公开(公告)号：US5422341A

公开(公告)日：1995-06-06

申请号：US103490

申请日：1993-08-06

申请人： Mark J. Macielag ,  Ramalinga Dharanipragada ,  James R. Florance ,  Mary S. Marvin ,  Alphonse Galdes

发明人： Mark J. Macielag ,  Ramalinga Dharanipragada ,  James R. Florance ,  Mary S. Marvin ,  Alphonse Galdes

IPC分类号： C07K7/04 ,  A61K38/00 ,  A61P3/00 ,  A61P3/02 ,  C07K14/575 ,  C07K14/63 ,  C07K5/00 ,  C07K7/00 ,  C07K17/00

CPC分类号： C07K14/63 ,  A61K38/00

摘要： This invention pertains to polypeptides, other than motilin, having gastrointestinal motor stimulating activity and represented by the formula: ##STR1## wherein A and D are lipophilic aliphatic or alicyclic amino acids; B is L-proline or L-alanine; E is an aromatic, lipophilic aliphatic, or alicyclic amino acid; F is an aromatic or heteroaromatic amino acid; G is glycine or D-alanine; H is L-glutamic acid or L-glutamine; I is L-glutamine, L-glutamic acid, or L-alanine; J is a direct bond or is selected from, inter alia Z, Z-Leu, Z-Leu-Gln, Z-Leu-Gln-Glu (SEQ ID NO:2) or Z-Leu-Gln-Glu-Lys (SEQ ID NO:3), wherein Z is, inter alia, arginine, D-arginine, D-homoarginine, or D-lysine, and further wherein the amino acids represented by A, D, E and F are L-stereoisomers; R.sub.1 is lower-alkyl or allyl; R.sub.2 is hydrogen, lower-alkyl, propargyl, or allyl; R.sub.3 is hydrogen, lower-alkyl, and allyl; R.sub.4 is lower-alkyl, cycloalkyl, heteroaryl, unsubstituted aryl, and aryl substituted by halogen, hydroxy, or lower-alkoxy; R.sub.5 is --CH.sub.2 CONH.sub.2, aminoalkyl, or guanidinoalkyl; R.sub.6 is --COOH or --CONH.sub.2 ; and m is 0 or 1, and the asymmetric carbon represented by * may be D or L configuration, with certain specified provisos.

摘要翻译： 本发明涉及具有胃肠运动刺激活性并由下式表示的除胃动素以外的多肽：其中A和D是亲脂性脂族或脂环族氨基酸; B是L-脯氨酸或L-丙氨酸; E是芳族，亲脂性脂族或脂环族氨基酸; F是芳族或杂芳族氨基酸; G是甘氨酸或D-丙氨酸; H是L-谷氨酸或L-谷氨酰胺; 我是L-谷氨酰胺，L-谷氨酸或L-丙氨酸; J是直接键或选自Z，Z-Leu，Z-Leu-Gln，Z-Leu-Gln-Glu（SEQ ID NO：2）或Z-Leu-Gln-Glu-Lys（SEQ 其中Z特别是精氨酸，D-精氨酸，D-高精氨酸或D-赖氨酸，其中由A，D，E和F表示的氨基酸是L-立体异构体; R1是低级烷基或烯丙基; R2是氢，低级烷基，炔丙基或烯丙基; R3是氢，低级烷基和烯丙基; R4是低级烷基，环烷基，杂芳基，未取代的芳基和被卤素，羟基或低级烷氧基取代的芳基; R5是-CH2CONH2，氨基烷基或胍基烷基; R6是-COOH或-CONH 2; 并且m为0或1，并且由*表示的不对称碳可以是D或L构型，具有特定的条件。