Octahydroindolizinepropanoic acid derivatives as enzyme inhibitors.

摘要

Octahydro-5oxoindolizine-6-propanoic acids and octahydro-6-oxopyrido [1,2-a] pyridine-7-propanoic acids, the decarboxy and related ester and perhydro derivatives are disclosed, of the following formula
<Chemistry id="chema01" num="0001"><Image id="ia01" he="23" wi="85" file="IMGA0001.TIF" imgContent="chem" imgFormat="TIFF" inline="no" /></Chemistry>in which Y is
<Chemistry id="chema02" num="0002"><Image id="ia02" he="10" wi="13" file="IMGA0002.TIF" imgContent="chem" imgFormat="TIFF" inline="no" /></Chemistry>or -CH<Sub>2</Sub>-CH(R<Sub>2</Sub>)-,
<UnorderedLists id="ula01" listStyle="none"><ListItem>R<Sub>2</Sub> is hydrogen or hydroxy;</ListItem><ListItem>R<Sub>4</Sub> is hydrogen, hydroxy, C<Sub>2</Sub>-C<Sub>5</Sub> alkanoyloxy, halo-substituted C<Sub>2</Sub>-C<Sub>5</Sub>alkanoyloxy,or a sulfonyloxy group formula
<Chemistry id="chema03" num="0003"><Image id="ia03" he="21" wi="26" file="IMGA0003.TIF" imgContent="chem" imgFormat="TIFF" inline="no" /></Chemistry></ListItem><ListItem>in which R<Sub>5</Sub> is C<Sub>1</Sub>-C<Sub>4</Sub> alkyl or phenyl group of the formula
<Chemistry id="chema04" num="0004"><Image id="ia04" he="19" wi="35" file="IMGA0004.TIF" imgContent="chem" imgFormat="TIFF" inline="no" /></Chemistry></ListItem><ListItem>in which R. is hydrogen, C<Sub>1</Sub>-C<Sub>4</Sub> alkyl, C<Sub>1</Sub>-C<Sub>4</Sub> alkoxy, nitro, or halogen;</ListItem><ListItem>n is 1 or 2; X is hydrogen or COOR<Sub>1</Sub>;</ListItem><ListItem>R and R<Sub>1</Sub>, independently, are hydrogen, C,-C. alkyl, indanyl, phthalidyl, or an acyloxymethyl group of the formula
<Chemistry id="chema05" num="0005"><Image id="ia05" he="14" wi="31" file="IMGA0005.TIF" imgContent="chem" imgFormat="TIFF" inline="no" /></Chemistry>in which R<Sub>3</Sub> is C<Sub>1</Sub>-C<Sub>4</Sub> alkyl, phenyl, halophenyl, C<Sub>1</Sub>-C<Sub>4</Sub> alkylphenyl, C<Sub>1</Sub>-C<Sub>4</Sub> alkoxyphenyl, or 3,4-methylenedioxyphenyl; or a pharmaceutically-acceptable salt thereof, provided that when X is COOR<Sub>1</Sub>, R<Sub>4</Sub> may not be hydroxy. The compounds inhibit angiotensin I converting enzyme and are hypotensive agents. Hydrogenation of A58365 factors A and B, obtained by culturing Streptomyces chromofuscus, provides these compounds.</ListItem></UnorderedLists>