Aminosulfonyl substituted 4-(aminomethyl)-piperidine benzamides as 5ht 4-antagonists

• US 20060142339A1
• Filed: 06/10/2004
• Published: 06/29/2006
• Est. Priority Date: 06/19/2003
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Mevellec, Laurence Anne, Gijsen, Henricus Jacobus Maria, Bosmans, Jean-Paul Rene Marie Andre
• Granted Patent: US 7,652,040 B2
• Time in Patent Office: Days
• US Class Current: 514/320
• 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 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/12 Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links

Abstract

The present invention is concerned with novel compounds of formula (I) having 5HT₄-antagonistic properties. The invention further relates to methods for preparing such novel compounds, pharmaceutical compositions comprising said novel compounds as well as the use as a medicine of said compounds.

Claims

1. A compound of formula (I)

2. A compound as claimed in claim 1 wherein the —

OR⁵ radical is situated at the 3-position of the piperidine moiety having the trans configuration.

3. A compound as claimed in claim 2 wherein the absolute configuration of said piperidine moiety is (3S, 4S).

4. A compound as claimed in claim 1 wherein L is a radical of formula (b-1) wherein Alk is C_1-4alkanediyl, and R⁶ aminosulfonyl or aminosulfonyl substituted with C_1-4alkyl or phenyl.

5. A compound as claimed in claim 1 wherein L is a radical (b-5) wherein Alk is C_1-4alkanediyl, and R ¹¹ is C_1-4alkyl.

6. A compound as claimed in claim 1 wherein L is a radical (b-7) wherein Alk is C_1-4alkanediyl and R¹¹ is C_1-4alkyl.

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

10. A process for preparing a compound of formula (I) wherein

a) an intermediate of formula (II) is reacted with an carboxylic acid derivative of formula (III) or a reactive functional derivative thereof;

b) an intermediate of formula (IV) is N-alkylated with an intermediate of formula (V), in a reaction-inert solvent and, optionally in the presence of a suitable base;

wherein in the above reaction schemes the radicals —

R¹—

R²—

, R³, R⁴, R⁵, and L are as defined in claim 1 and W is an appropriate leaving group;

c) or, compounds of formula (I) are converted into each other following art-known transformation reactions;

or if desired;

a compound of formula (I) is converted into a pharmaceutically acceptable acid addition salt, or conversely, an acid addition salt of a compound of formula (I) is converted into a free base form with alkali; and

, if desired, preparing stereochemically isomeric forms thereof.

11. A method for the treatment of 5HT₄ related disorders comprising administering to a patient in need thereof an effective amount of a compound according to claim 1.

12. A method for treating patients suffering from gastrointestinal conditions comprising administering to the patient an effective amount of a compound according to claim 1.

13. A method for treating hypermotility, irritable bowel syndrome, constipation or diarrhea predominant IBS, pain and non-pain predominant IBS and bowel hypersensitivity comprising administering to a patient in need thereof an effective amount of a compound according to claim 1.

8. (canceled)

9. (canceled)