Ghrelin analogs

Ghrelin analogs

  • CN 1,832,753 A
  • Filed: 07/23/2003
  • Published: 09/13/2006
  • Est. Priority Date: 07/23/2002
  • Status: Active Application
First Claim
Patent Images

1. formula (I) chemical compound:

  • (R 2R 3)-A 1-A 2-A 3-A 4-A 5-A 6-A 7-A 8-A 9-A 10-A 11-A 12-A 13-A 14-A 15-A 16-A 17-A 18-A 19-A 20-A 20-A 21-A 22-A 23-A 24-A 25-A 26-A 27-A 28-R 1????(I) Or its pharmaceutically acceptable salt, wherein;

    A 1Be meant Gly, Aib, Ala, β

    -Ala or Ace;

    A 2Be meant Ser, Aib, Act, Ala, Acc, Abu, Act, Ava, Thr or Val;

    A 3Be meant Ser, Ser (C (O)-R 4), Asp (O-R 8), Asp (NH-R 9), Cys (S-R 14), Dap (S (O) 2-R 10), Dab (S (O) 2-R 11), Glu (O-R 6), Glu (NH-R 7), Thr, Thr (C (O)-R 5) or HN-CH ((CH 2) N-N (R 12R 13))-C (O);

    A 4Be meant Phe, Acc, Aic, Cha, 2Fua, 1Nal, 2Nal, 2Pal, 3Pal, 4Pal, hPhe, (X 1, X 2, X 3, X 4, X 5) Phe, Taz, 2Thi, 3Thi, Trp or Tyr;

    A 5Be meant Leu, Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle or Val;

    A 6Be meant Ser, Abu, Acc, Act, Aib, Ala, Gly, Thr or Val;

    A 7Be meant Pro, Dhp, Dmt, 3Hyp, 4Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or do not exist;

    A 8Be meant Glu, Acc, Aib, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn, HN-CH ((CH 2) n-N (R 12R 13))-C (O), or do not exist;

    A 9Be meant His, Apc, Aib, Acc, 2Fua, 2Pal, 3Pal, 4Pal, Taz, 2Thi, 3Thi, (X 1, X 2, X 3, X 4, X 5-) Phe, or do not exist;

    A 10Be meant Gln, Acc, Aib, Asn, Asp, Glu, or do not exist;

    A 11Be meant Arg, Apc, hArg, Dab, Dap, Lys, Orn, HN-CH ((CH 2) n-N (R 12R 13))-C (O), or do not exist;

    A 12Be meant Val, Abu, Acc, Aib, Ala, Cha, Nva, Gly, Ile, Leu, Nle, Tle, Cha, or do not exist;

    A 13Be meant Gln, Acc, Aib, Asn, Asp, Glu, or do not exist;

    A 14Be meant Gln, Acc, Aib, Asn, Asp, Glu, or do not exist;

    A 15Be meant Arg, hArg, Acc, Aib, Apc, Dab, Dap, Lys, Orn, HN-CH ((CH 2) n-N (R 12R 13)))-C (O), or do not exist;

    A 16Be meant Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN-CH ((CH 2) n-N (R 12R 13))-C (O), or do not exist;

    A 17Be meant Glu, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn, HN-CH ((CH 2) n-N (R 12R 13))-C (O), or do not exist;

    A 18Be meant Ser, Abu, Acc, Act, Aib, Ala, Thr, Val, or do not exist;

    A 19Be meant Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN-CH ((CH 2) n-N (R 12R 13))-C (O), or do not exist;

    A 20Be meant Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN-CH ((CH 2) n-N (R 12R 13))-C (O), or do not exist;

    A 21Be meant Pro, Dhp, Dmt, Inc, 3Hyp, 4Hyp, Ktp, Oic, Pip, Thz, Tic, or do not exist;

    A 22Be meant Pro, Dhp, Dmt, 3Hyp, 4Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or do not exist;

    A 23Be meant Abu, Acc, Act, Aib, Ala, Apc, Gly, Nva, Val, or do not exist;

    A 24Be meant Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN-CH ((CH 2) n-N (R 12R 13))-C (O), or do not exist;

    A 25Be meant Leu, Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, Val, or do not exist;

    A 26Be meant Gln, Aib, Asn, Asp, Glu, or do not exist;

    A 27Be meant Pro, Dhp, Dmt, 3Hyp, 4Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or do not exist;

    A 28Be meant Acc, Aib, Apc, Arg, hArg, Dab, Dap, Lys, Orn, HN-CH ((CH 2) n-N (R 12R 13))-C (O), or do not exist;

    R 1Be meant-OH ,-NH 2,-(C 1-C 30) alkoxyl or NH-X 6-CH 2-Z 0, X wherein 6Be meant (C 1-C 12) alkyl, (C 2-C 12) thiazolinyl, and Z 0Be meant-H ,-OH ,-CO 2H or-C (O)-NH 2Each R that occurs 2And R 3All be H, (C independently 1-C 20) alkyl or (C 1-C 20) acyl group;

    Each R that occurs 4, R 5, R 6, R 7, R 8, R 9, R 10, R 11And R 14All be (C independently 1-C 40) alkyl, (C 2-C 40) (the C of thiazolinyl, replacement 1-C 40) (the C of alkyl, replacement 2-C 40) thiazolinyl, alkylaryl, substituted alkyl aryl, aryl or substituted aryl;

    Each R that occurs 12And R 13All be H, (C independently 1-C 40) alkyl, (C 1-C 40) acyl group, (C 1-C 30) alkyl sulphonyl or-C (NH)-NH 2, work as R 12Be (C 1-C 40) acyl group, (C 1-C 30) alkyl sulphonyl or-C (NH)-NH 2The time, R 13Be H or (C 1-C 40) alkyl;

    Each n that occurs is 1,2,3,4 or 5 independently;

    Each X that occurs 1, X 2, X 3, X 4And X 5All be H, F, Cl, Br, I, (C independently 1-C 10) alkyl, replace (C 1-C 10) alkyl, aryl, the aryl of replacement, OH, NH 2, NO 2Or CN;

    Condition is to contain at least a aminoacid that is selected from following group in the peptide;

    A 2Be meant Aib, Acc or Act;

    A 3Be meant Dap (S (O) 2-R 10), Dab (S (O) 2-R 11), Glu (NH-hexyl) or Cys (S-decyl);

    A 5Be meant Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle or Val;

    A 6Be meant Abu, Acc, Act, Aib, Ala, Gly, Thr or Val;

    A 7Be meant Dhp, Dmt, 3Hyp, 4Hyp, Inc, Ktp, Oic, Pip, Thz or Tic;

    A 8Be meant Acc, Aib, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn or HN-CH ((CH 2) n-N (R 12R 13))-C (O);

    A 9Be meant Aib, Acc, Apc, 2Fua, 2Pal, 3Pal, 4Pal, Taz, 2Thi, 3Thi, or (X 1, X 2, X 3, X 4, X 5-) Phe;

    And A 10Be meant Acc, Aib, Asn, Asp or Glu;

    And further condition is that this peptide is not (Lys 8) hGhrelin (1-8)-NH 2Or (Arg 8) hGhrelin (1-8)-NH 2

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