Thromboxane synthase inhibitors as insulin lowering agents and antiobesity agents

• US 4,731,363 A
• Filed: 01/16/1986
• Issued: 03/15/1988
• Est. Priority Date: 12/26/1979
• Status: Expired due to Fees

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Tobias, Lawrence D., Sullivan, Ann C., Hamilton, James G., Triscari, Joseph
• Primary Examiner(s): Robinson, Douglas W.
• Application Number:
  US06/819,319
• Time in Patent Office: 789 Days
• Field of Search: 514/397, 514/398, 514/399, 514/396, 514/210, 514/256
• US Class Current: 514/204
• CPC Class Codes: A61K 31/38 having sulfur as a ring hetero atom
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim

Abstract

The present disclosure relates to the use of thromboxane synthase inhibitors as antiobesity agents and insulin lowering agents. Such compounds fall into a variety of classes among which are 1-substituted imidazoles, 4-substituted imidazoles, 3-substituted pyridines, 3-substituted indoles, 4-substituted pyrimidines, 5-substituted tetrazoles, pyrazolidines, quinazolines, and substituted xanthene carboxylic acids.

Claims

1. A method for the lowering of insulin levels in mammals which comprise administering to the mammal to be treated a therapeutically effective amount of a thromboxane synthase inhibitor selected from the group consisting of 4-phenylpyrimidine, alpha-oxo-4-pyrimidinepropanoic acid ethyl ester and [6R-(6α

,7β

)]-2-carboxy-8-oxo-3-[(4-pyrimidinylthio)methyl]5thia-1-azabicyclo-[4.2.0]oct-2-en-7-aminum hydroxide inner salt.

2. The method of claim 1 wherein said thromboxane synthase inhibitor is 4-phenylpyrimidine.

3. The method of claim 1 wherein said thromboxane synthase inhibitor is alpha-oxo-4-pyrmidinepropanoic acid ethyl ester.

4. The method of claim 1 wherein said thromboxane synthase inhibitor is [6R-(6α

,7β

)]-2-carboxy-8-oxo-3-[(4-pyrimidinylthio)methyl]5-thia-1-azabicyclo-[4.2.0]oct-2-en-7-aminum hydroxide inner salt.

5. The method of claim 1 wherein said thromboxane synthase inhibitor is administered in dosages ranging from 0.1-200 mg per kg per day.

6. The method of claim 1 wherein said thromboxane synthase inhibitor is administered in dosages ranging from 0.1-50 mg per kg per day.

7. The method of claim 1 wherein said thromboxane synthase inhibitor is administered in dosages ranging from 0.1-10 mg per kg per day.

8. A composition for lowering insulin levels in mammals which comprises a pharmaceutically-acceptable carrier material and a therapeutically effective amount of a thromboxane synthase inhibitor selected from the group consisting of 4-phenylpyrimidine, alpha-oxo-4-pyrimidinepropanoic acid ethyl ester and [6R-(6α

,7β

)]-2-carboxy-8-oxo-3-[(4-pyrimidinylthio)methyl]5-thia-1-azabicyclo-[4.2.0]oct-2-en-7-aminum hydroxide inner salt.

9. The composition of claim 8 wherein said thromboxane synthase inhibitor is 4-phenylpyrimidine.

10. The composition of claim 8 wherein said thromboxane synthase inhibitor is alpha-oxo-4-pyrimidinepropanoic acid ethyl ester.

11. The composition of claim 8 wherein said thromboxane synthase inhibitor is [6R-(6α

,7β

)-2-carboxy-8-oxo-3-[(4-pyrimidinylthio)methyl]5-thia-1-azabicyclo-[4.2.0]oct-2-en-7-aminum hydroxide inner salt.