Crf analogs

Details Crf analogs Crf analogs

C - Chemistry, Metallurgy

07

K

C07K 14/575 (2006.01)

Patent

CA 2110901

2110901 9222576 PCTABS00018 Disclosed are improved CRF peptide antagonists such as those having the formula: Y-D-Phe-Xaa13-Leu-Leu-Arg-Xaa17-Xaa18-Leu-Xaa20-Nle-Xaa22-Xaa23-Xaa24-Xaa25-X_ aa26-Leu-Xaa28-Xaa29-Gln-Xaa31-Xaa32-Xaa33-Xaa34-Arg-Xaa36-Xaa37-Nle -Xaa39-Xaa40-Xaa41-NH2, wherein Y is Ac or hydrogen; Xaa13 is His, Tyr or Glu; Xaa17 is CML, Glu, Asn or Lys; Xaa18 is Val, Nle or Met; Xaa20 is Glu, D-Glu, Aib or D-Ala; Xaa22 is Ala, Aib, Thr, Asp or Glu; Xaa23 is Arg, Orn, Har or Lys; Xaa24 is Ala or Aib; Xaa25 is Asp or Glu; Xaa26 is Gln, Asn or Lys; Xaa28 is Ala or Aib; Xaa29 is Gln, Aib or Glu, Xaa31 is Ala or Aib; Xaa32 is His, Aib, Gly, Tyr or Ala; Xaa33 is Ser, Aib, Asn, Leu, Thr or Ala; Xaa34 is Asn or Aib; Xaa36 is Lys, Orn, Arg, Har or Leu; Xaa37 is Leu or Tyr; Xaa39 is Glu, Aib or Asp; Xaa40 is Ile, Aib, Thr, Glu, Ala, Val, Leu, Nle, Phe, Nva, Gly or Gln; and Xaa41 is Ala, Ile, Gly, Val, Leu, Nle, Phe, Nva or Gln, wherein CML may be substituted for Leu. Specific CRF antagonists disclosed include [D-Phe12, D-Ala20, Nle21,38]-rCRF(12-41), [D-Phe12, Nle21,38, Aib34]-rCRF(12-41), [D-Phe12, CML17, Nle21,38]-rCRF(12-41), [D-Phe12, Aib20, Nle21,38]-rCRF(12-41), [D-Phe12, Aib29, Nle21,38]-rCRF(12-41), [D-Phe12, CML14, Nle21,38, Aib24,28,31]-rCRF(12-41) and [D-Phe12, CML15, Nle21,38, Aib24,28,31]-rCRF(12-41).

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