6-(((Substituted)pyridin-3-yl)alkyl)-and alkenyl)-tetrahydro-4-hydroxypyran-2-one inhibitors of cholesterol biosynthesis

A compound of structural Formula I ##STR10## and the N-oxide thereof, wherein X is --CH2CH2-- or --CH.dbd.CH--;

• R.sub.1 and R.sub.4 are each independently
• alkyl of from one to six carbons;
• trifluoromethyl;
• cyclopropyl;
• cyclohexyl;
• cyclohexylmethyl;
• phenyl;
• phenyl substituted with
• fluorine,
• chlorine,
• bromine;
• hydroxy,
• trifluoromethyl,
• alkyl of from one to four carbon atoms, or
• alkoxy of from one to four carbon atoms;
• phenylmethyl;
• phenylmethyl substituted with
• fluorine,
• chlorine,
• bromine;
• hydroxy,
• trifluoromethyl,
• alkyl of from one to four carbon atoms, or
• alkoxy of from one to four carbon atoms;
• 2-pyridinyl;
• 2-pyridinyl-N-oxide;
• 3-pyridinyl;
• 3-pyridinyl-N-oxide;
• 4-pyridinyl;
• 4-pyridinyl-N-oxide;
• 2-pyrimidinyl;
• 4-pyrimidinyl;
• 5-pyrimidinyl;
• 2-thienyl;
• 3-thienyl;
• CH.sub.2 OH;
• chlorine;
• bromine;
• NR'R" wherein R' and R" are each independently hydrogen, alkyl of from one to four carbon atoms, or together with the N to which they are attached form ##STR11## wherein n' is an integer of from 0 to 5;
• ##STR12## wherein Y is hydrogen or an alkyl of from one to four carbon atoms;
• or R.sub.1 is
• CN;
• OR;
• or
• S(O).sub.n R
• wherein n is 0, 1, or 2 and R is lower alkyl phenyl, substituted phenyl, benzyl or substituted benzyl;
• R.sub.2 is
• hydrogen;
• alkyl of from one to six carbon atoms;
• trifluoromethyl;
• cyclopropyl;
• phenyl;
• phenyl substituted with
• fluorine,
• chlorine,
• bromine;
• hydroxy,
• trifluoromethyl,
• alkyl of from one to four carbon atoms, or
• alkoxy of from one to four carbon atoms;
• 2-pyridinyl;
• 2-pyridinyl-N-oxide;
• 3-pyridinyl;
• 4-pyridinyl;
• 2-pyrimidinyl;
• 4-pyrimidinyl;
• 5-pyrimidinyl;
• 2-thienyl;
• 3-thienyl;
• CH.sub.2 OH;
• chlorine;
• bromine;
• or
• NR'R" wherein R' and R" are as above;
• R.sub.3 is
• hydrogen;
• alkyl of from one to six carbon atoms;
• cyano;
• nitro;
• --NR.sub.5 R.sub.6 where R.sub.5 and R.sub.6 are independently
• hydrogen or alkyl of from one to four carbon atoms;
• phenyl;
• --NHCOR.sub.7 where R.sub.7 is alkyl of from one to four carbon atoms;
• --COR.sub.8 where R.sub.8 is
• hydroxyl,
• alkoxyl of from one to six carbon atoms,
• phenoxy,
• NR.sub.5 R.sub.6, where R.sub.5 and R.sub.6 are as defined above,
• vinyl,
• alkoxy of from one to four carbon atoms,
• hydrogen, or
• CH.sub.2 OH;
• a corresponding dihydroxy-acid compound of Formula II corresponding to the opened form of the lactone ring of a compound of Formula I above ##STR13## or the N-oxide thereof, wherein X, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are as defined above, or a lower alkyl ester or pharmaceutically acceptable salt thereof, all of the compounds being in the trans racemate of the tetrahydropyran moiety.