Antidepressant indoletetrahydropyridine derivatives of 2,3-dihydro-7H-[1,4]dioxino[2,3-e]indole

• US 20020183352A1
• 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: Bravo, Byron A., Stack, Gary P., Tran, Megan
• Granted Patent: US 6,593,350 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 25/32 Alcohol-abuse
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• CPC Class Codes: C07D 491/04 Ortho-condensed systems

Abstract

Compounds of the formula

are useful in the treatment of central nervous system disorders including depression, obsessive compulsive disorder, panic attacks, generalized anxiety disorder, sexual dysfunction, eating disorders and addictive disorders caused by ethanol or cocaine abuse.

Claims

1. A compound of formula I:

2. A compound of claim 1 wherein R¹ is hydrogen, halogen, cyano, trifluoromethyl, alkyl of 1 to 6 carbon atoms, or alkoxy of 1 to 6 carbon atoms.

3. A compound of claim 1 wherein R² is hydrogen, trifluoromethyl or alkyl of 1 to 6 carbon atoms.

4. A compound of claim 1 wherein R³, R⁴ and R⁵ are independently selected from hydrogen, halogen, cyano, carboxamido, alkyl of 1 to 6 carbon atoms, and alkoxy of 1 to 6 carbon atoms.

5. A compound of claim 1 in which R¹ is hydrogen, halogen, cyano, trifluoromethyl, alkyl of one to six carbon atoms or alkoxy of one to six carbon atoms;

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

6. A compound of claim 1 in which R¹ is hydrogen, halo, cyano, trifluoromethyl, alkyl of one to six carbon atoms or alkoxy of one to six carbon atoms, R² is hydrogen, trifluoromethyl or alkyl of one to six carbon atoms, R³, R⁴ and R⁵ are independently selected from hydrogen, halo and cyano, R⁶ is hydrogen, Z is CR⁷ and R⁷ is hydrogen, halo or cyano.

7. A compound of claim 1 wherein R¹ is hydrogen, R² is hydrogen or lower alkyl, R³, R⁴ and R⁵ are independently selected from hydrogen or halogen, R⁶ is hydrogen, Z is CR⁷ and R⁷ is hydrogen or halogen.

8. A compound of claim 1 which is 2-[(4-(1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl]-8-methyl-2,3-dihydro-7H-[1,4]dioxino[2,3-e]indole or a pharmaceutically acceptable salt thereof.

9. A compound of claim 1 which is 2-[(4-(1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl]-2,3-dihydro-7H-[1,4]dioxino[2,3-e]indole or a pharmaceutically acceptable salt thereof.

10. A compound of claim 1 which is 2-{[4-(5-fluoro-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl]methyl}-2,3-dihydro-7H-[1,4]dioxino[2,3-e]indole or a pharmaceutically acceptable salt thereof.

11. A compound of claim 1 which is 8-ethyl-2-[(4-(1H-indol-3-yl)-3,6-dihydro-pyridin-1(2H)nyl)methyl]-2,3-dihydro-7H-[1,4]dioxino[2,7-e]indole or a pharmaceutically acceptable salt thereof.

12. A compound of claim 1 which is 8-ethyl-2-[(4-(5-fluoro-1H-indol-3-yl)3,6-dihydropyridin-1(2H)-yl)methyl]-2,3-dihydro-7H-[1,4]dioxino[2,7-e]indoleor a pharmaceutically acceptable salt thereof.

14. The method of claim 13 wherein the condition is depression.

15. The method of claim 13 wherein the condition is selected from the group consisting of obsessive compulsive disorder, panic attacks, generalized anxiety disorder, and social anxiety disorder.

16. The method of claim 13 wherein the subject is a human.

13. 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

17. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I: