Patent ID: 6262229
Filing Date: 2001-07-17
Classification: C07K

Abstract:
A compound of the formula: ##STR3##or a pharmaceutically acceptable salt thereof, whereinA.sup.1 is a D- or L-isomer of an aromatic amino acid, or is deleted;A.sup.2 is a D-isomer selected from the group consisting of Cys, Pen, an aromatic amino acid, and an aliphatic amino acid;A.sup.3 is an aromatic amino acid;A.sup.4 is Trp or D-Trp;A.sup.6 is Thr, Thr(Bzl), Gly, Ser, an Eaa, Ala, Aib, Val, Leu, Tle, Ile, Nle, Nva or Abu;A.sup.7 is Cys, Pen, or an aromatic or an aliphatic amino acid;A.sup.8 is a D- or L-isomer selected from the group consisting of Thr, Ser, an aromatic amino acid, and an aliphatic amino acid;each of R.sub.1 and R.sub.2, is, independently, H or substituted or unsubstituted lower alkyl, aryl, aryl lower alkyl, heterocycle, heterocycle lower alkyl, E.sub.1 SO.sub.2 or E.sub.1 CO (where E.sub.1, is aryl, aryl lower alkyl, heterocycle, or heterocycle lower alkyl), where said substituent is halo, lower alkyl, hydroxy, halo lower alkyl, or hydroxy lower alkyl; andR.sub.3 is OH, NH.sub.2, C.sub.1-12 alkoxy, or NH--Y--CH.sub.2 --Z, wherein Y is a C.sub.1-12 hydrocarbon moiety and Z is H, OH, CO.sub.2 H, or CONH.sub.2, or R.sub.3, together with the carbonyl group of A.sup.8 attached thereto, are reduced to form H, lower alkyl, or hydroxy lower alkyl; provided if A.sup.2 is D-Cys or D-Pen, and A.sup.7 is Cys or Pen, then a disulfide bond links the side chains of A.sup.2 and A.sup.7, and if A.sup.1 is D-Phe or p-NO.sub.2 -Phe; A.sup.2 is D-Cys; A.sup.3 is Phe or Tyr; A.sup.6 is Thr or Val; and A.sup.7 is Cys; then A.sup.8 is .beta.-Nal, and further provided that:(1) the compound is not H.sub.2 -D-Nal-D-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH.sub.2 or H.sub.2 -D-Nal-D-Cys-Tyr-D-Trp-Lys-Thr-Cys-Nal-NH.sub.2 ;(2) When A.sup.1 is present, A.sup.2 is D-Cys, A.sup.3 is an optionally substituted aromatic amino acid selected from the group consisting of phenylalanine, biphenylalanine, naphthylalanine, indolylalanine and imidazolylalanine, A.sup.4 is D-Trp, A.sup.6 is Thr, Thr(Bzl), Val, Leu, Ile, Nle or Abu, A.sup.7 is Cys, and A.sup.8 is an optionally substituted aromatic amino acid selected from the group consisting of phenylalanine, biphenylalanine, naphthylalanine, indolylalanine and imidazolylalanine, then A.sup.1 is not an optionally substituted aromatic amino acid selected from the group consisting of phenylalanine, biphenylalanine, naphthylalanine, indolylalanine and imidazolylalanine; and(3) when A.sup.1 is present and is optionally substituted indolylalanine, naphthylalanine, phenylalanine, pentafluorophenylalanine, biphenylalanine, imidazolylalanine, or histidine, A.sup.2 is D-Cys, A.sup.4 is D-Trp, A.sup.6 Leu, Ile, Nle, Val, Thr or Ser, A.sup.7 is L-Cys, then A.sup.3 is not F.sub.5 Phe, Phe or X-Phe where X is Halo, NO.sub.2, CH.sub.3 or OH.