1-isopropyl-2-oxo-1,2-dihydropyridine-3-carboxamide derivatives having 5-HT4 receptor agonistic activity

• US 8,362,038 B2
• Filed: 02/18/2010
• Issued: 01/29/2013
• Est. Priority Date: 01/29/2004
• Status: Expired due to Fees

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Kato, Tomoki, Kawamura, Kiyoshi, Uchida, Chikara
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US12/708,012
• Publication Number:
  US 20100144789A1
• Time in Patent Office: 1,076 Days
• Field of Search: 514/318, 546/194
• US Class Current: 514/318
• 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 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings

Abstract

This invention provides a compound of formula (I): wherein R¹ represents an alkyl group having from 1 to 4 carbon atoms or a halogen atom, R² represents an alkyl group having from 1 to 4 carbon atoms, R³ represents a hydrogen atom or a hydroxy group, and A represents an oxygen atom or a group of the formula —C(R⁴)(R⁵)— (in which R⁴ represents a hydrogen atom or an alkyl group having from 1 to 4 carbon atoms and R⁵ represents a hydroxy group or an alkoxy group having from 1 to 4 carbon atoms) or a pharmaceutically acceptable salts thereof. These compounds have 5-HT₄ receptor agonistic activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans.

Claims

1. A compound of the formula (I):

2. The compound of claim 1, wherein R¹ is halogen.

3. The compound of claim 1, wherein R² is alkyl having 1 to 2 carbons.

4. The compound of claim 2, wherein R² is alkyl having 1 to 2 carbons.

5. The compound of claim 1, wherein R³ is hydroxy.

6. The compound of claim 2, wherein R³ is hydroxy.

7. The compound of claim 4, wherein R³ is hydroxy.

9. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof together with at least one pharmaceutically acceptable carrier.

10. A method for treating gastroesophageal reflux disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), dyspepsia, esophagitis, or gastroesophageral disease, comprising administering to a mammal in need of such treatment a therapeutically effective mount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

11. A method for treating gastroesophageal reflux disease comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

8. A compound which is

5-chloro-N-{[1-(cyclohexylmethyl)piperidin-4-yl]methyl}-1-isopropyl-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;

5-chloro-N-({1-[(1-hydroxycyclohexyl)methyl]piperidin-4-yl}methyl)-1-isopropyl-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;

5-chloro-N-({1-[(cis-1-hydroxy-4-methoxycyclohexyl)methyl]piperidin-4-yl}methyl)-1-isopropyl-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;

5-chloro-N-({1-[(trans-1-hydroxy-4-methoxycyclohexyl)methyl]piperidin-4-yl}methyl)-1-isopropyl-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;

or

5-chloro-N-({1-[(trans-1,4-Dihydroxy-4-methylcyclohexyl)methyl]piperidin-4-yl}methyl)-1-isopropyl-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;

and pharmaceutically acceptable salt thereof.