Compounds for control of appetite, blood pressure, cardiovascular response, libido, and circadian rhythm

• US 6,235,718 B1
• Filed: 12/02/1999
• Issued: 05/22/2001
• Est. Priority Date: 08/09/1996
• Status: Expired due to Term

• Current Assignee: University of Cincinnati
• Original Assignee: University of Cincinnati
• Inventors: Balasubramanium, Ambikaipakan, Chance, William T.
• Primary Examiner(s): Carlson, Karen Cochrane
• Assistant Examiner(s): Tu, Stephen
• Application Number:
  US09/449,914
• Time in Patent Office: 537 Days
• Field of Search: 514/18, 514/19, 530/331
• US Class Current: 530/330
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/06 Tripeptides
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: H01L 21/28247 passivation or protection of the electrode, e.g. using re-oxidation

Abstract

This invention relates generally to dipeptides and tripeptides and to methods for pharmaceutical treatment of mammals using analogs of such dipeptides and tripeptides. More specifically, the invention relates to tripeptides and their analogs, to pharmaceutical compositions containing such dipeptides and tripeptides and to methods of treatment of mammals using such dipeptides and tripeptides. In addition, the invention relates to methods of treatment of mammals using such dipeptides and tripeptides for control of appetite, blood pressure, cardiovascular response, libido, and circadian rhythm.

Claims

1. A compound having the formula:

wherein each R1 and R2, independently, is selected from the group consisting of H, C1-C12 alkyl, C6-C18 aryl, C1-C18 acyl, C7-C18 aralkyl, C7-C18 alkaryl, and a dihydrotrigonellinate group;

A1 is an amino acid selected from the group consisting of Trp, Gln, a tethered amino acid with an indole ring Phe, Hyp, any Trp derivative, Cα

Me-Trp, Cα

Me-Gln, Des-amino-Trp, Pyr, Bth, Nal, Tcc, Asn, Nva, Abu, Tyr, Tic-OH, Phe, Tip, and Dip;

A2 is an amino acid selected from the group consisting of Arg, N-Me-Arg, Cα

Me-Arg, Orn, Cit, hArg(R)2, where R is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, and alkylaryl, and Lys-e-NH-R, where R is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, and alkylaryl;

A3 is an amino acid selected from the group consisting of N-Me-Tyr, Cα

Me-Tyr, Tic-OH, Tic, Dip, Trp, Phe, des-carboxylic-Tyr (tyramine), and Tyr-(R), where R is hydrogen or a lipophilic group;

W is selected from the group consisting of —

OH, —

N—

R3R4, and OR5, where R3, R4, and R5, independently, is selected from the group consisting of H, C1-C12 alkyl, C6-C18 aryl, C1-C12 acyl, C7-C18 aralkyl, C7-C18 alkaryl; and

each dash (“

-”

) between two amino acids or amino acid derivatives represents either a peptide bond or a pseudopeptide bond.

2. The compound of claim 1, wherein said compound has a formula selected from the group consisting of N-α

-Ac-Trp-Arg-Tyr-NH₂, Ac-Gln-Arg-Tcc-Arg-Tyr-NH₂, Ac-Tcc-Arg-Tyr-NH₂, Ac-Trp-Arg-Tic(OH)-NH₂ and Ac-Tcc-Arg-Tic(OH)-NH₂.

3. A pharmaceutically acceptable salt of the compound of claim 1 or 2.