Phosphonic acid derivatives as inhibitors of protein tyrosine phosphatase 1B (PTP-1B)

A compound represented by formula I:

• 48
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 and R2 are selected from the group consisting of:
• C1-10alkyl(Ra)0-7, C2-10alkenyl(Ra)0-7, Aryl(Ra)0-3 and Het(Ra)0-3;
• wherein, each Ra independently represents a member selected from the group consisting of. Aryl, OH, CN, halogen, CO2H, CO2C1-6alkyl, OC1-6alkyl, C1-6alkyl, OC1-10alkyleneCO2H, OAryl, C0-6alkyleneSO3H, C0-6alkyleneCO2H, C0-6alkyleneCO2C1-6alkyl, C0-6alkyleneCO2C2-6alkenyl, C0-6alkyleneC(O)C1-6alkyl, C(O)NR3′R4′, NR3′R4′, C1-6haloalkyl, OC1-6haloalkyl, S(O)yC1-6alkyl, S(O)yNR3′R4′, and Het, wherein y is 0, 1, or 2, wherein Het, Aryl, alkyl, and alkenyl in Ra are optionally substituted with 1-3 substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, CO2H, CO2C1-6alkyl, OC1-10alkyl, OH, Het and Aryl, where said Het and Aryl are optionally substituted with 1-2 substituents independently selected from halogen, C1-3alkyl, OC1-3alkyl, CF3, and OCF3;
• Aryl is a 6-14 membered carbocyclic aromatic ring system comprising 1-3 phenyl rings, wherein said rings are fused together so that adjacent rings share a common side when there is more than one aromatic ring;
• Het represents a 5-10 membered aromatic ring system comprising one ring or two fused rings, 1-4 heteroatoms, 0-4 of which are N atoms and 0-2 of which are O or S(O)y wherein y is 0-2, and 0-2 carbonyl groups;
• y, Z1 and Z2 each independently represents —(CR3R4)a—X—(CR3R4)b—wherein a and b are either 0 or 1, such that the sum of a and b equals 0, 1 or 2;
• X represents a bond, O, S(O)y, NR3′, C(O), OC(O), C(O)O, C(O)NR3′, NR3′C(O) or —CH═CH—, where y is as previously defined;
• R3 and R4 are independently H, halo, C1-3alkyl, or C1-3haloalkyl;
• each R3′ is independently selected from the group consisting of:
• H, C1-6alkyl, C1-6haloalkyl, OH, C(O)C1-6alkyl, C(O)Aryl, C(O)Het, C(O)C1-6 haloalkyl, Aryl and Het;
• each R4′ is independently selected from the group consisting of:
• H, C1-6alkyl, C1-6haloalkyl, Aryl and Het;
• and
• each W1 is independently selected from the group consisting of:
• H, OH, CN, halogen, OC1-6alkyl(Ra)0-3, S(O)yC1-6alkyl(Ra)0-3, with y equal to 0-2, S(O)3H, C1-6alkyl(Ra)0-3, C1-6haloalkyl(Ra)0-3, CO2H, CO2C1-6alkyl(Ra)0-3, CO2C1-6haloalkyl(Ra)0-3, CO2C2-6alkenyl(Ra)0-3, C(O)C1-6alkyl(Ra)0-3, C(O)NR3′R4′, S(O)yNR3′R4′, NR3′R4′, Aryl and Het, wherein R3′ and R4′ are as defined above, and wherein Aryl and Het may be unsubstituted or are optionally substituted with 1-3 substituents independently selected from the group consisting of halogen, C1-6alkyl, C1-6haloalkyl, CO2H, CO2C1-6alkyl, OC1-6alkyl, OC1-6haloalkyl, and OH;
• or the two W1 groups are on adjacent positions of the aromatic ring and are taken in combination to represent a fused phenyl ring.