Arylalkyl(thio) amides

• US 5,554,642 A
• Filed: 05/22/1995
• Issued: 09/10/1996
• Est. Priority Date: 10/02/1992
• Status: Expired due to Fees

• Current Assignee: Les Laboratoires Servier (Servier Sas)
• Original Assignee: Adir SA
• Inventors: Adam, G erard, Renard, Pierre, Langlois, Michel
• Primary Examiner(s): Kumar, Shailendra
• Application Number:
  US08/446,409
• Time in Patent Office: 477 Days
• Field of Search: 548/469, 548/484, 548/485, 548/486, 548/490, 548/491, 548/494, 548/495, 514/415, 514/418, 514/419
• US Class Current: 514/415
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 233/18 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 233/20 having the carbon atom of the carboxamide group bound to a carbon atom of an acyclic unsaturated carbon skeleton
• CPC Class Codes: C07C 233/60 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/04 with a four-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2602/10 the other ring being six-membered, e.g. tetraline
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 307/79 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 319/18 Ethylenedioxybenzenes, not substituted on the hetero ring

Abstract

A compound which is selected from those of formula (I): ##STR1## in which A, R₁, R₂, R₃, R₄, R₅ and R₆ are as defined in the description,

its optical isomers and its addition salts thereof with a pharmaceuticaliy-accepable acid or base,

and medicinal products containing the same which are useful for treating a disorder of the melatoninergic system.

Claims

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

##STR21## in which;

A represents a --CH₂ --CH₂ -- chain, unsubstituted or substituted with lower alkyl,

R₁ represents hydrogen or lower alkyl,

R₂ represents hydrogen, halogen or lower alkyl,

R₃ and R₄, together with the benzene ring which carries them, form an indole ring-system E₃ on the understanding that the portion of the ring-system E₃ formed by R₃ and R₄ and the two carbon atoms of the benzene ring which carry them is;

unhydrogenated or partially hydrogenated,

and unsubstituted or substituted with one or more radicals chosen from;

halogen, hydroxyl, lower alkyl, lower alkoxy, lower alkoxycarbonyl, and trifluoromethyl,

R₅ represents hydrogen or lower alkyl,

R₆ represents a group ##STR22## in which X represents oxygen and R₇ represents a radical chosen from;

lower alkyl, unsubstituted or substituted with one or more radicals chosen from halogen, hydroxyl, and lower alkoxy,

linear or branched alkenyl having 2 to 7 carbon atoms, inclusive, unsubstituted or substituted with one or more radicals chosen from halogen, hydroxyl, and lower alkoxy,

and --(CH₂)_m --E₄ in which m represents 0 or 1 to 4, inclusive, and E₄ represents a mono- or bicyclic cycloalkyl having 3 to 12 carbon atoms, inclusive, unsubstituted or substituted with one or more radicals chosen from halogen, and lower alkyl,

its optical isomers, and addition salts thereof with a pharmaceutically-acceptable acid or base when R₃ or R₄ represents a satisfiable group,

on the understanding that the terms "lower alkyl" and "lower alkoxy" denote linear or branched groups having 1 to 6 carbon atoms, inclusive, and that the terms "cycloalkenyl" and "alkenyl" denote hydrocarbon groups containing one or more double bonds.

2. A compound as claimed in claim 1 in which R₁ represents a methyl radical.

3. A compound as claimed in claim 1 in which R₃ and R₄, together with the benzene ring which carries them, form an indole ring-system E₃ benzofuran, indole, on the understanding that the portion of the ring-system E₃ formed by R₃ and R₄ and the 2 carbon atoms of the benzene ring which carry them is:

substituted with one or more radicals chosen from;

halogen, hydroxyl, lower alkyl, lower alkoxy, lower alkoxycarbonyl and trifluoromethyl.

4. A compound as claimed in claim 1 in which R₃ and R₄, together with the benzene ring which carries them, form an indole,

on the understanding that the benzene ring formed by R₃, R₄ and the 2 carbon atoms which carry them is unhydrogenated and unsubstituted or substituted with one or more radicals chosen from halogen, hydroxyl, lower alkyl, lower alkoxy, lower alkoxycarbonyl, and trifluoromethyl.

5. A compound as claimed in claim 1 in which R₁ represents a methyl radical and R₃ and R₄, together with the benzene ring which carries them, form an indole on the understanding that the benzene ring formed by R₃ and R₄ and the 2 carbon atoms which carry them is unsubstituted or substituted with one or more radicals chosen from:

halogen, hydroxyl, lower alkyl, lower alkoxy, lower alkoxycarbonyl, and trifluoromethyl.

6. A pharmaceutical composition containing as active principle a compound as claimed in claim 1, in combination with one or more pharmaceutically-acceptable excipients.

7. A method of treating a mammal afflicted with a sleep disorder comprising the step of administering to the said mammal an amount of a compound as claimed in claim 1 which binds at melatonin receptors and is effective in the treatment of said disorder.

8. A compound as claimed in claim 1 which is N-[2-(5-methoxy-4-indolyl)ethyl]acetamide.

9. A compound as claimed in claim 1 which is N-[2-(5-methoxy-4-indolyl)ethyl]propionamide.

10. A compound as claimed in claim 1 which is N-[2-(5-methoxy-4-indolyl)ethyl]cyclopropylcarboxamide.

11. A compound as claimed in claim 1 which is N-[2-(5-methoxy-4-indolyl)ethyl]trifluoroacetamide.