4-amino-N-(4-methyl-4-piperidinyl)-2-methoxybenzamides for treating smooth muscle contraction disorders

• US 5,498,618 A
• Filed: 07/08/1993
• Issued: 03/12/1996
• Est. Priority Date: 07/17/1992
• Status: Expired due to Fees

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Leysen, Josepha E. M. F., Van Daele, Georges H. P.
• Primary Examiner(s): Chano, Ceila
• Application Number:
  US08/367,111
• Time in Patent Office: 978 Days
• Field of Search: 546/224, 514/329
• US Class Current: 514/329
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 211/58 attached in position 4

Abstract

Piperidinyl substituted benzamides of formula ##STR1## the pharmaceutically acceptable acid addition salts thereof and the stereoisomeric forms thereof, wherein R¹ is hydrogen or halo; R² is halo; R³ is hydrogen or halo; R⁴ and R⁵ each independently are hydrogen, C_1-4 alkyl or haloC_1-4 alkyl; and the group NR⁴ R⁵ may also be azido, Alk is C_2-4 alkanediyl; pharmaceutical compositions containing said compounds of formula (I) as active ingredient; use of said compounds as a medicine; process of preparing said compounds; compounds of formula (I) containing a radioactive isotope; process of marking 5HT₂ -receptor sites; and process for imaging an organ are disclosed.

Claims

1. A compound having the formula ##STR7## a pharmaceutically acceptable acid addition salt thereof or a stereoisomeric form thereof, wherein

R¹ represents hydrogen or halo;

R² represents halo;

R³ represents hydrogen or halo;

R⁴ and R⁵ each independently represent hydrogen, C_1-4 alkyl or haloC_1-4 alkyl;

the group NR⁴ R⁵ may also be azido, and

Alk represents C_2-4 alkanediyl.

2. A compound according to claim 1 wherein the compound is

4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide;

4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-2-methoxybenzamide;

4-amino-5-bromo-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-2-methoxybenzamide;

4-amino-N-[1-[3-(2-bromo-4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-chloro-2-methoxybenzamide;

4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-2-methoxybenzamide;

4-azido-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-2-methoxybenzamide;

4-azido-N-[1-[3-(4-fluorophenoxy)propyl]-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide;

4-azido-5-bromo-N-[1-[3-(4-4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-2-methoxybenzamide, or a pharmaceutically acceptable acid addition salt thereof.

3. A compound according to claim 1 having at least one halo which is a radioactive isotope of iodine, bromine or fluorine.

4. A compound according to claim 1 wherein the compound is 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide, [5-¹²⁵ I] or [5-¹²³ I].

5. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredient a compound as claimed in claim 1 in an amount effective for treating serotonin mediated conditions.

6. A process of treating smooth muscle contraction disorders in warm blooded mammals that are related to the excessive release of serotonin, which comprises administering to warm blooded mammals a therapeutically effective amount of a compound as defined in claim 1.

7. A process of treating smooth muscle contraction disorders in warm blooded mammals that are related to the excessive release of serotonin, which comprises administering to warm blooded mammals a therapeutically effective amount of a compound as defined in claim 2.