Boronic ester and acid compounds, synthesis and uses

A compound having the formula (1a):

• or a pharmaceutically acceptable salt thereof;
• wherein
• P is R7—C(O)— or R7—SO2—, and R7 is an optionally substituted aryl or aralkyl;
• A is zero;
• X2 is —C(O)—NH—;
• R is hydrogen;
• R2 is benzyl;
• R3 is C4 alkyl;
• and
• Z1 and Z2 are independently one of hydroxy, alkoxy, or aryloxy, or together Z1 and Z2 form a moiety derived from a dihydroxy compound having at least two hydroxy groups separated by at least two connecting atoms in a chain or ring, said chain or ring comprising carbon atoms and, optionally, a heteroatom or heteroatoms which can be N, S, or O.

A composition, which upon combination with a physiologically acceptable saline carrier forms a solution suitable for intravenous, intramuscular or subcutaneous administration to a patient, said solution comprising a compound of the formula (1a):

• or a pharmaceutically acceptable salt thereof;
• wherein
• P is hydrogen or an amino group protecting moiety;
• A is zero;
• X2 is —C(O)—NH—;
• R is hydrogen or C1-8 alkyl;
• R2 is —CH2—R5;
• R3 is C4 alkyl;
• R5 is aryl or cycloalkyl, wherein R5 is optionally substituted by one or two substituents independently selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl, C1-6alkyl(C3-8)cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, cyano, amino, C1-6 alkylamino, di(C1-6)alkylamino, benzylamino, dibenzylamino, nitro, carboxy, carbo(C1-6)alkoxy, trifluoromethyl, halogen, C1-6 alkoxy, C6-10 aryl, C6-10 aryl(C1-6)alkyl, C6-10 aryl(C1-6)alkoxy, hydroxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C6-10 arylthio, C6-10 arylsulfinyl, C6-10 arylsulfonyl, C1-6 alkyl(C6-10)aryl, and halo(C6-10)aryl;
• Z1 and Z2 are both hydroxy.

A composition, which upon combination with a physiologically acceptable saline carrier forms a solution suitable for intravenous, intramuscular or subcutaneous administration to a patient, said solution comprising a compound of the formula (1a):

• or a pharmaceutically acceptable salt thereof;
• wherein
• P is R7—C(O)— or R7—SO2—, and R7 is an optionally substituted aryl or aralkyl;
• A is zero;
• X2 is —C(O)—NH—;
• R is hydrogen;
• R2 is benzyl;
• R3 is C4 alkyl;
• and
• Z1 and Z2 are both hydroxy.