Cyclic motilin-like polypeptides with gastrointestinal motor...

C - Chemistry – Metallurgy – 07 – K

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C07K 14/63 (2006.01) A61K 38/12 (2006.01) A61K 38/22 (2006.01) C07K 7/56 (2006.01) C07K 7/60 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2200935

This invention pertains to cyclic polypeptides having gastrointestinal motor stimulating activity which may be represented by formula (1): Image 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 R1 is lower alkyl; R2 is hydrogen or lower alkyl; R3 is hydrogen or lower alkyl; R4 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; R5 is -OH or -NH2; 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 R5 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.

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