Somatostatin-dopamine chimeric analogs

摘要

The present invention relates to novel somatostatin-dopamine chimeric analogs and their therapeutic uses for the inhibition, prevention, and/or treatment of neoplasia, neuroendocrine tumors, Cushing's disease/syndrome, and other conditions.

主权项

1. A method of treating a neuroendocrine tumor in a subject, wherein said neuroendocrine tumor is selected from the group consisting of a neuroendocrine tumor of the pituitary, an ACTH-producing tumor, a growth hormone producing tumor, a prolactin-producing tumor, thyroid stimulating hormone secreting tumor, a nonfunctioning pituitary adenoma, gonadotropinoma, a carcinoid tumor, glucagonoma, VIPoma and insulinoma, said method comprising administering to said subject a therapeutically effective amount of a compound, wherein the compound is:(SEQ ID NO: 4)Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Phe);(SEQ ID NO: 5)Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe);(SEQ ID NO: 6)Dop1-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe);(SEQ ID NO: 12)Dop1-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Tyr);(SEQ ID NO: 13)Dop1-Lys(Dop1)-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Tyr);(SEQ ID NO: 14)Dop1-Lys(Dop1)-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Phe);(SEQ ID NO: 15)Dop1(SO2)-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe);(SEQ ID NO: 18)Dop1(SO)-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Tyr);(SEQ ID NO: 19)Dop1(SO)-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe);(SEQ ID NO: 20)Dop1(SO)-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe);(SEQ ID NO: 21)Dop1(SO)-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Phe);(SEQ ID NO: 22)Dop1(SO)-Lys[Dop1(SO)]-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Tyr);(SEQ ID NO: 23)Dop1(SO)-Lys[Dop1(S0)]-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Phe);(SEQ ID NO: 24)Dop1(SO2)-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe);(SEQ ID NO: 25)Dop1(SO2)-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Tyr);(SEQ ID NO: 26)Dop1(SO2)-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Phe);(SEQ ID NO: 28)Dop1-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Phe);(SEQ ID NO: 29)Dop1-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Phe);(SEQ ID NO: 30)Dop1-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Tyr);(SEQ ID NO: 31)Dop1-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-Phe);(SEQ ID NO: 35)bis[Dop1-psi(CH2N)]-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Phe);(SEQ ID NO: 39)Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-Phe);(SEQ ID NO: 40)Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-Tyr);(SEQ ID NO: 41)Dop1-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe);(SEQ ID NO: 42)bis[Dop1-psi(CH2N)]-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Tyr);(SEQ ID NO: 43)Dop1-DTyr-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-Phe);(SEQ ID NO: 44)Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-3Pal-DTrp-Lys-Thr-Phe);(SEQ ID NO: 45)bis[Dop1-psi(CH2N)]-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe);(SEQ ID NO: 46)bis[Dop1-psi(CH2N)]-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-Phe);(SEQ ID NO: 47)Dop1-DTyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-Phe);(SEQ ID NO: 50)Dop1-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-Phe);(SEQ ID NO: 51)Dop1-DTyr-psi(CH2NH)-cyclo(DLys-Arg-4Pal-Tyr-DTrp-Lys-Thr-Phe);or(SEQ ID NO: 52)Dop1-Lys(Dop1)-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe); or a pharmaceutically acceptable salt thereof, and wherein said therapeutically effective amount is the amount effective to treat said neuroendocrine tumor in said subject.