Patent ID: 6365592
Filing Date: 2002-04-02
Classification: A61K,C07K

Abstract:
A compound represented by formula I: or a pharmaceutically acceptable salt or hydrate thereof wherein:at least one of B1a, B1b, B2a and B2b represents CF2â€”PO3H2 or CF2â€”CO2H, at least one of B1a, B1b, B2a and B2b represents H, and the others are selected from the group consisting of: R4, OH, halo, CHF2, CF3, CHFâ€”CO2H, CF2â€”CO2H, CF2â€”C(R5)(R6)OH, CHFâ€”PO3H2, CH2â€”PO3H2, C(R5)(R6)OH, S(O)yR5, wherein y is 0, 1 or 2, S(O)2NR5R6, CFHSO3H,CF2SO3H, CFHS(O)2NR5R6, CF2S(O)2 NR5R6, NR6S(O)2R5, CFH-Hetcy, CF2-Hetcy, CH2S(O)2-Hetcy, CFHS(O)2-Hetcy, CF2S(O)2-Hetcy, CH2S-Hetcy, CFHS-Hetcy, CF2S-Hetcy, OC(R5)(R6)F, C(R5)(R6)F, Oâ€”CF2CO2R4, Oâ€”CH2CO2R4, C(R5)(R6)CO2R4, CO2R4, CFH-aryl, CF2-aryl, CH2S(O)2-aryl, CFHS(O)2-aryl, CF2S(O)2-aryl, CH2S-aryl, CFHS-aryl and CF2S-aryl; such that when one of B1a and B1b represents CF2â€”CO2H, at least one of B2a and B2b represents CF2â€”PO3H2 or CF2â€”CO2H, and when one of B2a and B2b represents CF2â€”CO2H, at least one of B1a and B1b represents CF2â€”PO3H2 or CF2â€”CO2H; Hetcy is selected from the group consisting of: (a) a 5-15 membered heteroaryl group containing 1-4 heteroatoms selected from O, S(O)y and N, wherein y is as defined above, and 0-2 carbonyl groups, optionally substituted with 1-4 members selected from Ra; and (b) a non-aromatic carbocyclic structure containing 5-15 carbon atoms, interrupted by 1-4 heteroatoms selected from O, S(O)y wherein y is as previously defined, and N, and optionally containing 1-2 carbonyl groups, and optionally substituted with 1-4 members selected from Ra; aryl is a 6-10 membered aromatic ring system that is optionally substituted with 1-4 members selected from Ra; each Ra is independently selected from the group consisting of: halo, NO2, N3, OH, CN, C(O)NH2, C(O)NHC1-3alkyl, C(O)N(C1-3alkyl)2, CO2H, CO2â€”C1-10alkyl, C1-10alkyl, C1-10 haloalkyl, C1-10haloalkoxy, C1-10alkoxy, C1-10alkylthio, C1-10 alkylsulfinyl, C1-10alkylsulfonyl, phenylsulfonyl and phenyl; X is OH or NH2, Y is selected from the group consisting of: H, C1-6alkyl, R1ZCOâ€”, R2â€” and R3S(O)2â€”; Z represents a bond or is selected from O, S(O)yCH2, NR4 or CH&boxH;CH; R4 represents H, C1-6alkyl, Hetcy or aryl, said alkyl, Hetcy and aryl being optionally substituted with 1-3 members selected from Ra; R1 is selected from the group consisting of: (a) C1-10alkyl; (b) C1-6fluoroalkyl, optionally substituted with a hydroxy group; (c) aryl optionally substituted with 1-3 substituents selected from Ra; (d) heteroaryl, said heteroaryl group being a monocyclic aromatic ring of 5 atoms, said ring having one heteroatom which is O, S or N, and optionally 1, 2, or 3 additional N atoms; or a monocyclic ring of 6 atoms, said ring having one heteroatom which is O, S or N, and optionally 1, 2, or 3 additional N atoms, said heteroaryl group being optionally substituted with from 1-3 substituents selected from Ra; (e) benzoheterocycle in which the heterocycle is a 5, 6, or 7-membered ring containing 1 or 2 heteroatoms selected from O, S and N, optionally containing a carbonyl, sulfinyl or sulfonyl group; said benzoheterocycle being optionally substituted with 1-3 substituents selected from Ra; (f) a heterocycloalkyl group of 5, 6 or 7 members which contains 1 or 2 heteroatoms selected from O, S and N, and optionally containing a carbonyl group or a sulfonyl group; (g) a benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, optionally substituted with 1-2 substituents selected from Ra; (h) a bicyclic heteroaryl group having 8, 9 or 10 members, containing 1 to 5 heteroatoms selected from O, S and N, optionally substituted with 1-2 substituents selected from Ra; and (i) hydrogen; R2 is the acyl residue of an amino acid, the amino group of which may be optionally substituted by C1-6 alkyl or an acyl group of the structure R1ZCOâ€”, and in the case of a dicarboxylic amino acid, the terminal carboxyl may optionally be in the form of a C1-4alkyl ester; R3is selected from the group consisting of: (a) C1-10alkyl, (b) C1-6fluoroalkyl, and (c) C6-10aryl optionally substituted as defined above, and R5 and R6 independently represent members selected from the group consisting of: H, C1-10alkyl, C2-10alkenyl, aryl ,Hetcy, CONH2, CO2H, CO2â€”R4, C(O)R4, C1-6fluoroalkyl, aryl, and Hetcy groups being optionally substituted with 1-3 substituents selected from Ra; or R5 and R6 are taken in combination and represent a 7 membered carbocyclic ring, optionally interrupted with 1-3 heteroatoms selected from O, S(O)y and N, and optionally substituted with 1-3 members selected from Ra.