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The somatostatin analog D-Phe-Cys-Phe-D-TrpLys-Thr-Cys-NH-CH(CH2OH)CHOHCH3 4815The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

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Die Derivate (IIc)‐(IIf), (VI), (VIId)‐(VIIg) und (IX) der Titelverbindungen (IIa) bzw. (VIIa) [THIP == Tetra.‐ hydroisoxazolo‐pyridin‐3‐ol werden ‐ wie im Formelschema skizziert ‐ dargestellt und besitzen teilweise Weitere Substanzen mit ähnlichem Substitutionsmuster werden ebenfalls synthetisiert, sind aber biologisch weniger relevant.

SummaryThe synthesis and biological testing of analogues of Met-enkephalin, a recently discovered opioid peptide from mammalian brain, are described. Testing involved determination of affinity constants for an opiate receptor site and of analgesic potency in the tail-flick test in mouse. The effects on opioid activity of modifying various parts of the enkephalin molecule are discussed. Tyr-D-Ala-Gly-MePheMet (O)-oll) (FK 33-824), which was highly active in these tests, was subsequently selected for clinical testing.The use of two complementary models -in vitro binding studies and in vivo test for analgesia -for the assessment of biological activity in the evaluation of analogues is explained.