| 摘要 |
PCT No. PCT/US92/05101 Sec. 371 Date Dec. 14, 1993 Sec. 102(e) Date Dec. 14, 1993 PCT Filed Jun. 12, 1992 PCT Pub. No. WO92/22576 PCT Pub. Date Dec. 23, 1992.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-Xaa26-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, Aib24,28,31]-rCRF(12-41).
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