Nitrogen heterocycles

Details Nitrogen heterocycles Nitrogen heterocycles

1995-12-07

1997-10-28

Ivy, C. Warren

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

546157, 546158, A61K 3147, C07D215227

Patent

active

056818394

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/GB 95/00278, filed Feb. 10, 1995 published as WO95/21824 Aug. 17, 1995.
This invention relates to nitrogen heterocycles, more particularly to substituted quinolinones, partially or totally saturated, to processes for preparing them, and compositions containing them. The compounds have pharmaceutical uses conferred by their ability to block voltage gated potassium channels.
Voltage gated potassium ion (K.sup.+) channels which produce transient outward currents (TOC) are present in the cell membranes of neurones and serve to repolarise the cell following a depolarisation by opening and allowing potassium ions to flow from the inside of the cell to the outside. They are, therefore, one of the main regulating influences on the nerve cell firing and determine the amount of current reaching the terminal regions of the cells. This in turn regulates the amount of neurotransmitter substances released from the nerve terminals. In addition, they help to determine the refractory period of the nerve cell and hence the probability of the cell firing again within a certain time. This governs neuronal excitability and also the tendency of a cell to undergo repetitive firing. An ability to modify the functioning of these channels by chemical means is likely to produce therapeutically useful agents. So far the agents which are known to block the TOC channels are toxins such as the snake toxin dendrotoxin, or 4-aminopyridine and its derivatives. Blockade of the TOC channels leads to a change in the pattern of transmitter release and depending upon the pattern and type of neurone affected different therapeutic ends will result. For example TOC blockers which increase dopaminergic transmission in the substantia nigra will be of use in treatment of Parkinson's disease. Likewise, an increase in cholinergic function is of use in Alzheimer's disease and in cognition enhancement. Because of the complicated neural networks in the brain blockade of the TOC may also lead to increase in more than one transmitter substance at a time and this can act synergistically where a disease state is associated with more than one transmitter deficit as is often the case. It is evident, therefore that TOC blockers may be of use in areas of depression, pain, psychoses, cognition, memory and learning, anxiety, Parkinson's disease and Alzheimer's disease. In addition they can be used as a treatment for conditions where there is an impairment of nerve transmission such as multiple sclerosis.
Compounds which act to increase channel function may be termed channel openers and these serve to increase the braking action of the channels on the cells. In this respect they will also reduce the likelihood of the cells to undergo repetitive firing and may be used as anticonvulsants in the treatment of epilepsy. Also, their action to reduce neurotransmitter release means that they may be used as anaesthetics, analgesics, sedatives and anxiolytics.
This invention provides compounds of generic formula (I): ##STR2## or a pharmaceutically acceptable salt thereof, where the dotted lines represent optional bonds, group; said heteroaryl group containing 5 to 10 ring atoms of which one or more (e.g up to 3) of said atoms are heteroatoms selected from oxygen, nitrogen and sulphur, the same or different; said aryl or heteroaryl radicals being optionally substituted by one or more substituents the same or different, eg substituents commonly used in pharmaceutical chemistry such as for example: C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 alkoxy or such groups substituted by C.sub.6 -C.sub.10 aryl or heteroaryl as defined above; halogen; halo C.sub.1 -C.sub.6 alkyl; halo C.sub.1 -C.sub.6 alkoxy; carboxy; hydroxy(C.sub.1 -C.sub.6)alkyl; (C.sub.1 -C.sub.6 alkoxy)carbonyl; amino including substituted amino, e.g mono- or di- (C.sub.1 -C.sub.6 alkyl)-amino; nitro; hydroxy; mercapto; C.sub.1 -C.sub.6 alkylthio; (C.sub.1 -C.sub.6)alkyl carbonyl; (C.sub.6 -C.sub.10 aryl)carbonyl; (C.sub.2 -C.sub.7)alkanoyloxy; (C.sub.7 -C.sub.11)aroyloxy; (C.sub.1 -C.sub

REFERENCES:
patent: 3994900 (1976-11-01), Krapcho
patent: 4576949 (1986-03-01), Smith
patent: 4792561 (1988-12-01), Walker
patent: 4921862 (1990-05-01), Walker
patent: 5110815 (1992-05-01), Effland
Albrecht, Arch Pharm (Ewinheim), 318, pp. 1105-1115, 1985.
Zimmerman and Zeng, J. Org. Chem. 55(16), 4789-91 (1990).
Bennett and Minor, J. Het. Chem. 16(4), 633-35 (1990).
Albrecht and Shroder, Arch. Pharm (Weinheim) 308(8), 588-94 (1975).
Zymalkowski and Kothari, Arch. Pharm (Weinhiem) 303 (8), 667-75 (1970).
Reimann and Friesinger, Arch Pharm. (Weinheim), 318, 1105-1115 (1985).

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