The invention provides novel compounds having the general formula (I) ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11 and R.sup.23 are as described herein, compositions including the compounds and methods of using the compounds.

The invention provides a new oligopeptide linker intermediate and a preparation method thereof. The preparation method of the oligopeptide intermediate is easily carried out under mild reaction conditions, and since almost no side reactions occur in the reaction, the method produces a high-purity product with fewer impurities and easy to be purified, achieving unexpected technical effects.

The invention relates to the synthesis of boronic ester and acid compounds. More particularly, the invention provides improved synthetic processes for the large-scale production of boronic ester and acid compounds, including the peptide boronic acid proteasome inhibitor bortezomib.

The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

In one aspect, an active agent-conjugate, methods of preparing the active agent-conjugate, and uses thereof is provided.

In one aspect, the present disclosure provides tubulysin analogs of the formula (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, drug conjugates with cell targeting moieties of the compounds are also provided.

##STR00001##

It is an objective of the present invention to provide a method of producing imidazole dipeptides that reduces burden and time for an elution treatment when compared to the prior arts, and furthermore, that can produce high purity imidazole dipeptides with less contamination of creatinine. The above objective is achieved by a method of producing high purity imidazole dipeptides, comprising: (1) subjecting an animal extract containing imidazole dipeptides and creatinine to an ion adsorption treatment in which the animal extract is brought into contact with a strongly acidic cation exchange resin having an alkali metal salt type of ion exchange group at a predetermined pH value to adsorb the imidazole dipeptides onto the resin; and (2) subjecting the strongly acidic cation exchange resin adsorbing the imidazole dipeptides to an elution treatment with the use of an aqueous alkaline solution and at a predetermined pH value to obtain high purity imidazole dipeptides.

It is an objective of the present invention to provide a method of producing imidazole dipeptides that reduces burden and time for an elution treatment when compared to the prior arts, and furthermore, that can produce high purity imidazole dipeptides with less contamination of creatinine. The above objective is achieved by a method of producing high purity imidazole dipeptides, comprising: (1) subjecting an animal extract containing imidazole dipeptides and creatinine to an ion adsorption treatment in which the animal extract is brought into contact with a strongly acidic cation exchange resin having an alkali metal salt type of ion exchange group at a predetermined pH value to adsorb the imidazole dipeptides onto the resin; and (2) subjecting the strongly acidic cation exchange resin adsorbing the imidazole dipeptides to an elution treatment with the use of an aqueous alkaline solution and at a predetermined pH value to obtain high purity imidazole dipeptides.

The disclosure provides compositions and methods relating to aromatic-cationic peptides. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof. For example, the peptides may be administered to subjects in need of a mitochondrial-targeted antioxidant.

Methods for the prevention and treatment of ocular disorders, in particular glaucoma, through blocking the toxic effects of β-amyloid (Aβ) derivatives, and pharmaceutical compositions for effecting such prevention and treatment thereof.