Water soluble prodrugs of azole compounds
AssigneeBristol-Myers Squibb Company
InventorsYasutsugu Ueda, John D. Matiskella, Jerzy Golik, Thomas W. Hudyma, Chung-Pin Chen
Life of this patent
Estimating the term…
Abstract
Water-soluble prodrugs of triazole antifungal compounds having a secondary or tertiary hydroxy group are provided. More particularly, new water-soluble triazole antifungal compounds are provided having the general formula 1 wherein A is the non-hydroxy portion of a triazole antifungal compound of the type containing a secondary or tertiary hydroxyl group and R and R1 are as defined in the specification.
Claims20
A compound of the formula
- 23
- wherein A is the non-hydroxy portion of a triazole antifungal compound of the type containing a secondary or tertiary hydroxy group, and R and R1 are each independently hydrogen or (C1-C6)alkyl, or a pharmaceutically acceptable salt thereof.
The compound named (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-[(dihydrogen phosphonoxy)methoxy]butane, or a pharmaceutically acceptable salt thereof.
The crystalline bis lysine salt of (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-[(dihydrogen phenoxy)methoxy]butane.
The crystalline tertiary-butylamine salt of (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-[(dihydrogen phenoxy)methoxy]butane.
A compound of the formula
- 26
- wherein B is the non-hydroxy portion of a triazole antifungal compound of the type containing a secondary hydroxy group, and R and R1 can each independently be hydrogen or (C1-C6)alkyl, or a pharmaceutically acceptable salt thereof.
A process for the preparation of a water-soluble prodrug of the formula
- 28
- wherein A is the non-hydroxy portion of a triazole antifungal compound of the type containing a secondary or tertiary hydroxy group, R and R1 are each independently hydrogen or (C1-C6)alkyl, or a pharmaceutically acceptable salt thereof, which comprises
- (a) reacting a compound of the formula A—OH wherein A is the non-hydroxy portion of a triazole antifungal compound of the type containing a secondary or tertiary hydroxy group with a compound of the formula
- 29
- in which R and R1 are as defined above and Pr represents a hydroxyl-protecting group in an inert organic solvent in the presence of base at a temperature of from about 25° C. to 50° C. to form an intermediate of the formula
- 30
- wherein Pr, A, R and R1 are as defined above, and
- (b) removing the protecting groups Pr by conventional means to produce a compound of the formula
- 31
- and, if desired, converting said compound I by conventional means to a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.