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Biomedical subjects

A A Patchett

Publications and source records attributed to A A Patchett.

At least 91 records · Page 5Linked to original sources
PubMed1980

A new class of angiotensin-converting enzyme inhibitors.

Much current attention focuses on the renin-angiotensin system in relation to mechanisms controlling blood pressure and renal function. Recent demonstrations (ref. 1, ref. 2 and refs therein) that angiotensin-converting enzyme inhibitors show promising clinical antihypertensive properties have been of particular interest. We now report on the design of a novel series of substituted N-carboxymethyl-dipeptides which are active in inhibiting angiotensin-converting enzyme at nanomolar levels. We suggest that these compounds are transition-state inhibitors and that extensions of this design to other metalloendopeptidases merit further study.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1980

Inactivation of 3-(3,4-dihydroxyphenyl)alanine decarboxylase by 2-(fluoromethyl)-3-(3,4-dihydroxyphenyl)alanine.

2-(Fluoromethyl)-3-(3,4-dihydroxyphenyl)alanine [alpha-FM-Dopa (I)] causes rapid, time-dependent, stereospecific, and irreversible inhibition of hog kidney aromatic amino acid (Dopa) decarboxylase. The inactivation occurs with loss of both the carboxyl carbon and fluoride from I and results in the stoichimetric formation of a covalent enzyme-inhibitor adduct. The data are consistent with I being a suicide inactivator of the enzyme, and a plausible mechanism for the inactivation process is presented. The inactivation is highly efficient in that there is essentially no enzymatic turnover of I to produce the corresponding amine, 1-(fluoromethyl)-2-(3,4-dihydroxyphenyl)ethylamine [alpha-FM-dopamine (II)]. Amine II is also a potent inactivator of the enzyme. In vivo compound I is found to inactivate both brain and peripheral (liver) Dopa decarboxylase activity. The possible significance of these data with respect to the known antihypertensive effect of I is discussed.

Alanine↗
PubMed1980

Synthesis and biological activity of flavipucine analogues.

A series of analogues of flavipucine was prepared possessing side chain as well as nuclear variants. The analogue with an octyl side chain (5d) was found to exhibit enhanced activity against several bacteria and fungi as compared with the natural product itself. The separation and characterization of the individual diastereoisomeric pairs both spectroscopically and with respect to chromatographic mobility have been effected.

Anti-Bacterial Agents↗
PubMed1977

5,11-dimethyl-2,9-bis(phenylacetyl)-5,11-diazatetracyclo[6.2.2.0(2,7).0(4,9)]dodecane, a potent, novel analgesic.

5,11-Dimethyl-2,9-bis(phenylacetyl)-5,11-diazatetracyclo[6.2.2.0(2,7)90(4,9)]dodecane (2a) has been found to be a potent narcotic analgesic of unusual structure. All of the analgesic activity was attributable to the levorotatory isomer 2b which was approximately three times as potent as morphine in the rat. Removal of one N-methyl group from 2a reduced, but did not abolish, the analgesic activity. However N-allyl analogues were neither agonists nor antagonists. Replacement of one of the phenyls of 2a with a cyclohexyl group yielded an analogue with considerable activity. Structural similarities with derivatives of ethenooripavine are noted.

Analgesics, Opioid↗
PubMed1977

Anticoccidial 1-substituted 4(1H)-pyridinone hydrazones.

4-Chlorobenzaldehyde 1-(4-chlorophenyl)-4(1H)-pyridinylidene hydrazone fluorusulfonate (4) was found to have excellent anticoccidial activity in chickens. The synthesis and biological evaluation of related analogues are presented. Presumably 4 shares a common mechanism of action with robenidine (25) since it was not active on a robenidine tolerant strain of E. tenella. Structural comparisons of the two molecules are presented.

Animals↗
PubMed1975

Substituted pyrazolo corticoids as topical antiinflammatory agents.

The synthesis of a series of substituted pyrazolo corticoids is described. Of these 11beta,17alpha,21-trihydroxy-6,16alpha-dimethyl-4,6-pregnadieno[3,2-c]-2'-(4-pyridly)pyrazole (21) shows an excellent separation of systemic to local activity in the model animal test. Compound 21 exhibits high vasoconstriction activity in human volunteers and is clinically effective in the treatment of psoriasis.

Administration, Topical↗