Melanocortin Receptor-Specific Peptides for Treatment of Obesity / 669

1 . A cyclic peptide of formula (I):

including all enantiomers, stereoisomers or diastereoisomers thereof, or a pharmaceutically acceptable salt of any of the foregoing,

wherein:

R 1 is —C(═O)—NH— or —NH—C(═O)—;

R 2 is —H or —CH 2 —, wherein if R 2 is —CH 2 —, then R 2 forms a pyrrolidine ring with R 3 of the structure

R 3 is —(CH 2 ) 2 —

wherein if R 3 is —(CH 2 ) 2 —, then R 3 forms a pyrrolidine ring with R 2 ; and

R 4 is —OH or —NH 2 ;

wherein

if R 1 is —C(═O)—NH—, then x is 1 and y is 4 or x is 2 and y is 3,

and if R 1 is —NH—C(═O)—, then x is 3 and y is 2.

2 . The cyclic peptide of claim 1 of formula (II):

or a pharmaceutically acceptable salt thereof, wherein R 1 , R 4 , x and y are as defined in claim 1 .

3 . The cyclic peptide of claim 2 that is:

Ac-Arg-cyclo(Glu-Ser(Bzl)-D-Phe-Arg-Trp-Orn)-OH (SEQ ID NO:4);

Ac-Arg-cyclo(Orn-Ser(Bzl)-D-Phe-Arg-Trp-Glu)-OH (SEQ ID NO:5);

Ac-Arg-cyclo(Asp-Ser(Bzl)-D-Phe-Arg-Trp-Lys)-OH (SEQ ID NO:6); or

Ac-Arg-cyclo(Asp-Ser(Bzl)-D-Phe-Arg-Trp-Lys)-NH 2 (SEQ ID NO:7).

4 . The cyclic peptide of claim 1 of formula (III):

or a pharmaceutically acceptable salt thereof, wherein R 1 , R 4 , x and y are as defined in claim 1 .

5 . The cyclic peptide of claim 4 that is:

Ac-Arg-cyclo(Asp-Pro-D-Phe-Arg-Trp-Lys)-NH 2 (SEQ ID NO:8);

Ac-Arg-cyclo(Orn-Pro-D-Phe-Arg-Trp-Glu)-NH 2 (SEQ ID NO:9); or

Ac-Arg-cyclo(Asp-Pro-D-Phe-Arg-trp-Lys)-OH. (SEQ ID NO: 10).

6 . A pharmaceutical composition comprising a cyclic peptide or a pharmaceutically acceptable salt thereof of claim 1 and a pharmaceutically acceptable carrier.

7 . A method for treating a melanocortin receptor-mediated disease, indication, condition or syndrome in a human or non-human mammal in need thereof, comprising administering to the human or non-human mammal a therapeutically effective amount of the pharmaceutical composition of claim 6 .

8 . A method for treating a condition responsive to changes in melanocortin receptor function in a human or non-human mammal in need thereof, comprising administering to the human or non-human mammal a therapeutically effective amount of the pharmaceutical composition of claim 6 .

9 . The method of claim 8 , wherein the condition is obesity, diabetes, modulation of feeding behavior or related metabolic syndrome.

10 - 12 . (canceled)

13 . A method of treating a disease, disorder and/or condition responsive to activation of the MC4 receptor in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a peptide according to claim 1 .

14 . A method of treating diabetes, obesity, overweight and/or diseases, disorders and/or conditions associated with obesity and/or overweight, including insulin resistance; impaired glucose tolerance; type 2 diabetes; metabolic syndrome; dyslipidemia; hyperlipidemia; hypertension; heart disorders; cardiovascular disorders; non-alcoholic fatty liver disease; joint disorders; secondary osteoarthritis; gastroesophageal reflux; sleep apnea; atherosclerosis; stroke; macro and micro vascular diseases; steatosis; gall stones; and gallbladder disorders comprising administering to a patient in need thereof a therapeutically effective amount of a peptide according to claim 1 .

15 . A method of reducing food intake, body weight and/or body weight gain comprising administering to an individual in need thereof a pharmacologically effective amount of a peptide according to claim 1 .