An analogue of a tripeptide inhibitor of angiotensin converting enzyme, Bz-Phe-Gly-Pro, has been synthesized in which the amide bond connecting phenylalanine and glycine has been replaced by a ketomethylene group. This nonpeptide analogue, 20, shows more potent converting enzyme inhibiting activity, I50 = 0.07 microM, than Bz-Phe-Gly-Pro, I50 = 9.4 microM, or than the orally active D-3-mercapto-2-methylpropanoyl-L-proline (captopril, 1), I50 = 0.30 microM. Compound 20 has a Ki of 1.06 X 10(-7) and either competitive or noncompetitive enzyme kinetics depending on what substrate is used in the converting enzyme assay. In tests for inhibition of angiotensin I induced contractions in the guinea pig ileum, 20 has one-tenth the activity of 1.

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ing wakefulness which seems to be characteristic of the midpontine preparation deserves more attention, and its mechanisms are being presently investigated (7). Suffice it to say here that the behavioral and electroencephalographic patterns of the "midpontine" animal do not appear to result from hypoventilation and consequent hypercapnia, as demonstrated by blood gas measurement before and after appropriate brain-stem transection (7). A synchronizing, or possibly sleep-inducing, influence exerted by some structure in the caudal brain stem can be tentatively envisaged, and its existence will be tested experimentally. This might provide a new interpretation of Roger, Rossi, and Zirondoli's finding (5) that trigeminal deafferentation precipitates electroencephalographic sleep patterns in the encephale isole cat.

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