Claims for Patent: 6,812,238

Summary for Patent: 6,812,238

Title:	N-substituted carbamoyloxyalkyl-azolium derivatives
Abstract:	N-substituted carbamoyloxyalkyl-azolium derivatives which have antifungal activity and are useful for the treatment of fungal diseases.
Inventor(s):	Hiroshi Fukuda, Tadakatsu Hayase, Eisaku Mizuguchi, Nobuo Shimma, Jun Ohwada, Nobuhiro Oikawa, Masahiro Sakaitani, Masao Tsukazaki, Isao Umeda
Assignee:	Basilea Pharmaceutica International AG
Application Number:	US09/702,944
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,812,238
Patent Claims:	1. A compound of the formula (I), wherein Q is a 3-[4-(4-cyanophenyl)thiazol-2-yl)]-2-(2,5-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-butan-2-ol moiety which is linked to the remainder of the compound of formula (I) by a nitrogen in the triazole; R1 is hydrogen or alkyl; R2 is hydrogen, alkyl, alkylcarbonyloxyalkyl, alkoxycarbonyl, alkylcarbonyl, mono- or dialkylaminoalkylcarbonyloxyalkyl; R3 is pyridin-2-yl or substituted pyridin-2-yl; and X− is a pharmaceutically acceptable anion, wherein when R3 is substituted pyridin-2-yl, the substituent is selected from the group consisting of halogen, alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, carboxy, alkyloxycarbonyl, cyano, trifluoromethyl, trifluoromethoxy, nitro, aminosulfonyl, alkylaminocarboyloxyalkyl, sulfo, alkylcarbonyloxyalkyl and aminoalkylcarbonyloxyalkyl; or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1 wherein R3 is substituted pyridin-2-yl. 3. The Compound of claim 2 having formula (II), wherein is pyridin-2-yl; R4 and R5 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, carboxy, alkyloxycarbonyl, cyano, trifluoromethyl, trifluoromethoxy nitro, aminosulfonyl, alkylaminocarboyloxyalkyl, sulfo, alkylcarbonyloxyalkyl and aminoalkylcarbonyloxyalkyl; and R6 is hydroxy, alkoxycarbonylalkylamino, alkoxycarbonylamino, amino, alkylamino, alkylcarbonyloxy, alkoxycarbonylalkylaminoalkylcarbonyloxy, alkoxycarbonylamino-alkylcarbonyloxy, alkylaminoalkylcarbonyloxy, aminoalkylcarbonyloxy, alkylcarbonylamino, alkylcarbonylalkylamino, acyloxy, acylamino, acylalkylamino wherein said acyl group is a hydrolizable radical. 4. Compounds of claim 3 having formula (III), wherein R4 and R5 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, carboxy, alkyloxycarbonyl, cyano, trifluoromethyl, trifluoromethoxy, nitro, aminosulfonyl or sulfo; and R6 is hydroxy, alkoxycarbonylalkylamino, alkoxycarbonylamino, amino, alkylamino, alkylcarbonyloxy, alkoxycarbonylalkylaminoalkylcarbonyloxy, alkoxycarbonylamino-alkylcarbonyloxy, alkylaminoalkylcarbonyloxy, aminoalkylcarbonyloxy, alkylcarbonylamino, alkylcarbonylalkylamino, acyloxy, acylamino, acylalkylamino wherein said acyl is a hydrolizable radical. 5. The compound of claim 4 wherein R4 and R5 are independently selected from the group consisting of hydrogen, halogen, alkoxy, cyano, trifluoromethyl, trifluoromethoxy and nitro. 6. The compound of claim 5 wherein R4 and R5 are independently selected from the group consisting of hydrogen, halogen and alkoxy. 7. The compound of claim 4 wherein R4 and R5 are hydrogen. 8. The compound of claim 4 wherein R6 is alkylamino, alkylcarbonyloxy, alkylaminoalkylcarbonyloxy or aminoalkylcarbonyloxy. 9. The compound of claim 8 wherein R6 is alkylaminoalkylcarbonyloxy. 10. The compound of claim 1 wherein R1 is hydrogen or alkyl. 11. The compound of claim 10 wherein R1 is methyl. 12. The compound of claim 1 wherein R2 is hydrogen or alkyl. 13. The compound of claim 12 wherein R2 is alkyl. 14. The compound of claim 1 wherein X is a halogen. 15. The compound of claim 14 wherein X is chloro. 16. A compound selected from the group consisting of 1-[[N-methyl-N-3-[(methylamino)acetoxyethyl]pyridin-2-yl]carbamoyloxy]ethyl-1-[(2R,3R)-2-(2,5-difluorophenyl)-2-hydroxy-3-[4-(4-cyanophenyl)thiazol-2-yl]butyl]-1H-[1,2,4]triazol-4-ium chloride dihydrochloride, 1-[[N-methyl-N-3-[(methylamino)acetoxymethyl]pyridin-2-yl]carbamoyloxy]ethyl-1-[(2R,3R)-2-(2,5-difluorophenyl)-2-hydroxy-3-[4-(4-cyanophenyl)thiazol-2-yl]butyl]-1H-[1,2,4]triazol-4-ium chloride hydrochloride, or 1-[[N-methyl-N-3-(acetoxymethyl)pyridin-2-yl]carbamoyloxy]ethyl-1-[(2R,3R)-2-(2,5-difluorophenyl)-2-hydroxy-3-[4-(4-cyanophenyl)thiazol-2-yl]butyl]-1H-[1,2,4]triazol-4-ium chloride hydrochloride. 17. A compound which is 1-[[N-methyl-N-3-[(methylamino)acetoxymethyl]pyridin-2-yl]carbamoyloxy]ethyl-1-[(2R,3R)-2-(2,5-difluorophenyl)-2-hydroxy-3-[4-(4-cyanophenyl)thiazol-2-yl]butyl]-1H-[1,2,4]triazol-4-ium chloride hydrochloride. 18. An pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier. 19. A method of treating fungal infections comprising administering to the infected organism an effective amount of a compound of claim 1.