US 4,963,568 AGranted

Dopamine agonists

AssigneeAbbott Laboratories

InventorsRobert W. Schoenleber, John W. Kebabian, Yvonne C. Martin, Michael P. DeNinno, Richard J. Perner, David M. Stout, Chi-Nung W. Hsiao, Stanley DiDomenico, Jr., John F. DeBernardis, Fatima Z. Basha, Michael D. Meyer, Biswanath De

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Abstract

Novel compounds which are selective dopamine agonists are useful for treating disorders characterized by abnormal dopamine levels, such as Parkinson's Disease, as well as cardiovascular disorders.

Claims8

Dependent claims

A compound having the formula:

##STR78## wherein A is O, CH, or CH.sub.2 ;
R.sub.1 and R.sub.2 are the same and are selected from hydrogen or a acyl or cyclic borate leaving group or a protecting group selected from alkyl, alkenyl, cyclopropylmethyl, cyclohexyl, aryl, or cyclohexylidenyl
m is zero or 1 and n is zero;
R.sub.3 is alkyl, substituted alkyl, carbocyclic aryl, cycloalkyl, or taken together with R.sub.4 can form a spiroalkyl;
R4 is H or alkyl, or taken together with R.sub.3 can form a spiroalkyl;
R.sub.5 is H or alkyl, or can be taken together with R.sub.3 to form a fused cycloalkyl;
R.sub.6 is H, alkyl, or substituted alkyl, or taken together with R8 can form an N containing saturated heterocyclic ring having 5-6 ring members
R.sub.7 is H, alkyl, alkenyl, cycloalkyl, or carbocyclic arylalkyl wherein the alkyl contains from one to twelve carbon atoms;
with the proviso that when R.sub.6 is alkyl R.sub.7 cannot be carbocyclic arylalkyl;
R.sub.8 is H, alkyl;
wherein alkyl is of from one to twelve carbon atoms;
alkenyl is of from one to twelve carbon atoms;
cycloalkyl is of from of from three to twelve carbon atoms;
substituted alkyl is alkyl as previously defined substituted with a group selected from cycloalkyl, hydroxy, amino, (lower alkyl) amino, carbocyclic aryl, carbocyclic aryloxy, pyrrolidino, piperidino, and morpholino;
or a pharmaceutically acceptable salt, ester or amide thereof.

12 more elements

A compound selected from the group consisting of:

1-Aminomethyl 3,4-dihydro-5,6-dihydroxy-3-phenyl-naphthalene hydrobromide;
1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-phenyl-naphthalene hydrochloride;
1-Aminomethyl-5,6-bis(acetoxy)-3,4-dihydro-3-phenylnaphthalene hydrochloride;
1-Aminomethyl-5,6-bis(trimethylacetoxy)-3,4-dihydro-3-phenyl naphthalene hydrochloride;
[1R,3S]1-Aminomethyl-5,6-dihydroxy-3-phenyl-1,2,3,4-tetrahydro-naphthalene hydrobromide;
1-Aminomethyl-3-cyclohexyl-3,4-dihydro-5,6-dihydroxynaphthalene hydrobromide;
[1R,3S]1-Aminomethyl-3-cyclohexyl-5,6-dihydroxy-1,2,3,4-tetrahydro-naphthal ene hydrobromide;
[1R,3S]1-Aminomethyl-3-t butyl-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyran hydrochloride;
[1R,3S]1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-phenyl-1H-2 benzopyran hydrochloride;
[1R,3S]1 Aminomethyl-3-cyclohexyl-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyran hydrochloride;
[1R,3R]1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-ethyl-1H-2 benzopyran hydrochloride;
Spiro[(1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1H 2-benzopyran)-3,1'-cyclohexane]hydrochloride;
[1R,3S]1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-(4'-methoxy)phenoxymethyl- 1H-2 benzopyran hydrochloride;
[1R*,3S*]1-Aminomethyl-3,4-dihydro 5,6-dihydroxy-3-phenyl-1H 2-benzopyran hydrochloride;
[1R,3S]1 Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-phenoxymethyl-1H-2 benzopyran hydrochloride;
[1R,3S]1 Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-(2'-phenyl)phenoxymethyl-1H-2-benz opyran hydrochloride;
[1R,3S]1-Aminomethyl-3-(4'-t butyl)phenoxymethyl-3,4-dihydro-5,6-dihydroxy-1H-2 benzopyran hydrochloride;
[1R,3S]1-Aminomethyl-3-(4'-bromo)phenoxymethyl-3,4-dihydro-5,6-dihydroxy 1H 2-benzopyran hydrochloride;
[1R,3S]3-(1'-Adamantyl)-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1H-2-benzop yran hydrochloride;
[1R,3R]1-Aminomethyl-3-benzyl-3,4-dihydro 5,6-dihydroxy-1H-2-benzopyran hydrochloride;
[1R,3R]1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-(2'-phenyl)ethyl-1H-2-benz opyran hydrochloride;
[1R,3S] 1-Aminomethyl-8-bromo-3,4-dihydro-5,6-dihydroxy-3-phenyl-1H-2-benzopyran hydrochloride;
[1R,3R]1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-n-octyl-1H-2 benzopyran hydrochloride;
[1R,3R]1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-(1'-hex 5'-ene)-1H-2-benzopyran hydrochloride;
[1R,3S]1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-ethyl-1H-2 benzopyran hydrochloride;
[1R,3R]1 Aminomethyl 3,4 dihydro 5,6-dihydroxy 3-n-hexyl-1H-2 benzopyran hydrochloride;
1R,3S]1-Aminomethyl-3-(4'-bromo)phenyl-3,4 dihydro-5,6-dihydroxy-1H-2-benzopyran hydrochloride;
[1R,3S]1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-(3'-hydroxy)phenyl-1H-2-be nzopyran hydrochloride;
[1R,3S]3-Cyclohexyl-3,4-dihydro-5,6-dihydroxy-1-(N-methyl)-aminomethyl-1H-2 -benzopyran hydrochloride;
[1R,3S]3-t-Butyl-3,4-dihydro-5,6-dihydroxy-1-(N-methyl)-aminomethyl-1H-2-be nzopyran hydrochloride;
[1R,3S]1-(N-Allyl)-aminomethyl-3-cyclohexyl-3,4-dihydro-5,6-dihydroxy-1H 2-benzopyran hydrochloride;
[1R,3S]3-Cyclohexyl-1-(N-cyclopropyl)-aminomethyl-3,4-dihydro-5,6-dihydroxy -1H-2-benzopyran hydrochloride;
[1R,3S]1-(N-Benzyl)-aminomethyl-3-cyclohexyl-3,4-dihydro-5,6-dihydroxy-1H-2 -benzopyran hydrochloride;
[1R,3S]1,3-Bis(aminomethyl)-3,4 dihydro 5,6-dihydroxy-1H-2-benzopyran dihydrochloride;
[1R,3S]1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-hydroxymethyl-1H 2-benzopyran hydrochloride;
[1R,3S]1-Aminomethyl-3,4-dihydro-5,6dihydroxy-3-(N-piperidino)methyl-1H-2-b enzopyran dihydrochloride;
[1R,3S]-5,6-Dihydroxy-3-phenyl-1-(2'R-pyrrolidino)-1,2,3,4-tetrahydro-napht halene hydrobromide;
[1R,3R]5,6-Dihydroxy-3-phenyl-1-(2'R pyrrolidino)-1,2,3,4-tetrahydro-haphthalene hydrobromide;
3,4-Dihydro-5,6-dihydroxy-1-(N methyl)-aminomethyl-3-phenyl-naphthalene hydrochloride;
1R,3S]5,6-Dihydroxy 1-(N methyl)-aminomethyl 3-phenyl-1,2,3,4-tetrahydro-naphthalene hydrochloride;
1Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-(3'-hydroxy)phenyl-naphthalene hydrobromide;
1-Aminomethyl-3,4-dihydro-5,6-dihydroxy-3-(4'-hydroxy)phenyl-naphthalene hydrobromide;
and
[1R,3S]1-Aminomethyl-5,6-dihydroxy-3-(3'-hydroxy)phenyl-1,2,3,4-tetrahydro- naphthalene hydrobromide or a pharmaceutically acceptable salt, ester or amide thereof.

41 more elements

Dependencies are inferred from the claim text.

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