N-('-B-hydroxyethylpiperid-4-yl esters and amides

• US 4,853,394 A
• Filed: 11/03/1986
• Issued: 08/01/1989
• Est. Priority Date: 11/02/1985
• Status: Expired due to Fees

• Current Assignee: Beecham Group PLC (GSK plc)
• Original Assignee: Beecham Group PLC (GSK plc)
• Inventors: King, Francis D., Martin, Roger T., Watts, Eric A.
• Primary Examiner(s): Rotman, Alan L.
• Application Number:
  US06/926,427
• Time in Patent Office: 1,002 Days
• Field of Search: 546/224, 514/329
• US Class Current: 369/47.29
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 451/04 with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system

Abstract

Compounds of formula (I) and pharmaceutically acceptable salts thereof:

Ar--CO--X--Y--Z--OR.sub.1                                  (I)

wherein: Ar is a group of formula (a): ##STR1## wherein either R₂ is C_1-6 alkoxy and one of R₃, R₄ and R₅ is hydrogen and the other two are selected from hydrogen, halogen, CF₃, CX_1-6 alkylthio, C_1-7 acyl, C_1-6 alkoxy, C_1-10 carboxylic acylamino, C_1-6 alkyl S(O)n wherein n is 1 or 2, nitro or amino, aminocarbonyl or aminosulphonyl optionally substituted by one or two groups selected from C_1-6 alkyl, C_3-8 cycloalkyl, C_3-8 cycloalkyl C_1-4 alkyl or phenyl C_1-4 alkyl groups any of which phenyl moieties may be substituted by one or two groups selected from halogen, CF₃, C_1-6 alkyl or C_1-6 alkoxy; or R₂ is hydrogen and R₃, R₄ and R₅ are independently selected from hydrogen, C_1-6 alkyl, hydroxy, C_1-6 alkoxy, C_1-6 alkylthio or halo; or any two on adjacent carbon atoms together are C_1-2 alkylenedioxy and the third is hydrogen, C_1-6 alkyl, C_1-6 alkoxy or halo;

X is NH; when Ar is of formula (a) and R₂ is hydrogen,

Y is a group of formula (c), ##STR2## Z is C₂ or C₃ polymethylene optionally substituted by one or two C_1-4 alkyl groups; and

R₁ is hydrogen or C_1-6 alkyl or OR₁ is an in vivo hydrolysable acyloxy group; having gastric motility enhancing activity, anti-emetic activity and/or 5-HT receptor antagonist activity, and their use as pharmaceuticals.

Claims

1. A compound according formula (II):

##STR13## wherein R₂¹ is C_1-6 alkoxy;

R₄¹ is amino or C_1-7 alkanoylamino;

R₅¹ is halo or C_1-6 alkylthio.

2. A compound according to claim 1 wherein R₂¹ is methoxy, R₄¹ is amino and R₅¹ is chloro, bromo or methylthio.

3. A pharmaceutical composition for the treatment of disorders relating to migraine or cluster headaches comprising an effective amount of a compound of formula (II) as defined in claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

4. A method of treatment of disorders relating to migraine or cluster headaches which comprises the administration of an effective amount of a compound of formula (II) as defined in claim 1, or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition for the treatment of disorders relating to trigeminal neuralgia comprising an effective amount of a compound of formula (II) as defined in claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

6. A method of treatment of disorders relating to trigeminal neuralgia which comprises the administration of an effective amount of a compound of formula (II) as defined in claim 1, or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition for the treatment of disorders relating to impaired gastro-intestinal motility or emesis comprising an effective amount of a compound of formula (II) as defined in claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

8. A method of treatment of disorders relating to impaired gastro-intestinal motility or emesis which comprises an effective amount of a compound of formula (II) as defined in claim 1, or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition for the treatment of disorders relating to impaired gastro-intestinal motility and emesis comprising an effective amount of a compound of formula (I) as defined in claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

10. A method of treatment of disorders relating to impaired gastro-intestinal motility and emesis which comprises the administration of an effective amount of a compound of formula (I) as defined in claim 1, or a pharmaceutically acceptable salt thereof.