Pyridoxal analogues and methods of treatment

• US 7,230,009 B2
• Filed: 06/03/2003
• Issued: 06/12/2007
• Est. Priority Date: 03/08/1999
• Status: Expired due to Fees

• Current Assignee: University of Manitoba
• Original Assignee: Medicure, Inc., University of Manitoba
• Inventors: Haque, Wasimul, Charlton, James L.
• Primary Examiner(s): McKane; Joseph K.
• Assistant Examiner(s): SHIAO, REI TSANG
• Application Number:
  US10/453,414
• Publication Number:
  US 20030195236A1
• Time in Patent Office: 1,470 Days
• Field of Search: 514/233.8, 514/302, 514/219, 544/127, 544/106, 546/116
• US Class Current: 514/302
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• 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: A61P 9/12 Antihypertensives
• 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 491/04 Ortho-condensed systems

Abstract

Pyridoxal analogues can be useful for treating B₆ deficiency and related diseases; cardiovascular and related diseases; melanoma and related diseases; and symptoms thereof. One such analogue is a compound of the formula:

or a pharmaceutically acceptable acid addition salt thereof, in which R₁ is alkyl, alkenyl, in which alkyl or alkenyl can be interrupted by nitrogen, oxygen, or sulfur, and can be substituted at the terminal carbon by hydroxy, alkoxy, alkanoyloxy, alkanoyloxyaryl, alkoxyalkanoyl, alkoxycarbonyl, or dialkylcarbamoyloxy; alkoxy; dialkylamino; alkanoyloxy; alkanoyloxyaryl; alkoxyalkanoyl; alkoxycarbonyl; dialkylcarbamoyloxy; or aryl, aryloxy, arylthio, or aralkyl, in which aryl can be substituted by alkyl, alkoxy, amino, hydroxy, halo, nito, or alkanoyloxy. These analogues can be administered, either alone or concurrently with known medications, to treat the above-described diseases.

Claims

1. A composition comprising a compound of formula VI

2. A composition according to claim 1, wherein R₁ is phenyl or naphthyl in which phenyl or naphthyl is unsubstituted or substituted by one or more groups of C_1-4 alkyl, C_1-4 alkoxy, amino, hydroxy, halo, nitro, or C_1-4 alkanoyloxy.

3. A composition according to claim 1, wherein R₁ is (2-acetoxy-2-methyl)propanyl, dimethylamino, or 1-ethanoyloxy-1-methylethyl.

4. A composition according to claim 1, wherein R₁ is tert-butyl.

5. A composition according to claim 1, wherein R₁ is methoxy or ethoxy.

6. A composition according to claim 1, wherein R₁ is toluyl, naphthyl, phenyl, acetylphenyl, or 1-ethanoyloxyphenyl.

7. A composition according to claim 1, wherein R₁ is acetylsalicyl, dimethylamino, or 2,2-dimethylethyl.

8. A composition according to claim 1, wherein said compound is 2-methyl-3-toluoyloxy-4-formyl-5-hydroxymethylpyridine.

9. A composition according to claim 1, wherein said compound is 2-methyl-3-β

-naphthoyloxy-4-formyl-5-hydroxymethylpyridine.

10. A composition of claim 1, wherein said R₂ of the formula

11. A composition of claim 1, wherein R₂ is selected from the group consisting of piperazino and morpholino.