Methods of increasing nitric oxide synthesis

• US 5,811,437 A
• Filed: 04/22/1997
• Issued: 09/22/1998
• Est. Priority Date: 05/21/1996
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Wood, Danny Lee, Singh, Jai Pal
• Primary Examiner(s): HENLEY III, RAYMOND J
• Application Number:
  US08/840,528
• Time in Patent Office: 518 Days
• Field of Search: 514/324
• US Class Current: 514/324
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• 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

Abstract

The current invention provides methods for increasing the concentration of nitric oxide (NO) in vascular endothelial cells, comprising administering a compound of formula I ##STR1## Wherein: R is hydrogen, --OH, --O(C₁ -C₄ alkyl), --OCO(C₁ -C₄ alkyl), or --OCOAr where Ar is a phenyl or optionally substituted phenyl;

R₁ is R, --C₁, or --F;

R₂ is 1-pyrrolidinyl, 1-piperidinyl, or 1-hexamethyleneimino;

or a pharmaceutically acceptable salt or solvate thereof.

Claims

1. A method for increasing nitric oxide (NO) synthesis in vascular endothelial cells in a human in need thereof, comprising administering to said human a compound of formula I ##STR3## Wherein:

R is hydrogen, --OH, --O(C₁ -C₄ alkyl), --OCO(C₁ -C₄ alkyl), or --OCOAr where Ar is a phenyl or optionally substituted phenyl;

R₁ is R, --Cl, or --F;

R₂ is 1-pyrrolidinyl, 1-piperidinyl, or 1-hexamethyleneimino;

or a pharmaceutically acceptable salt or solvate thereof.

2. A method according to claim 1 wherein said compound of formula I is 2-(4-hydroxyphenyl)-6-hydroxybenzo b!thien-3-yl! 4- 2-(1-piperidinyl)ethoxy!phenyl!methanone hydrochloride.

3. A method for inhibiting a physiological condition associated with a lack of or need for, nitric oxide (NO) by increasing NO concentration comprising administering to a human in need thereof a compound of formula (I) ##STR4## Wherein:

R is hydrogen, --OH, --O(C₁ -C₄ alkyl), --OCO(C₁ -C₄ alkyl), or --OCOAr where Ar is a phenyl or optionally substituted phenyl;

R₁ is R, --Cl,or --F;

R₂ is 1-pyrrolidinyl, 1-piperidinyl, or 1-hexamethyleneimino;

or a pharmaceutically acceptable salt or solvate thereof.

4. A method of according to claim 3 wherein said compound of formula (I) is 2-(4-hydroxyphenyl)-6-hydroxybenzo b!thien-3-yl! 4- 2-(1-piperidinyl)ethoxy!phenyl!methanone hydrochloride.