Stability-enhancing compositions and methods of preparing compounds
AssigneeFoghorn Therapeutics Inc.
InventorsLiyue HUANG, David B. TERRY, Joshua D. WAETZIG, Chong-Hui GU
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Abstract
Chiral glutarimide stereochemical identity-preserving methods and compositions are disclosed. Also disclosed are methods of preparing chiral glutarimides stereoretentively.
Claims83
A method of determining the level of a chiral glutarimide comprising an epimerizable stereogenic center at the α-carbon of the glutarimide ring in a subject, the method comprising:
- collecting a body fluid from the subject into a container comprising a solution comprising citric acid to form a composition;
- and
- determining the level of the chiral glutarimide in the composition,
- thereby determining the level of a chiral glutarimide in a subject.
A method of preparing a composition comprising a chiral glutarimide comprising an epimerizable stereogenic center at the α-carbon of the glutarimide ring and a body fluid, the method comprising collecting the body fluid from a subject into a container comprising a solution comprising citric acid, the body fluid comprising the chiral glutarimide.
A composition comprising a chiral glutarimide comprising an epimerizable stereogenic center at the α-carbon of the glutarimide ring, a body fluid, and citrate buffer, wherein the composition is enriched for one of the stereoisomers of the epimerizable stereogenic center.
A method of determining the level of a chiral glutarimide comprising an epimerizable stereogenic center at the α-carbon of the glutarimide ring in a subject, the method comprising:
- collecting a body fluid from the subject;
- separating the body fluid into two or more components;
- combining one of the components and citric acid to form a composition;
- and
- determining the level of the chiral glutarimide in the composition,
- thereby determining the level of a chiral glutarimide in a subject.
A method of preparing a composition comprising a chiral glutarimide comprising an epimerizable stereogenic center at the α-carbon of the glutarimide ring and a component of a body fluid, the method comprising combining citric acid and the component of the body fluid collected from a subject.
A composition comprising a chiral glutarimide comprising an epimerizable stereogenic center at the α-carbon of the glutarimide ring, a component of a body fluid, and citrate buffer, wherein the composition is enriched for one of the stereoisomers of the epimerizable stereogenic center.
The method or composition of any one of claims 25 to 34, wherein q is 0 or 1.
A method of preparing a chiral glutarimide or a salt thereof comprising an epimerizable stereogenic center at the α-carbon of the glutarimide ring, the epimerizable stereogenic center being enriched for one of the stereoisomers, and the method comprising reacting a stereoenriched aminoglutarimide with a carboxybenzaldehyde,
- wherein the chiral glutarimide is of the following structure:
- wherein
- *designates the stereoenriched epimerizable stereogenic center at the α-carbon of the glutarimide ring;
- Y1 is
- R3 is H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;
- q is 0, 1, 2, 3, or 4;
- each R2 is, independently, halogen, optionally substituted C1-C8 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, hydroxyl, thiol, or optionally substituted amino;
- and
- Z is L-A;
- wherein L is a linker;
- and
- A is a protein binding moiety;
- wherein the enantioenriched aminoglutarimide is of the following structure:
- or a salt thereof,
- wherein all variables are same as those in the chiral glutarimide;
- and
- wherein the carboxybenzaldehyde is of the following structure:
- wherein
- PG is an O-protecting group, and
- all remaining variables are same as those in the chiral glutarimide.
Dependencies are inferred from the claim text.