Bicyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives

• US 8,318,742 B2
• Filed: 09/20/2011
• Issued: 11/27/2012
• Est. Priority Date: 07/11/1997
• Status: Expired due to Fees

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Bosmans, Jean-Paul René Marie André, DeCleyn, Michel Anna Jozef, Surkyn, Michel
• Primary Examiner(s): Chang, Celia
• Application Number:
  US13/237,330
• Publication Number:
  US 20120028987A1
• Time in Patent Office: 434 Days
• Field of Search: 514/252, 514/320, 514/321, 544/239, 546/197
• US Class Current: 514/252
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 211/42 attached in position 3 or 5
• CPC Class Codes: C07D 211/44 attached in position 4
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The present invention of compounds of formula (I)

a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

Claims

1. A compound of formula (I)

2. The compound according to claim 1, wherein the —

OR⁴ radical of the central piperidine moiety has the trans configuration.

3. The compound according to claim 1 wherein L is C_3-6cycloalkyl or C_2-6alkenyl;

or L is a radical of formula (b-1), wherein each Alk is C_1-6alkanediyl, and R⁶ is hydrogen, hydroxy, cyano, amino, C_1-6alkylsulfonylamino, C_3-6cycloalkyl or Het¹, wherein Het¹ is tetrahydrofuran;

dioxolane;

dioxolane substituted with C_1-6alkyl;

tetrahydropyran;

pyridazinyl substituted with one or more substituents that is hydroxy, halo or C_1-6alkyl;

or a radical of formula (c-1), (c-3) or (c-4) wherein R¹³ is C_1-4alkyl;

or L is a radical of formula (b-2), wherein Alk is C_1-6alkanediyl, X is O, and R⁷ is C_1-6alkyl or hydroxyC_1-6alkyl;

or L is a radical of formula (b-2), wherein Alk is C_1-6alkanediyl, R⁷ is Het² wherein Het² is pyrazinyl substituted with C_1-6alkyl, and X is NR⁸ wherein R⁸ is hydrogen or C_1-6alkyl;

or L is a radical of formula (b-3) wherein Y is a direct bond, and R⁹ is C_1-6alkyl, hydroxy or C_1-6alkyloxy;

or L is a radical of formula (b-4) wherein Y is a direct bond, and R¹¹ and R¹² are C_1-6alkyl, or R¹¹ and R¹² combined with the nitrogen atom bearing R¹¹ and R¹² form pyrrolidinyl.

4. The compound according to claim 1 wherein L is -Alk-R⁶ (b-1).

5. The compound according to claim 1 wherein L is -Alk-R⁶ (b-1), wherein Alk is C_1-6alkanediyl and R⁶ is Het¹.

6. The compound according to claim 1 wherein L is -Alk-R⁶ (b-1), wherein Alk is C_1-6alkanediyl and R⁶ is Het¹, and wherein Het¹ is tetrahydrofuran;

dioxolane;

dioxolane substituted with C_1-6alkyl;

tetrahydropyran;

pyridazinyl substituted with one or more substituents that is hydroxy, halo or C_1-6alkyl.

7. The compound according to claim 1 that is:

8. The compound according to claim 1 that is:

9. The compound according to claim 1 that is:

10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically active amount of a compound according to claim 1.

11. A process for preparing a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically active amount of a compound according to claim 1 comprising intimately mixing the compound according to claim 1 with a pharmaceutically acceptable carrier.

12. A method of treating decreased gastro-intestinal motility comprising administering to a subject in need thereof an effective amount of a compound according to claim 1.