Inotropic agents

• US 4,537,889 A
• Filed: 05/03/1984
• Issued: 08/27/1985
• Est. Priority Date: 12/27/1982
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Spitzer, Wayne A.
• Primary Examiner(s): Ford, John M.
• Application Number:
  US06/606,806
• Time in Patent Office: 481 Days
• Field of Search: 544/184, 424/249
• US Class Current: 514/243
• CPC Class Codes: C07C 317/00 Sulfones; Sulfoxides
• CPC Class Codes: C07C 323/00 Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
• CPC Class Codes: C07C 45/46 Friedel-Crafts reactions
• CPC Class Codes: C07C 45/54 of compounds containing doubly bound oxygen atoms, e.g. esters
• CPC Class Codes: C07C 45/673 by change of size of the carbon skeleton
• CPC Class Codes: C07C 45/71 being hydroxy groups
• CPC Class Codes: C07C 49/825 all hydroxy groups bound to the ring
• CPC Class Codes: C07C 49/84 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

This invention provides for certain phenyl-substituted imidazo compounds, their pharmaceutical formulations, and their use as positive inotropic agents and vasodilators.

Claims

1. Compounds of the formula ##STR8## and their pharmaceutically acceptable salts, wherein two of A₁, A₂, A₃, and A₄ are N, and the remaining A₁, A₂, A₃, and A₄ are CH, and each of R₁, R₂, and R₃ is independently hydrogen, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, allyloxy, benzyloxy, (C₁ -C₄ alkyl)thio, (C₁ -C₄ alkyl)sulfinyl, (C₁ -C₄ alkyl)sulfonyl, hydroxy, halo, cyano, amino, mono- or di-(C₁ -C₄ alkyl)amino, trifluoromethyl, or Z-Q-substituted C₁ -C₄ alkoxy, wherein Q is oxygen, sulfur, sulfinyl, sulfonyl, or a bond, and Z is C₁ -C₄ alkyl, phenyl or phenyl substituted with halo C₁ -C₄ alkyl, C₁ -C₄ alkoxy, hydroxy, nitro, amino, C₁ -C₄ alkylthio, C₁ -C₄ alkylsulfinyl, or C₁ -C₄ alkylsulfonyl, with the proviso that R₁, R₂, and R₃ may not all be hydrogen at the same time.

2. The compounds of claim 1 wherein R₁ is methoxy.

3. The compounds of claim 2 wherein R₂ is methylsulfinyl.

4. The compounds of claim 2 wherein R₂ is methoxy.

5. The compounds of claim 2 wherein R₂ is methylsulfonyl.

6. Th compounds of claim 1 which are 6-substituted-imidazo[1,2-b][1,2,4]triazines.

7. The compounds of claim 1 which are 7-substituted-imidazo[1,2-a]-1,3,5-triazines.

8. The compound of claim 6 which is 6-(2,4-dimethoxyphenyl)imidazo[1,2-b][1,2,4]triazine or a pharmaceutically acceptable salt thereof.

9. A method of producing a positive inotropic effect or causing vasodilation in a warm-blooded mammal, which comprises the administration to such mammal an effective amount of a compound of claim 1.

10. A pharmaceutical formulation useful for producing a positive inotropic effect or causing vasodilation in a mammal comprising from 5 to 500 mg of a compound of claim 1 in association with a pharmaceutically acceptable carrier or diluent.