Brain-specific analogues of centrally acting amines
AssigneeUniversity of Florida
InventorNicholas S. Bodor
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Abstract
The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are compounds of the formula ##STR1## and the non-toxic pharmaceutically acceptable salts thereof, wherein D is the residue of a centrally acting primary, secondary or tertiary amine and ##STR2## is an unsubstituted or substituted dihydropyridyl, dihydroquinolyl or dihydroisoquinolyl radical. The corresponding ionic pyridinium, quinolinium and isoquinolinium salts ##STR3## wherein X.sup.- is the anion of a non-toxic pharmaceutically acceptable acid, are also disclosed.
Claims16
A compound of the formula ##STR559## or a non-toxic pharmaceutically acceptable salt thereof, wherein D is a residue of the formula ##STR560## is a radical of the formula ##STR561## wherein the dotted line indicates the presence of a double bond in either the 4- or 5-position of the dihydropyridine ring;
- n is zero, one or two;
- and each R is independently selected from the group consisting of halo, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 alkoxy, C.sub.2 -C.sub.8 alkoxycarbonyl, C.sub.2 -C.sub.8 alkanoyloxy, C.sub.1 -C.sub.7 haloalkyl, C.sub.1 -C.sub.7 alkylthio, C.sub.1 -C.sub.7 alkylsulfinyl, C.sub.1 -C.sub.7 alkylsulfonyl, --CH.dbd.NOR'" wherein R'" is H or C.sub.1 -C.sub.7 alkyl, and --CONR'R", wherein R' and R", which can be the same or different, are each H or C.sub.1 -C.sub.7 alkyl.
A pharmaceutical composition comprising an effective antidepressant amount of a compound of the formula ##STR564## or a non-toxic pharmaceutically acceptable salt thereof, wherein D is a residue of the formula ##STR565## is a radical of the formula ##STR566## wherein the dotted line indicates the presence of a double bond in either the 4- or 5-position of the dihydropyridine ring;
- n is zero, one or two;
- and each R is independently selected from the group consisting of halo, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 alkoxy, C.sub.2 -C.sub.8 alkoxycarbonyl, C.sub.2 -C.sub.8 alkanoyloxy, C.sub.1 -C.sub.7 haloalkyl, C.sub.1 -C.sub.7 alkythio, C.sub.1 -C.sub.7 alkylsulfinyl, C.sub.1 -C.sub.7 alkylsulfonyl, --CH.dbd.NOR'" wherein R'" is H or C.sub.1 -C.sub.7 alkyl, and --CONR'R", wherein R' and R", which can be the same or different, are each H or C.sub.1 -C.sub.7 alkyl;
- and a non-toxic pharmaceutically acceptable carrier therefor.
A method for eliciting an antidepressant response in an animal in need thereof, comprising administering to said animal an effective antidepressant amount of a compound of the formula ##STR569## or a non-toxic pharmaceutically acceptable salt thereof, wherein D is a residue of the formula ##STR570## is a radical of the formula ##STR571## wherein the dotted line indicates the presence of a double bond in either the 4- or 5-position of the dihydropyridine ring;
- n is zero, one or two;
- and each R is independently selected from the group consisting of halo, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 alkoxy, C.sub.2 -C.sub.8 alkoxycarbonyl, C.sub.2 -C.sub.8 alkanoyloxy, C.sub.1 -C.sub.7 haloalkyl, C.sub.1 -C.sub.7 alkylthio, C.sub.1 -C.sub.7 alkylsulfinyl, C.sub.1 -C.sub.7 alkylsulfonyl, --CH.dbd.NOR'" wherein R'" is H or C.sub.1 -C.sub.7 alkyl, and --CONR'R", wherein R' and R", which can be the same or different, are each H or C.sub.1 -C.sub.7 alkyl.
Dependencies are inferred from the claim text.