Antidepressant azaheterocyclylmethyl derivatives of oxaheterocycle-fused-[1,4]-benzodioxans

• US 20020183353A1
• Filed: 04/24/2002
• Published: 12/05/2002
• Est. Priority Date: 04/26/2001
• Status: Active Grant

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Gao, Hong, Stack, Gary P., Gildersleeve, Elizabeth S.
• Granted Patent: US 6,552,049 B2
• Time in Patent Office: Days
• US Class Current: 514/300
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: C07D 493/04 Ortho-condensed systems

Abstract

Compounds of the formula

useful for the treatment of depression such as obsessive compulsive disorder, panic attacks, generalized anxiety disorder, social anxiety disorder, sexual dysfunction, eating disorders, obesity, addictive disorders caused by ethanol or cocaine abuse and related illnesses

Claims

1. ) A compound of formula I

2. ) A compound of claim 1 wherein R¹ is hydrogen.

3. ) A compound of claim 1 wherein R² is hydrogen or lower alkyl.

4. ) A compound of claim 1 wherein R³, R⁴, and R⁵ are independently selected from hydrogen, halogen and cyano.

5. ) A compound of claim 1 wherein R⁶ is hydrogen or lower alkyl.

6. ) A compound of claim 1 wherein Y is C(R²)₂.

7. ) A compound of claim 1 wherein X is CR⁷.

8. ) A compound of claim 1 wherein Y and X, taken together are CR²═

CH.

9. ) A compound of claim 1 in which R¹ is hydrogen, hydroxy, halo, cyano, trifluoromethyl, alkyl of one to six carbon atoms or alkoxy of one to six carbon atoms;

R² is hydrogen or lower alkyl;

R³, R⁴, and R⁵ are independently selected from hydrogen, hydroxy, halo, cyano, carboxamido, alkyl of one to six carbon atoms, or alkoxy of one to six carbon atoms;

n is an integer 0 or 1;

or a pharmaceutically acceptable salt thereof.

10. ) A compound of claim 9 wherein X is C R⁷ and R⁷ is hydrogen, hydroxy, halo, cyano, carboxamido, alkyl of one to six carbon atoms, or alkoxy of one to six carbon atoms.

11. ) A compound of claim 1 in which R¹ is hydrogen, halo or methoxy, R² and R⁶ are hydrogen, R³, R⁴, and R⁵ are independently selected from hydrogen, halo or cyano, n is 0 and the dotted represents a double bond;

or a pharmaceutically acceptable salt thereof.

12. ) A compound of claim 11 wherein X is CR⁷ and R⁷ is hydrogen, halo or cyano.

13. ) The compound of claim 1 which is 3-(1-{[8-methyl-2,3-dihydrofuro[2,3-f]-[1,4]benzodioxin-2-yl]methyl}-1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole or a pharmaceutically acceptable salt thereof.

14. ) The compound of claim 1 which is 3-{1-[2,3,8,9-tetrahydrofuro[3,2-f]-[1,4]benzodioxin-2-ylmethyl]-1,2,3,6-tetrahydro-4-pyridinyl}-1H-indole or a pharmaceutically acceptable salt thereof.

15. ) The compound of claim 1 which is 3-{1-[2,3-dihydrofuro[3,2-f]-[1,4]-benzodioxin-2-ylmethyl]-1,2,3,6-tetrahydropyridin-4-yl}-1H-indole or a pharmaceutically acceptable salt thereof.

16. ) The compound of claim 1 which is 3-{1-[2,3,9,10-tetrahydro-8H-[1,4]-dioxino[2,3-f]chromen-2-ylmethyl]-1,2,3,6-tetrahydro-4-pyridinyl}-1H-indole or a pharmaceutically acceptable salt thereof.

17. ) The compound of claim 1 which is 5-fluoro-3-{1-[2,3,9,10-tetrahydro-8H-[1,4]-dioxino[2,3-f]chromen-2-ylmethyl]-1,2,3,6-tetrahydro-4-pyridinyl}-1H-indole or a pharmaceutically acceptable salt thereof.

19. ) The method of claim 16 wherein wherein the condition is depression.

20. ) The method of claim 16 wherein the condition is obsessive compulsive disorder, panic attacks, generalized anxiety disorder or social anxiety disorder.

21. ) The method of claim 16 wherein the subject is a human.

18. ) A method of treating a subject suffering from a condition selected from the group consisting of depression, anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, attention deficit disorder, obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, obesity, eating disorders, vasomotor flushing, cocaine and alcohol addiction, and sexual dysfunction, which comprises providing to the subject suffering from said condition, a therapeutically effective amount of a compound of formula I

22. ) A pharmaceutical composition comprising a compound of formula I