Melatonergic agents

• US 5,661,185 A
• Filed: 12/14/1995
• Issued: 08/26/1997
• Est. Priority Date: 10/14/1994
• Status: Expired due to Term

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Watson, Brett T., Parker, Michael F., Karageorge, George N., Keavy, Daniel J., Takaki, Katherine S.
• Primary Examiner(s): Kumar, Shailendra
• Application Number:
  US08/572,838
• Time in Patent Office: 621 Days
• Field of Search: 514/596, 514/598, 514/923, 514/595, 534/52, 534/56
• US Class Current: 514/595
• 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 235/08 having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic 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 275/24 containing six-membered aromatic rings

Abstract

New melatonergic agents are phenyl alkanyl or phenyl alkyl substituted carboxamides and ureas of Formula I: ##STR1## wherein: R₁ =C_1-3 alkyl, allyl, C_3-6 cycloalkyl substituted C_1-4 alkyl;

R₂ =hydrogen, halogen or C_1-4 alkoxy;

R₃ =hydrogen or C_1-4 alkyl;

R₄ =C_1-4 alkyl, C_1-4 alkyl substituted amino, carboxylic acid substituted

C_1-4 alkyl or C_3-6 cycloalkyl, C_3-6 cycloalkyl, or straight or branched chain

C_2-4 alkenyl;

A=a linear C_2-4 alkanediyl or alkenediyl chain, provided that A not be --CH₂ CH₂ -- when X is a bond; and

X=a covalent bond or oxygen.

Claims

1. A compound of formula I:

##STR25## wherein;

R₁ =C_1-3 alkyl, allyl, or C_3-6 cycloalkyl substituted C_1-4 alkyl;

R₂ =hydrogen, halogen, or C_1-4 alkoxy;

R₃ =hydrogen or C_1-4 alkyl;

R₄ =C_1-4 alkyl substituted amino;

A=a linear C_2-4 alkanediyl or alkenediyl chain, provided that A not be --CH₂ CH₂ -- when X is a bond; and

X=a covalent bond or oxygen.

2. The compound of claim 1 wherein R₃ is hydrogen and X is a convalent bond.

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

N-[4-(3-methoxyphenyl)butyl]-N'"'"'-methyl urea;

N-[4-(3-methoxyphenyl)butyl]-N'"'"'-ethyl urea;

N-[3-(3-methoxyphenyl)propyl]-N'"'"'-ethyl urea;

N-[3-(3-methoxyphenyl)propyl]-N'"'"'-methyl urea;

N-[3-(3,4-dimethoxyphenyl)propyl]-N'"'"'-ethyl urea; and

N-[3-(2,3-dimethoxyphenyl)propyl]-N'"'"'-ethyl urea.

4. A pharmaceutical composition for treating a sleep or circadian rhythm disorder in a patient in need thereof comprising an effective amount of the compound of claim 1 and a suitable amount of a pharmaceutically acceptable carrier.

5. The composition of claim 4 containing from about 0.1 to about 10 weight % of a compound of claim 1.

6. A method of treating a sleep or circadian rhythm disorder in a patient in need of such treatment comprising the administration of an effective amount of a compound of claim 1.

7. The method of claim 5 wherein the amount used is from about 0.1 to about 100 mg per dose.