Trisubstituted naphthylalkylamides for disorders of the melatoninergic system

• US 5,591,775 A
• Filed: 12/06/1994
• Issued: 01/07/1997
• Est. Priority Date: 12/07/1993
• Status: Expired due to Term

• Current Assignee: Les Laboratoires Servier (Servier Sas)
• Original Assignee: Adir SA
• Inventors: Delagrange, Philippe, Mansour, Hamid A., Renard, Pierre, Lesieur, Daniel, Depreux, Patrick, Lefoulon, Fran.cedilla.ois, Adam, Gerard
• Primary Examiner(s): Cintins, Marianne M.
• Assistant Examiner(s): Spivack, Phyllis G.
• Application Number:
  US08/349,914
• Time in Patent Office: 763 Days
• Field of Search: 514/580, 514/588, 514/613, 514/599, 514/595, 514/617, 564/17, 564/57, 564/58, 564/189, 564/190, 564/192, 564/209
• US Class Current: 514/580
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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 233/31 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
• 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 233/61 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-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 2601/16 the ring being unsaturated
• CPC Class Codes: C07C 275/24 containing six-membered aromatic rings
• CPC Class Codes: C07C 275/26 having nitrogen atoms of urea groups bound to carbon atoms of rings other than six-membered aromatic rings
• CPC Class Codes: C07C 327/42 to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
• CPC Class Codes: C07C 327/46 having carbon atoms of thiocarboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings

Abstract

The invention relates to a compound selected from those of formula (I): ##STR1## in which R, R₁, R₂ and R₃ are as defined herein for use in the treatment of a disorder of the melatoninergic system.

Claims

1. A compound of formula (I):

##STR28## in which;

R represents hydrogen or a radical chosen from alkyl, substituted alkyl and --O--R'"'"';

with R'"'"' representing hydrogen or a radical selected from alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, substituted cycloalkylalkyl, phenyl, substituted phenyl, phenylalkyl, substituted phenylalkyl, diphenylalkyl and substituted diphenylalkyl;

R₁ represents hydrogen or alkyl;

R₂ represents a) ##STR29## in which X¹ represents sulfur or oxygen and R₄₀ represents hydrogen or a radical chosen from alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, substituted cycloalkylalkyl, alkenyl, substituted alkenyl, alkynyl and substituted alkynyl;

or b) ##STR30## in which X² represents sulfur or oxygen and R₄₁ represents hydrogen or a radical chosen from alkyl, cycloalkyl and cycloalkylalkyl;

R₃ represents a radical chosen from;

(C₂ -C₆) alkyl,

substituted (C₂ -C₆) alkyl,

cycloalkylalkyl,

substituted cycloalkylalkyl,

alkenyl,

substituted alkenyl,

alkynyl,

substituted alkynyl,

hydroxyl in 3-position,

R₅ -alkyl-, with R₅ being substituted or unsubstituted and representing a radical chosen from phenyl and naphthyl;

R₆ --CO--O--,

and R₆ --CO--,

with R₆ representing a radical chosen from (C₁ -C₅)alkyl, substituted (C₁ -C₅)alkyl, cycloalkyl, substituted cycloalkyl, cycloalkyl(C₁ -C₅)alkyl, substituted cycloalkyl(C₁ -C₅)alkyl, R₅ - and R₅ -alkyl- where R₅, being unsubstituted or substituted, is as defined above,

it being understood that the compound of formula (I) cannot be N-{2-[(4-acetyl)naphth-1-yl]ethyl}acetamide,

wherein the terms "alkyl" and "alkoxy" denoting inclusively, except where otherwise mentioned, linear or branched groups of 1 to 6 carbon atoms,

the terms "alkenyl" and "alkynyl" denoting inclusively unsaturated, linear or branched groups of 2 to 6 carbon atoms,

the term "cycloalkyl" denoting inclusively a cyclic group of 3 to 8 carbon atoms,

the term "substituted", applied to "alkyl", "alkoxy", "alkenyl", "alkynyl", "cycloalkyl" or "cycloalkylalkyl", means that these groups are substituted with one or more radicals chosen from alkyl, alkoxy and halogen;

the term "substituted" associated with R₅ and with "phenyl", "phenylalkyl" or "diphenylalkyl" means that these groups are substituted with one or more radicals chosen from alkyl, alkoxy, halogen, hydroxyl and trifluoromethyl;

their enantiomers and diastereoisomers,

and their addition salts with a pharmaceutically acceptable acid or base.

2. A compound of claim 1, which is N-[2-(7-methoxy-3-benzoylnaphth-1-yl)ethyl]acetamide.

3. A compound of claim 1, which is N-[2-(7-methoxy-3-acetylnaphth-1-yl)ethyl]acetamide.

4. A compound of claim 1, which is N-[2(7-methoxy-3-acetylnaphth-1-yl)ethyl]cyclopropylcarboxamide.

5. A compound of claim 1, which is N-[2(7-methoxy-3-ethylnaphth-1-yl)ethyl]acetamide.

6. A compound of claim 1, which is N-[2(7-methoxy-3-propylnaphth-1-yl)ethyl]acetamide.

7. A compound of claim 1 which is N-[2(7-methoxy-3-hydroxynaphth-1-yl)ethyl]acetamide.

8. A compound of claim 1 which is N-[2-(7-methoxy-3-cyclopropylcarbonylnaphth-1-yl)ethyl]acetamide.

9. A compound of claim 1 which is N-[2-(7-methoxy-3-acetoxynaphth-1-yl)ethyl]acetamide.

10. A compound of claim 1 which is N-[2-(7-methoxy-3-hydroxynaphth-1-yl)ethyl]acetamide.

11. A compound of claim 1 which is N-[2-(3,7-dihydroxynaphth-1-yl)ethyl]acetamide.

12. A compound of claim 1 which N-[2-(7-methoxy-3-benzylnaphth-1-yl)ethyl]acetamide.

13. A compound of claim 1 which is N-[2-(7-methoxy-3-ethylnaphth-1-yl)ethyl]cyclopropylcarboxamide.

14. A compound of claim 1 which is N-[2-(7-methoxy-3-cyclopropylmethylnaphth-1-yl)ethyl]acetamide.

15. A pharmaceutical composition useful in treating sleep disorders containing a compound of claim 1 in combination with one or more pharmaceutically-acceptable excipients.

16. A method of treating a mammal afflicted with a disorder of the melatoninergic system comprising the step of administrating to said mammal an effective amount of a compound according to claim 1 for alleviation of said disoder.

17. A method of treating a mammal afflicted with a sleeping disorder comprising the step of administering to said mammal an effective amount of a compound according to claim 1 for alleviation of said disorder.