Patent EA-001486-B1 (EA)
Title: Benzoxazinone dopamine d4 receptor antagonists
Inventor: BELLIOTTI THOMAS
IPC: C07D265/36
Filed: 1997-05-20
Abstract: 1. A compound having the Formula I   wherein R<1> and R<2> are independently hydrogen or alkyl with 1 to 6 carbon atoms; X is C, N or CH; wherein in case X=C the dotted line means a bond and is absent in the rest of the cases; R<3> is phenyl, naphthyl, heteroaryl, substituted phenyl, substituted naphthyl or substituted heteroaryl wherein each substituent is independently selected from halogen, alkoxy-group with 1 to 6 carbon atoms , alkyl with 1 to 6 carbon atoms, cyano-group, trifluoromethyl or sulphonamido-group; and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof. 2. A compound of claim 1 wherein the group   is attached to the benzoxazinone group at the 6 or 7 position. 3. A compound of claim 1 wherein R<1> and R<2> are hydrogen. 4. A compound of claim 1 wherein R<3> is phenyl, methyltolyl, tolyl or sulfonamido-group. 5. A compound of claim 1 wherein X is N. 6. A compound of claim 1 wherein wherein X is N or CH; dotted line is absent; R<1> is hydrogen; and R<2> is hydrogen or methyl; R<3> is phenyl or substituted phenyl wherein each substituent is independently selected from alkyl with 1 to 6 carbon atoms, or sulphonamido-group. 7. A compound of claim 1 wherein the group,   is attached to the benzoxazinone group at the 6 or 7 position and wherein X is N or CH; dotted line is absent; R<1> is hydrogen; and R<2> is hydrogen or methyl; R<3> is phenyl or substituted phenyl wherein each substituent is independently selected from alkyl with 1 to 6 carbon atoms, or sulphonamido-group. 8. A compound of claim 1 wherein X is N or CH; dotted line is absent; R<1> and R<2> is hydrogen; R<3> is phenyl or substituted phenyl wherein each substituent is independently selected from alkyl with 1 to 6 carbon atoms, or sulphonamido-group. 9. A compound of claim 1 wherein X is N or CH; dotted line is absent; R<1> is hydrogen; and R<2> is hydrogen or methyl; R<3> is phenyl, methyltolyl, tolyl, or sulfonamido-group. 10. A compound of claim 1 wherein the compound is 4-[4-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-piperazin-1-yl]-benzenesulfonamide; 6-[4-(3,4-dimethyl-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-(4-p-tolyl-piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one; 6-[4-phenyl-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 7-(4-p-tolyl-piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one; 7-(4-phenyl-piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one; 7-[4-(3,4-dimethyl-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-[4-(5-methyl-pyridin-2-yl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-(4-p-tolyl-piperidin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one; 6-[4-(3,4-dimethyl-phenyl)-piperidin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-(4-thiazol-2-yl-piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one; 6-(4-benzothiazol-2-yl-piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one; 6-[4-(4,5-dimethyl-thiazol-2-yl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-(4-naphthalene-2-yl-piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one; 6-[4-(3-chloro-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-[4-(3,4-dichloro-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 2-[4-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-piperazin-1-yl]-benzonitrile; 6-[4-(4-methoxy-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; or 6-[4-(2-chloro-4-methyl-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one. 11. A compound of claim 1 wherein the compound is 6-[4-(4-fluoro-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-[4-(3-trifluoromethyl-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-[4-(3,5-dimethyl-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-[4-(2-chloro-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-[4-(4-trifluoromethyl-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-[4-(4-chloro-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 7-[4-(5-methyl-pyridin-2-yl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 7-[4-(4-methoxy-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 7-[4-(4-chloro-phenyl)-piperazin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 7-[4-(3,4-dimethyl-phenyl)-piperidin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 6-[4-(4-methoxy-phenyl)-piperidin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 7-[4-(4-methoxy-phenyl)-piperidin-1-ylmethyl]-4H-benzo[1,4]oxazin-3-one; 7-(4-phenyl-piperidin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one; 7-(4-naphthalene-2-yl-piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one; and 7-(4-p-tolyl-piperidin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one. 12. A method of treating psychosis or schizophrenia comprising administering to a patient suffering therefrom a therapeutically effective amount of a compound of claim 1. 13. A pharmaceutically acceptable composition that comprises a compound of claim 1.