Fluoro-substituted adamantane derivatives
AssigneePfizer Inc.
InventorsVytautas John Jasys, Robert A. Volkmann
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Abstract
The invention relates to fluoro-substituted adamantane derivatives of the formula ##STR1## and to pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are as defined herein. The invention also relates to methods of treating neurological disorders, such as memory loss and Parkinson's disease, and bacterial and viral infections, through administration of a therapeutically effective amount of a compound of formula I. The invention also relates to a method of increasing the metabolic stability of an adamantane-containing pharmaceutical compound by incorporating a fluoro substituent on at least one bridge-head carbon of the adamantyl group of said adamantane-containing pharmaceutical compound
Claims11
A compound of the formula ##STR5## or a pharmaceutically acceptable salt thereof, wherein:
- R.sup.1 is --NHC(O)R.sup.5, --C(O)NHR.sup.5, --(CR.sup.5 R.sup.6),NR.sup.5 R.sup.6 or --(CR.sup.5 R.sup.6).sub.n CO.sub.2 R.sup.5 wherein n is integer ranging from 0 to 4;
- R2, R3 and R4 are each fluoro;
- and
- each R.sup.5 and R.sup.6 is independently H or C.sub.1 -C.sub.4 alkyl.
A method of increasing the metabolic stability of a pharmaceutically active adamantane compound which comprises including a fluoro substituent on three bridge-head carbons of the adamantyl group of said adamantane compound.
An adamantane compound selected from the group consisting of amantadine, adatanserin, tromantadine, amantanium bromide, rimantadine, memantine, somantadine, adapalene, N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine, dopamantine, adaprolol maleate, (-)-N-(2-(8-methyl-1,4-benzodioxan-2-ylmethylamino)ethyl)adamantane-1-carb oxamide, N-(1-adamantyl) -N',N'-(1,5-(3-(4(5)-1 H-imidazolyl-pentanediyl)))formamidine, adamantoyl-Lys-Pro-Tyr -Ile-Leu, 1-(2-pyridyl)-4-( 1-methyl-2-( 1-adamantylamino)ethyl)piperazine, adafenoxate, (1R,3S)-3-(1 '-adamantyl)-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1 H-2-benzopyran, adamantylamide L-Ala-L-isoGlu, 2-adamantylamino-benzoic acid, N(alpha)-(1-adamantanesulphonyl)-N-(4-carboxybenzoyl)-L-lysyl-alanyl-L-val inal, 4-acylamino-1-aza-adamantane, L-leucyl-D-methionyl-glucyl-N-(2-adamantyl)-L-phenylalanylamide, Tyr-(D)-Met-Gly-Phe-adamantane, 1-N-(p-bromobenzoyl)methyladamantyl amine, 4-butyl-1,2-dihydro-5-((1-adamantanecarbonyl)oxy)-1,2-diphenyl-3H-pyrazol- 3-one, N(alpha)-(1-adamantanesulphonyl)-N(epsilon)-succinyl-L-lysyl-L-prolyl-L-va linal, and the amantadine salt of N-acetyl-DL-phenylalanine;
- which adamantane compound further comprises a fluoro substituent on three bridge-head carbons of the adamantyl group of said adamantane compound.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier, and an adamantane compound selected from the group consisting of amantadine, adatanserin, tromantadine, amantanium bromide, rimantadine, memantine, somantadine, adapalene, N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine, dopamantine, adaprolol maleate, (-)-N-(2-(8-methyl-1,4-benzodioxan-2-ylmethylamino)ethyl)adamantane-1-carb oxamide, N-(1-adamantyl) -N',N'-(1,5-(3-(4(5)-1 H-imidazolyl-pentanediyl)))formamidine, adamantoyl-Lys-Pro-Tyr -Ile-Leu, 1-(2-pyridyl)-4-(1-methyl-2-(1-adamantylamino)ethyl)piperazine, adafenoxate, (1 R,3S)-3-(1 '-adamantyl)-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1 H-2-benzopyran, adamantylamide L-Ala-L-isoGlu, 2-adamantylamino-benzoic acid, N(alpha)-(1-adamantanesulphonyl)-N-(4-carboxybenzoyl)-L-lysyl-alanyl-L-val inal, 4-acylamino-1aza-adamantane, L-leucyl-D-methionyl-glucyl-N-(2-adamantyl)-L-phenylalanylamide, Tyr-(D)-Met-Gly-Phe-adamantane, 1-N-(p-bromobenzoyl)methyladamantyl amine, 4-butyl-1,2-dihydro-5-((1-adamantanecarbonyl)oxy)-1,2-diphenyl-3H-pyrazol- 3-one, N(alpha)-(1-adamantanesulphonyl)-N(epsilon)-succinyl-L-lysyl-L-prolyl-L-va linal, and the amantadine salt of N-acetyl-DL-phenylalanine, which adamantane compound further comprises a fluoro substituent on three bridge-head carbons of the adamantyl group of said adamantane compound.
Dependencies are inferred from the claim text.