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Abstract

This invention pertains to polypeptides having gastrointestinal motor inhibitory activity represented by the formula: ##STR1## including optically active isomeric forms and the pharmaceutically acceptable acid addition salts thereof wherein A is the L-stereoisomer of a lipophilic aliphatic or alicyclic amino acid; B is selected from the group consisting of L and D aromatic, heteroaromatic, lipophilic aliphatic, and alicyclic amino acids; D is the L-stereoisomer of a lipophilic aliphatic or alicyclic amino acid; E is the L-stereoisomer of an aromatic, aliphatic, or alicyclic amino acid; F is the L-stereoisomer of 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 between I and group --NH-- or is selected from the group consisting of Z, Z-Leu, Z-Leu-Gln, Z-Leu-Gln-Glu (SEQ ID NO:2), Z-Leu-Gln-Glu-Lys (SEQ ID NO:3), Zleu-Gln-Glu-Lys-Glu (SEQ ID NO:4), Z-Leu-Gln-Glu-Lys-Glu-Arg (SEQ ID NO:5), ZLeu-Gln-Glu-Lys-Glu-Arg-Asn (SEQ ID NO:6), Z-Leu-Gln-Glu-Lys-Glu-Arg-AsnLys (SEQ ID NO:7), and Z-Leu-Gln-Glu-Lys-Glu-Arg-Asn-Lys-Gly (SEQ ID NO:8), wherein Z is selected from the group consisting of arginine, D-arginine, D-homoarginine, D-lysine, D-ornithine, D-2,4-diaminobutyric acid, D-glutamine, D-asparagine, and D-alanine; R.sub.1 and R.sub.2 are independently hydrogen or lower alkyl; R.sub.3 is selected from the group consisting of lower-alkyl, cycloalkyl, substituted and unsubstituted aryl, and heteroaryl, wherein the aryl group may be substituted with one or more substituents selected from the group consisting of halogen, hydroxy, and lower-alkoxy; R.sub.4 is selected from the group consisting of --CH.sub.2 CONH.sub.2, aminoalkyl groups containing from 1 to 3 carbon atoms, and guanidinoalkyl groups containing 2 or 3 carbon atoms; R.sub.5 is --COOH or --CONH.sub.2 ; and the symbol * represents an asymmetric carbon atom which may be in the D or L configuration, and each lower-alkyl group contains from 1 to 4 carbon atoms, with the proviso that R.sub.4 is --CH.sub.2 CONH.sub.2 only when J is Z-Leu or Z-Leu-Gln-Glu-Lys-Glu-Arg-Asn-Lys-Gly (SEQ ID NO:8).

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First Claim