Patent NZ-333498-A (NZ)
Title: optionally substituted salicylic acid derivatives and analogs useful for treating picornavirus caused diseases
Inventor: ARAD DORIT
IPC: C07D217/24
Filed: 1997-06-15
Abstract: The optionally substituted salicylic acid derivatives, analogs and pharmaceutically acceptable salts thereof have the formula I wherein: X is C=O, S=O, C=S, (C=O)-N-R, (C=O)-O and (C=O)-S; R1 is selected from the group consisting of:  a) hydrogen, hydroxyl or an optionally saturated fluorinated C1-10 hydrocarbon chain which can be optionally substituted with at least one R11 except the hydrocarbon chain has at least 3 carbons when X is C=O, Z is OH, Z' and Y are H, Y' is either H or Cl and R3 is H or Cl;  b) an oligopeptide of 1 to 12 amino acids or a peptidomimetic molecule having substantially similar binding properties as the oligopeptide and  c) C3-6 cycloalkyl, C6-10 bicycloalkyl, C3-7 cycloalkylmethyl, C7-10 arylalkyl, a benzo-fused phenyl or a C5-8 heterocyclic ring system including at least one nitrogen, oxygen or sulphur atom, which may be additionally substituted with R11; R11 is selected from:  d) C1-4 alkyl, C2-4 alkenyl, C3-8 cycloalkyl, an optionally substituted aryl or C6-10 bicycloalkyl which can be benzo-fused to Z' when Z' is C1-4 alkyl, OH, carbonyl, amino or sulphydryl;  e) halogen, cyano, nitro, amino, hydroxy, adamantyl, carbamoyl, carbamoyloxy or keto;  f) an oligopeptide of 1-3 amino acid residues and  g) NR13R14, CO2R13, O(C=OR13), SO2R14, SOR14, (C=O)NR13R14 or NR14(C=O)R13; R13 is hydrogen, phenyl, benzyl, alkyl or alkoxyalkyl; R14 is hydrogen, hydroxyl, alkyl or benzyl; R3 is selected from:  h) hydrogen, phenyl, hydroxyl, chlorine, C1-12 hydrocarbon chain or O-C1-12 hydrocarbon chain which may be additionally substituted with at least one R11 and  i) an oligopeptide of 1 to 3 amino acids, an oligopeptide of 1 to 3 amino acids joined to the backbone by an oxygen or a peptidomimetic; Z is hydroxyl, sulphydryl, amino, carboxyl and NHR11 except R11 is not a 3,5-trifluoromethyl-aryl when X is C=O and R1, R3, Y, Y' and Z' are H; Z' is selected from:  j) hydroxyl, amino, carbamido, sulphydryl, carbamoyl, carbamoyloxy, carbonyl or halogen;  k) hydrogen except when Z is OH, X is C=O, R1 is a fluorinated carbon, Y is H or halogen, Y' is H or halogen and R3 is OH or methoxy and  l) C1-4 alkyl, C2-5 alkenyl, C3-7 cycloalkenyl, or C1-6 alkoxy which may be additionally substituted with at least one R11; Y and Y' are independently selected from:  m) hydrogen, halogen, C1-4 haloalkyl, or C1-4 haloalkoxy;  n) carbamoyl, carbamido, cyano, keto, vinyl, sulphoxide, nitro, C1-3 alkylsulphonyl or sulphone except Y' is a keto of at least 5 carbons when X is C=O, R1 and Z are OH and Y and R3 are H;  o) C1-3 alkyl which may be additionally substituted with at least one R11 and  p) an oligopeptide of 1 to 3 amino acids or a peptidomimetic;  or alternatively Z' and R1 collectively form a ring system selected from:  q) optionally saturated C5-8 carbocyclic ring which may be additionally substituted with at least one R11 and  r) optionally saturated C5-10 heterocyclic ring system which includes at least one nitrogen, oxygen or sulphur atom and which may be additionally substituted with at least one R11; with the proviso that when X-R1 is a fluorinated keto acyl, Z is hydroxyl and Z' is H and that the compound is not 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)-hexan-1-one or 1-(3,5-dichloro-2,4-dihydroxy-6-methoxyphenyl)-hexan-1-one. A pharmaceutical composition thereof is used for treating a disease caused by a picornavirus species or inhibiting 3C protease or a cysteine protease having an active site similar to a 3C protease. The compound can be used to determine the presence of a picornavirus species in a sample.