompasses a broad spectrum of initial events which are characterised by the initiation of progressive processes that sooner or later lead to neuronal cell death and dysfunction. Stroke, cerebral ischaemia, trauma or a neurodegenerative disease such as Alzheimer's disease or Parkinson's disease are all commonly occurring conditions that are associated with neurodegeneration of the brain and/or spinal cord.
The ongoing search for potential treatments of neurodegenerative disorders has involved investigation of excitatory amino acid antagonists, inhibitors of lipid peroxidation, calcium channel antagonists, inhibitors of specific pathways of the arachidonic acid cascade, kappa opioid agonists, adenosine agonists, PAF antagonists and diverse other agents. At the present time there is no consensus of the relative importance of the role played by compounds belonging to any of these general classes.
In a paper on the reactions of 2-halothiazoles with ketone enolates, J. F. Wolfe and co-workers (J. Org. Chem., 1986, 51, 1184-1188) describe bis(2-thiazolyl) derivatives of the following formula: ##STR3##
In a paper on the synthesis of 2-aroyloxazoles (Synthesis, 1984, 1048-1050), the following compound is disclosed: ##STR4##
No pharmacological activity is associated with any of the above compounds. The substitution pattern of the above compounds places them outside the scope of the present invention.
In patent application DE 2801794 (U.S. Pat. No. 4,371,734) a process for the preparation of thiazoles of general formula: ##STR5## is claimed. A specific example of said thiazoles is 4-methyl-.alpha.-(4-phenyl-2-thiazolyl)-2-thiazoleacetonitrile. Said compounds are useful as intermediates in the preparation of certain dyestuffs. No pharmacological action is ascribed to said compounds. The definition of the groups R.sub.1 and R.sub.2 places these compounds outside the scope of the present invention.
In a paper on the synthesis of deuterium--labelled thiazoles, Roussel and Metzger (Bull. Soc. Chim. Fr., 1962, 2075-2078) describe the isolation and partial characterisation of 1,1-di(2-thiazolyl)ethanol. No pharmacological activity is associated with this compound. This compound is deleted from the scope of the present invention by a disclaimer in claim 1.
A primary objective of the present invention is to provide structurally novel heterocyclic compounds which by virtue of their pharmacological profile are expected to be of value in the treatment of acute and chronic neuropsychiatric disorders characterised by progressive processes that sooner or later lead to neuronal cell death and dysfunction. Such disorders include stroke; cerebral ischaemia; dysfunctions resulting from brain and/or spinal trauma; hypoxia and anoxia, such as from drowning, and including perinatal and neonatal hypoxic asphyxial brain damage; multi-infarct dementia; AIDS dementia; neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's chorea, epilepsy, multiple sclerosis and amytrophic lateral sclerosis; brain dysfunction in connection with surgery involving extracorporeal circulation or in connection with brain surgery, including endarterectomy of the carotid arteries; and CNS dysfunctions as a result of exposure to neurotoxins or radiation. This utility is manifested, for example, by the ability of these compounds to inhibit delayed neuronal death in the gerbil bilateral occlusion model of ischaemia.
The present invention relates to a compound having the general formula (1) ##STR6## wherein: X.sub.1 and X.sub.2 are independently O, S or Se; one of
REFERENCES:
patent: 4371734 (1983-02-01), Seybold
patent: 5665747 (1997-09-01), Boar
Dondoni et al., "Synthesis of (Trimethylsilyl)thiazoles and Reactions with Carbonyl Compounds. Selectivity Aspects and Synthetic Utility," J. Org. Chem. vol. 53, pp. 1748-1861 (1988).
Hodges et al., "Reactions of Lithiooxazole," J. Org. Chem., vol. 56, pp. 449-452 (1991).
Pridgen et al., "A New Facile Synthesis of 2-Aroyloxazoles from 2-Lithiooxazoles," Synthesis, pp. 1048-1050 (Dec. 1984).
Roussel et al., "Synthese et etude spectrale infrarouge des deutero-thiazoles," Bulletin Soc. Chim. France, pp. 2075-2078 (1962).
Strekowski et al., "Efficient Preparation of Ketones from N-(Ethoxymethylene)aniline and Organometallic Reagents," J. Org. Chem., vol. 54, pp. 6120-6123 (1989).
Boar Robin Bernard
Gray Duncan Alastair
O'Shea Dennis Mark
Astra Aktiebolag
Gerstl Robert
LandOfFree
1, 1-BIS (heteroazolyl) alkane derivatives and their use as neur does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 1, 1-BIS (heteroazolyl) alkane derivatives and their use as neur, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 1, 1-BIS (heteroazolyl) alkane derivatives and their use as neur will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2395987