Patent EA-001311-B1 (EA)
Title: Pyrimidine derivatives as 5-ht2c-receptor antagonists
Inventor: FLIPPIN LEE ALLEN
IPC: C07D239/80
Filed: 1996-09-19
Abstract: 1. A compound of the formula   wherein: R<1>, R<2>, R<3>, R<4>, and R<5> are independently hydrogen, C1-C8alkyl, C1-C8alkoxy, halogen, or trifluoromethyl; X is oxygen, sulfur, NR<7>, or CH2; Y is NR<7>; in which R<7> is hydrogen or C1-C8alkyl; and R<6> is C1-C8alkyl or optionally substituted aryl which means a monocyclic or bicyclic aromatic ring, such as phenyl, naphthyl, thiophene, furan, imidazole, pyridine, pyrimidine or indole, which may substituted with a substituent selected from the group consisting of C1-C8alkyl, C1-C8alkoxy, hydroxy, nitro, trifluoromethyl and halogen; and the pharmaceutically acceptable acid addition salts thereof. 2. A compound of claim 1, wherein X is CH2, or a pharmaceutically acceptable salt thereof. 3. A compound of claim 2, wherein R<5> is hydrogen and R<6> is optionally substituted aryl, or a pharmaceutically acceptable salt thereof. 4. A compound of claim 3, wherein R<7> is hydrogen, or a pharmaceutically acceptable salt thereof. 5. A compound of claim 4, wherein R<1>, R<2>, R<3>, and R<4> are independently hydrogen or C1-C8alkoxy, or a pharmaceutically acceptable salt thereof. 6. A compound of claim 5, wherein R<1>, R<2>, and R<3> are hydrogen, and R<4> is C1-C8alkoxy, or a pharmaceutically acceptable salt thereof. 7. A compound of claim 6, wherein R<6> is phenyl optionally mono-, di-, or trisubstituted by C1-C8alkoxy group, or a pharmaceutically acceptable salt thereof. 8. A compound of claim 7 selected from the following group consisting of: 7-methoxy-2-(3,4,5-trimethoxyanilino)-5,6-dihydrobenzo[h]-quinazoline, 7-methoxy-2-(3,4,5-triethoxyanilino)-5,6-dihydrobenzo[h]-quinazoline and 7-methoxy-2-(3,5-dimethoxy-4-ethoxyanilino)-5,6-dihydrobenzo[h]quinazoline, or a pharmaceutically acceptable salt thereof. 9. A compound of claim 1, wherein R<6> is indole optionally mono-, di-, or trisubstituted by C1-C8alkyl, or a pharmaceutically acceptable salt thereof. 10. The compound of claim 9, wherein R<6> is 1-methyl-1H-indol-5-yl, namely 7-methoxy-2-[(1-methyl-1H-indol-5-yl)amino]-5,6-dihydrobenzo[h]quinazoline, or a pharmaceutically acceptable salt thereof. 11. A medicament comprising a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, in admixture with one or more pharmaceutically acceptable non-toxic carriers for the treatment of diseases. 12. A medicament according to claim 11 for the treatment of diseases based on therapeutic indications for 5-HT2C-receptor antagonists, such as generalized anxiety disorder, panic disorder, obsessive compulsive disorder, alcoholism, depression, migraine, sleep disorder, anorexia nervosa and priapism. 13. A process for preparing a compound of formula I or a pharmaceutically acceptable salt thereof as defined in claim 1, which process comprises reacting a compound of the formula (5) or (5a):                         wherein R<1>-R<5> and X are as defined above in claim 1, with an anion of a compound of formula R<6>YH, where R<6> is C1-C8alkyl or optionally substituted aryl as defined in claim 1, and Y is NR<7>, in which R<7> is hydrogen or C1-C8alkyl, further isolation of received compound in free form or converting a compound into a pharmaceutically usable acid addition salt. 14. A process for preparing a compound of formula I or a pharmaceutically acceptable salt thereof as defined in claim 1, which process comprises reacting a compound of the formula (4)   wherein R<1>-R<5> and X are as defined above in claim 1, with a compound of formula R<6>YC(NH)NH2 (7), where R<6> and Y are as defined above in claim 13, and, if desired, received in free form compound of formula I is converted into a pharmaceutically usable acid addition salt. 15. The use of a compound in accordance with any one of claims 1-10 for the treatment of diseases based on therapeutic indications for 5-HT2C-receptor antagonists, which include generalized anxienty disorder, panic disorder, obsessive compulsive disorder, alcoholism, depression, migraine, sleep disorder, anorexia nervosa and priapism or for the manufacture of a medicament containing such a compound.  16. A method for the treatment of diseases based on therapeutic indications for 5-HT2C-receptor antagonists in a patient suffering from said diseases by administering to said patient a medicament comprising a pharmaceutically acceptable compound or formula I as defined in claim 1 and a pharmaceutically acceptable carrier wherein said compound is present in said medicament in an amount sufficient to treat said diseases.