Bipyridine manganese complexes

• US 6,541,490 B1
• Filed: 11/27/2000
• Issued: 04/01/2003
• Est. Priority Date: 08/17/1998
• Status: Expired due to Fees

• Current Assignee: Eukarion, Inc.
• Original Assignee: Eukarion, Inc.
• Inventors: Box, Philip Charles, Giblin, Gerard Martin Paul, Walker, Ann Louise, Tranter, George Edward, Campbell, Ian Baxter
• Primary Examiner(s): Rotman, Alan L.
• Assistant Examiner(s): ROBINSON, BINTA M
• Application Number:
  US09/722,799
• Time in Patent Office: 855 Days
• Field of Search: 546/5, 514/332
• US Class Current: 514/332
• CPC Class Codes: A61K 33/32 Manganese; Compounds thereof
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 39/04 : Chelating agents
• CPC Class Codes: A61P 39/06 : Free radical scavengers or antioxidants
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• 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 213/53 : Nitrogen atoms
• CPC Class Codes: C07F 13/005 : Compounds without a metal-carbon linkage
• CPC Class Codes: C07F 5/04 : Esters of boric acids

Abstract

Compounds and methods of preparing compounds represented by structural formula (I):

wherein X represents any suitable counter-anion;

R¹ and R² independently represent hydrogen, C_1-6 alkoxy or nitro;

R³, R⁴, R⁵ and R⁶ each independently represents hydrogen, hydroxy, halo, C_1-6 alkyl, C_2-6 alkenyl or C_1-6 alkoxy; and

R⁷, R⁸, R⁹ and R¹⁰ each independently represents hydrogen, hydroxy, halo, C_1-6 alkyl, C_2-6 alkenyl or C_1-6 alkoxy.

Compounds represented by structural formula (I) are useful in treating or preventing free radical-associated diseases or conditions in mammals.

Claims

1. A method of preparing a compound represented by Structural Formula (I):

and solvates thereof, wherein;

X represents a counter-anion;

R¹ and R² each, independently, represent hydrogen, C_1-6 alkoxy or nitro; and

R³, R⁴, R⁵ and R⁶ each, independently, represents hydrogen, hydroxy, halo, C_1-6 alkyl, C_2-6 alkenyl or C_1-6 alkoxy, comprising the steps of;

a) reacting a bipyridine derivative represented by Structural Formula (III);

 

wherein L¹ and L² are each, independently, a leaving group, with a first boronic acid derivative represented by Structural Formula (IV);

 

wherein R^a and R^b are each, independently, hydrogen or a C_1-6 alkyl, or R^a and R^b together form a straight-chain or branched alkylene, to form a first intermediate represented by the following structural formula

b) contacting the second intermediate with a manganese(II) salt, thereby forming said compound.

2. A method of treating ischemia or reoxygenation injury in a human or an animal, comprising administering to the human or animal a therapeutically effective amount of a compound represented by Structural Formula (I):

and solvates thereof, wherein;

X represents a counter-anion;

R¹ and R² each, independently, represent hydrogen, C_1-6 alkoxy or nitro;

R³-R¹⁰ each, independently, represents hydrogen, hydroxy, halo, C_1-6 alkyl, C_2-6 alkenyl or C_1-6 alkoxy.