Methods of use and compositions for benzylidene- and cinnamylidene-anabaseines
AssigneeUniversity of Florida
InventorsEdwin Meyer, William Kem, Franz van haaren, John A. Zoltewicz, Christopher M. De Fiebre, Roger Papke, Arthur Day
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Abstract
This invention relates to compositions for benzylidene- and cinnamylidene-anabaseines and methods for using these compositions for treating conditions associated with defects or malfunctioning of nicotinic subtypes brain receptors. These compositions target the alpha7 receptor subtype with little or no activation of the alpha4beta2 or other receptor subtypes.
Claims94
A composition of matter comprising a compound of the formula:
- ##STR20## or a salt thereof, wherein R.sup.1, R.sup.6, and R.sup.7 are hydrogen or C.sub.1 -C.sub.4 alkyl;
- and R.sup.2 is .dbd.CHCH.dbd.CHX, wherein X is ##STR21## wherein R.sup.3, R.sup.4, and R.sup.5 are selected from the group consisting of hydrogen, C.sub.1 -C.sub.4 alkyl optionally substituted with NN-dialkylamino having 1 to 4 carbons in each of the alkyls, C.sub.1 -C.sub.6 alkoxy optionally substituted with N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, carboalkoxy having 1 to 4 carbons in the alkoxy, amino, amino having 1 to 4 carbons in the acyl, cyano, N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, halo, hydroxyl, and nitro.
A composition of matter comprising a cinnamylidene-anabaseine.
A composition of matter comprising 3-(4-isopropoxybenzylidene) anabaseine.
A method of moderating or preventing tobacco-withdrawal effects in a mammal in need thereof, comprising administering to an animal in need thereof a therapeutically effective amount of a compound of the formula:
- ##STR22## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.6, and R.sup.7 are hydrogen or C.sub.1 -C.sub.4 alkyl;
- and R.sup.2 is .dbd.CHX, .dbd.CCH.sub.3 X, or .dbd.CHCH.dbd.CHX, wherein X is ##STR23## wherein R.sup.3, R.sup.4, and R.sup.5 are selected from the group consisting of hydrogen, C.sub.1 -C.sub.4 alkyl optionally substituted with N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, C.sub.1 -C.sub.6 alkoxy optionally substituted with N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, carboalkoxy having 1 to 4 carbons in the alkoxy, amino, amino having 1 to 4 carbons in the acyl, cyano, N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, halo, hydroxyl, and nitro.
A method of treating tobacco-withdrawal symptoms comprising administering to an animal in need thereof a therapeutically effective amount of a benzylidene-anabaseine or a cinnamylidene-anabaseine capable of selectively activating alpha7 receptors, or a pharmaceutically acceptable salt thereof.
A method of stimulating brain alpha7 receptors antagonized by ethanol in a mammal, comprising administering to an animal in need thereof a therapeutically effective amount of a compound of the formula:
- ##STR24## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.6, and R.sup.7 are hydrogen or C.sub.1 -C.sub.4 alkyl;
- and R.sup.2 is .dbd.CHX, .dbd.CCH.sub.3 X, or .dbd.CHCH.dbd.CHX, wherein X is ##STR25## wherein R.sup.3, R.sup.4, and R.sup.5 are selected from the group consisting of hydrogen, C.sub.1 -C.sub.4 alkyl optionally substituted with N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, C.sub.1 -C.sub.6 alkoxy optionally substituted with N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, carboalkoxy having 1 to 4 carbons in the alkoxy, amino, amino having 1 to 4 carbons in the acyl, cyano, N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, halo, hydroxyl, and nitro.
A method of stimulating brain alpha7 receptors antagonized by ethanol comprising administering to an animal in need thereof a therapeutically effective amount of a benzylidene-anabaseine or a cinnamylidene-anabaseine capable of selectively activating alpha7 receptors, or a pharmaceutically acceptable salt thereof.
A method of protecting against cell loss induced by ischemia in a mammal, comprising administering to an animal in need thereof a therapeutically effective amount of a compound of the formula:
- ##STR26## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.6, and R.sup.7 are hydrogen or C.sub.1 -C.sub.4 alkyl;
- and R.sup.2 is .dbd.CHX, .dbd.CCH.sub.3 X, or .dbd.CHCH.dbd.CHX, wherein X is ##STR27## wherein R.sup.3, R.sup.4, and R.sup.5 are selected from the group consisting of hydrogen, C.sub.1 -C.sub.4 alkyl optionally substituted with N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, C.sub.1 -C.sub.6 alkoxy optionally substituted with N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, carboalkoxy having 1 to 4 carbons in the alkoxy, amino, amino having I to 4 carbons in the acyl, cyano, N,N-dialkylamino having 1 to 4 carbons in each of the alkyls, halo, hydroxyl, and nitro.
A method of protecting against cell loss induced by ischemia comprising administering to an animal in need thereof a therapeutically effective amount of a benzylidene-anabaseine or a cinnamylidene-anabaseine capable of selectively activating alpha7 receptors, or a pharmaceutically acceptable salt thereof.
A method of prophylaxis against cell loss from focal ischemic insult, comprising administering to a mammal in need thereof an amount of an alpha7 nicotinic agonist selected from the group consisting of a benzylidene-anabaseine and a cinnamylidene-anabaseine before occurrence of ischemia in an amount effective to protect against the cell loss.
A method of treating age related learning or memory impairment comprising administering to an animal in need thereof a therapeutically effective amount of a cinnamylidene-anabaseine.
Dependencies are inferred from the claim text.