Claims for Patent: RE46791

Summary for Patent: RE46791

Title:	Substituted dihydroquinazolines
Abstract:	The invention relates to substituted dihydroquinazolines and to processes for their preparation and also to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular for use as antiviral agents, in particular against cytomegalo viruses.
Inventor(s):	Tobias Wunberg, Judith Baumeister, Ulrich Betz, Mario Jeske, Thomas Lampe, Susanne Nikolic, Jurgen Reefschlager, Rudolf Schohe-Loop, Frank Sussmeier, Holger Zimmermann, Rolf Grosser, Kerstin Henninger, Guy Hewlett, Jorg Keldenich, Dieter Lang, Peter Nell
Assignee:	AIC246 AG and Co KG
Application Number:	US14/682,512
Patent Claims:	1. A compound of the formula in which Ar represents aryl which may be substituted by 1 to 3 substituents, where the substituents are selected independently of one another from the group consisting of alkyl, alkoxy, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl, amino, alkylamino, aminocarbonyl and nitro, where alkyl may be substituted by 1 to 3 substituents, where the substituents are selected independently of one another from the group consisting of halogen, amino, alkylamino, hydroxyl and aryl, R1 represents hydrogen, amino, alkyl, alkoxy, alkylamino, alkylthio, cyano, halogen, nitro or trifluoromethyl, R2 represents hydrogen, alkyl, alkoxy, alkylthio, cyano, halogen, nitro or trifluoromethyl, R3 represents amino, alkyl, alkoxy, alkylamino, alkylthio, cyano, halogen, nitro, trifluoromethyl, alkylsulphonyl or alkylaminosulphonyl R4 represents hydrogen or alkyl, R5 represents hydrogen or alkyl or the radicals R4 and R5 are attached to carbon atoms directly opposing each other in the piperazine ring and form a methylene bridge which is optionally substituted by 1 or 2 methyl groups, R6 represents alkyl, alkoxy, alkylthio, formyl, carboxyl, aminocarbonyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl or nitro, R7 represents hydrogen, alkyl, alkoxy, alkylthio, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl or nitro, and R8 represents hydrogen, alkyl, alkoxy, alkylthio, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl or nitro, wherein R1 is attached to the phenyl ring via the position ortho to the point of attachment of the phenyl ring, or a salt, solvate, or solvate of a salt thereof. 2. A compound according to claim 1, wherein Ar represents phenyl which may be substituted by 1 to 3 substituents, where the substituents are selected independently of one another from the group consisting of C1-C6-alkyl, C1-C6-alkoxy, carboxyl, C1-C6-alkylcarbonyl, C1-C6-alkoxycarbonyl, trifluoromethyl, fluorine, chlorine, bromine, cyano, hydroxyl, amino, C1-C6-alkylamino and nitro, R1 represents hydrogen, C1-C3-alkyl, C1-C3-alkoxy, C1-C3-alkylthio, fluorine or chlorine, R2 represents hydrogen, C1-C3-alkyl, C1-C3-alkoxy, C1-C3-alkylthio, fluorine or chlorine, R3 represents C1-C4-alkyl, cyano, fluorine, chlorine, nitro, trifluoromethyl or C1-C3-alkylsulphonyl, R4 represents hydrogen or methyl, R5 represents hydrogen, R6 represents C1-C3-alkyl, C1-C3-alkoxy, carboxyl, aminocarbonyl, trifluoromethyl, fluorine, chlorine, cyano, hydroxyl or nitro, R7 represents hydrogen, C1-C3-alkyl, C1-C3-alkoxy, fluorine, chlorine, cyano or hydroxyl and R8 represents hydrogen, C1-C3-alkyl, C1-C3-alkoxy, fluorine, chlorine, cyano or hydroxyl. 3. A compound according to claim 1 wherein Ar represents phenyl which may be substituted by 1 or 2 substituents, where the substituents are selected independently of one another from the group consisting of methyl, methoxy, fluorine and chlorine, R1 represents hydrogen, methyl, methoxy, methylthio, fluorine or chlorine, R2 represents hydrogen, R3 represents methyl, isopropyl, tert-butyl, cyano, fluorine, chlorine, nitro or trifluoromethyl, R4 represents hydrogen, R5 represents hydrogen, R6 represents aminocarbonyl, fluorine, chlorine, cyano or hydroxyl, R7 represents hydrogen and R8 represents hydrogen, fluorine or chlorine. 4. A compound according to claim 1, wherein R1 represents hydrogen, methyl, methoxy or fluorine. 5. A compound according to claim 1, wherein R1 represents methoxy. 6. A compound according to claim 1, wherein R1 is attached to the phenyl ring via the position ortho to the point of attachment of the phenyl ring. 7. A compound according to claim 1, wherein R2 represents hydrogen. 8. A compound according to claim 1, wherein R3 represents trifluoromethyl, chlorine, methyl, isopropyl or tert-butyl. 9. A compound according to claim 1, wherein R3 represents trifluoromethyl, chlorine or methyl. 10. A compound according to claim 1, wherein R1 is attached to the phenyl ring via the position ortho to the point of attachment of the phenyl ring and R3 is attached to the phenyl ring via the position meta to the point of attachment of the phenyl ring, which position is opposite to that of R1. 11. A compound according to claim 1, wherein R4 and R5 represent hydrogen. 12. A compound according to claim 1, wherein R6 represents fluorine. 13. A compound according to claim 1, wherein R7 represents hydrogen. 14. A compound according to claim 1, wherein R8 represents hydrogen, methyl or fluorine. 15. A compound according to claim 1, wherein Ar represents phenyl which may be substituted by 1 or 2 substituents, where the substituents are selected independently of one another from the group consisting of methyl, methoxy, fluorine and chlorine. 16. A process for preparing a compound of the formula (I) according to claim 1, wherein or a salt, solvate, or solvate of a salt thereof in which Ar represents aryl which may be substituted by 1 to 3 substituents, where the substituents are selected independently of one another from the group consisting of alkyl, alkoxy, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl, amino, alkylamino, aminocarbonyl and nitro, where alkyl may be substituted by 1 to 3 substituents, where the substituents are selected independently of one another from the group consisting of halogen, amino, alkylamino, hydroxyl and aryl, R1 represents hydrogen, amino, alkyl, alkoxy, alkylamino, alkylthio, cyano, halogen, nitro or trifluoromethyl, R2 represents hydrogen, alkyl, alkoxy, alkylthio, cyano, halogen, nitro or trifluoromethyl, R3 represents amino, alkyl, alkoxy, alkylamino, alkylthio, cyano, halogen, nitro, trifluoromethyl, alkylsulphonyl or alkylaminosulphonyl R4 represents hydrogen or alkyl, R5 represents hydrogen or alkyl or the radicals R4 and R5 are attached to carbon atoms directly opposing each other in the piperazine ring and form a methylene bridge which is optionally substituted by 1 or 2 methyl groups, R6 represents alkyl, alkoxy, alkylthio, formyl, carboxyl, aminocarbonyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl or nitro, R7 represents hydrogen, alkyl, alkoxy, alkylthio, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl or nitro, and R8 represents hydrogen, alkyl, alkoxy, alkylthio, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl or nitro, said process comprising: reacting a compound of the formula II in which Ar, R1, R2, R3, R4, R5, R6, R7 and R8 are as defined in claim 1 and R9 represents alkyl selected from the group consisting of methyl, ethyl, and tert-butyl, is reacted with a base or an acid. 17. A medicament comprising a compound according to claim 1 in combination with an inert non-toxic pharmaceutically acceptable auxiliary. 18. A method for treating infection by Herpes viridae in humans and animals by administering an antivirally effective amount of at least one compound according to claim 1, or a medicament according to claim 17. 19. The method according to claim 18, wherein the Heprpes Herpes viridae is selected form the group consisting of cytomegalovirus a cytomegalovirus (CMV) and human cytomegalovirus (HCMV) or another representative of the group of the Herpes viridae. 20. The method according to claim 18, wherein the Herpes viridae is human cytomegalovirus (HCMV). 21. A method for treating infection by HCMV in humans by administering an antiviral effective amount of the compound: or a physiologically acceptable salt thereof. 22. The method according to claim 21, wherein said compound is: or a physiologically acceptable salt thereof. 23. The compound of claim 1, wherein said compound is: or a physiologically acceptable salt thereof. 24. The compound of claim 1, wherein said compound is: 25. The compound of claim 1, wherein said compound is a physiologically acceptable salt of: 26. The compound of claim 1, wherein said compound is: or a physiologically acceptable salt thereof. 27. The compound of claim 1, wherein said compound is: 28. The compound of claim 1, wherein said compound is a physiologically acceptable salt of the compound: 29. The compound of claim 1, wherein said compound is of the formula: wherein R1, R2, R3, R4, R5, R7, R8, and Ar are as defined in claim 6, and R6 is fluorine; or a physiologically acceptable salt thereof. 30. The compound of claim 3, wherein said compound is of the formula: wherein R1, R2, R3, R4, R5, R7, R8, and Ar are as defined in claim 3, and R6 is fluorine; or a physiologically acceptable salt thereof. 31. The medicament of claim 17, wherein said compound is: or a physiologically acceptable salt thereof. 32. The medicament of claim 17, wherein said compound is: or a physiologically acceptable salt thereof. 33. The compound of claim 1, which is the compound of formula (I) or a physiologically acceptable salt thereof. 34. A compound according to claim 1, wherein R6 represents alkoxy, alkylthio, formyl, carboxyl, aminocarbonyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl or nitro. 35. A compound according to claim 30, wherein R1 is methoxy. 36. A compound according to claim 30, wherein R3 is trifluoromethyl, chlorine or methyl. 37. A compound according to claim 36, wherein R3 is trifluoromethyl. 38. A compound according to claim 30, wherein R8 is hydrogen. 39. A compound according to claim 30, wherein R1 is methoxy and wherein R3 is trifluoromethyl, chlorine or methyl. 40. A compound according to claim 30, wherein R3 is trifluoromethyl and is attached to the phenyl ring via the position meta to the point of attachment of the phenyl ring, which position is opposite to that of R1. 41. A compound according to claim 26, having an enantiomeric excess of more than 90%. 42. A compound according to claim 27, having an enantiomeric excess of more than 90%. 43. A compound according to claim 28, having an enantiomeric excess of more than 90%. 44. A compound according to claim 2, wherein R6 represents C1-C3-alkoxy, carboxyl, aminocarbonyl, trifluoromethyl, fluorine, chlorine, cyano, hydroxyl or nitro.