公开(公告)号：US5734012A

公开(公告)日：1998-03-31

申请号：US648644

申请日：1996-05-16

申请人： Ramalinga Dharanipragada ,  Mark J. Macielag ,  Jung Kim-Dettelback ,  James Florance

发明人： Ramalinga Dharanipragada ,  Mark J. Macielag ,  Jung Kim-Dettelback ,  James Florance

IPC分类号： A61K38/00 ,  A61P1/00 ,  C07K14/63 ,  C07K5/12 ,  C07K7/00 ,  C07K7/08

CPC分类号： C07K14/63 ,  A61K38/00

摘要： This invention pertains to cyclic polypeptides having gastrointestinal motor stimulating activity which may be represented by formula (1): ##STR1## including optically active isomeric forms and the pharmaceutically acceptable acid addition salts thereof, wherein groups A and D are linked to from a cyclic structure; and R.sub.1 is lower alkyl; R.sub.2 is hydrogen or lower alkyl; R.sub.3 is hydrogen or lower alkyl; R.sub.4 is phenyl or substituted phenyl, wherein the phenyl group may be substituted with one or more substituents selected from the group consisting of halogen, hydroxy, and lower alkoxy; R.sub.5 is --OH or --NH.sub.2 ; A is selected from the group consisting of L-glutamic acid, L-aspartic acid, L-lysine, L-ornithine, and L-2,4-diaminobutyric acid; B is L-alanine or L-glutamine; C is L-arginine or D-arginine; D is selected from the group consisting of L-lysine, L-ornithine, L-2,4-diaminobutyric acid, L-glutamic acid, and L-aspartic acid; E is a direct bond between group D and group R.sub.5 or is L-lysine or D-lysine; m is 0 or 1; the symbol * represents an asymmetric carbon atom which may be in the D or L configuration, with the proviso that: (a) when A is L-glutamic acid or L-aspartic acid, D is L-lysine, L-ornithine, or L-2,4-diaminobutyric acid; and (b) when A is L-lysine, L-ornithine, or L-2,4-diaminobutyric acid, D is L-glutamic acid or L-aspartic acid. This invention also pertains to methods for using the novel cyclic polypeptides.

摘要翻译： 本发明涉及具有胃肠运动刺激活性的环状多肽，其可以由式（1）表示：（1）包括旋光异构体形式及其药学上可接受的酸加成盐，其中基团A和D与 循环结构; 且R 1为低级烷基; R2是氢或低级烷基; R3是氢或低级烷基; R4是苯基或取代的苯基，其中苯基可以被一个或多个选自卤素，羟基和低级烷氧基的取代基取代; R5是-OH或-NH2; A选自L-谷氨酸，L-天冬氨酸，L-赖氨酸，L-鸟氨酸和L-2,4-二氨基丁酸; B是L-丙氨酸或L-谷氨酰胺; C是L-精氨酸或D-精氨酸; D选自L-赖氨酸，L-鸟氨酸，L-2,4-二氨基丁酸，L-谷氨酸和L-天冬氨酸; E是D组和R5组之间的直接键，或是L-赖氨酸或D-赖氨酸; m为0或1; 符号*表示可以是D或L构型的不对称碳原子，条件是：（a）当A是L-谷氨酸或L-天冬氨酸时，D是L-赖氨酸，L-鸟氨酸或 L-2,4-二氨基丁酸; 和（b）当A是L-赖氨酸，L-鸟氨酸或L-2,4-二氨基丁酸时，D是L-谷氨酸或L-天冬氨酸。 本发明还涉及使用新型环状多肽的方法。