Methods for the synthesis of pyridoxamine

• US 7,214,799 B2
• Filed: 02/09/2005
• Issued: 05/08/2007
• Est. Priority Date: 02/09/2004
• Status: Active Grant

• Current Assignee: Praetego, Inc.
• Original Assignee: BioStratum, Inc.
• Inventors: Degenhardt, Thorsten, Koellner, Christoph, Brand, Stephen Robert, Keilitz, Roland, Khalifah, Raja
• Primary Examiner(s): NORTHINGTON DAVIS, ZINNA
• Application Number:
  US11/054,527
• Publication Number:
  US 20050272781A1
• Time in Patent Office: 818 Days
• Field of Search: 514/352, 546/184, 546/300, 544/124
• US Class Current: 546/300
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 213/66 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
• CPC Class Codes: C07D 213/67 2-Methyl-3-hydroxy-4,5-bis(hydroxy-methyl)pyridine, i.e. pyridoxine
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links

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.

Claims

1. 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;

2. A method of claim 1 wherein step (a) comprises treating the compound of formula (II) with a hydroxyl protecting reagent.

3. A method according to claim 1 wherein step (b) comprises treating the compound of formula (III) with a cyclic imide.

4. A method according to claim 1 wherein R is selected from the group consisting of:

alkanoyl, arylcarbonyl, lower alkoxycarbonyl;

lower alkenyloxycarbonyl;

aryl lower alkoxycarbonyl, and a sulfonyl derivative.

5. A method according to claim 1 wherein the cyclic imide substituent is selected from the group consisting of phthalimidyl and succinimidyl.

6. A method according to claim 1 wherein the product of step (c) is isolated prior to carrying out step (d).

7. A method according to claim 1 wherein the product of step (c) is not isolated prior to carrying out step (d).

8. A method according to claim 1, wherein;

step (a) comprises acylating the hydroxyls of pyridoxamine, or salt thereof, to form a triester, or salt thereof, of the formula;

9. A method according to claim 8 wherein the product of step (c) is not isolated prior to carrying out step (d).

10. A method according to claim 8 wherein the product of step (c) is isolated prior to carrying out step (d).