US 7,498,300 B2
CRFR1 selective ligands
Jean E. F. Rivier, La Jolla, Calif. (US); Wyle W. Vale, Jr., La Jolla, Calif. (US); Marilyn H. Perrin, La Jolla, Calif. (US); and Jozsef Gulyas, Julian, Calif. (US)
Assigned to The Salk Institute for Biological Studies, San Diego, Calif. (US)
Filed on Jan. 22, 2004, as Appl. No. 10/763,935.
Application 10/763935 is a continuation of application No. PCT/US02/24238, filed on Jul. 30, 2002.
Claims priority of provisional application 60/309504, filed on Aug. 01, 2001.
Prior Publication US 2004/0204564 A1, Oct. 14, 2004
Int. Cl. A61K 38/00 (2006.01)
U.S. Cl. 514—9 9 Claims
 
1. A 38-residue or 39-residue CRF cyclic peptide, or a nontoxic salt thereof, which binds to CRFR1 with an affinity substantially greater than it binds to CRFR2, which peptide has the following formula:

OG Complex Work Unit Drawing
wherein the sidechains of Glu and Lys indicated are covalently linked; Y1 is an acyl group having not more than 15 carbon atoms or is radioiodinated tyrosine; R14 is CML or Leu; R15 is CML or Leu; R17 is Glu or CML; R18 is Val or CML; R19 is CML or Leu; R27 is CML or Leu; R32 is His or D-His; R33 is Aib, D-Ala, D-Ser or Ser; R36 is Lys or CML; R37 is CML or Leu; R40 is Ile or CML; and R41 is Ile or CML; provided that D-β-(2-napthyl)alanine(D-2Nal) or D-Leu may be substituted for D-Phe.