Interphenylene 9-thia-11-oxo-12-aza-prostanoic acids
AssigneeMerck & Co., Inc.
InventorsEdward J. Cragoe, Jr., Ta-jyh Lee, John B. Bicking
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Abstract
This invention relates to novel interphenylene 9-thia-11-oxo-12-azaprostanoic acid compounds, salts, and derivatives thereof. These compounds are exceptionally potent renal vasodilators and antihypertensives which are active when administered orally but which have a more specific type of biological activity than that of many of the natural prostaglandins and their synthetic analogs or derivatives.
Claims65
A compound of the formula:
- ##STR47## wherein R is carboxy, a carboxy salt, a carboxy ester of the formula COOR.sup.5 wherein R.sup.5 is C.sub.1-10 alkyl, or CONHR.sup.6 wherein R.sup.6 is amino or methylsulfonyl;
- A is a p-phenylene or a m-phenylene or substituted phenylene derivative in which one or two of the phenylene hydrogens is replaced by a methyl or a halo substituent, or 2,5-thienylene or 2,5-furylene;
- n is 3 or 4;
- m is 0, 1, or 2;
- R.sup.1 is hydrogen, deuterium, or methyl;
- Z is alkylene or unsaturated alkylene having from 2-3 carbon atoms;
- R.sup.2 is hydrogen or lower alkanoyl;
- R.sup.3 is hydrogen or straight chain C.sub.1-3 alkyl;
- and
- R.sup.4 is lower straight chain or branched alkyl having from 3-7 carbon atoms, an unsaturated alkyl having from 3-7 carbon atoms, or a substituted lower alkyl selected from polyfluoro alkyl of from 3-7 carbon atoms and lower alkoxy methylene;
- or
- R.sup.3 and R.sup.4 taken together with the carbon atom connecting R.sup.3 and R.sup.4 is a cyclic substituent selected from a bridged or unbridged alicyclic ring of from 5-9 carbon atoms or a heterocyclic ring containing sulfur or oxygen and from 5-7 ring-forming carbon atoms.
A pharmaceutical composition for improving renal function in patients with renal impairment comprising an aqueous, oily, or enteric-coated pharmaceutical carrier and an effective renal vasodilator amount of a compound of the formula:
- ##STR55## wherein R is carboxy, a carboxy salt, a carboxy ester of the formula COOR.sup.5 wherein R.sup.5 is C.sub.1-10 alkyl, or CONHR.sup.6 wherein R.sup.6 is amino or methylsulfonyl;
- A is a p-phenylene or a m-phenylene or substituted phenylene derivative in which one or two of the phenylene hydrogens is replaced by a methyl or a halo substituent, or 2,5-thienyl or 2,5-furylene;
- n is 3 or 4;
- m is 0, 1, or 2;
- R.sup.1 is hydrogen, deuterium, or methyl;
- Z is alkylene or unsaturated alkylene having from 2-3 carbon atoms;
- R.sup.2 is hydrogen or lower alkanoyl;
- R.sup.3 is hydrogen or straight chain C.sub.1-3 alkyl;
- and
- R.sup.4 is a lower straight chain or branched alkyl having from 3-7 carbon atoms, an unsaturated alkyl having from 3-7 carbon atoms, or a substituted lower alkyl selected from polyfluoro alkyl of from 3-7 carbon atoms and lower alkoxy methylene;
- or
- R.sup.3 and R.sup.4 taken together with the carbon atom connecting R.sup.3 and R.sup.4 is a cyclic substituent selected from a bridged or unbridged alicyclic ring of from 5-9 carbon atoms or a heterocyclic ring containing sulfur or oxygen and from 5-7 ring-forming carbon atoms.
Dependencies are inferred from the claim text.