| 摘要 |
1487115 Octapeptide ABBOTT LABORATORIES 8 May 1975 [10 May 1974] 19511/75 Heading C3H [Also in Division C2] An octapeptide of Formula (I) which may be represented as wherein R is N,N-dimethylglycyl, N-methylisoleucyl, guanidylacetyl, sarcosyl; R<SP>1</SP> is ethyl, hydroxy methoxy (X is a residue of isoleucine, threonine, O-methylthreonine respectively) and the optically-active amino acid residues have the L-configuration may be prepared by a Merrifield synthesis which comprises the esterification of an N-protected amino acid of formula werein R<SP>11</SP> is a protective group and R 1 is ethyl, methoxy or benzyloxy with a chloromethylstyrene/divinylbenzene copolymer, removing the protective group and coupling the amino-acid ester with similarly N-protected proline, (N<SP>1m</SP>-benzyl)-histidine, isoleucine, (O- benzyl)tyrosine, valine, nitroarginine, and finally coupling the hexapeptide so obtained with N,N-dimethylglycine, N-protected N-methylisoleucine, N-protected guanidylacetic acid or N- protected sarcosine, wherein the N-protective group (R<SP>11</SP>) is removed after each coupling, removing the protective groups in the histidine, tyrosine, arginine and, if present, the benzyl in O-benzylthreonine moieties, and splitting the octapeptide from the resin. In the examples, Boc is the N-protective group, the octapeptides prepared being: Pharmacetical compositions consist of the octapeptide (I) dissolved in a liquid, pharmaceutically-acceptable vehicle wherein the concentration of (I) is 50-6000 ng./ ml. of said vehicle, preferably as an oil solution, or in aqueous solution buffered to a pH of 7À0-7À5, and which may contain 1 to 5% by weight of a preservative. The oil is preferably cod-liver oil, sesame oil or refined coconut oil. |
