Imidazolidinedione derivatives

Claim 1

An analogy process for preparing s p iro-hydantoin derivatives of the formulae: and the pharmaceutically acceptable salts thereof, wherein X and Y are each hydrogen, fluorine, chlorine, bromine, nitro or amino; Z is hydrogen or amino, with the proviso that Z is always other than amino when at least one of X and Y is other than hydrogen; R is a member selected from the group consisting of hydrogen, aryl and aralkyl having up to three carbon atoms in the alkyl moiety wherein each of said aryl moieties is chosen from the group consisting of pyridyl and ring-subsituted pyridyl, with each ring substituent being chosen from the group consisting of fluorine, chlorine, bromine and alkyl having from one to four carbon atoms, with the proviso that said R is always other than hydrogen when each of X, Y and Z is other than amino; =A- B = D - of formula II represents = N - CH =CH-, = CH - CH =N- or =CH-N=CH-; R' is a member selected from the group consisting of hydrogen, alkyl having from one to four carbon atoms, aryl and aralkyl having up to three carbon atoms in the alkyl moiety wherein each of said aryl moieties is chosen from the group consisting of pyridyl, thienyl, phenyl and mono and di-substituted phenyl, with each ring substituent being chosen from the group consisting of fluorine, chlorine, bromine, alkyl and alkoxy each having up to four carbon atoms and trifluoromethyl; and R" is hydrogen, hydroxy, fluorine, chlorine, alkyl or alkoxy each having up to four carbon atoms or trifluoromethyl, characterized by: (a) condensing an appropriately substituted carbonyl ring compound of the respectively formulae: wherein X,Y,Z,R,R' and R" are each as previously defined with an alkali metal cyanide and ammonium carbonate to form the corresponding s p iro-oxindole imidazolidinedione final product of formula I or II; (b) or when X and Y are each hydrogen and Z is amino in formula I, alkylating sodio-ethyl hydantoin-5-carboxylate with 2,4-dinitrobenzene, followed by reductive cyclization; (c) or, when R' is hydrogen in formula II, alkylating sodio-ethyl hydantoin-5-carboxylate with an appropriate halonitro-disubstituted pyridine, followed by reductive cyclization; (d) or, when X is halogen as previously defined, Y is amino and Z is hydrogen in formula I, halogenating the compound wherein X, Y and Z are each hydrogen to form the corresponding 5'-halo derivative wherein X is halogen, followed by nitration at the 7'-position and subsequent reduction; and thereafter, if required, converting a compound of formula II wherein R' is hydrogen to a corresponding compound where R' is other than hydrogen; and, if desired, converting a compound of formula I or II to a pharmaceutically acceptable salt thereof.