The present invention relates to new methods of manufacturing benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), and intermediates thereof.

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The present invention relates to new methods of manufacturing benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), and intermediates thereof.

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The present invention relates to new methods of manufacturing benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), and intermediates thereof.

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This document describes biochemical pathways for producing a difunctional product having an odd number of carbon atoms in vitro or in a recombinant host, or salts or derivatives thereof, by forming two terminal functional groups selected from carboxyl, amine, formyl, and hydroxyl groups in an aliphatic carbon chain backbone having an odd number of carbon atoms synthesized from (i) acetyl-CoA and propanedioyl-CoA via one or more cycles of methyl ester shielded carbon chain elongation or (ii) propanedioyl-[acp] via one or more cycles of methyl ester shielded carbon chain elongation. The biochemical pathways and metabolic engineering and cultivation strategies described herein rely on enzymes or homologs accepting methyl ester shielded aliphatic carbon chain backbones and maintaining the methyl ester shield for at least one further enzymatic step following one or more cycles of methyl ester shielded carbon chain elongation.

This document describes biochemical pathways for producing a difunctional product having an odd number of carbon atoms in vitro or in a recombinant host, or salts or derivatives thereof, by forming two terminal functional groups selected from carboxyl, amine, formyl, and hydroxyl groups in an aliphatic carbon chain backbone having an odd number of carbon atoms synthesized from (i) acetyl-CoA and propanedioyl-CoA via one or more cycles of methyl ester shielded carbon chain elongation or (ii) propanedioyl-[acp] via one or more cycles of methyl ester shielded carbon chain elongation. The biochemical pathways and metabolic engineering and cultivation strategies described herein rely on enzymes or homologs accepting methyl ester shielded aliphatic carbon chain backbones and maintaining the methyl ester shield for at least one further enzymatic step following one or more cycles of methyl ester shielded carbon chain elongation.

The present invention provides small molecule drugs and pharmaceutical compositions for the treatment and prevention of diseases related to the formation of A42 oligomers in a subject. It further provides a method of reducing formation of or disrupting A42 oligomers in a subject, the method comprising the step of administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition.

The present invention provides small molecule drugs and pharmaceutical compositions for the treatment and prevention of diseases related to the formation of A42 oligomers in a subject. It further provides a method of reducing formation of or disrupting A42 oligomers in a subject, the method comprising the step of administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition.

Aspects of the present disclosure include G6PD-modulating agents and methods for modulating a glucose-6-phosphate dehydrogenase (G6PD) in a sample using such agents. A G6PD-modulating agent can be dimeric and include two terminal carbocyclic or heterocyclic groups connected via a linker. In some instances, the agent includes a diamino-containing linker. In certain cases, the agent includes two amino substituents. Also provided are methods for treating a subject for a G6PD deficiency-associated condition, that include administering to a subject an effective amount of a G6PD-modulating agent to selectively activate a mutant G6PD and treat the subject. Kits and compositions for practicing the subject methods are also provided.

The present invention provides small molecule drugs and pharmaceutical compositions for the treatment and prevention of diseases related to the formation of A42 oligomers in a subject. It further provides a method of reducing formation of or disrupting A42 oligomers in a subject, the method comprising the step of administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition.

The present invention provides small molecule drugs and pharmaceutical compositions for the treatment and prevention of diseases related to the formation of A42 oligomers in a subject. It further provides a method of reducing formation of or disrupting A42 oligomers in a subject, the method comprising the step of administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition.