Heterocyclic aminomethyl compounds

• US 5,919,784 A
• Filed: 11/07/1997
• Issued: 07/06/1999
• Est. Priority Date: 11/08/1996
• Status: Expired due to Fees

• Current Assignee: Les Laboratoires Servier (Servier Sas)
• Original Assignee: Adir SA
• Inventors: Carato, Pascal, Rettori, Marie-Claire, Bonte, Jean-Paul, Millan, Mark, Caignard, Daniel-Henri, Renard, Pierre, Lesieur, Daniel, Depreux, Patrick, Newman-Tancredi, Adrian
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): KESSINGER, ANN
• Application Number:
  US08/966,040
• Time in Patent Office: 606 Days
• Field of Search: 544/364, 544/368, 544/295, 514/253
• US Class Current: 514/253.1
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: C07D 263/58 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
• CPC Class Codes: C07D 265/36 condensed with one six-membered ring
• CPC Class Codes: C07D 277/68 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
• CPC Class Codes: C07D 279/16 condensed with one six-membered ring

Abstract

A compound of general formula (I): ##STR1## where A, X, R₁, Y, n and Ar are defined in the description. Medicinal products containing the same are useful as D₄ receptor Ligands.

Claims

1. A compound selected from those of general formula (I):

##STR24## in which;

R₁ represents hydrogen or lower alkyl, or alternatively

R₁ represents a group ##STR25## in which m is 1 to 4 inclusive to Ar₁ represents either CO--Ar₂ where Ar₂ represents phenyl unsubstituted or substituted with one or more radicals chosen from halogen, hydroxyl, lower alkyl, trifluoromethyl and lower alkoxy,

or ═

C--(Ar₂)₂ where Ar₂ has the same meaning as above,

n represents 0 or 1

A represents oxygen or sulfur

X represents a single bond

Y represents nitrogen

Ar represents phenyl or naphthyl either in unsubstituted or substituted with one, two or three groups chosen from halogen, hydroxyl, lower alkoxy, lower alkyl, (lower alkoxy)(lower alkyl), aminosulfonyl, or Ar represents pyridyl, or 3-(benzo d!1,2-thiazolyl) also known as 3-benzisothiazolyl;

##STR26## and where appropriate its isomers, pure or mixed, as well as its addition salts with a pharmaceutically-acceptable acid, or a pharmaceutically-acceptable base when R₁ ═

H, on the understanding that, except where otherwise stated,

the terms "lower alkyl" and "lower alkoxy" correspond to linear or branched groups having 1 to 6 carbon atoms inclusive.

2. A compound of claim 1 in which:

R₁ is hydrogen, methyl, or a group ##STR27## for which m equals 2 and Ar₁ represents either a ##STR28## group or alternatively a ##STR29## group A is sulfur and X represents a single bond, or

A is oxygen and X represents a single bond,

the side chain is attached grafted at position c

n represents 0

Y represents nitrogen

Ar represents phenyl substituted with fluorine, chlorine, or methoxy, as well as its isomers, pure or mixed, as well as its addition salts with a pharmaceutically-acceptable acid, or a pharmaceutically-acceptable base when R₁ ═

H.

3. A compound of claim 1, from selected the group consisting of:

3-methyl-6-{ 4-(2-methoxyphenyl)-1-piperazinyl!methyl}benzoxazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(2-methoxyphenyl)-1-piperazinyl!methyl}benzothiazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(2-fluorophenyl)-1-piperazinyl!methyl}benzothiazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(2-fluorophenyl)-1-piperazinyl!methyl}benzoxazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(4-chlorophenyl)-1-piperazinyl!methyl}benzoxazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(4-chlorophenyl)-1-piperazinyl!methyl}benzothiazolinone, and its addition salts with a pharmaceutically-acceptable acid,

6-{ 4-(2-fluorophenyl)-1-piperazinyl!methyl}benzoxazolinone, and its addition salts with a pharmaceutically-acceptable acid or base,

6-{ 4-(2-fluorophenyl)-1-piperazinyl!methyl}benzothiazolinone, and its addition salts with a pharmaceutically-acceptable acid or base,

3-{2- 4-(4-fluorobenzoyl)piperidyl!ethyl}-6-{ 4-(2-fluorophenyl)-1-piperazin !methyl}benzoxazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-{2- 4-(4'"'"',4"-difluorobenzhydrylidene)-1-piperidyl!ethyl}-6-{ 4-(2fluorophenyl)-1-piperazinyl!methyl}benzoxazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-{2- 4-(4-fluorobenzoyl)-1-piperidyl!ethyl}-6-{ 4-(2-fluorophenyl)-1-piperazinyl!methyl}, benzothiazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(benzo d! 1,2!thiazolyl)-1-piperazinyl!methyl}benzoxazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(benzo d! 1,2!thiazolyl)-1-piperazinyl!methyl}benzothiazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(4-aminosulfonylphenyl)-1-piperazinyl!methyl}benzoxazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(4-aminosulfonylphenyl)-1-piperazinyl!methyl}benzothiazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(3-methoxyphenyl)-1-piperazinyl!methyl}benzoxazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(4-methoxyphenyl)-1-piperazinyl!methyl}benzothiazolinone, and its addition salts with a pharmaceutically-acceptable acid,

3-methyl-6-{ 4-(4-methoxyphenyl)-1-piperazinyl!methyl}benzoxazolinone, and its addition salts with a pharmaceutically-acceptable acid.

4. A compound of claim 1 which is 3-methyl-6-{ 4-(2-fluorophenyl)-1-piperazinyl!methyl} benzothiazolinone or an addition salt thereof with a pharmaceutically-acceptable acid.

5. A compound of claim 1 which is 3-methyl-6-{ 4-(4-chlorophenyl)-1-piperazinyl!methyl} benzoxazolinone or an its addition salt thereof with a pharmaceutically acceptable acid.

6. A method for treating a living body afflicted with a condition selected from anxiety and depression, comprising the step of administering to the living body an amount of a compound of claim 1 which is effective for alleviation of said condition.

7. A pharmaceutical composition comprising as active principle an effective amount of a compound as claimed in claim 1, together with one or more pharmaceutically-acceptable excipients or vehicles.

8. A pharmaceutical composition comprising as active principle an effective amount of a compound as claimed in claim 3, together with one or more pharmaceutically-acceptable excipients or vehicles.

9. A method for treating a living body afflicted with a condition selected from anxiety and depression, comprising the step of administering to the living body an amount of a compound of claim 3 which is effective for alleviation of said condition.