Biphenyl butyric acids and their derivatives as inhibitors of matrix metalloproteinases

A compound of Formula II

• wherein R and R1 are the same or different and are
• hydrogen,
• alkyl,
• halogen,
• nitro,
• cyano,
• trifluoromethyl,
• OCF3,
• OCF2H,
• OCH2F,
• —OR6 wherein R6 is hydrogen,
• alkyl,
• aryl,
• arylalkyl,
• heteroaryl, or
• cycloalkyl,
• wherein R6 and R6a are the same or different and are as defined above for R6,
• wherein R6 is as defined above,
• wherein R6 is as defined above,
• wherein R6 is as defined above,
• —SR6
• wherein R6 is as defined above,
• wherein R6 is as defined above,
• —CH2—OR6
• wherein R6 is as defined above,
• wherein R6 and R6a are the same or different and are as defined above for R6,
• wherein R6 and R6a are the same or different and are as defined above for R6,
• wherein R6 is as defined above,
• wherein R6 is as defined above,
• cycloalkyl, or
• heteroaryl;
• R3, R3a, R4, and R4a are the same or different and are
• hydrogen,
• fluorine,
• alkyl,
• —(CH2)n-aryl wherein n is an integer from 1 to 6,
• —(CH2)n-heteroaryl wherein n is as defined above,
• —(CH2)n-cycloalkyl wherein n is as defined above,
• —(CH2)n—X—(CH2)q-aryl wherein X is O, S, SO, SO2, or NH, and p and q are each zero or an integer of 1 to 6, and the sum of p+q is not greater than six,
• —(CH2)p—X—(CH2)q-heteroaryl wherein X, p and q are as defined above, or
• —(CH2)n—R7 wherein R7 is
• N-phthalimido,
• N-2,3-naphthylimido,
• —OR6 wherein R6 is as defined above,
• wherein R6 and R6a are the same or different and are as defined above for R6,
• —SR6 wherein R6 is as defined above,
• wherein R6 is as defined above,
• wherein R6 is as defined above,
• wherein R6 is as defined above,
• wherein R6 and R6a are the same or different and are as defined above for R6,
• wherein R6 is as defined above,
• wherein R6 is as defined above, or
• wherein R6 and R6a are the same or different and are as defined above for R6, and
• n is as defined above;
• R5 is OH, SH, or OR5a wherein R5a is alkyl, arylalkyl, cycloalkyl, or acyloxymethyl;
• with the proviso that at least one of R3, R3a, R4, or R4a is fluorine;
• or corresponding isomers thereof;
• or a pharmaceutically acceptable salt thereof.