The present disclosure relates to a process to prepare esters of an amino carboxylic acid of the formula (I) comprising the steps of reacting an aminocarboxylic acid present as a cyclic amide of the formula II and an alkanol of the formula R—(O-A)mOH in the presence of the Brønsted-Lowry acid at a temperature of between 60 and 200 degrees C. wherein the total molar amount of aminocarboxylic acid to the molar amount of the alkanol is between 1:0.8 and 1:1.5 and wherein the Brønsted-Lowry acid is not added to the reaction mixture until least 50% of the total of the alkanol and cyclic amide are added to the reaction mixture.

The present disclosure relates to a process to prepare esters of an amino carboxylic acid of the formula (I) comprising the steps of reacting an aminocarboxylic acid present as a cyclic amide of the formula II and an alkanol of the formula R—(O-A)mOH in the presence of the Brønsted-Lowry acid at a temperature of between 60 and 200 degrees C. wherein the total molar amount of aminocarboxylic acid to the molar amount of the alkanol is between 1:0.8 and 1:1.5 and wherein the Brønsted-Lowry acid is not added to the reaction mixture until least 50% of the total of the alkanol and cyclic amide are added to the reaction mixture.

The present disclosure relates to a process to prepare esters of an amino carboxylic acid of the formula (I) comprising the steps of reacting an aminocarboxylic acid present as a cyclic amide of the formula II and an alkanol of the formula R—(O-A)mOH in the presence of the Brønsted-Lowry acid at a temperature of between 60 and 200 degrees C. wherein the total molar amount of aminocarboxylic acid to the molar amount of the alkanol is between 1:0.8 and 1:1.5 and wherein the Brønsted-Lowry acid is not added to the reaction mixture until least 50% of the total of the alkanol and cyclic amide are added to the reaction mixture.

The present invention relates to a bifunctional chiral organocatalytic compound having excellent enantioselectivity, a preparation method therefor, and a method for producing a non-natural gamma amino acid from a nitro compound by using the chiral organocatalytic compound. According to the present invention, the bifunctional chiral organocatalytic compound having excellent enantioselectivity can be easily synthesized, gamma-amino acids with high optical selectivity can be obtained at a high yield by an economical and convenient method using the chiral organocatalytic compound, and various (R)-configuration gamma-amino acids, which are not present in nature, can be produced with high optical purity in large quantities by using a small amount of a catalyst, and therefore, the present invention can be widely utilized in various industrial fields including the pharmaceutical industry.

The present invention relates to a bifunctional chiral organocatalytic compound having excellent enantioselectivity, a preparation method therefor, and a method for producing a non-natural gamma amino acid from a nitro compound by using the chiral organocatalytic compound. According to the present invention, the bifunctional chiral organocatalytic compound having excellent enantioselectivity can be easily synthesized, gamma-amino acids with high optical selectivity can be obtained at a high yield by an economical and convenient method using the chiral organocatalytic compound, and various (R)-configuration gamma-amino acids, which are not present in nature, can be produced with high optical purity in large quantities by using a small amount of a catalyst, and therefore, the present invention can be widely utilized in various industrial fields including the pharmaceutical industry.

Disclosed herein are embodiments of a compound that inhibits c-Abl tyrosine kinase (also referred to herein as “c-Abl”). The compound embodiments described herein are novel c-Abl inhibitors that can bind to c-Abl at an allosteric site and inhibit its activity in various pathways. The compound embodiments also are capable of crossing the blood brain barrier and therefore are useful in inhibiting c-Abl activity as it affects pathways and/or proteins in the brain. The compound embodiments described herein are effective therapeutic agents for treating diseases involving c-Abl, such as cancers, motor neuron diseases, and neurodegenerative diseases. Also disclosed herein are embodiments of methods for making and using the c-Abl inhibitory compound embodiments.

Disclosed herein are embodiments of a compound that inhibits c-Abl tyrosine kinase (also referred to herein as “c-Abl”). The compound embodiments described herein are novel c-Abl inhibitors that can bind to c-Abl at an allosteric site and inhibit its activity in various pathways. The compound embodiments also are capable of crossing the blood brain barrier and therefore are useful in inhibiting c-Abl activity as it affects pathways and/or proteins in the brain. The compound embodiments described herein are effective therapeutic agents for treating diseases involving c-Abl, such as cancers, motor neuron diseases, and neurodegenerative diseases. Also disclosed herein are embodiments of methods for making and using the c-Abl inhibitory compound embodiments.

The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.