This present disclosure relates to protein kinase C (PKC) modulating compounds, methods of treating a subject with cancer using the compounds, and combination treatments with a second therapeutic agent.

This present disclosure relates to protein kinase C (PKC) modulating compounds, methods of treating a subject with cancer using the compounds, and combination treatments with a second therapeutic agent.

The present invention provides .sup.18F-labeled amino acids or derivatives thereof having formula (I) and methods of making same, which can be suitable for PET imaging: ##STR00001##

The present invention provides .sup.18F-labeled amino acids or derivatives thereof having formula (I) and methods of making same, which can be suitable for PET imaging: ##STR00001##

The present invention relates to pegylated amino acid compounds of Formula I:

##STR00001##

and pharmaceutically acceptable salts thereof, wherein X, R.sup.1, R.sup.2, R.sup.3A, R.sup.3B and n are as defined herein. The present invention also relates to compositions which comprise a pegylated amino acid compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, in combination with a high concentration of an active biological ingredient (ABI). In embodiments of the invention, the ABI is an anti-PD-1 antibody or antigen binding fragment thereof that specifically binds human programmed death receptor 1 (PD-1). The invention further relates to methods for lowering the viscosity of an aqueous solution of a pharmaceutical composition comprising adding a compound of the invention to the solution. The invention also provides methods for treating a pathological disease or condition, such as cancer, by administering to a subject in need of such treatment a therapeutically effective amount of a pharmaceutical composition of the invention.

The present invention relates to pegylated amino acid compounds of Formula I:

##STR00001##

and pharmaceutically acceptable salts thereof, wherein X, R.sup.1, R.sup.2, R.sup.3A, R.sup.3B and n are as defined herein. The present invention also relates to compositions which comprise a pegylated amino acid compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, in combination with a high concentration of an active biological ingredient (ABI). In embodiments of the invention, the ABI is an anti-PD-1 antibody or antigen binding fragment thereof that specifically binds human programmed death receptor 1 (PD-1). The invention further relates to methods for lowering the viscosity of an aqueous solution of a pharmaceutical composition comprising adding a compound of the invention to the solution. The invention also provides methods for treating a pathological disease or condition, such as cancer, by administering to a subject in need of such treatment a therapeutically effective amount of a pharmaceutical composition of the invention.

Disclosed herein are methods for preparing [(2S,3R)-N-[(2S)-3-(cyclopent-1-en-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[(2S)-2-[2-(morpholin-4-yl)acetamido]propanamido]propanamide (compound “G”): ##STR00001##
and precursors thereof.

Disclosed herein are methods for preparing [(2S,3R)-N-[(2S)-3-(cyclopent-1-en-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[(2S)-2-[2-(morpholin-4-yl)acetamido]propanamido]propanamide (compound “G”): ##STR00001##
and precursors thereof.

Disclosed herein are secondary amine compounds that inhibit tRNA synthetase. The compounds of the invention are useful in inhibiting tRNA synthetase in Gram-negative bacteria and are useful in killing Gram-negative bacteria. The secondary amine compounds of the invention are also useful in the treatment of tuberculosis.

The invention relates to a process for the preparation of Melphalan (4-[bis(2-5 chloroethyl)amino]-L-phenylalanine of formula (I) said process comprising the reaction of a 4-amino-L-phenylalanine protected at the carboxy and amino aminoacidic groups with an agent able to convert the aromatic amino group into a group of formula: —N(CH.sub.2CH.sub.2OS(O).sub.nO—).sub.2, wherein n is 1 or 2 followed by conversion of the .fwdarw.N(CH.sub.2CH.sub.2OS(O).sub.nO—).sub.2 group into a —N(CH.sub.2CH.sub.2Cl).sub.2 group. The invention also provides novel intermediates useful for the preparation of Melphalan.

##STR00001##