Aryldifluoromethylphosphonic acids for treatment of diabetes

A compound represented by formula I:

• 40
• or a pharmaceutically acceptable salt or prodrug thereof, wherein:
• X1 is selected from the group consisting of:
• halogen, CN, CO2H, CO2C1-6alkyl, CO2C2-6alkenyl, OC1-6alkyl, OC2-6alkenyl, C(O)C1-6alkyl, C(O)C2-6alkenyl, OC(O)C1-6alkyl, OC(O)C2-6alkenyl, C1-6alkyl, C2-6alkenyl, S(O)2NR1R2, C(O)NR1R2, and NR1R2, wherein each alkyl group and each alkenyl group in each substituent is optionally substituted with 1-7 groups independently selected from (a) 1-5 halogen atoms and (b) 1-2 substituents independently selected from OC1-3alkyl, C(O)C1-3alkyl, OC(O)C1-3alkyl, CO2H, and CO2C1-3alkyl;
• X2 is selected from the group consisting of:
• H, OH, halogen, CN, CO2H, CO2C1-6alkyl, CO2C2-6alkenyl, OC1-6alkyl, OC2-6alkenyl, C(O)C1-6alkyl, C(O)C2-6alkenyl, OC(O)C1-6alkyl, OC(O)C2-6alkenyl, C1-6alkyl, C2-6alkenyl, S(O)2NR1R2, C(O)NR1R2, and NR1R2, wherein each alkyl group and each alkenyl group in each substituent is optionally substituted with 1-7 groups independently selected from (a) 1-5 halogen atoms and (b) 1-2 substituents independently selected from OC1-3alkyl, C(O)C1-3alkyl, OC(O)C1-3alkyl, CO2H, and CO2C1-3alkyl;
• R1 and R2 are each independently selected from the group consisting of H and C1-6alkyl, wherein said alkyl substituents are optionally substituted with 1-5 halogen atoms;
• Alkyl, alkenyl, alkadienyl and alkynyl are linear or branched hydrocarbon structures, except where otherwise defined, containing the indicated number of carbon atoms and being substituted as indicated;
• X1, X2, CF2P(O)(OH)2 and Y—O—R are each substituted onto any position of the aromatic ring;
• Y is a C1-4alkylene group, wherein said alkylene group is linear and optionally has one double bond or one triple bond connecting two adjacent carbon atoms, wherein each carbon of said C-1-4alkylene group independently may have one optional substituent independently selected from the group consisting of C1-4alkyl, C2-4alkenyl, C2-4alkynyl, and halogen, said C1-4alkyl, C2-4alkenyl, and C2-4alkynyl substituents being optionally substituted with 1-3 halogens;
• R is selected from H, C1-6alkyl, and an aromatic group selected from phenyl, naphthyl, and biphenyl, wherein C1-6alkyl is linear and optionally has one double bond, one triple bond or one S atom connecting two adjacent carbon atoms, wherein each carbon of said C1-6alkyl group independently may have one optional substituent selected from the group consisting of C1-4alkyl, C2-4alkenyl, C2-4alkynyl, halogen, phenyl, naphthyl, biphenyl and phthalimide, said C1-4alkyl, C2-4alkenyl, and C2-4alkynyl substituents being optionally substituted with 1-4 substituents independently selected from 1-3 halogens and one aromatic group selected from phenyl, naphthyl, and biphenyl, wherein R comprises 0-2 aromatic substituents, wherein said aromatic substituents optionally may be substituted onto the same carbon atom of alkyl, alkenyl and alkynyl when there are two aromatic substituents, and wherein said 0-2 aromatic groups that are substituents on R when R is C1-6 alkyl are optionally substituted with 1-5 substituents independently selected from halogen, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, OC1-4alkyl, OC2-4alkenyl, OC2-4alkynyl, phenoxy, CO2H, CO2C1-4alkyl, SC1-4alkyl, S(O)C1-4alkyl, S(O)2C1-4alkyl, NO2 and CN, wherein said alkyl, alkenyl, alkynyl, Oalkyl, Oalkenyl, Oalkynyl and phenoxy substituents are optionally substituted with 1-5 halogens, and wherein when R is an aromatic group, said aromatic group is optionally substituted with 1-5 substituents selected from halogen, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, OC1-4alkyl, OC2-4alkenyl, OC2-4alkynyl, phenoxy, CO2H, CO2C1-4alkyl, SC1-4alkyl, S(O)C1-4alkyl, S(O)2C1-4alkyl, NO2 and CN, wherein said alkyl, alkenyl, alkynyl, Oalkyl, Oalkenyl, Oalkynyl and phenoxy substituents are optionally substituted with 1-5 halogens.