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Claims for Patent: 3,876,802

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Claims for Patent: 3,876,802

Title: Phenoxy-hydroxypropylamines, method and pharmaceutical preparations for treating cardiovascular diseases
Abstract:Para-substituted phenoxy-hydroxypropylamines having the general formula ##SPC1## And pharmaceutically acceptible, non-toxic acid addition salts thereof, wherein R is an isopropyl or tertiarybutyl radical; Z is a member selected from the group consisting of --OR", --SR", and --NHCOOR", R" being a straight or branched lower alkyl radical having 1 to 3 carbon atoms; and n is 1, 2, or 3, are disclosed as are methods for their preparation. Pharmaceutical preparations are prepared whose active ingredients include at least one of the newly discovered phenoxy-hydroxypropylamine compounds. Therapeutically effective does of these preparations selectively block the .beta.-receptors of the heart marking them useful in treating heart diseases in animals including humans.
Inventor(s): Brandstrom; Arne Elof (S-415 06 Molnlycke, SW), Carlsson; Per Arvid Emil (S-413 19 Molnlycke, SW), Carlsson; Stig Ake Ingemar (S-435 00 Molnlycke, SW), Corrodi; Hans Rudolf (S-151 33 Sodertalje, SW), Ek; Lars (S-430 34 Onsala, SW), Ablad; Arne Hjalmar (S-411 28 Goteborg, SW)
Assignee:
Application Number:05/433,565
Patent Claims: 1. A pharmaceutical preparation for treatment of cardiovascular diseases which comprises as an active ingredient a therapeutically effective dose of at least one para-substituted phenoxy-hydroxypropylamine compound selected from the group consisting of compounds having the formula ##SPC19##

and pharmaceutically acceptable, non-toxic acid addition salts thereof, wherein R' is an isopropyl or tertiary-butyl radical; Z is a member selected from the group consisting of --OR", and --SR", R" being a straight or branched alkyl radical having 1 to 3 carbon atoms and n is 1, 2 or 3, in association with a pharmaceutically acceptable carrier.

2. A pharmaceutical preparation according to claim 1 wherein the active ingredient is a therapeutically effective dose of at least one said compound in racemic form.

3. A pharmaceutical preparation according to claim 1 wherein the active ingredient is a therapeutically effective dose of at least one said compound as the optically active, dextro-rotatary isomer.

4. A pharmaceutical preparation according to claim 1 wherein the active ingredient is a therapeutically effective dose of at least one said compound as the optically active, levo-rotatary isomer.

5. A pharmaceutical preparation according to claim 1 wherein the para-substituted phenoxy-hydroxypropylamine compound comprises 0.1 to 95% by weight of the preparation.

6. A pharmaceutical preparation according to claim 1 in a form suitable for administration by injection wherein the para-substituted phenoxy-hydroxypropylamine compound comprises about 0.5% to about 20% by weight of the preparation.

7. A pharmaceutical preparation according to claim 6 for parenteral application which comprises an aqueous solution of a water soluble salt of said para-substituted phenoxy-hydroxypropylamine compound in an amount of about 0.5-10% by weight of the preparation.

8. A pharmaceutical preparation according to claim 1 in a form suitable for oral administration wherein the para-substituted phenoxy-hydroxypropylamine compound comprises about 0.2% to about 50% by weight of the preparation.

9. A pharmaceutical preparation according to claim 1 wherein the active ingredient is 1-isopropylamino-3-[p-(.beta.-methoxyethyl)-phenoxy]-propanol-2 or a pharmaceutically acceptable non-toxic addition salt thereof.

10. A pharmaceutical preparation according to claim 1 wherein the active ingredient is 1-isopropylamino-3-[p-(.beta.-ethoxyethyl)-phenoxy]-propanol-2 or a pharmaceutically acceptable non-toxic addition salt thereof.

11. A pharmaceutical preparation according to claim 1 wherein the active ingredient is 1-isopropylamino-3-(p-ethoxymethyl-phenoxy)-propanol-2 or a pharmaceutically acceptable non-toxic addition salt thereof.

12. A pharmaceutical preparation wherein the active ingredient is the compound of claim 1 wherein R' is isopropyl in association with a pharmaceutically acceptable carrier.

13. A pharmaceutical preparation wherein the active ingredient is the compound of claim 1 wherein Z is --OR" in association with a pharmaceutically acceptable carrier.

14. A pharmaceutical preparation wherein the active ingredient is the compound of claim 1 wherein Z is --SR" in association with a pharmaceutically acceptable carrier.

15. A pharmaceutical preparation wherein the active ingredient is the compound of claim 1 wherein R' is tertiary butyl in association with a pharmaceutically acceptable carrier.

16. A method for treating cardiovascular diseases in animals including humans which comprises adminstering a therapeutically effective dose of a para-substituted phenoxyhydroxypropylamine compound selected from the group consisting essentially of compounds having the formula ##SPC20##

and pharmaceutically acceptable, non-toxic acid addition salts thereof, wherein R' is an isopropyl or tertiary-butyl radical; Z is a member selected from the group consisting of --OR", and --SR", R" being a straight or branched alkyl radical having 1 to 3 carbon atoms: and n is 1, 2 or 3, in association with a pharmaceutically acceptable carrier.

17. A method according to claim 16 wherein the phenoxyhydroxypropylamine compound is 1-isopropylamino-3-[p-(.beta.-methoxyethyl)-phenoxy]-propanol-2.

18. A method according to claim 16 wherein the phenoxyhydroxypropylamine compound is 1-isopropylamino-3-[p-(.beta.-ethoxyethyl)-phenoxy]-propanol-2.

19. A method according to claim 16 wherein the phenoxyhydroxypropylamine compound is 1-isopropylamino-3-(p-ethoxymethyl-phenoxy)-propanol-2.

20. A method for treating cardiovascular diseases in animals including humans which comprises adminstering a therapeutically effective dose of a para-substituted phenoxyhydroxypropylamine compound according to claim 16 wherein R' is isopropyl.

21. A method for treating cardiovascular diseases in animals including humans which comprises administering a therapeutically effective dose of a para-substituted phenoxyhydroxypropylamine compound according to claim 16 wherein Z is --OR".

22. A method for treating cardiovascular diseases in animals including humans which comprises administering a therapeutically effective dose of a para-substituted phenoxyhydroxypropylamine compound according to claim 16 wherein Z is --SR".

23. A method for treating cardiovascular diseases in animals including humans which comprises administering a therapeutically effective dose of a para-substituted phenoxyhydroxypropylamine compound according to claim 16 wherein R' is tertiary butyl.
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