公开(公告)号：US20080090756A1

公开(公告)日：2008-04-17

申请号：US11973954

申请日：2007-10-11

申请人： David Coy ,  Walajapet Rajeswaran

发明人： David Coy ,  Walajapet Rajeswaran

IPC分类号： A61K38/12 ,  A61P1/00 ,  A61P3/00 ,  A61P35/00 ,  A61P5/00 ,  C07K7/50

CPC分类号： C07K14/6555 ,  A61K38/00

摘要： Claimed are a series of somatostatin agonists typically characterized by alkylation of the amide nitrogen, and uses thereof. Examples of claimed compounds are those according to formula (I), A1-cyclo{Cys-A2-D-Trp-A3-A4-Cys}-A5-Y1,  (I) wherein: A1 is an optionally substituted D- or L-aromatic α-amino acid or optionally substituted D- or L-cyclo(C3-6)alkylalanine; A2 is an optionally substituted aromatic α-amino acid or optionally substituted cyclo(C3-6)alkylalanine; A3 is Lys or Orn; A4 is β-Hydroxyvaline, Ser, hSer, or Thr; A5 is β-Hydroxyvaline, Ser, hSer, or Thr; and Y1 is OH, NH2 or NHR1, where R1 is (C1-6)alkyl; wherein each said optionally substituted aromatic α-amino acid and each said optionally substituted cyclo(C3-6)alkylalanine is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, NO2, OH, CN, (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, (C1-6)alkoxy, Bzl, O-Bzl, and NR9R10, where R9 and R10 each is independently H or (C1-6) alkyl; and wherein the amine nitrogen of each peptide bond and the amino group of A1 of formula (I) is optionally substituted with a methyl group, provided that there is at least one said methyl group; and further provided that said compound is not D-Phe-cyclo{Cys-Phe-D-Trp-Lys-(N-Me-Thr)-Cys}-Thr-NH2; or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20080020970A1

公开(公告)日：2008-01-24

申请号：US11894231

申请日：2007-08-20

申请人： David Coy ,  William Murphy ,  Walajapet Rajeswaran

发明人： David Coy ,  William Murphy ,  Walajapet Rajeswaran

IPC分类号： A61K38/00 ,  A61P9/00

CPC分类号： A61K38/08 ,  C07K14/655

摘要： A1-cyclo{D-Cys-A2-D-Trp-A3-A4-Cys}-A5-Y1   (I) The present invention is directed to a somatostatin antagonist according to formula (I), wherein A1 is an optionally substituted aromatic ax-amino acid; A2 is an optionally substituted aromatic α-amino acid; A3 is Dab, Dap, Lys or Orn; A4 is β-Hydroxyvaline, Ser, Hser, or Thr; A5 is an optionally substituted D- or L-aromatic-amino acid; and Y1 is OH, NH2 or NHR1, where R1 is (C1-6)alkyl; wherein each said optionally substituted aromatic-amino acid is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, NO2, OH, CN, (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, (C1-6)alkoxy, Bzl, O-Bzl, and NR9R10, where R9 ad R10 each is independently H, O, or (C1-6)alkyl; and wherein the amine nitrogen of each of amide peptide bond and the amino group of A1 of formula (I) is optionally substituted with a methyl group, provided that there is at least one said methyl group; or a pharmaceutically acceptable salt thereof, and to uses thereof.

摘要翻译： <？in-line-formula description =“In-line Formulas”end =“lead”？> A <1> Trp-A <3> -line-formula description =“In-line Formulas”end =“tail”？本发明涉及根据式（I）的生长抑素拮抗剂，其中A 1是任选取代的芳族 斧氨酸; A 2是任选取代的芳族α-氨基酸; Dab，Dap，Lys或Orn; Aβ4是β-羟基缬氨酸，Ser，Hser或Thr; A 5是任选取代的D-或L-芳族 - 氨基酸; 并且Y 1是OH，NH 2或NHR 1，其中R 1是（C 1） -6 N）烷基; 其中每个所述任选取代的芳族 - 氨基酸任选被一个或多个独立地选自卤素，NO 2，OH，CN，（C 1-6）烷基的取代基取代， （C 2-6 - ）烷基，（C 2-6）烯基，（C 2-6）炔基，（C 1-6 - ）烷氧基 ，Bzl，O-Bzl和NR 9 R 10，其中R 9和R 10各自独立地为 H，O或（C 1-6 - ）烷基; 并且其中酰胺肽键和式（I）的A 1的氨基的胺氮任选被甲基取代，条件是存在至少一个所述甲基; 或其药学上可接受的盐，及其用途。