Boronic ester and acid compounds, synthesis and uses

A compound of the structure:

• ##STR91## where P is H or an amino-group-protecting moiety;
• X.sup.2 is selected from the group consisting of ##STR92## R is hydrogen or alkyl;
• R.sup.3 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycle and --CH.sub.2 --R.sup.5,
• R.sup.2 is naphthylmethyl, pyridylmethyl, or quinolylmethyl,
• R.sup.5 is aryl, aralkyl, alkaryl, cycloalkyl, heterocycle or --Y--R.sup.6,
• where Y is a chalcogen, and R.sup.6 is alkyl;
• Z.sup.1 and Z.sup.2 are independently alkyl, hydroxy, alkoxy, aryloxy, or together form 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;
• and
• A is 0.

A method for reducing the rate of muscle protein degradation in a cell comprising contacting said cell with a proteasome inhibitor of the structure:

• ##STR93## where P is H or an amino-group-protecting moiety;
• X.sup.2 is selected from the group consisting of ##STR94## R is hydrogen or alkyl;
• R.sup.2 and R.sup.3 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycle and --CH.sub.2 --R.sup.5, heterocycle, or -chalcogen-alkyl;
• Z.sup.1 and Z.sup.2 are independently alkyl, hydroxy, alkoxy, aryloxy, or together form 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;
• and
• A is 0.

A method for reducing the rate of intracellular protein breakdown comprising contacting cells with a proteasome inhibitor of the structure:

• where
• P is H or an amino-group-protecting moiety;
• X.sup.2 is selected from the group consisting of ##STR101## R is hydrogen or alkyl;
• R.sup.2 and R.sup.3 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycle and --CH.sub.2 --R.sup.5,
• where R.sup.5 is aryl, aralkyl, alkaryl, cycloalkyl, heterocycle, or -chalcogen-alkyl;
• Z.sup.1 and Z.sup.2 are independently alkyl, hydroxy, alkoxy, aryloxy, or together form 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;
• and
• A is 0.

A method for reducing the rate of degradation of p53 protein in a cell comprising administering to said cell a proteasome inhibitor of the structure:

• ##STR102## where P is H or an amino-group-protecting moiety;
• X.sup.2 is selected from the group consisting of ##STR103## R is hydrogen or alkyl;
• R.sup.2 and R.sup.3 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycle and --CH.sub.2 --R.sup.5,
• where R.sup.5 is aryl, aralkyl, alkaryl, cycloalkyl, heterocycle, or -chalcogen-alkyl;
• Z.sup.1 and Z.sup.2 are independently alkyl, hydroxy, alkoxy, aryloxy, or together form 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;
• and
• A is 0.

A method for inhibiting cyclin degradation in a cell comprising contacting said cell with a proteasome inhibitor of the structure:

• ##STR104## where P is H or an amino-group-protecting moiety;
• X.sup.2 is selected from the group consisting of ##STR105## R is hydrogen or alkyl;
• R.sup.2 and R.sup.3 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycle and --CH.sub.2 --R.sup.5,
• where R.sup.5 is aryl, aralkyl, alkaryl, cycloalkyl, heterocycle, or -chalcogen-alkyl;
• Z.sup.1 and Z.sup.2 are independently alkyl, hydroxy, alkoxy, aryloxy, or together form 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;
• and
• A is 0.

A method for inhibiting antigen presentation in a cell comprising administering to said cell a proteasome inhibitor of the structure:

• ##STR106## where P is H or an amino-group-protecting moiety;
• X.sup.2 is selected from the group consisting of ##STR107## R is hydrogen or alkyl;
• R.sup.2 and R.sup.3 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycle and --CH.sub.2 --R.sup.5,
• where R.sup.5 is aryl, aralkyl, alkaryl, cycloalkyl, heterocycle, or -chalcogen-alkyl;
• Z.sup.1 and Z.sup.2 are independently alkyl, hydroxy, alkoxy, aryloxy, or together form 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;
• and
• A is 0.

A method for inhibiting cell adhesion in an animal comprising administering to said animal a proteasome inhibitor of the structure:

• ##STR108## where P is H or an amino-group-protecting moiety;
• X.sup.2 is selected from the group consisting of ##STR109## R is hydrogen or alkyl;
• R.sup.2 and R.sup.3 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycle and --CH.sub.2 --R.sup.5,
• where R.sup.5 is aryl, aralkyl, alkaryl, cycloalkyl, heterocycle, or -chalcogen-alkyl;
• Z.sup.1 and Z.sup.2 are independently alkyl, hydroxy, alkoxy, aryloxy, or together form 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;
• and
• A is 0.