Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-08-25
2000-10-10
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514290, 514297, 546 61, 546 79, 546 93, 546102, 546104, 546105, A61K 31473, C07D22118, C07D22108
Patent
active
061302287
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND
The present invention relates to compounds which have been found to exhibit anti-acetylcholinesterase activity and/or inhibition of 5-HT uptake and/or inhibition of noradrenaline uptake. More specifically, the invention concerns polycyclic compounds and analogues thereof, methods for their preparation, pharmaceutical formulations containing them and their use as neurotransmitter potentiating agents, in particular in the treatment of symptoms of Alzheimer's disease.
Much work has been done in research in the area of drugs affecting neurotransmitter systems in the central nervous system (CNS). Neurotransmitter molecules are involved in rapid communication in the normal CNS and in pathologic conditions of the CNS. Most of the drugs available to the psychiatrist or neurologist for the treatment of CNS disease function by affecting neurotransmitter pathways directly or indirectly. Of all the CNS disorders known to date, those associated with organic or degenerative dementia are not able to be treated effectively with the range of drugs currently available. A particular disorder, Alzheimer's disease, also known as degenerative dementia, senile dementia, senile dementia of the Alzheimer type and organic brain syndrome, has no known effective treatment therefor.
Certain drugs, such as so-called centrally active muscarinic drugs (i.e. drugs which act directly on the acetylcholine receptors to produce a response), act on so-called muscarinic receptors. Muscarinic receptors have been found to be made up of at least 3 subclasses: M.sub.1, M.sub.2 and M.sub.3. These receptors are found in the brain, heart and gut, and as a result, the use of muscarinic drugs carries with it the possibility of undesirable side effects such as nausea or slowing or stopping of the heart.
Tacrine, a tricyclic acetylcholine esterase inhibitor is known to produce liver damage as a side effect, which, although not believed to be irreversible in nature, is nevertheless undesirable.
There exists a need to provide more effective drugs for the treatment of, or alleviation of symptoms of organic or degenerative dementia diseases of the CNS.
SUMMARY OF INVENTION
It is an object of the invention to provide more effective and/or selective polycyclic drugs for the treatment of, or alleviation of symptoms of organic or degenerative dementia diseases of the CNS.
This and other objects of the invention will become apparent from the following description and examples.
STATEMENT OF INVENTION
According to the present invention there is provided compounds of general Formula (I): ##STR2## wherein R.sup.1 is selected from NH.sub.2, OH, H, F, Cl, Br, I, OCH.sub.3, C.sub.1 -C.sub.6 alkyl or aryl (phenyl); C.sub.1 -C.sub.6 alkoxy; alkyl; alkyl; (CH.sub.2).sub.1-4 NR.sup.6 R.sup.7, OH, C.sub.1 -C.sub.4 alkyl and C.sub.1 -C.sub.4 alkoxy; or 4; selected from 1, 2, or 3; -C.sub.6 alkyl or aryl; to Ring C at any face of Ring C which does not extend from a carbon of Ring D such that when Ring B is fused to Ring C, Ring C is optionally substituted at unfused carbon atoms by one or more groups independently selected from H, C.sub.1 -C.sub.6 alkyl or --COOR.sup.8 wherein R.sup.8 is selected from H or C.sub.1 -C.sub.6 alkyl with the proviso that when Ring C is a 5 or 6 carbon membered ring and is not fused to a ring B at least one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is not H.
Generic Formula (I) can be viewed as two further sub-generic Formulae (II) and (III). Formula (II) may be viewed as: ##STR3## wherein R.sup.5 is selected from H, F, Br, Cl, NO.sub.2, NR.sup.6 R.sup.7, (CH.sub.2).sub.1-4 NR.sup.6 R.sup.7, OH, C.sub.1 -C.sub.4 alkyl and C.sub.1 -C.sub.4 alkoxy; Cl and OCH.sub.3 ; carbon of Ring D; groups independently selected from C.sub.1 -C.sub.6 alkyl or COOR.sup.8 wherein R.sup.8 is H or C.sub.1 -C.sub.6 alkyl; and
Naturally the skilled addressee will appreciate that free acid addition salts of compounds of Formula (I) and Formula (II) are encompassed within the present invention.
Suitable acid addition salts include those formed from hydrochl
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Harvey Alan Lang
McKenna Maureen Theresa
Mullins Steven John
Proctor George Rennet
Desai Rita
Rotman Alan L.
University of Strathclyde
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