US 5,670,522 AGranted

Dopamine receptor subtype ligands

AssigneeMerck Sharp & Dohme Corp.

InventorsPaul David Lesson, Michael Rowley

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Abstract

Fused tricyclic heteroaromatic compounds of formula ##STR1## wherein one of X and Y represents nitrogen, and the other of X and Y represents oxygen, sulphur or N--R.sup.2 ; Q represents a substituted five- or six-membered monocyclic heteroaliphatic ring which contains one nitrogen atom as the sole heteroatom and is linked to the five-membered heteroatomic ring containing the moieties X and Y via a carbon atom: as well as substituted 3,4-dihydro-1-hydroxy-2-oxomethyl-naphthalene precursors thereto, are ligands for dopamine receptor subtypes within the body and are therefore useful in the treatment of disorders of the dopamine system, in particular schizophrenia.

Claims6

Dependent claims

A compound of formula I, or a pharmaceutically acceptable salt thereof or a prodrug thereof:

##STR11## wherein the broken circle represents two non-adjacent double bonds in any position within the five-membered ring;
one of X and Y represents nitrogen, and the other of X and Y represents oxygen, sulphur or N--R.sup.2 ;
Q represents a ring of formula Qa to Qe ##STR12## R.sup.1 and R.sup.2 independently represent hydrogen or C.sub.1-6 alkyl;
R.sup.3, R.sup.4 and R.sup.5 independently represent hydrogen, halogen, cyano, trifluoromethyl, nitro, --OR.sup.a, --SR.sup.a, --SOR.sup.a, --SO.sub.2 R.sup.a, --SO.sub.2 NR.sup.a R.sup.b, --NR.sup.a R.sup.b, --NR.sup.a COR.sup.b, --NR.sup.a CO.sub.2 R.sup.b, --COR.sup.a, --CO.sub.2 R.sup.a, --CONR.sup.a R.sup.b, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl(C.sub.1-6)alkyl, aryl, aryl(C.sub.1-6)alkyl, aryl(C.sub.2-6)alkenyl, aryl(C.sub.2-6)alkynyl, C.sub.3-7 heterocycloalkyl, C.sub.3-7 heterocycloalkyl(C.sub.1-6)alkyl, heteroaryl or heteroaryl(C.sub.1-6)alkyl wherein the heterocycloalkyl and heteroaryl groups contain one or two heteroatoms selected from O, N or S;
R.sup.a and R.sup.b independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl(C.sub.1-6)alkyl, aryl, aryl(C.sub.1-6)alkyl, aryl,(C.sub.2-6)alkenyl, aryl(C.sub.2-6)alkynyl, C.sub.3-7 heterocycloalkyl, C.sub.3-7 heterocycloalkyl(C.sub.1-6)alkyl, heteroaryl or heteroaryl(C.sub.1-6)alkyl wherein the heterocycloalkyl and heteroaryl groups containing one or two heteroatoms selected from O, N or S;
and
wherein one of R.sup.6 and R.sup.7 represents C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl(C.sub.1-6)alkyl, aryl, aryl(C.sub.1-6)alkyl, aryl(C.sub.2-6)alkenyl, aryl(C.sub.2-6)alkynyl, C.sub.3-7 heterocycloalkyl, C.sub.3-7 heterocycloalkyl(C.sub.1-6)alkyl, heteroaryl or heteroaryl(C.sub.1-6)alkyl wherein the heterocycloalkyl and heteroaryl groups contain one or two heteroatoms selected from O, N or S and the other of R.sup.6 and R.sup.7 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl(C.sub.1-6)alkyl, aryl, aryl(C.sub.1-6)alkyl, aryl(C.sub.2-6)alkenyl, aryl(C.sub.2-6)alkynyl, C.sub.3-7 heterocycloalkyl, C.sub.3-7 heterocycloalkyl(C.sub.1-6)alkyl, heteroaryl or heteroaryl(C.sub.1-6)alkyl wherein the heterocycloalkyl and heteroaryl groups contain one or two heteroatoms selected from O, N or S.

4 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of formula I, or a pharmaceutically acceptable salt thereof or a prodrug thereof:

##STR11## wherein the broken circle represents two non-adjacent double bonds in any position within the five-membered ring;
one of X and Y represents nitrogen, and the other of X and Y represents oxygen, sulphur or N--R.sup.2 ;
Q represents a ring of formula Qa to Qe ##STR12## R.sup.1 and R.sup.2 independently represent hydrogen or C.sub.1-6 alkyl;
R.sup.3, R.sup.4 and R.sup.5 independently represent hydrogen, halogen, cyano, trifluoromethyl, nitro, --OR.sup.a, --SR.sup.a, --SOR.sup.a, --SO.sub.2 R.sup.a, --SO.sub.2 NR.sup.a R.sup.b, --NR.sup.a R.sup.b, --NR.sup.a COR.sup.b, --NR.sup.a CO.sub.2 R.sup.b, --COR.sup.a, --CO.sub.2 R.sup.a, --CONR.sup.a R.sup.b, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl(C.sub.1-6)alkyl, aryl, aryl(C.sub.1-6)alkyl, aryl(C.sub.2-6)alkenyl, aryl(C.sub.2-6)alkynyl, C.sub.3-7 heterocycloalkyl, C.sub.3-7 heterocycloalkyl(C.sub.1-6)alkyl, heteroaryl or heteroaryl(C.sub.1-6)alkyl wherein the heterocycloalkyl and heteroaryl groups contain one or two heteroatoms selected from O, N or S;
R.sup.a and R.sup.b independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl(C.sub.1-6)alkyl, aryl, aryl(C.sub.1-6)alkyl, aryl,(C.sub.2-6)alkenyl, aryl(C.sub.2-6)alkynyl, C.sub.3-7 heterocycloalkyl, C.sub.3-7 heterocycloalkyl(C.sub.1-6)alkyl, heteroaryl or heteroaryl(C.sub.1-6)alkyl wherein the heterocycloalkyl and heteroaryl groups containing one or two heteroatoms selected from O, N or S;
and
wherein one of R.sup.6 and R.sup.7 represents C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl(C.sub.1-6)alkyl, aryl, aryl(C.sub.1-6)alkyl, aryl(C.sub.2-6)alkenyl, aryl(C.sub.2-6)alkynyl, C.sub.3-7 heterocycloalkyl, C.sub.3-7 heterocycloalkyl(C.sub.1-6)alkyl, heteroaryl or heteroaryl(C.sub.1-6)alkyl wherein the heterocycloalkyl and heteroaryl groups contain one or two heteroatoms selected from O, N or S and the other of R.sup.6 and R.sup.7 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl(C.sub.1-6)alkyl, aryl, aryl(C.sub.1-6)alkyl, aryl(C.sub.2-6)alkenyl, aryl(C.sub.2-6)alkynyl, C.sub.3-7 heterocycloalkyl, C.sub.3-7 heterocycloalkyl(C.sub.1-6)alkyl, heteroaryl or heteroaryl(C.sub.1-6)alkyl wherein the heterocycloalkyl and heteroaryl groups contain one or two heteroatoms selected from O, N or S.

4 more elements