| abstract |
Described herein are antipyschotic compounds of formula (I) wherein, A is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; Alk is (C<SUB>1-4</SUB>) alkylene optionally substituted with OH, methoxy, ethoxy, or F; Ar is optionally substituted phenyl, naphthyl, monocyclic heteroaromatic, or bicyclic heteroaromatic; R<SUP>1 </SUP>is hydrogen or (C<SUB>1-4</SUB>) alkyl optionally substituted with OH, OR<SUP>3</SUP>, or OCH<SUB>2</SUB>CH<SUB>2</SUB>OH, wherein R<SUP>3 </SUP>is (C<SUB>1-2</SUB>) alkyl; R<SUP>2 </SUP>is H, (C<SUB>1-6</SUB>) alkyl, halogen, fluorinated (C<SUB>1-6</SUB>) alkyl, OR<SUP>4</SUP>, SR<SUP>4</SUP>, NO<SUB>2</SUB>, CN, COR<SUP>4</SUP>, CONR<SUP>5</SUP>R<SUP>6</SUP>, SO<SUB>2</SUB>NR<SUP>5</SUP>R<SUP>6</SUP>, NR<SUP>5</SUP>R<SUP>6</SUP>, NR<SUP>5</SUP>COR<SUP>4</SUP>, NR<SUP>5</SUP>SO<SUB>2</SUB>R<SUP>4</SUP>, or optionally substituted phenyl, wherein R<SUP>4 </SUP>is hydrogen, (C<SUB>1-6</SUB>) alkyl, fluorinated (C<SUB>1-6</SUB>) alkyl, or optionally substituted phenyl, R<SUP>5 </SUP>and R<SUP>6 </SUP>are independently hydrogen, (C<SUB>1-6</SUB>) alkyl, or optionally substituted phenyl; Z is one or two substituents independently selected from hydrogen, halogen, (C<SUB>1-6</SUB>) alkyl, fluorinated (C<SUB>1-6</SUB>) alkyl, OR<SUP>7</SUP>, SR<SUP>7</SUP>, NO<SUB>2</SUB>, CN, COR<SUP>7</SUP>, CONR<SUP>8</SUP>R<SUP>9</SUP>, SO<SUB>2</SUB>NR<SUP>8</SUP>R<SUP>9</SUP>, NR<SUP>8</SUP>SO<SUB>2</SUB>R<SUP>7</SUP>, NR<SUP>8</SUP>R<SUP>9</SUP>, or optionally substituted phenyl, wherein R<SUP>7 </SUP>is hydrogen, (C<SUB>1-6</SUB>) alkyl, fluorinated alkyl, or optionally substituted phenyl, R<SUP>8 </SUP>and R<SUP>9 </SUP>are independently hydrogen, (C<SUB>1-6</SUB>) alkyl, or optionally substituted phenyl; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D<SUB>2 </SUB>receptor and as agents for the treatment of psychosis and bipolar disorder, and pharmaceutical formulations of the compounds of formula (I). |