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US 7,410,949 B2Granted
Neuropeptide-2 receptor (Y-2R) agonists and uses thereof
AssigneeHoffmann-La Roche Inc.
InventorsWaleed Danho, George Ehrlich, David C Fry, Wajiha Khan, Joseph Swistok
Life of this patent
Estimating the term…
Abstract
Provided herein are neuropeptide-2 receptor agonists of the formula (I): Y—R1—R2—X—R3—R4—R5—R6—R7—R8—R9—R10—R11—R12—R13—R14—NH2, (I) as well as pharmaceutically acceptable salts, derivatives and fragments thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity.
Claims17
A neuropeptide-2 receptor agonist of the formula (I):
- Y—R1—R2—X—R3—R4—R5—R6—R7—R8—R9—R10—R11—R12—R13—R14—NH2 (I)
- wherein:
- X is selected from the group consisting of N-piperazin-1-yl-4(3H)-quinozolinone-3-acetic acid (Pqa), N-(5-O-carboxymethyl )-serotonin (Cms), 4-(2-aminoethyl)-6-dibenzofuranpropanoic acid, 4-(1-piperidin-4-yl)-butanoic acid and 4-(2-aminoethyl) -1-carboxymethyl piperazine,
- Y is H, a substituted or unsubstituted alkyl, a substituted or unsubstituted lower alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted alkoxy or a poly(ethylene) glycol moiety,
- R1 is Ile, Ala, (D) Ile, N-methyl Ile, Aib, 1-1 Aic, 2-2 Aic, Ach or Acp,
- R2 is Lys, Ala, (D) Lys, NMelys, Nle or (Lys-Gly),
- R3 is Arg, Ala, (D)Arg, N-methylArg, Phe, 3,4,5- TrifluoroPhe or 2,3,4,5,6-pentafluoro Phe,
- R4 is His, Ala, (D)His, N-methyl His, 4-MeOApc, 3-Pal or 4-Pal,
- R5 is Tyr, Ala, (D) Tyr, N- methyl Tyr, Trp, Tic, Bip, Dip, (1)Nal, (2)Nal, 3,4,5-TrifluroPhe or 2,3,4,5,6- Pentafluoro Phe,
- R6 is Leu, Ala, (D)Leu or N-methyl Leu,
- R7 is Asn, Ala or (D)Asn,
- R8 is Leu, Ala, (D)Leu or N-methyl Leu,
- R9 is Val, Ala, (D) Val or N-methyl Val,
- R10 is Thr, Ala or N-methyl Thr,
- R11 is Arg, (D) Arg or N-methyl Arg,
- R12 is Gln or Ala,
- R13 is Arg, (D)Arg or N-methyl Arg, and
- R14 is Tyr, (D) Tyr or N- methyl Tyr,
- or a pharmaceutically acceptable salt thereof.
16 more elements
A pharmaceutical composition, comprising a neuropeptide-2 agonist of the formula (I):
- Y—R1—R2—X—R3—R4—R5—R6—R7—R8—R9—R10—R11—R12—R13—R14—NH2 (I)
- wherein:
- X is selected from the group consisting of N-piperazin-1-yl-4(3H)-quinozolinone-3-acetic acid (Pqa), N-(5-O-carboxymethyl)-serotonin (Cms), 4-(2-aminoethyl)-6-dibenzofuranpropanoic acid, 4-( 1-piperidin-4-yl)-butanoic acid and 4-(2-aminoethyl)-1-carboxymethyl piperazine,
- Y is H, a substituted or unsubstituted alkyl, a substituted or unsubstituted lower alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted alkoxy or a poly(ethylene) glycol moiety,
- R1 is Ile, Ala, (D) Ile, N-methyl Ile, Aib, 1-1Aic, 2-2 Aic, Ach or Acp,
- R2 is Lys, Ala, (D) Lys, NMelys, Nle or (Lys-Gly),
- R3 is Arg, Ala, (D)Arg, N-methylArg, Phe, 3,4,5- TrifluoroPhe or 2,3,4,5,6-Pentafluoro Phe,
- R4 is His, Ala, (D)His, N-methyl His. 4-MeOApc, 3-Pal or 4-Pal,
- R5 is Tyr, Ala, (D) Tyr, N- methyl Tyr, Trp, Tic, Bip, Dip, (1)Nal, (2)Nal, 3,4,5-TrifluroPhe or 2,3,4,5,6- Pentafluoro Phe,
- R6 is Leu, Ala, (D)Leu or N-methyl Leu,
- R7 is Asn, Ala or (D)Asn,
- R8 is Leu, Ala, (D)Leu or N-methyl Leu,
- R9 is Val, Ala, (D) Val or N-methyl Val,
- R10 is Thr, Ala or N-methyl Thr,
- R11 is Arg, (D) Arg or N-methyl Arg,
- R12 is Gln or Ala,
- R13 is Arg, (D)Arg or N-methyl Arg, and
- R14 is Tyr, (D) Tyr or N- methyl Tyr,
- or a pharmaceutically acceptable salt thereof,
- and a pharmaceutically acceptable carrier.
17 more elements
A method of treating obesity in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a neuropeptide-2 receptor agonist of the formula (I):
- Y—R1—R2—X—R3—R4—R5—R6—R7—R8—R9—R10—R11—R12—R13—R14—NH2 (I)
- wherein:
- X is selected from the group consisting of N-piperazin-1-yl-4(3H)-quinozolinone-3-acetic acid (Pqa), N-(5-O-carboxymethyl)-serotonin (Cms), 4-(2-aminoethyl )-6-dibenzofuranpropanoic acid, 4-(1-piperidin-4-yl)-butanoic acid and 4-(2-aminoethyl)-1 -carboxymethyl piperazine,
- Y is H, a substituted or unsubstituted alkyl, a substituted or unsubstituted lower alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted alkoxy or a poly(ethylene) glycol moiety,
- R1 is Ile, Ala, (D) Ile, N-methyl Ile, Aib, 1-1 Aic, 2-2 Aic, Ach or Acp,
- R2 is Lys, Ala, (D) Lys, NMelys, Nle or (Lys-Gly),
- R3 is Arg, Ala, (D)Arg, N-methylArg, Phe, 3,4,5-TrifluoroPhe or 2,3,4,5,6-Pentafluoro Phe,
- R4 is His, Ala, (D)His, N-methyl His, 4-MeOApc, 3-Pal or 4-Pal,
- R5 is Tyr, Ala, (D) Tyr N- methyl Tyr, Trp, Tic, Bip, Dip, (1)Nal, (2)Nal, 3,4,5-TrifluroPhe or 2,3,4,5,6- Pentafluoro Phe,
- R6 is Leu, Ala, (D)Leu or N-methyl Leu,
- R7 is Asn, Ala or (D)Asn,
- R8 is Leu, Ala, (D)Leu or N-methyl Leu,
- R9 is Val, Ala, (D) Val or N-methyl Val,
- R10 is Thr, Ala or N-methyl Thr,
- R11 is Arg, (D) Arg or N-methyl Arg,
- R12 is Gln or Ala,
- R13 is Arg, (D)Arg or N-methyl Arg, and
- R14 is Tyr, (D) Tyr or N- methyl Tyr, or a pharmaceutically acceptable salt thereof.
15 more elements
Dependencies are inferred from the claim text.