| abstract |
Compounds characterized generally as ethynyl alanine amino diol derivatives are useful to inhibit enzymatic conversion of angiotensinogen to angiotensin I. Such enzymatic inhibition is useful to treat disorders mediated by plasma renin activity. An example of such disorders is hypertension. Compounds of particular interest are those of Formula I.wherein A is selected from CO and SO2 wherein X is selected from oxygen atom and methylene; wherein each of R1 and R9 is a group independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, benzyl, b, b, b-trifluoroethyl, t-butyloxycarbonyl and methoxymethylcarbonyl, and wherein the nitrogen atom to which R1 and R9 are attached may be combined with oxygen to form an N-oxide; wherein R2 is selected from hydrido, methyl, ethyl and isopropyl; wherein R3 is selected from benzyl, cyclohexylmethyl, phenethyl, imidazolemethyl, pyridylmethyl and 2-pyridylethyl; wherein R5 is propargyl or a propargyl-containing moiety; wherein R7 is cyclohexylmethyl; wherein each of R4 and R6 is independently selected from hydrido and methyl; wherein R8 is selected from ethyl, n-propyl, isobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclohexylmethyl, cyclohexylethyl, allyl, vinyl and fluorovinyl; wherein each of R11 and R12 is independently selected from hydrido, alkyl and phenyl; wherein m is zero; and wherein n is a number selected from zero through three; or a pharmaceutically-acceptable salt thereof. |