Methods for the Synthesis of Pyridoxamine
AssigneeNephroGenex, Inc.
InventorsRaja Khalifah, Roland Keilitz, Christoph Koellner, Thorsten Degenhardt, Stephen Robert Brand
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Abstract
The invention provides non-oxidative methods for the large scale manufacture of pyridoxamine (I) (4-aminomethyl-3-hydroxy-5-hydroxymethyl-2-methylpyridine): and salts thereof. The invention also provides intermediate compounds for the synthesis of pyridoxamine, as well as compositions and methods for the treatment and/or prevention of conditions associated with the formation of post-Amadori advanced glycation end-products.
Claims25
A method for preparing pyridoxamine, or salt thereof, the method comprising the steps of:
- (a) protecting the hydroxyls of a compound of formula (II), or salt thereof, to form a compound of formula (III), or salt thereof:
- wherein R at each occurrence is a hydroxyl protecting group;
- (b) converting the compound of formula (III), or salt thereof, to a compound of formula (IV), or salt thereof:
- and wherein
- represents a cyclic imide substituent;
- (c) converting the compound of formula (IV), or salt thereof, to a compound of formula (V)
- wherein R1 is H or is R,
- wherein when R1 is R, step (c) is followed by step (d), wherein step (d) comprises:
- (d) converting the compound of formula (V), or salt thereof, to pyridoxamine (I), or a salt thereof:
A method for preparing pyridoxamine, the method comprising the steps of:
- (a) acylating the hydroxyls of pyridoxine, to form an triester, or salt thereof, of the formula:
- (b) treating the triester formed in step (a) with phthalimide, or salt thereof, to form an phthalimido compound, or salt thereof, of the formula:
- (c) treating the phthalilimido compound formed in step (b) with a primary amine to form an amide compound, or salt thereof, of the formula:
- and
- (d) treating the amide formed in step (c) with a deprotecting agent to form pyridoxamine, or salt thereof.
A method according to claim 11 wherein the product of step (c) is not isolated prior to carrying out step (d).
A composition comprising pyridoxamine, or a pharmaceutically acceptable salt thereof, and a compound of the formula (X), or a pharmaceutically acceptable salt thereof:
A composition comprising pyridoxamine, or a pharmaceutically acceptable salt thereof, and a compound of the formula (XX), or a pharmaceutically acceptable salt thereof:
A composition comprising:
- pyridoxamine, or a pharmaceutically acceptable salt thereof;
- a compound of the formula (X), or a pharmaceutically acceptable salt thereof;
- and a compound of the formula (XX), or a pharmaceutically acceptable salt thereof
A zwitterion of the structure:
A compound of formula (III), or salt thereof:
- wherein R at each occurrence is a hydroxyl protecting group.
A compound of formula (IV), or salt thereof:
A compound of formula (V), or salt thereof:
- wherein R1 is a hydroxyl protecting group.
Dependencies are inferred from the claim text.