Patent ID: 6642355
Filing Date: 2003-11-04
Classification: A61K,C07K,C12N,C12R

Abstract:
A peptide represented by the following formula (I):X-A-Trp-B-Gly-Thr-E-G-Y â€ƒâ€ƒ(I) SEQ ID NO: 2 whereinA represents Asn or Asp; B represents His or Lys; E represents Ala or Ser; G represents Ala or Pro; X represents X1-Gly or Y represents hydroxy, lower alkoxy, amino, or whereineach of X1 and X3 represents hydrogen, benzyloxy-carbonyl, t-butyloxycarbonyl or 9-fluorenylmethyloxycarbonyl, or carbonyl-substituted or unsubstituted lower alkanoyl; each of X2 and Y2 represents hydrogen; Y1 represents hydroxy, lower alkoxy or amino; or X1 and Y1, or X2 and Y2 are combined together to form a single bond as X1â€”Y1 or X2â€”Y2; and Z represents hydroxy, lower alkoxy, benzyloxy, benzhydryloxy, amino, whereZ2 is hydroxy, lower alkoxy, benzyloxy, benzhydryloxy or amino, â€ƒGly-Z1 whereZ1 is hydroxy, lower alkoxy, benzyloxy, benzhydryloxy, amino, where Z2 is as defined previously, or Z1 is combined with X1 to form a single bond as X1-Z1, Ala-Z1 where Z1 is as defined previously, Val-Z1 where Z1 is as defined previously, Trp-Z1 where Z1 is as defined previously, Trp-Gly-Z1 where Z1 is as defined previously, Trp-Asn-Tyr-Tyr-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 3 where Z1 is as defined previously, â€ƒTrp-Phe-Phe-Asn-Tyr-Tyr-7Hyt-Z1 â€ƒâ€ƒSEQ ID NO: 4where Z1 is as defined previously, and 7Hyt represents 7-hydroxytryptophan, Trp-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 5 where Z1 is as defined previously, Trp-Val-Tyr-Phe-W-His-Leu-Asp-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 6 where Z1 is as defined previously, and W represents Ala, Ser or Cys, Trp-W-His-Leu-Asp-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 7 where Z1 and W are as defined previously, Trp-Val-Tyr-Tyr-W-His-Leu-Asp-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 8 wherein Z1 and W are as defined previously, Trp-Leu-Tyr-Phe-W-His-Gln-Asp-Val-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 9 wherein Z1 and W are as defined previously, Trp-Val-Tyr-Phe-W-Phe-Phe-Asn-Tyr-Tyr-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 10 wherein Z1 and W are as defined previously, Trp-Phe-Phe-Asn-Tyr-Tyr-W-His-Leu-Asp-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 11 wherein Z1 and W are as defined previously, Trp-Phe-Phe-Asn-Tyr-Tyr-Asn-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 12 wherein Z1 is as defined previously, J-Phe-M-Q-Tyr-R-T-Z1 â€ƒâ€ƒSEQ ID NO: 13 whereJ is Trp or a single bond, M is Phe or a single bond, Q is Asn or a single bond, R is Tyr or a single bond, T is Trp, Ala, Phe, Tyr, Trp-Trp, Asn-Tyr-Tyr-Trp, â€ƒâ€ƒSEQ ID NO: 14 Trp-Asn-Tyr-Tyr-Trp, â€ƒâ€ƒSEQ ID NO: 15 â€ƒTrp-Val-Tyr-Phe-W-His-Leu-Asp-Ile-Ile-Trp, â€ƒâ€ƒSEQ ID NO: 16where W is as defined previously, or a single bond,2 or more of J, M, Q, R and T are not a covalent bond simultaneously, and Z1 is as defined previously, provided that (1) when G represents Pro; X represents X1-Gly; Y represents wherein X1 and Y1 are combined together to form a single bond as X1-Y1; then Z is not a group selected from the group consisting of (a) Trp-Phe-Phe-Asn-Tyr-Tyr-7Hyt-Z1 â€ƒâ€ƒSEQ ID NO: 4 where Z1 is as defined previously, and 7Hyt represents 7-hydroxytryptophan, (b) Trp-Val-Tyr-Phe-Ala-His-Leu-Asp-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 6 where Z1 is as defined previously, (c) Trp-Ala-His-Leu-Asp-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 7 where Z1 is as defined previously, (d) Trp-Val-Tyr-Tyr-Ala-His-Leu-Asp-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 8 where Z1 is as defined previously, (e) Trp-Leu-Tyr-Phe-W-His-Gln-Asp-Val-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 9 where Z1 and W are as defined previously, (f) Trp-Phe-Phe-Asn-Tyr-Tyr-T1-Z1 â€ƒâ€ƒSEQ ID NO: 13 where Z1 is as defined previously; T1 is Trp, Ala, Phe, Tyr, Trp-Trp, Asn-Tyr-Tyr-Trp, â€ƒâ€ƒSEQ ID NO: 14 Trp-Asn-Tyr-Tyr-Trp, â€ƒâ€ƒSEQ ID NO: 15 or Trp-Val-Tyr-Phe-W-His-Leu-Asp-Ile-Ile-Trp, â€ƒâ€ƒSEQ ID NO: 16 where W is as defined previously, and (g) Trp-Phe-Phe-Asn-Tyr-Tyr-T-Z3 â€ƒâ€ƒSEQ ID NO: 13 where T is as defined previously; Z3 is hydroxy, â€ƒwhere Z2 is as defined previously; (2) when G represents Pro; X represents X1-Gly; Y represents X1 represents hydrogen and Y1 represents hydroxy; then Z is not a group selected from the group consisting of (h) Trp-Val-Tyr-Phe-Ala-His-Leu-Asp-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 6 where Z1 is as defined previously, (i) Trp-Val-Tyr-Tyr-Ala-His-Leu-Asp-Ile-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 8 (j) Trp-Leu-Tyr-Phe-Ala-His-Gln-Asp-Val-Ile-Trp-Z1 â€ƒâ€ƒSEQ ID NO: 9 where Z1 is as defined previously, or a pharmaceutically acceptable salt thereof.