Analgesic and tranquilizing spiro[dihydrobenzofuran]piperidines and pyrrolidines

• US 4,166,119 A
• Filed: 04/14/1978
• Issued: 08/28/1979
• Est. Priority Date: 04/14/1978
• Status: Expired due to Term

• Current Assignee: American Hoechst Corporation (Sanofi )
• Original Assignee: American Hoechst Corporation (Sanofi )
• Inventors: Strupczewski, Joseph T., Effland, Richard C., Gardner, Beth A.
• Primary Examiner(s): Rotman, Alan L.
• Assistant Examiner(s): Schwartz, Richard A.
• Application Number:
  US05/896,622
• Time in Patent Office: 501 Days
• Field of Search: 260/293.58, 260/293.66, 260/326.13 H, 260/326.5 CA, 260/326.14 R, 260/326.34, 260/326.15, 424/267, 424/274, 546/17
• US Class Current: 514/278
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 211/52 having an aryl radical as the second substituent in position 4
• CPC Class Codes: C07D 491/10 Spiro-condensed systems

Abstract

Novel Spiro[dihydrobenzofuran-piperidine and pyrrolidine]s and methods of preparing same are described. These compounds are useful as analgetics and tranquilizers and as intermediates.

Claims

1. A compound of the formula ##STR14## or a pharmaceutically acceptable acid addition salt thereof in which X is hydrogen, nitro, amino, chlorine, fluorine, bromine or methoxy;

R is hydrogen, alkyl, alkenyl, hydroxyethyl, alkanoyl, alkoxyoxalyl, unsubstituted or substituted phenylalkanoyl, unsubstituted or substituted benzoyl, unsubstituted or substituted phenylalkyl, cycloalkylalkyl, cycloalkylcarbonyl, furfuryl, furoyl, alkoxycarbonyl, phenoxycarbonyl, unsubstituted or substituted phenoxyalkyl, N-[2-(3-indolyl)ethyl] or (indol-3-yloxalyl) wherein said alkyl, alkenyl, alkanoyl and alkoxy groups have from 1 to 6 carbon atoms, said cycloalkyl groups have from 3 to 7 carbon atoms and the substituents of said substituted groups are selected from nitro, amino, halogen and methoxy; and

n is the integer 1 or 2.

2. A compound defined in claim 1 in which R is hydrogen or benzyl.

3. A compound defined in claim 2 in which n is 2.

4. A compound defined in claim 1 in which R is alkyl, alkenyl, hydroxyethyl, alkanoyl, unsubstituted or substituted phenylalkanoyl, unsubstituted or substituted benzoyl, unsubstituted or substituted phenylalkyl, cycloalkylalkyl, cycloalkylcarbonyl, furfuryl, furoyl, alkoxycarbonyl, phenoxycarbonyl, unsubstituted or substituted phenoxyalkyl, N-[2-(3-indolyl)ethyl] or (indol-3-yloxalyl).

5. A compound defined in claim 4 in which R is alkyl of between 1 and 3 carbon atoms;

alkenyl of between 2 and 4 carbon atoms;

hydroxyethyl;

alkanoyl of between 2 and 4 carbon atoms;

unsubstituted or substituted phenylacetyl;

benzyl, unsubstituted or substituted phenylethyl, cycloalkylmethyl, cycloalkylcarbonyl, furfuryl, furoyl, ethoxycarbonyl, phenoxycarbonyl or unsubstituted or substituted phenoxyalkyl in which the alkyl portion contains between 1 and 4 carbon atoms.

6. A compound defined in claim 5 in which n is 2.

7. A compound defined in claim 5 in which n is 1.

8. A compound defined in claim 4 in which R is N-[2-(3-indolyl)ethyl] or N-(indol-3-yloxalyl).

9. A compound defined in claim 8 in which n is 2.

10. The compound defined in claim 1 which is 2,3-dihydro-1'"'"'-methylspiro[benzofuran-2,4'"'"'-piperidine] or a pharmaceutically acceptable acid addition salt thereof.

11. The compound defined in claim 1 which is 2,3-dihydro-1'"'"'-cyclobutylmethylspiro[benzofuran-2,4'"'"'-piperidine] or a pharmaceutically acceptable acid addition salt thereof.

12. The compound defined in claim 1 which is 2,3-dihydro-1-(β

-phenethyl)spiro[benzofuran-2,4'"'"'-piperidine] or a pharmaceutically acceptable acid addition salt thereof.

13. The compound defined in claim 1 which is 2,3-dihydro-1'"'"'-(β

-phenethyl)spiro[benzofuran-2,3'"'"'-pyrrolidine] or a pharmaceutically acceptable acid addition salt thereof.

14. The compound defined in claim 1 which is 2,3-dihydro-5-nitrospiro[benzofuran-2,4'"'"'-piperidine] or a pharmaceutically acceptable acid addition salt thereof.

15. The compound defined in claim 1 which is 2,3-dihydrospiro[benzofuran-2,4'"'"'-piperidine] or a pharmaceutically acceptable acid addition salt thereof.

16. The compound defined in claim 1 which is 2,3-dihydrospiro[benzofuran-2,3'"'"'-pyrrolidine]hydrochloride or a pharmaceutically acceptable acid addition salt thereof.

17. The compound defined in claim 1 which is 2,3-dihydro-6-chlorospiro[benzofuran-2,4'"'"'-piperidine]hydrochloride or a pharmaceutically acceptable acid addition salt thereof.

18. The compound defined in claim 1 which is 2,3-dihydro-5-chlorospiro[benzofuran-2,4'"'"'-piperidine]hydrochloride or a pharmaceutically acceptable acid addition salt thereof.

19. A method of alleviating pain in a patient which comprises administering to a patient an analgesically effective amount of a compound defined in claim 1.

20. A method of tranquilizing a patient which comprises administering to the patient an effective tranquilizing amount of a compound defined in claim 1.

21. An analgesic or tranquilizer composition comprising between 0.5 and 70% by weight of a compound defined in claim 1 and a pharmaceutically acceptable carrier therefor.

22. The method as defined in claim 19 wherein said amount of said compound is from 0.05 to 300 mg/kg of body weight per day.

23. The method as defined in claim 20 wherein said amount of said compound is from 0.05 to 300 mg/kg of body weight per day.