Esters of thienyl carboxylic acids and amino alcohols and their quaternization products

• US 5,610,163 A
• Filed: 03/16/1995
• Issued: 03/11/1997
• Est. Priority Date: 09/16/1989
• Status: Expired

• Current Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Bauer, Rudolf, Banholzer, Rolf, Reichl, Richard
• Primary Examiner(s): Datlow, Philip I.
• Application Number:
  US08/405,111
• Time in Patent Office: 726 Days
• Field of Search: 546/91, 546/125, 514/291, 514/304
• US Class Current: 514/291
• CPC Class Codes: C07D 451/10 acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
• CPC Class Codes: C07D 451/14 containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof

Abstract

Compounds of the formula ##STR1## of which, in exemplary compounds, the thienyl group is attached via the 2-position and:

(a) A is 3α-(6β, 7β-epoxy)-tropanyl methobromide and R₁ is 2-thienyl;

(b) A is 3α-(6, 7dehydro)-tropanyl methobromide and R₁ is 2-thienyl;

(c) A is 3β-tropanyl methobromide and R₁ is 2-thienyl; and,

(d) A is 3α-(N-isopropyl)-nortropanyl methobromide and R₁ is cyclopentyl.

These are anticholinergics. Administered by inhalation, they are useful for the treatment of chronic obstructive bronchitis or slight to moderately severe asthma. Administered by the intravenous or oral routes, they are useful for the treatment of vagally induced sinus bradycardia.

Claims

1. A compound of the formula ##STR26## wherein Q is a group of the formula --CH₂ --CH₂ --, --CH═

CH-- or ##STR27## R and R'"'"' are each independently C₁ -C₄ -alkyl;

R₁ is thienyl, phenyl, cyclopentyl or cyclohexyl; and

,

X^- is a physiologically acceptable anion.

2. A compound in accordance with claim 1, of the formula ##STR28## wherein R is CH₃, C₂ H₅, n-C₃ H₇, or i-C₃ H₇ ;

R'"'"' is CH₃ ; and

,

R₁, Q and X^- are as defined in claim 1.

3. A compound in accordance with claim 2 wherein R₁ is thienyl.

4. A compound in accordance with claim 2 wherein X^- is Br^- or CH₃ SO₃.

11. A method for treating chronic obstructive bronchitis which comprises administering, by inhalation, to a subject suffering from the same, a therapeutic amount of a compound in accordance with claims 1, 2, 3, 4 6, 7, 8, 9, 10.

12. A method for treating slight to moderately severe asthma which comprises administering, by inhalation, to a subject suffering from the same, a therapeutic amount of a compound in accordance with claims 1, 2, 3, 4, 6, 7, 8, 9, 10.

13. A method for treating vagally induced sinus bradycardia which comprises administering, by the intravenous or oral routes, to a subject suffering from the same, a therapeutic amount of a compound in accordance with claims 1, 2, 3, 4, 6, 7, 8, 9, 10.

14. A pharmaceutical composition, for administration by inhalation, suitable for the treatment of chronic obstructive bronchitis or slight to moderately severe asthma, which comprises a compound in accordance with claims 1, 2, 3, 4, 6, 7, 8, 9, 10.

15. A pharmaceutical composition, for oral administration, suitable for the treatment of vagally induced sinus bradycardia, which comprises a compound in accordance with claims 1, 2, 3, 4, 6, 7, 8, 9, 10.

16. A pharmaceutical composition, for intravenous administration, suitable for the treatment of vagally induced sinus bradycardia, which comprises a compound in accordance with claims 1, 2, 3, 4, 6, 7, 8, 9, 10.

5. A compound of the formula ##STR29## wherein X^- is a physiologically acceptable anion.

6. A compound of the formula ##STR30## wherein X^- is a physiologically acceptable onion.

7. A compound of the formula ##STR31##

8. A compound of the formula ##STR32## wherein R₁ is 2-thienyl and A is 3α

-(6,7-dehydro)-tropanyl methobronide.

9. A compound of the formula ##STR33## wherein R₁ is 2-thienyl and A is 3β

-tropanyl methobromide.

10. A compound of the formula ##STR34## wherein R₁ is cyclopentyl and A is 3α

-(N-isopropyl)-nortropanyl methobromide.