EP0524595A1 — Substituted beta-lactam compounds useful as hypocholesterolemic agents and processes for the preparation thereof

USPTO Abstract

Novel compounds of the formula wherein    A is -CH=CH-B; -C≡C-B; -(CH₂) p -X-B, wherein p is 0-2 and X is a bond, -NH- or-S(O)₀₋₂; optionally substituted heteroaryl or benzofused heteroaryl; -C(O)-B; or wherein k is 1-2;    D is B'-(CH₂) m C(O)-, wherein m is 1-5; B'-(CH₂) q -, wherein q is 2-6; B'-(CH₂) e -Z-(CH₂) r -, wherein Z is -O-, -C(O)-, phenylene, -NR₈- or -S(O)₀₋₂-, e is 0-5 and r is 1-5, provided that the sum of e and r is 1-6; B'-(alkenylene)-; B'-(alkadienylene)-; B'-(CH₂) t -Z-(alkenylene), wherein t is 0-3, provided that the sum of t and the number of carbon atoms in the alkenylene chain is 2-6; B'-(CH₂) f -V-(CH₂) g -, wherein V is cycloalkylene, f is 1-5 and g is 0-5, provided that the sum of f and g is 1-6; B'-(CH₂) t -V-(alkenylene) or B'-(alkenylene)-V-(CH₂) t -, provided that the sum of t and the number of carbon atoms in the alkenylene chain is 2-6; B'-(CH₂)a-Z-(CH₂)b-V-(CH₂)d-, wherein a, b and d are 0-6, provided that the sum of a, b and d is 0-6; T(CH₂) s -, wherein T is cycloalkyl and s is 1-6; naphthylmethyl or optionally substituted heteroarylmethyl;    B is optionally substituted phenyl;    B' is naphthyl, optionally substituted heteroaryl or optionally substituted phenyl;    R is hydrogen, fluoro, alkyl, alkenyl, alkynyl, or B-(CH₂)h-, wherein h is 0-3;    R4 is optionally substituted phenyl, indanyl, benzofuranyl, tetrahydronaphthyl, pyridyl, pyrazinyl, pyrimidinyl or quinolyl; are disclosed, as well as their use as hypocholesterolemic agents; the method of using compounds of the formula II wherein    R₂₀ is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted heteroaryl, or optionally substituted benzofused heteroaryl,    R₂₁, R₂₂ and R₂₃ are independently selected from H or R₂₀;    E, F and G are independently a bond; cycloalkylene; alkylene; alkenylene; alkynylene; a substituted alkylene, alkenylene or alkynylene chain ; an interrupted alkylene, alkenylene or alkynylene chain ; or an interrupted alkylene, alkenylene or alkynylene chain substituted by one or more substituents; or one of R₂₁-E and R₂₂-F is selected from the group consisting of halogeno, OH, alkoxy, -OC(O)R₅, -NR₁₀R₁₁, -SH or -S(alkyl);    R₅ is alkyl, phenyl, R₁₄-phenyl, benzyl or R₁₄-benzyl;    R₁₀ and R₁₁ are independently selected from H and lower alkyl, or a pharmaceutically acceptable salt thereof, in a pharmaceutically aceptable carrier as hypocholesterolemic agents is also disclosed.