Motilin-like polypeptides that inhibit gastrointestinal motor activity

A method for treating a condition of increased basal level of gastrointestinal motor activity in a mammal which comprises administering to the mammal a therapeutically effective amount of a polypeptide represented by the formula:

• ##STR6## including optically active isomeric forms and the pharmaceutically acceptable acid addition salts thereof wherein:
• A is the L-stereoisomer of a lipophilic aliphatic amino acid;
• B is selected from the group consisting of phenylalanine, p-fluorophenylalanine, p-chlorophenyanine, p-bromophenylalanine, p-iodophenylalanine, tyrosine, p-methoxyphenylalanine, 1 -naphthylalanine, 2-naphthylalanine, tryptophan, .beta.-2-thienylalanine, homophenylalanine, .beta.-3-pyridylalanine, .alpha.-aminobutyric acid, norvaline, norleucine, leucine, and cyclohexylalanine;
• D is the L-stereoisomer of a lipophilic aliphatic 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 land 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), Z-Leu-Gln-Glu-Lys-Glu (SEQ ID NO:4), Z-Leu-Gln-Glu-Lys-Glu-Arg (SEQ ID NO:5), Z-Leu-Gln-Glu-Lys-Glu-Arg-Asn (SEQ ID NO:6), Z-Leu-Gln-Glu-Lys-Glu-Arg-Asn-Lys (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 cycloalkyl or aryl which may be unsubstituted or 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).