9-(1,4-Benzodioxan-2-ylalkyl and hydroxyalkyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-ones

• US 4,353,901 A
• Filed: 10/19/1981
• Issued: 10/12/1982
• Est. Priority Date: 10/19/1981
• Status: Expired due to Fees

• Current Assignee: Syntec Incorporated (Atos SE)
• Original Assignee: Syntec Incorporated (Atos SE)
• Inventors: Clark, Robin D.
• Primary Examiner(s): Milestone, Norma S.
• Application Number:
  US06/312,447
• Time in Patent Office: 358 Days
• Field of Search: 544/71, 424/248.57
• US Class Current: 514/230.8
• CPC Class Codes: C07D 498/10 Spiro-condensed systems

Abstract

Compounds useful in the prevention and/or treatment of hypertension, congestive heart failure, arrhythmia, migraine, vasospastic disorders, and asthma are represented by the formula: ##STR1## wherein:

R¹ is ##STR2##

R², R³, and R⁴ are independently hydrogen or lower alkyl of one to four carbon atoms;

X is hydrogen, lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo;

m is 1 or 2; and

n is 1, 2 or 3; and

the pharmaceutically acceptable acid addition salts thereof.

Claims

1. A compound of the formula:

##STR16## wherein;

R¹ is ##STR17## R², R³, and R⁴ are independently hydrogen or lower alkyl of one to four carbon atoms;

X is hydrogen, lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo;

m is 1 or 2; and

n is 1, 2 or 3; and

and the pharmaceutically acceptable acid addition salts thereof.

2. A compound of claim 1 of the formula:

##STR18## wherein;

R², R³ and R⁴ are independently hydrogen or lower alkyl of one to four carbon atoms;

X is hydrogen, lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo;

m is 1 or 2; and

n is 1, 2 or 3; and

the pharmaceutically acceptable acid additions salts thereof.

3. A compound of claim 2 wherein R⁴ is hydrogen and R² and R³ are independently hydrogen or lower alkyl of one to four carbon atoms.

4. A compound of claim 3 wherein R² and R³ are independently hydrogen.

5. A compound of claim 4 wherein R², R³, R⁴ and X are each hydrogen and n is 1 which is 9-(1,4-benzodioxan-2-yl-methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one and the pharmaceutically acceptable acid addition salts thereof.

6. A compound of claim 4 wherein R², R³, R⁴ and X are each hydrogen and n is 2 which is 9-[2-(1,4-benzodioxan-2-yl)ethyl]-1-oxa-4,9-diazaspiro[5.5]undecan-3-one and the pharmaceutically acceptable acid addition salts thereof.

7. A compound of claim 1 of the formula:

##STR19## wherein;

R², R³ and R⁴ are independently hydrogen or lower alkyl of one to four carbon atoms;

X is hydrogen, lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo;

m is 1 or 2; and

the pharmaceutically acceptable acid addition salts thereof.

8. A compound of claim 7 wherein R⁴ is hydrogen and R² and R³ are independently hydrogen or lower alkyl of one to four carbon atoms.

9. A compound of claim 8 wherein R², R⁴ and X are each hydrogen, and R³ is methyl which is erythro-9-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethyl]-4-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one and the pharmaceutically acceptable acid addition salts thereof.

10. A compound of claim 8 wherein R² and X are each hydrogen, and R³ is ethyl which is erythro-9-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethyl]-5-ethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one and the pharmaceutically acceptable acid addition salts thereof.

11. A compound of claim 8 wherein R² and R³ are independently hydrogen.

12. A compound of claim 11 wherein R², R³, R⁴ and X are each hydrogen which is erythro-9-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethyl]-1-oxa-4,9-diazaspiro[5.5]undecan-3-one and the pharmaceutically acceptable acid addition salts thereof.

15. A method of claim 1 for treating and/or preventing hypertension in a mammalian subject.

13. A pharmaceutical composition comprising 5 to 95% by weight of a compound of the formula:

##STR20## or a pharmaceutically acceptable acid addition salt thereof, wherein;

R¹ is;

##STR21## R², R³, and R⁴ are independently hydrogen or lower alkyl of one to four carbon atoms;

X is hydrogen, lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo;

m is 1 or 2; and

n is 1, 2 or 3; and

the pharmaceutically acceptable acid addition salts thereof in admixture with 95 to 5% of a pharmaceutically acceptable, non-toxic carrier.

14. A method for treating and/or preventing hypertension, congestive heart failure, arrhythmia, migraine, vasospastic disorders and asthma in a mammalian subject comprising administering to said subject a therapeutically effective amount of a compound of the formula:

##STR22## or a pharmaceutically acceptable acid addition salt thereof, wherein;

R¹ is;

##STR23## R², R³, and R⁴ are independently hydrogen or lower alkyl of one to four carbon atoms;

X is hydrogen, lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo;

m is 1 or 2; and

n is 1, 2 or 3; and

the pharmaceutically acceptable acid addition salts thereof or a pharmaceutical composition containing such compound as an active ingredient.