Stereoisomer Conjugates of Dextrorphan
AssigneeZevra Therapeutics, Inc.
InventorsSven Guenther, Travis Mickle, Sanjib Bera, Amarraj Chakraborty
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Abstract
The present technology provides a class of compounds which are amino acid ester conjugates of dextrorphan, wherein the amino acids are diestereomerically pure, which have improved bioavailability. The present technology further provides methods of manufacturing the same. The present technology still further provides pharmaceutical compositions comprising said compounds and methods of treating diseases or conditions using the same.
Claims22
A compound having a structure of Formula I:
- where L is A1-G1 or A1-A2-G2, and
- A1 and A2 are independently selected optically active amino acids, wherein at least one of A1 and A2 has a chiral center,
- G1 is an acyl group, and
- G2 is an acyl group or absent;
- or
- a pharmaceutically acceptable salt thereof.
18-47. (canceled)
A method of manufacturing a chiral amino acid ester prodrug of dextrorphan having a structure of Formula II:
- where L is A1_G1,
- A1 is an optically active amino acids, wherein the optically active amino acid has a chiral center, and
- G1 is an acyl group, and
- the method comprising:
- reacting a protected diestereomerically pure amino acid with dextrorphan in a solvent in the presence of a base for form a protected amino acid ester intermediate;
- and
- reacting the protected amino acid ester intermediate with an acid to produce a compound of Formula II.
49-52. (canceled)
A method of manufacturing a chiral amino acid ester prodrug of dextrorphan comprising a compound having Formula III:
- where L is A1-A2-G2,
- A1 and A2 are independently selected optically active amino acids, wherein at least one of A1 and A2 has a chiral center, and
- G2 is an acyl group or absent;
- the method comprising:
- reacting a first protected diestereomerically pure amino acid with dextrorphan in a solvent in the presence of a base to produce a first intermediate;
- reacting the first intermediate with an acid to form a deprotected amino acid ester intermediate;
- reacting the deprotected amino acid ester intermediate with a second protected diestereomerically pure amino acid to produce a protected dipeptide intermediate in a second solvent in the presence of a second base;
- and
- reacting the protected dipeptide intermediate with an acid to produce a compound of Formula III.
54-59. (canceled)
Dependencies are inferred from the claim text.