IMIDAZOLONE DERIVATIVES FOR THE TREATMENT OF VIRAL DISEASES

Abstract: The invention describes novel imidazolone derivatives as well as hydrolyzable esters or ethers of compounds of formula I and pharmaceutically acceptable salts thereof, a process for their manufacture, pharmaceutical compositions and the use of such compounds in medicine (formula I) wherein R<1>, R<2>, R<3>, A and X are as defined in the description. The compounds of formula I are the human immunodeficiency virus reverse transcriptase enzyme which is involved in viral replication. Consequently the compounds of this invention may be advantageously used as therapeutic agents for HIV madiated process.

Description: Imidazolone Derivatives for the Treatment of Viral Diseases The invention is concerned with novel imidazolone derivatives, a process for their manufacture, pharmaceutical compositions and the use of such compounds in medicine. In particular, the compounds are inhibitors of the human immunodeficiency virus reverse transcriptase enzyme which is involved in viral replication. Consequently the compounds of this invention ma be advantageously used as therapeutic agents for the treatment of diseases mediated by the human immunodeficiency virus (HIV). The disease Acquired Immunodeficiency Syndrome (AIDS) is the end result of infection by the distinct retroviruses, human immunodeficiency virus type-1 (HIN-1) or type-2 (HIV-2). Several critical points in the virus life cycle have been identified as possible targets for therapeutic intervention. Inhibition of one of these, the transcription of viral RΝA to viral DΝA (reverse transcriptase, RT), has provided a number of the current therapies used in treating AIDS. Inhibition of reverse transcriptase provided the first form of treatment for HIV infection with 3'-azido-3'-deoxythyrnidine (AZT). Since then several inhibitors have been launched, broadly forming two classes: nucleoside analogues and non-nucleosides. As an example of the latter it has been found that certain benzoxazinones, e.g. efavirenz are useful in the inhibition of HIV RT. However, development of strains of the virus resistant to current RT inhibitors is a constant problem. Therefore, development of compounds effective against resistant strains is an important goal. Imidazolone derivatives have been described in the literature with different uses in the treatment of the human body. WO 94/10168 describes imidazolone derivatives and their use as tachykinin receptor antagonists. WO 96/38421 describes imidazolone derivatives and their use as anti-coagulants. WO 00/35907 describes imidazolone derivatives and their use in treating benign prostatic hyperplasia. The object of the present invention is to provide novel compounds which are potent inhibitors of the human immunodeficiency virus reverse transcriptase enzyme, which is involved in viral replication, and which accordingly show a potential to be efficacious as antiviral drugs. This object can be achieved with compounds of formula I wherein R 1 is hydrogen, alkyl, cycloalkyl, aryl or alkyl substituted with optionally substituted phenyl; R 2 is hydrogen, alkenyl, alkyl or alkyl substituted with optionally substituted phenyl; R 3 is alkyl, cycloalkyl, optionally substituted phenyl, optionally substituted benzyl or heterocyclyl; A is alkyl, hydroxy- alkyl, alkenyl, substituted alkenyl, aryl-CH(OH)-, substituted alkyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or alkyl and Z represents heterocyclyl or optionally substituted aryl; X represents S or O; with the provisos that (i) only one of R 1 and R 2 is hydrogen; (ii) when X is O, then R 1 cannot be aryl; as well as hydrolyzable esters or ethers of compounds of formula I and pharmaceutically acceptable salts thereof. The term "alkyl" as used herein denotes an optionally substituted straight or branched chain hydrocarbon residue containing 1 to 12 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl including their different isomers. Preferably, the term "alkyl" denotes an optionally substituted straight or branched chain hydrocarbon residue containing 1 to 7 carbon atoms. Suitable substituents for the alkyl chain can be selected from one or more of aryl, heterocyclyl, alkoxy, hydroxy or halogen. Aryl or heterocyclyl as substituents for the alkyl group can also be substituted with 1, 2, 3, 4, 5 or where possible more methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, methoxy, ethoxy, n-propyloxy, iso-propyloxy, n-butyloxy, iso- butyloxy, tert.-butyloxy, hydroxy, fluorine, chlorine, bromine or iodine. Alkyl in R 1 , R 2 and R 3 is preferably an optionally substituted straight or branched chain hydrocarbon residue containing 1 to 7 carbon atoms. Suitable substituents for the alkyl group are selected from aryl, heterocyclyl, hydroxy or halogen. Preferred alkyl groups in R 1 , R 2 and R 3 are unsubstituted straight or branched chain hydrocarbon residues containing 1 to 7 carbon atoms and more preferred alkyl groups in R 1 , R 2 and R 3 are methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl or pentyl. Most preferred alkyl group in R 1 , R 2 and R 3 are methyl, ethyl, propyl, isopropyl, n-butyl, sec- butyl, isobutyl, tert.-butyl. Alkyl for R 1 is preferably isopropyl. Alkyl for R 2 is preferably methyl. Alkyl for the substituent A is as defined above, preferably a straight or branched chain hydrocarbon residue containing 1 to 7 carbon atoms. More preferred alkyl group for the substituent A are methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.- butyl or pentyl. The term "alkoxy" as used herein denotes an optionally substituted straight or branched chain alkyl-oxy group wherein the "alkyl" portion is as defined above such as methoxy, ethoxy, n-propyloxy, iso-propyloxy, n-butyloxy, iso-butylαxy, tert.-butyloxy, pentyloxy, hexyloxy, heptyloxy including their different isomers. More preferred alkoxy groups within the invention are methoxy, ethoxy, n-propyloxy, iso-propyloxy, n-butyloxy, iso-butyloxy or tert.-butyloxy. The term or heterocyclyl-oxy" as used herein denotes a Cι.4-alkyl, preferably Cι- 2 -alkyl as defined above which may be substituted with 1-3, preferably 1-2 and more preferably on substituents selected from . 4 -alkoxy (preferred C 1 . 2 -alkoxy ), Cι. 4 -alkyl-carbonyl-oxy- (preferred Cι- 2 -alkyl-carbonyl-oxy-) and heterocyclyl-oxy. Preferred examples are methoxymethyl, ethoxymethyl, methyl-carbonyl-oxy-, ethyl-carbonyl-oxy-, 4-pyridyl-oxy-methyl, 3- pyridyl-oxy-methyl, 2-pyridyl-oxy-methyl. The term "Cι. 4 -alkyl substituted with optionally substituted phenyl" as used herein denotes a - 4 -alkyl, preferably Cι. 2 -alkyl as defined above which may be substituted with a phenyl group or with a substituted phenyl group which may be substituted with 1,2,3,4 or 5 substituents, preferably 1, 2 or 3 substituents selected from Cι. 4 -alkyl, - 4 -alkoxy, hydroxy, fluorine, chlorine or bromine, preferably methyl, ethyl, methoxy, ethoxy, hydroxy, fluorine, chlorine or bromine. Examples are phenylmethyl (benzyl), phenylethyl, phenylpropyl, phenylbutyl, tolylmethyl, tolylemyl, tolylpropyl, tolylbutyl, 2,3- dimethylphenylmethyl, 2,4-dimethylphenylmethyl, 2,5-dimethylphenylmethyl, 2, 6- dimethylphenylmethyl, 3, 4- dimethylphenylmethyl, 3, 5 -dimethylphenylmethyl, 3,6- dimethylphenylmethyl, 2-methoxy- phenylmethyl, 3-methoxy-phenylmethyl, 4-methoxy- phenylmethyl, methoxy-phenylethyl, methoxy-phenylpropyl, methoxy-phenylbutyl, dimethoxy-phenylmethyl, dimethoxy-phenylethyl, dimethoxy-phenylpropyl, dimethoxy- phenylbutyl, 2-hydroxyphenylmethyl, 3-hydroxyphenylmethyl, 4-hydroxyphenylmethyl, 2,3-dihydroxyphenylmethyl, 2,4-dihydroxyphenylmethyl, 2,5-dihydroxyphenylmethyl, 2,6-dihydroxyphenylmethyl, 3,4-dihydroxyphenylmethyl, 3,5-dihydroxyphenylmethyl, 3,6-dihydroxyphenylmethyl, 2-hydroxyphenylethyl, 3-hydroxyphenylethyl, 4- hydroxyphenylethyl, 2-hydroxyphenylpropyl, 3-hydroxyphenylpropyl, 4- hydroxyphenylpropyl, 2-hydroxyphenylbutyl, 3-hydroxyphenylbutyl, 4- hydroxyphenylbutyl, 2-fluorophenylmethyl, 3-fluorophenylmethyl, 4-fluorophenylmethyl, 2,3-difluorophenylmethyl, 2,4-difluorophenylmethyl, 2,5-difluorophenylmethyl, 2,6-difluorophenylmethyl, 3,4-difluorophenylmethyl, 3,5-difluorophenylmethyl, 3,6- difluorophenylmethyl, 2-fluorophenylethyl, 3-fiuorophenylethyl or 4-fluorophenylethyl, 2-chlorophenylmethyl, 3-chlorophenylmethyl, 4-chlorophenylmethyl, 2,3- dichlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,5-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 3,4-dichlorophenylmefhyl, 3,5-dichlorophenylmethyl, 3,6- dichlorophenylmethyl, 2-chlorophenylethyl, 3-chlorophenylethyl, 4-chlorophenylethyl, 2- bromophenylmethyl, 3-bromophenylmethyl, 4-bromophenylmethyl, 2,3- dibromophenylmethyl, 2,4-dibromophenylmethyl, 2,5-dibromophenylmethyl, 2,6-dibromophenylmethyl, 3,4-dibromophenylmethyl, 3,5-dibromophenylmethyl, 3,6- dibromophenylmethyl, 2-bromophenylethyl, 3-bromophenylethyl or 4-bromophenylethyl. In case more than one substituent is attached to the phenyl group, these substituents can be identical or different from each other and are also encompassed by the scope of the present invention. For example dimethoxy-phenylmethyl means that both methoxy substituents maybe attached to the phenyl ring in the 2,3-position, the 2,4-position, the 2,5-position, the 2,6-position, the 3,4-position, the 3,5-position and the 3,6-position. . -alkyl groups substituted with optionally substituted phenyl in R 1 are as defined above and preferably phenylmethyl (benzyl), phenylethyl, tolylmethyl, tolylethyl, 2,3- dimethylphenylmethyl, 2,4-dimethylphenylmethyl, 2,5-dimethylphenylmethyl, 2,6-dimethylphenylmethyl, 3,4-dimethylphenylmethyl, 3,5-dimethylphenylmethyl, 3,6- dimethylphenylmethyl, 2-methoxy-phenylmethyl, 3-methoxy-phenylmethyl, 4-methoxy- phenylmethyl, methoxy-phenylethyl, dimethoxy-phenylmethyl, dimethoxy-phenylethyl, 2- hydroxyphenylmethyl, 3-hydroxyphenylmethyl, 4-hydroxyphenylmethyl, 2,3- dihydroxyphenylmethyl, 2,4-dihydroxyphenylmethyl, 2,5-dihydroxyphenylmethyl, 2,6-dihydroxyphenylmethyl, 3,4-dihydroxyphenylmethyl, 3,5-dihydroxyphenylmethyl, 3,6-dihydroxyphenylmethyl, 2-hydroxyphenylethyl, 3-hydroxyphenylethyl, 4- hydroxyphenylethyl, 2-fluorophenylmethyl, 3-fluorophenylmethyl, 4-fluorophenylmethyl, 2,3-difluorophenylmethyl, 2,4-difluorophenylmethyl, 2,5-difluorophenylmethyl, 2,6-difluorophenylmethyl, 3,4-difluorophenylmethyl, 3,5-difluorophenylmethyl, 3,6- difiuorophenylmethyl, 2-fluorophenylethyl, 3-fluorophenylethyl or 4-fluorophenylethyl, 2-chlorophenylmethyl, 3-chlorophenylmethyl, 4-chlorophenylmethyl, 2,3- dichlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,5-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 3,4-dichlorophenylmethyl, 3,5-dichlorophenylmethyl, 3,6- dichlorophenylmethyl, 2-chlorophenylethyl, 3-chloroρhenylethyl, 4-chlorophenylethyl, 2- bromophenylmethyl, 3-bromophenylmethyl, 4-bromophenylmethyl, 2,3- dibromophenylmethyl, 2,4-dibromophenylmethyl, 2,5-dibromophenylmethyl, 2,6-dibromophenylmethyl, 3,4-dibromophenylmethyl, 3,5-dibromophenylmethyl, 3,6- dibromophenylmethyl, 2-bromophenylethyl, 3-bromophenylethyl or 4-bromophenylethyl. Most preferred C] . . 4 -alkyl substituted with optionally substituted phenyl in R 1 are phenylmethyl (benzyl), phenylethyl, tolylmethyl, tolylethyl, 2,3-dimethylphenylrnethyl, 2,4-dimethylphenylmethyl, 2,5-dimethylphenylmethyl, 2,6-dimethylphenylmethyl, 3,4- dimethylphenylmethyl, 3,5-dimethylphenylmethyl or 3,6-dimethylphenylmethyl. . -alkyl groups substituted with optionally substituted phenyl in R 2 are as defined above and preferably phenylmethyl (benzyl), phenylethyl, tolylmethyl, tolylethyl, 2,3- dimethylphenylmethyl, 2,4-dimethylphenylmethyl, 2,5-dimethylphenylmethyl, 2,6-dimethylphenylmethyl, 3,4-dimethylphenylmethyl, 3,5-dimethylphenylmethyl, 3,6- dimethylphenylmethyl, 2-methoxy-phenylmethyl, 3-methoxy-phenylmethyl, 4-methoxy- phenylmethyl, methoxy-phenylethyl, dimethoxy-phenylmethyl, dimethoxy-phenylethyl, 2- hydroxyphenylmethyl, 3-hydroxyphenylmethyl, 4-hydroxyphenylmethyl, 2,3- dihydroxyphenylmethyl, 2,4-dihydroxyphenylmethyl, 2,5-dihydroxyphenylmethyl, 2,6-dihydroxyphenylmethyl, 3,4-dihydroxyphenylmethyl, 3,5-dihydroxyphenylmethyl, 3,6-dihydroxyphenylmethyl, 2-hydroxyphenylethyl, 3 -hydroxyphenylethyl, 4- hydroxyphenylethyl, 2-fluorophenylmethyl, 3-fluorophenylmethyl, 4-fluorophenylmethyl, 2,3-difluorophenylmethyl, 2,4-difluorophenylmethyl, 2,5-difluorophenylmethyl, 2,6-difluorophenylmethyl, 3,4-difluorophenylmethyl, 3,5-difluorophenylmethyl, 3,6- difluorophenylmethyl, 2-fluorophenylethyl, 3-fluorophenylefhyl or 4-fluorophenylethyl, 2-chlorophenylmethyl, 3-chlorophenylmethyl, 4-chlorophenylmethyl, 2,3- dichlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,5-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 3,4-dichlorophenylmethyl, 3,5-dichlorophenylmethyl, 3,6- dichlorophenylmethyl, 2-chlorophenylethyl, 3-chlorophenylethyl, 4-chlorophenylethyl, 2- bromophenylmethyl, 3-bromophenylmethyl, 4-bromophenylmethyl, 2,3- dibromophenylmethyl, 2,4-dibromophenylmethyl, 2,5-dibromoρhenylmethyl, 2,6-dibromophenylmethyl, 3,4-dibromophenylmethyl, 3,5-dibromophenylmethyl, 3,6- dibromophenylmethyl, 2-bromophenylethyl, 3-bromophenylethyl or 4-bromophenylethyl. Most preferred Cι_ 4 -alkyl substituted with optionally substituted phenyl in R 2 are phenylmethyl (benzyl), phenylethyl, tolylmethyl, tolylethyl, 2,3-dimethylphenylmethyl, 2,4-dimethylphenylmethyl, 2,5-dimethylphenylmethyl, 2,6-dimethylphenylmethyl, 3,4- dimethylphenylmethyl, 3,5-dimethylphenylmethyl, 3,6-dimethylphenylmethyl, methoxy- phenylmethyl, methoxy-phenylethyl, dimethoxy-phenylmethyl or dimethoxy-phenylethyl. - 4 -alkyl groups substituted with optionally substituted phenyl for the substituent A are as defined above, preferably phenylmethyl (benzyl), phenylethyl, tolylmethyl, tolylethyl, 2,3-dimethylphenylmethyl, 2,4-dimethylphenylmethyl, 2,5- dimethylphenylmethyl, 2,6-dimethylphenylmethyl, 3,4-dimethylphenylmethyl, 3,5- dimethylphenylmethyl, 3,6-dimethylphenylmethyl, 2-methoxy-phenylmethyl, 3-methoxy- phenylmethyl, 4-methoxy-phenylmethyl, methoxy-phenylethyl, dimethoxy-phenylmethyl, dimethoxy-phenylethyl, 2-hydroxyphenylmethyl, 3-hydroxyphenylmethyl, 4- hydroxyphenylmethyl, 2,3-dihydroxyphenylmethyl, 2,4-dihydroxyphenylmethyl, 2,5- dihydroxyphenylmethyl, 2,6-dihydroxyphenylmethyl, 3,4-dihydroxyphenylmethyl, 3,5- dihydroxyphenylmethyl, 3,6-dihydroxyphenylmethyl, 2-hydroxyphenylethyl, 3- hydroxyphenylethyl, 4-hydroxyphenylethyl, 2-fluorophenylmethyl, 3-fluorophenylmethyl, 4-fluorophenylmethyl, 2,3-difluorophenylmethyl, 2,4-difluorophenylmethyl, 2,5- difluorophenylmethyl, 2,6-difluorophenylmethyl, 3,4-difluorophenylmethyl, 3,5- difluorophenylmethyl, 3,6-difluorophenylmethyl, 2-fluorophenylethyl, 3- fluorophenylethyl or 4-fluorophenylethyl, 2-chlorophenylmethyl, 3-chlorophenylmethyl, 4-chlorophenylmethyl, 2,3-dichlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,5- dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 3,4-dichlorophenylmethyl, 3,5- dichlorophenylmethyl, 3,6-dichlorophenylmethyl, 2-chlorophenylethyl, 3- chlorophenylethyl, 4-chlorophenylethyl, 2-bromophenylmethyl, 3-bromophenylmethyl, 4- bromophenylmethyl, 2,3-dibromophenylmethyl, 2,4-dibromophenylmethyl, 2,5- dibromophenylmethyl, 2,6-dibromophenylmethyl, 3,4-dibromophenylmethyl, 3,5- dibromophenylmethyl, 3,6-dibromophenylmethyl, 2-bromophenylethyl, 3- bromophenylethyl or 4-bromophenylethyl. Most preferred Ci_ -alkyl substituted with optionally substituted phenyl for the substituent A are phenylmethyl (benzyl), phenylethyl, tolylmethyl, tolylethyl, 2,3-dimethylphenylmethyl, 2,4-dimethylphenylmethyl, 2,5- dimethylphenylmethyl, 2,6-dimethylphenylmethyl, 3,4-dimethylphenylmethyl, 3,5- dimethylphenylmethyl, 3,6-dimethylphenylmethyl, 2-hydroxyphenylmethyl, 3- hydroxyphenylmethyl, 4-hydroxyphenylmethyl, 2,3-dihydroxyphenylmethyl, 2,4- dihydroxyphenylmethyl, 2,5-dihydroxyphenylmefhyl, 2,6-dihydroxyphenylmethyl, 3,4- dihydroxyphenylmethyl, 3,5-dihydroxyphenylmethyl, 3,6-dihydroxyphenylmethyl, 2- hydroxyphenylethyl, 3 -hydroxyphenylethyl or 4-hydroxyphenylethyl. The term "cycloalkyl" as used herein denotes an optionally substituted cycloalkyl group containing 3 to 8 carbon atoms, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. Suitable substituents for cycloalkyl can be selected from those named for alkyl, in addition however an oxo group (=O) can be added to the selection. Cycloalkyl in R 1 is as defined above and preferably cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclopropyl or cyclobutyl and most preferred cyclopropyl. Cycloalkyl in R 3 is as defined above, preferably cyclopentyl, cyclohexyl or cycloheptyl and most preferred cyclohexyl. The term "alkenyl" as used herein, and if not specified by the number of carbon atoms, denotes an unsubstituted or substituted hydrocarbon chain radical having from 2 to 8 carbon atoms, preferably from 2 to 4 carbon atoms, and having at least one olefinic double bond, including their different isomers. Examples are vinyl or allyl. A substituted alkenyl group as part of the invention can have the (E) or (Z) configuration. Both isomeric forms of these compounds are embraced by the present invention. Suitable substituents for the alkenyl group can be selected from 1-2 (preferably 1) substituents selected from cyano, amino-carbonyl and C -alkyl-oxy-carbonyl. Alkenyl in R 2 is as defined above, preferably allyl. Alkenyl for the substituent A is as defined above, preferably a vinyl group or a substituted vinyl group substituted with 1-2 (preferably 1) substituents selected from cyano, amino-carbonyl and C 1 . -alkyl-oxy-carbonyl. Examples are vinyl, acrylic acid ethyl ester, acrylonitrile, acrylamide. Both, the (E) or (Z) configuration are embraced by the present invention, however the (E) configuration is preferred. The term "hydroxy-Cι. 4 -alkyl" as used herein denotes a Ci . 4 - alkyl, preferably a Cι. 2 -alkyl as defined above which is substituted with a hydroxy group. Examples are hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2-hydroxypropyl, 3- hydroxypropyl, 1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl. The term "hydroxy- . 4 - alkyl" for the substituent A is as defined above, preferably hydroxymethyl, 1-hydroxyethyl or 2-hydroxyethyl. Formula "Z-CH 2 -Y-CH 2 -" as used herein denotes a chemical group wherein Y represents O or NR wherein R is hydrogen or ^-alkyl as defined above, preferably hydrogen; and Z represents heterocyclyl or optionally substituted aryl with 1-3 benzyl-oxy groups (preferably 1-2 benzyl-oxy groups, more preferred 1 benzyl-oxy group). More preferred Z represents aryl or heterocyclyl as defined below, preferably phenyl or 2-pyridyl, 3-pyridyl or 4-pyridyl. Examples of the chemical group of formula "-CH 2 -Y-CH 2 -Z" are benzylaminomethyl, benzyloxymethyl, (pyridin-4-ylmethyl)aminomethyl, pyridin-4- ylmethoxymethyl, pyridin-3-ylmethoxymethyl, pyridin-4-ylmethoxymethyl or 4- b enzyloxy-b enzyloxymethyl. The term "aryl" as used herein denotes an optionally substituted phenyl and naphthyl, both optionally benz-fused to an optionally substituted saturated, partially unsaturated or aromatic monocyclic, bicyclic or tricyclic heterocycle or carbocycle e.g. to cyclohexyl or cyclopentyl. Suitable substituents for aryl can be selected froml,2,3,4 or 5 those named for alkyl and - 4 -alkyl, Cι. -alkoxy, hydroxy, fluorine, chlorine or bromine; they can be identical or different from each other. Preferred substituents for aryl are selected from . 4 - alkyl, Cι. 4 -alkoxy, hydroxy, fluorine, chlorine or bromine. In case more than one substituent is attached to the aryl group, these substituents can be identical or different from each other and are also encompassed by the scope of the present invention. For example dimethoxy-phenyl means that both methoxy substituents maybe attached to the phenyl ring in the 2,3-position, the 2,4-position, the 2,5-position, the 2,6-position, the 3,4-position, the 3,5-position and the 3,6-position. Examples of aryl groups are phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl- phenyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 3,6-dimethylphenyl, 2-methoxy-phenyl, 3- methoxy-phenyl, 4-methoxy-phenyl, 2,3-dimethoxy-phenyl, 2,4-dimethoxy-phenyl, 2,5- dimethoxy-phenyl, 2,6-dimethoxy-phenyl, 3,4-dimethoxy-phenyl, 3,5-dimethoxy-phenyl, 3,6-dimethoxy-phenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2,3- dihydroxyphenyl, 2,4-dihydroxyphenyl, 2,5-dihydroxyphenyl, 2,6-dihydroxyphenyl, 3,4- dihydroxyphenyl, 3,5-dihydroxyphenyl, 3,6-dihydroxyphenyl, 2-fluorophenyl, 3- fluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl, 2,4-difluorophenyl, 2,5-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 3,6-difluorophenyl 2- chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 2,6-dichlorophenyl, 3,4-dichloroρhenyl, 3,5-dichlorophenyl, 3,6- dichlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2,3-dιbromophenyl, 2,4-dibromophenyl, 2,5-dibromophenyl, 2,6-dibromophenyl, 3,4-dibromophenyl, 3,5- dibromophenyl or 3,6-dibromophenyl. Aryl in R is as defined above and preferably phenyl, 2-methyl-phenyl, 3-methyl- phenyl, 4-methyl-phenyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 3,6-dimethylphenyl, 2- chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl and most preferably phenyl. Aryl in the formula "Z-CH 2 -Y-CH 2 -" as used herein denotes preferably one of the following groups: phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 2,3- dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4- dimethylphenyl, 3,5-dimethylphenyl, 3,6-dimethylphenyl, 2-chloro-phenyl, 3-chlorophenyl, 4-chloro-phenyl and most preferably phenyl. The term "optionally substituted phenyl" in R 3 as used herein denotes a phenyl group which may be substituted with 1,2,3,4 or 5 substituents, preferred 1, 2 or 3 substituents, more preferred 1 or 2 substituents selected from Cι. 4 -alkyl, . 4 -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano or selected from Cι. 4 -alkyl, Ci. 4 -alkoxy, hydroxy, fluorine, chlorine or bromine, preferably methyl, ethyl, methoxy, ethoxy,. hydroxy, fluorine, chlorine, bromine; or preferably methyl, ethyl, methoxy, ethoxy, hydroxy, fluorine, chlorine, bromine and cyano. Further preferred embodiments for "optionally substituted phenyl" in R 3 are 2-substituted phenyl rings and the more preferred 3-substituted phenyl rings. An especially preferred embodiment for "optionally substituted phenyl" in R 3 are 3,5-disubstituted phenyl rings. Preferred examples are phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4- dimethylphenyl, 3,5-dimethylphenyl, 3,6-dimethylphenyl, 2-methoxy-phenyl, 3-methoxy- phenyl, 4-methoxy-ρhenyl, 2,3-dimethoxyphenyl, 2,4-dimethoxyphenyl, 2,5- dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,6- dimethoxyphenyl, 2-fluorophenyl, 3 -fluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl, 2,4-difluorophenyl, 2,5-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 3,5- difluorophenyl, 3,6-difluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3- dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 2,6-dichlorophenyl, 3,4- dichlorophenyl, 3,5-dichlorophenyl, 3,6-dichlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2,3-dibromophenyl, 2,4-dibromophenyl, 2,5-dibromophenyl, 2,6-dibromophenyl, 3,4-dibromophenyl, 3,5-dibromophenyl, 3,6-dibromophenyl, 2- cyano-phenyl, 3-cyano-phenyl, 4-cyano-phenyl, 2,3-dicyanophenyl, 2,4-dicyanophenyl, 2,5-dicyanophenyl, 2,6-dicyanophenyl, 3,4-dicyanophenyl, 3,5-dicyanophenyl or 3,6- dicyanophenyl. Most preferred optionally substituted phenyl in R 3 are phenyl, 2- chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 2,6-dichlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 3,6- dichlorophenyl. The term "optionally substituted benzyl" in R 3 as used herein denotes a benzyl group which ma be substituted with 1,2,3,4 or 5 substituents, preferably 1, 2 or 3 substituents selected from ^-alkyl, Cι- 4 -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano or selected from ^-alkyl, . 4 -alkoxy, hydroxy, fluorine, chlorine or bromine, preferably methyl, ethyl, methoxy, ethoxy, hydroxy, fluorine, chlorine or bromine. Preferred examples are benzyl, 2-methyl-benzyl, 3-methyl-benzyl, 4-methyl-benzyl, 2,3- dimethylbenzyl, 2,4-dimethylbenzyl, 2,5-dimethylbenzyl, 2,6-dimethylbenzyl, 3,4- dimethylbenzyl, 3,5-dimethylbenzyl, 3,6-dimethylbenzyl, 2-methoxy-benzyl, 3-methoxy- benzyl, 4-methoxy-benzyl, 2,3-dimethoxybenzyl, 2,4-dimethoxybenzyl, 2,5- dimethoxybenzyl, 2,6-dimethoxybenzyl, 3,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, 3,6- dimethoxybenzyl, 2-hydroxy-benzyl, 3-hydroxy-benzyl, 4-hydroxy-benzyl, 2,3- dihydroxybenzyl, 2,4-dihydroxybenzyl, 2,5-dihydroxybenzyl, 2,6-dihydroxybenzyl, 3,4- dihydroxybenzyl, 3,5-dihydroxybenzyl, 3,6-dihydroxybenzyl, 2-fluorobenzyl, 3- fluorobenzyl, 4-fluorobenzyl, 2,3-difluorobenzyl, 2,4-difluorobenzyl, 2,5-difluorobenzyl, 2,6-difluorobenzyl, 3,4-difluorobenzyl, 3,5-difluorobenzyl, 3,6-difluorobenzyl, 2- chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 2,5- dichlorobenzyl, 2,6-dichlorobenzyl, 3,4-dichlorobenzyl, 3,5-dichlorobenzyl, 3,6- dichlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2,3-dibromobenzyl, 2,4- dibromobenzyl, 2,5-dibromobenzyI, 2,6-dibromobenzyl, 3,4-dibromobenzyl, 3,5- dibromobenzyl 3,6-dibromobenzyl, 2-cyano-benzyl, 3-cyano-benzyl, 4-cyano-benzyl, 2,3- dicyanobenzyl, 2,4-dicyanobenzyl, 2,5-dicyanobenzyl, 2,6-dicyanobenzyl, 3,4- dicyanobenzyl, 3,5-dicyanobenzyl or3,6-dicyanobenzyl. More preferred optionally substituted benzyl in R 3 is benzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2,3- dichlorobenzyl, 2,4-dichlorobenzyl, 2,5-dichlorobenzyl, 2,6-dichlorobenzyl, 3,4- dichlorobenzyl, 3,5-dichlorobenzyl, 3,6-dichlorobenzyl and most preferably benzyl is the unsubstituted benzyl group. In case more than one substituent is attached to the benzyl group, these substituents can be identical or different from each other and are also encompassed by the scope of the present invention. For example dimethoxy-benzyl means that both methoxy substituents may be attached to the phenyl ring in the 2,3-position, the 2,4-position, the 2,5-position, the 2,6-position, the 3,4-position, the 3,5-position and the 3,6-position. The term "aryl-CH(OH)-" as used herein denotes a hydroxymethyl group which is substituted with an aryl group as defined above. A preferred aryl group is the phenyl group. The term "heterocyclyl" as used herein denotes optionally substituted aromatic or non-aromatic monocyclic or bicyclic heterocyclic systems which contains one or more hetero atoms selected from nitrogen, oxygen and sulfur, such as furyl, 1-pyrrolyl, 2- pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1-indolyl, 2-indolyl or 3-indolyl. Suitable substituents for heterocyclyl can be selected froml,2,3,4 or 5 those named for alkyl and Cι. 4 -alkyl, - 4 -alkoxy, hydroxy, fluorine, chlorine or bromine; they can be identical or different from each other. Preferred substituents for heterocyclyl are selected from Ci- 4 -alkyl, . 4 -alkoxy, hydroxy, fluorine, chlorine or bromine. In case more than one substituent is attached to the heterocyclyl group, these substituents can be identical or different from each other and are also encompassed by the scope of the present invention. For example dimethylpyridyl means that both methyl substituents may be attached to the pyridyl in the chemically possible positions. For example both methyl substituents maybe attached to the 2-pyridyl in the 3,4-position, the 4,5-position, the 5,6-position, the 3,5-position, the 3,6-position, the and the 4,6-position. Both methyl substituents maybe attached to the 3-pyridyl in the 2,4-position, the 2,5- position, the 2,6-position, the 4,5-position, the 4,6-position, the and the 5,6-position. Both methyl substituents may be attached to the 4-pyridyl in the 2,3-position, the 2,5-position, the 2,6-position, and the 3,5-position. Examples for "substituted heterocyclyl" are furyl, methylfuryl, dimethylfuryl, ethylfuryl, methoxyfuryl, dimethoxyfuryl, hydroxyfαryl, dihydroxyfuryl, fluorofuryl, difluorofuryl, chlorofuryl, dichlorofuryl, bromofuryl, dibromofuryl, pyrrolyl, methylpyrrolyl, dimethylpyrrolyl, ethylpyrrolyl, methoxypyrrolyl, dimethoxypyrrolyl, hydroxypyrrolyl, dihydroxypyrrolyl, fluoropyrrolyl, difluoropyrrolyl, chloropyrrolyl, dichloropyrrolyl, bromopyrrolyl, dibromopyrrolyl, pyridyl, methylpyridyl, dimethylpyridyl, ethylpyridyl, methoxypyridyl, dimethoxypyridyl, hydroxypyridyl, dihydroxypyridyl, fluoropyridyl, difluoropyridyl, chloropyridyl, dichloropyridyl, bromopyridyl, dibromopyridyl, indolyl, methylindolyl, dimethylindolyl, ethylindolyl, methoxyindolyl, dimethoxyindolyl, hydroxyindolyl, dihydroxyindolyl, fluoroindolyl, difluoroindolyl, chloroindolyl, dichloroindolyl, bromoindolyl or dibromoindolyl. For all the cited examples for "heterocyclyl" these substituents can be at any chemically possible position. For example methylpyridyl means that the methyl substituent maybe attached in the 3, 4, 5 or 6 position of a 2-pyridyl or in the 2, 4, 5 or 6 position of a 3-pyridyl or in the 2, 3, 5 or 6 position of a 4-pyridyl. Heterocyclyl in the formula "Z-CH 2 -Y-CH 2 -" as used herein denoted preferably one of the following groups as defined above, preferably unsubstituted furyl, 1 -pyrrolyl, 2- pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1-indolyl, 2-indolyl or 3-indolyl and most preferably 2-pyridyl, 3-pyridyl or 4-pyridyl. Heterocyclyl in R 3 is as defined above and preferably unsubstituted furyl, 1 -pyrrolyl, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1-indolyl, 2-indolyl or 3-indolyl. More preferably heterocyclyl in R 3 is 2-pyridyl, 3-pyridyl or 4-pyridyl and most preferred 4- pyridyl. The term "Cι- 4 -alkyl substituted with optionally substituted heterocyclyl" as used herein denotes a Cι- 4 -alkyl, preferably Cι. 2 -alkyl group as defined above which maybe substituted with an optionally substituted heterocyclyl group, preferably with an optionally substituted pyridyl group as defined above which may be substituted with 1,2,3 or 4 substituents, preferably 1 or 2 substituents selected from Ci- 4 -alkyl, Cι- 4 -alkoxy, hydroxy, fluorine, chlorine or bromine, preferably methyl, ethyl, methoxy, ethoxy, hydroxy, fluorine, chlorine or bromine. Examples are furylmethyl, furylethyl, furylpropyl, furylbutyl, methylfurylmethyl, methylfurylethyl, dimethylfurylmethyl, ethylfurylmethyl, methoxyfurylmethyl, methoxyfurylethyl, dimethoxyfurylmethyl, hydroxyfurylmethyl, hydroxyfurylethyl, dihydroxyfurylmethyl, fluorofurylmethyl, difluorofurylmethyl, chlorofurylmethyl, chlorofurylethyl, dichlorofurylmethyl, dichlorofurylmethyl, bromofurylmethyl, dibromofurylmethyl, pyrrolylmethyl, pyrrolylethyl, pyrrolylpropyl, pyrrolylbutyl, methylpyrrolylmethyl, methylpyrrolylethyl, dimethylpyrrolylmethyl, ethylpyrrolylmethyl, methoxypyrrolylmethyl, methoxypyrrolylethyl, dimethoxypyrrolylmethyl, hydroxypyrrolylmethyl, hydroxypyrrolylethyl, dihydroxypyrrolylmethyl, fluoropyrrolylmethyl, difluoropyrrolylmethyl, chloropyrrolylmethyl, chloropyrrolylethyl, dichloropyrrolylmethyl, dichloropyrrolylmethyl, bromopyrrolylmethyl, dibromopyrrolylmethyl, pyridylmethyl (more specific examples are 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl), pyridylethyl, pyridylpropyl, pyridylbutyl, methylpyridylmethyl, methylpyridylethyl, dimethylpyridylmethyl, ethylpyridylmethyl, methoxypyridylmethyl, methoxypyridylethyl, dimethoxypyridylmethyl, hydroxypyridylmethyl, hydroxypyridylethyl, dihydroxypyridylmethyl, fluoropyridylmethyl, difluoropyridylmetbyl, chloropyridylmethyl, chloropyridylethyl, dichloropyridylmethyl, dichloropyridylmethyl, bromopyridylmethyl, dibromopyridylmethyl, indolylmethyl, indolylethyl, indolylpropyl, indolylbutyl, methylindolylmethyl, methylindolylethyl, dimethylindolylmethyl, ethylindolylmethyl, methoxyindolylmethyl, methoxyindolylethyl, dimethoxyindolylmethyl, hydroxyindolylmethyl, hydroxyindolylethyl, dihydroxyindolylmethyl, fluoroindolylmethyl, difluoroindolylmethyl, chloroindolylmethyl, chloroindolylethyl, dichloroindolylmethyl, dichloroindolylmethyl, bromoindolylmethyl or dibromoindolylmethyl. For all the cited examples for "heterocyclyl" these substituents can be at any chemically possible position. For example methylpyridyl means that the methyl substituent may be attached in the 3, 4, 5 or 6 position of a 2-pyridyl or in the 2, 4, 5 or 6 position of a 3-pyridyl or in the 2, 3, 5 or 6 position of a 4-pyridyl. The term "X" represents S and O, preferably S. The term halogen stands for fluorine, chlorine, bromine and iodine. Any functional (i.e. reactive) group present in a side-chain may be protected, with the protecting group being a group which is known per se, for example, as described in "Protective Groups in Organic Synthesis", 2nd Ed., T.W. Greene and P.G.M. Wuts, John Wiley & Sons, New York, NY, 1991. For example, an amino group can be protected by tert.-butoxycarbonyl (BOC) or benzyloxycarbonyl (Z). The compounds of this invention may contain one or more asymmetric carbon atoms and may therefore occur as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. Furthermore, where a compound of the invention contains an olefinic double bond, this can have the (E) or (Z) configuration. Also, each chiral center ma be of the R or S configuration. All such isomeric forms of these compounds are embraced by the present invention. Compounds of formula I which are acidic can form pharmaceutically acceptable salts with bases such as alkali metal hydroxides, e.g. sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides, e.g. calcium hydroxide, barium hydroxide and magnesium hydroxide, and the like; with organic bases e.g. N-ethyl piperidine, dibenzylamine, and the like. Those compounds of formula (I) which are basic can form pharmaceutically acceptable salts with inorganic acids, e.g. with hydrohalic acids such as hydrochloric acid and hydrobromic acid, sulphuric acid, nitric acid and phosphoric acid, and the like, and with organic acids, e.g. with acetic acid, tartaric acid, succinic acid, fumaric acid, maleic acid, malic acid, salicylic acid, citric acid, methanesulphonic acid and p-toluene sulphonic acid, and the like. The formation and isolation of such salts can be carried out according to methods known in the art. Preferred embodiments of the invention are compounds of formula I wherein R 1 is hydrogen, Cι-ι 2 -alkyl, C 3 . 8 -cycloalkyl, aryl or ^-alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from Cι. 4 -alkyl, Cι. 4 -alkoxy, hydroxy, fluorine, chlorine and bromine, preferred wherein R 1 is Cι -i 2 -alkyl, aryl or Cι- 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from Ci- 4 -alkyl, ^-alkoxy, hydroxy, fluorine, chlorine and bromine, more preferred wherein R 1 is . 7 -alkyl, phenyl or . 4 -alkyl substituted with phenyl. most preferred wherein R 1 is Cι- 7 -alkyl or - 4 -alkyl substituted with phenyl; R 2 is hydrogen, C 2 . -alkenyl, .^-alkyl or Cι- 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from C 1 . -alkyl, Cι. 4 -alkoxy, hydroxy, fluorine, chlorine and bromine, preferred wherein R 2 is C 2 . - alkenyl, Ci. 12 -alkyl or ^-alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from . -alkyl, - 4 -alkoxy, hydroxy, fluorine, chlorine and bromine, more preferred wherein R 2 is C 2 - 4 -alkenyl, Cι. 7 -alkyl or Ci- 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from Cι„ 4 -alkyl, - 4 -alkoxy, hydroxy, fluorine, chlorine and bromine, most preferred wherein R 2 is C 2 - 4 -alkenyl, - 7 -alkyl or _ 4 -alkyl substituted with phenyl; R 3 is Ci-π-alkyl, C 3 . 8 - cycloalkyl, phenyl, benzyl or heterocyclyl, wherein a phenyl ring may be substituted with 1-5 substituents selected from - 4 -alkyl, C^-alkoxy, hydroxy, fluorine, chlorine, bromine and cyano, preferred wherein R 3 is Cι.i 2 -alkyl, C 3 . 8 -cycloalkyl, phenyl, benzyl or heterocyclyl, wherein a phenyl ring may be substituted with 1-5 substituents selected from - 4 - alkyl, Cι- 4 -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano, more preferred wherein R 3 is Cι- 7 -alkyl, C 3 . 6 -cycloalkyl, phenyl, benzyl or heterocyclyl, wherein a phenyl ring may be substituted with 1-5 substituents selected from Cι- 4 -alkyl, Cj- 4 -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano, most preferred wherein R 3 is - 4 -alkyl, C 3 . 6 -cycloalkyl or optionally substituted phenyl, wherein phenyl may be substituted with 1-5 substituents selected from Q. 4 - alkyl, . 4 - alkoxy, hydroxy, fluorine, chlorine, bromine and cyano; A is Cι.i 2 -alkyl, hydroxy-C ! . -alkyl, C 2 . 4 -alkenyl, substituted C 2 . 4 -alkenyl, aryl- CH(OH)-, Ci- 4 -alkyl substituted with Cι- 4 -alkoxy, C 1 . 4 -alkyl-carbonyl-oxy-, heterocyclyl-oxy or A is Ci . 4 - alkyl substituted with phenyl optionally substituted with 1-5 substituents or with heterocyclyl optionally substituted with 1-4 substituents selected from Ci - 4 - alkyl, Cι- 4 -alkoxy, hydroxy, fluorine, chlorine and bromine, wherein substituted C 2 - 4 -alkenyl is substituted with 1-2 substituents selected from cyano, amino-carbonyl and Cι- 4 -alkyl-oxy-carbonyl, or A signifies a group of formula Z-CH 2 -Y-CH -, wherein Y represents O or NR wherein R is hydrogen or Q. 4 -alkyl and Z represents heterocyclyl or optionally substituted aryl with 1-3 benzyl-oxy groups, preferred wherein A is Cι- 7 -alkyl, hydroxy-Cι- 4 -alkyl, C 2 - 4 -alkenyl, substituted C 2 . 4 -alkenyl, aryl- CH(OH)-, Q. 4 -alkyl substituted with Q_ 4 -alkoxy, Cι„ 4 -alkyl-carbonyl-oxy-, heterocyclyl-oxy or A is Q- 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents or with heterocyclyl optionally substituted with 1-4 substituents selected from Cι- 4 -alkyl, ^-alkoxy, hydroxy, fluorine, chlorine and bromine, wherein substituted C 2 - 4 -alkenyl is substituted with 1-2 substituents selected from cyano, amino-carbonyl and Cι- 4 -alkyl-oxy-carbonyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Ci- 4 -alkyl and Z represents heterocyclyl or optionally substituted aryl with 1-3 benzyl-oxy groups, more preferred wherein A is Ci- 7 -alkyl, hydroxy-Cι. 4 -alkyl, C 2 - 4 -alkenyl, substituted C 2 . 4 -alkenyl, phenyl- CH(OH)-, Cι. 4 -alkyl substituted with - 4 -alkoxy, Ci. 4 -alkyl-carbonyl-oxy-, heterocyclyl-oxy or A is Ci_ -alkyl substituted with phenyl optionally substituted with 1-5 substituents or with pyridyl optionally substituted with 1-4 substituents selected from Cι. -alkyl, Cι. -alkoxy, hydroxy, fluorine, chlorine and bromine, wherein substituted C 2 - 4 -alkenyl is substituted with 1-2 substituents selected from cyano, amino-carbonyl and ^-alkyl-oxy-carbonyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Cι. 4 -alkyl and Z represents pyridyl or optionally substituted phenyl with 1-3 benzyl-oxy groups, most preferred wherein A is Ci. 7 -alkyl, C 2 - 4 -alkenyl, substituted C 2 - 4 -alkenyl, ^-alkyl substituted with phenyl optionally substituted with 1-5 substituents or with pyridyl optionally substituted with 1-4 substituents selected from C h alky!, - 4 -alkoxy, hydroxy, fluorine, chlorine and bromine, wherein substituted C 2 . 4 -alkenyl is substituted with 1-2 substituents selected from cyano, amino-carbonyl and - 4 -alkyl-oxy-carbonyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Ci- 4 -alkyl and Z represents pyridyl or optionally substituted phenyl with 1-3 benzyl-oxy groups; X represents S or O; with the provisos that (i) only one of R 1 and R 2 is hydrogen; (ii) when X is O, then R 1 cannot be aryl; as well as hydrolyzable esters or ethers of compounds of formula I and pharmaceutically acceptable salts thereof. Further preferred embodiments of the invention are compounds of formula I wherein R 1 is Cι. 7 -alkyl, preferred wherein R 1 is Ci- 4 -alkyl, more preferred wherein R 1 is isopropyl; R 2 is Ci. 7 -alkyl, preferred wherein R 2 is Ci- 4 -alkyl, more preferred wherein R 2 is methyl or ethyl, most preferred wherein R 2 is methyl; R 3 is optionally substituted phenyl, wherein phenyl maybe substituted with 1-5 substituents selected from . 4 - alkyl, - 4 -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano, preferred wherein R 3 is optionally substituted phenyl, wherein phenyl may be substituted with 1-3 substituents selected from C h alky!, Ci- 2 -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano, more preferred wherein R 3 is optionally substituted phenyl, wherein phenyl may be substituted with 1-3 chlorine substituents;, most preferred wherein R 3 is optionally substituted phenyl, wherein phenyl maybe substituted with 1-2 chlorine substituents; A is Ci- 4 -alkyl substituted with phenyl optionally substituted with 1-3 substituents or with pyridyl optionally substituted with 1-2 substituents selected from C - alkyl, C -alkoxy, hydroxy, fluorine, chlorine and bromine, or A signifies a group of formula Z-CH -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Cι. 4 -alkyl and Z represents pyridyl or phenyl, preferred wherein A is Ci- 2 -alkyl substituted with phenyl optionally substituted with 1-3 substituents or with pyridyl optionally substituted with 1-2 substituents selected from C M -alkyl, Cι- 4 -alkoxy, hydroxy, fluorine, chlorine and bromine, or A signifies a group of formula Z-CH 2 -Y-CH2-, wherein Y represents O or NR wherein R is hydrogen or . 2 -alkyl and Z represents pyridyl or phenyl, more preferred wherein A is Ci. 2 -alkyl substituted with phenyl or pyridyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Cι- 2 -alkyl and Z represents pyridyl or phenyl, most preferred wherein A is Cι- 2 -alkyl substituted with pyridyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Ci. 2 -alkyl and Z represents pyridyl; X represents S or O; as well as hydrolyzable esters or ethers of compounds of formula I and pharmaceutically acceptable salts thereof. Another embodiment of the invention are compounds of formula I wherein R 1 is hydrogen, C^^-alkyl, C 3 . 8 -cycloalkyl, aryl or Ci. -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from Cι, 4 -alkyl, Ci. 4 -alkoxy, hydroxy, fluorine, chlorine and bromine; R 2 is hydrogen, Cι. 12 -alkyl or C M -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from Cι- 4 -alkyl, Cι. 4 -alkoxy, hydroxy, fluorine, chlorine and bromine; R 3 is Ci-i 2 -alkyl, C 3 . 8 -cycloalkyl, phenyl or benzyl, wherein a phenyl ring maybe substituted with 1-5 substituents selected from Cι-4-alkyl, CM-alkoxy, hydroxy, fluorine, chlorine and bromine; A is hydroxy-Ci- 4 -alkyl or aryl-CH(OH)-; or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or C -alkyl and Z represents aryl or heterocyclyl; or A signifies - 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents or with heterocyclyl optionally substituted with 1-4 substituents selected from - 4 -alkyl, . 4 -alkoxy, hydroxy, fluorine, chlorine and bromine; X represents S or O; with the proviso that only one of R 1 and R 2 is hydrogen; as well as hydrolyzable esters or ethers of compounds of formula I and pharmaceutically acceptable salts thereof. An especially preferred embodiment of the invention are compounds of formula I wherein X represents S; as well as hydrolyzable esters or ethers of compounds of formula I and pharmaceutically acceptable salts thereof. More preferred embodiments of compounds of formula I, as well as hydrolyzable esters or ethers of compounds of formula I and pharmaceutically acceptable salts thereof, are listed in table 1: Table 1 4-(3,5-Dichlorophenylthio)-3-isopropyl-l-methyl-5- { [(pyridin-4-ylmethyl)-amino] -methyl}- l,3-dihydro-2- imidazolone 5-(Benzylaminomethyl)-3-isopropyl-l-methyl-4- phenylthio-l,3-dihydro-2-imidazolone 3-Isopropyl-l-methyl-4-phenylthio-5-{[(pyridin-4- ylmethyl)amino]methyl}-l,3-dihydro-2-imidazolone 5-Benzyloxymethyl-4-(3,5-dichlorophenoxy)-3- isopropyl-l-methyl-l,3-dihydro-2-imidazolone 5-Benzyloxymethyl-4-(3,5-dichlorophenylthio)-l- methyl-3-phenyl-l,3-dihydro-2-imidazolone 4-(3,5-Dichlorothio)-3-isopropyl-l-methyl-5-(pyridin-4- ylmethoxymethyl)-l,3-dihydro-2-imidazolone 5-(Benzylaminomethyl)-4-(3,5-dimethylphenylthio)-3- isopropyl-l-methyl-l,3-dihydro-2-imidazolone 4-Cyclohexylthio-3-isopropyl-l-methyl-5-{[(pyridin-4- ylmethyl)amino]methyl}-l,3-dihydro-2-imidazolone 4-(3,5-Dimethylphenythio)-3-isopropyl-l-methyl-5- {[(pyridin-4-ylmethyl)amino]methyl}-l,3-dihydro-2- imidazolone 4-Benzylthio-3-isopropyl-l-methyl-5-{[(pyridin-4- ylmethyl)amino]methyl}-l,3-dihydro-2-imidazolone 4-(3-Chlorophenylthio)-3-isopropyl-l-methyl-5- {[(pyridin-4-ylmethyl)amino]methyl}-l,3-dihydro-2- imidazolone 3-[5-(3,5-Dichloro-phenylsulfanyl)-l-isopropyl-3- methyl-2-oxo-2,3-dihydro-lH-imidazol-4-ylj- acrylonitrile 3-[5-(3,5-Dichloro-phenylsulfanyl)-l-isopropyl-3- methyl-2-oxo-2,3-dihydro-lH-imidazol-4-yl]-acrylamide l-Benzyl-5-(3,5-dichloro-phenylsulfanyl)-3-methyl-4- vinyl-l,3-dihydro-imidazol-2-one 4-(3,5-Dichloro-phenylsulfanyl)-3-isopropyl-l-methyl-5- pyridin-4-ylmethyl-l,3-dihydro-imidazol-2-one The imidazolone derivatives provided by the present invention are useful in the treatment of the human or animal body. The imidazolone derivatives provided by the present invention are inhibitors of the human immunodeficiency virus reverse transcriptase enzyme. Accordingly, the present imidazolone derivatives are therapeutically active substances in the treatment of diseases mediated by the human immunodeficiency virus (HIV) and can be used as medicaments for the treatment of such diseases. They can be used as medicaments, especially for treating viral diseases, immune mediated conditions or diseases, bacterial diseases, parasitic diseases, inflammatory diseases, hyperproliferative vascular diseases, tumors, and cancer. In particular, compounds of the present invention and pharmaceutical compositions containing the same are useful as chemotherapeutic agents, inhibitors of viral replication and modulators of the immune system, and can be used for the treatment of diseases mediated by the human immunodeficiency virus (HIV) other viral diseases such as retroviral infections (either alone or in combination with other antiviral agents such as interferon or derivatives thereof, such as conjugates with polyethylene glycol). They can be used alone, or in combination with other therapeutically active agents, for example, an immunosuppressant, a chemotherapeutic agent, an anti-viral agent, an antibiotic, an anti-parasitic agent, an anti-inflammatory agent, an anti-fungal agent and/or an anti-vascular hyperproliferation agent. Compounds, whenever prepared by the processes of the present invention are also an object of the present invention. The compounds of the present invention can be prepared as shown in the following scheme: Reaction scheme 1: 6 th step la lb wherein R , R", R , X and Z are as defined for compounds of formula I. In accordance with the present invention, the preparation of compounds of formula wherein R , R , R and X are as defined in formula I; comprises reacting chloro compound of formula VII wherein R 1 and R are as defined in formula I with nucleophilic agent R 3 XH wherein R 3 and X are as defined in formula I. The reaction is described in more detail in reaction scheme 1 (fifth reaction step). In reaction scheme 1, the first reaction step is carried out in that glycine derivative of formula II (commercially available or prepared according to known methods in the art for example alkylation reaction of the nitrogen function of glycine) is reacted with an isocyanate derivative of formula III (commercially available or synfhesised according to known methods from textbooks on organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4 1 ed. John Wiley and Sons) in an appropriate solvent, in the presence of 0.5 - 1.5 equivalents, preferably 0.7 — 1.3 equivalents, most preferred 0.9 equivalents of a base such as potassium carbonate, sodium carbonate, magnesium carbonate, calcium carbonate, potassium hydroxide, sodium hydroxide, magnesium hydroxide, calcium hydroxide, N(CH 3 ) 3 , N(C 2 H 5 ) 3 , N(n-C 3 H 7 ) 3 , N(iso-C 3 H 7 ) 3 , preferably sodium hydroxide. The reaction is conveniently carried out at a reaction temperature from -5°C to boiling temperature of the reaction mixture, preferably at a reaction temperature between 0°C and about 80°C. The reaction can optionally be carried out under an inert atmosphere such as nitrogen or argon atmosphere. An appropriate solvent maybe water or an organic solvent such as alcohols (e.g. methanol, ethanol, propanol, butanol, octanol or cyclohexanol), ethers (e.g. tetrahydrofuran, diethyl ether, dibutyl ether or dioxane), halogenated hydrocarbons (e.g. dichloromethane or trichloromethane), hydrocarbons (e.g. cyclohexane, methyl cyclohexane, decaline, benzene, toluene, o-xylene, m-xylene or p-xylene) or a mixtures of the mentioned solvents, preferably water. After the reaction, the system is neutralised with an acid, preferably a protic acid such as HBr, HI, AcOH or citric acid, most preferred HCl, to yield the urea of formula IN In the second step of the reaction, urea of formula IV is converted in a ring-closure reaction to imidazoldione derivatives of formula V by dissolving compound of formula IV in water and an acid, preferably a protic acid such as HCl, HBr, HI, AcOH, citric or other, most preferred HCl. The reaction is conveniently carried out at a reaction temperature from room temperature to boiling temperature of the reaction mixture, preferably at a reaction temperature from 60°C to boiling temperature of the reaction mixture. The reaction can optionally be carried out in an inert organic solvent such as ethers (e.g. tetrahydrofuran, diethyl ether, dibutyl ether or dioxane), polar aprotic solvents such as dimethylsulfoxide (DMSO) or dimethylacetamide, halogenated hydrocarbons such as dichloromethane or trichloromethane, hydrocarbons such as cyclohexane, methyl cyclohexane, decaline, benzene, toluene, o-xylene, m-xylene or p-xylene, or mixtures of the mentioned solvents. In the third step of the reaction, imidazoldione derivatives of formula V is reacted with di- - 4 -alkylacetal of dimethylformamide, preferably dimethylformamide dimethylacetal (commercially available or synthesized according to methods known from textbooks about organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure", 4 l ed. John Wiley & Sons) to attach a dimethylaminomethylene group to the imidazoldione ring and to obtain the corresponding compound of formula VI. The reaction is carried out at a reaction temperature from room temperature to boiling temperature of the reaction mixture, preferably at a reaction temperature from 60°C to boiling temperature of the reaction mixture, most preferred at a reaction temperature from 80°C to boiling temperature of the reaction mixture. The reaction can optionally be carried out in an inert organic solvent such as ethers (e.g. tetrahydrofuran, diethyl ether, dibutyl ether or dioxane), polar aprotic solvents such as dimethylsulfoxide (DMSO), halogenated hydrocarbons such as dichloromethane or trichloromethane, hydrocarbons such as cyclohexane, methyl cyclohexane, decaline, benzene, toluene, o-xylene, m-xylene or p-xylene, or mixtures of the mentioned solvents. In the fourth step of the reaction, dimethylaminomethylene imidazoldione derivatives of formula VI are converted to the corresponding carbaldehyde chloro imidazolone compound of formula VII as described in US 4,345,936 or known from textbooks about organic chemistry. The reaction which includes a dimethylaminomethylene/ carbaldehyde and oxo/chlorine exchange may be carried out in the presence of a disubstituted formamide such as N,N-dimethylformamide, N,N- methylphenylformamide or N,N-diphenylformamide, preferably dimethylformamide in the presence of POCl 3 according the Vilsmeier reaction or in the presence of other chlorinating agents such as PCI 5 , SOCl 2 or (COCl) 2 . The reaction is optionally carried out under an inert atmosphere such as nitrogen or argon atmosphere at a reaction temperature from room temperature to boiling temperature of the reaction mixture, preferably at a reaction temperature between about 50°C and about 150°C. The reaction can optionally be carried out in an inert organic solvent such as ethers (e.g. tetrahydrofuran, diethyl ether, dibutyl ether or dioxane), polar aprotic solvents such as dimethylsulfoxide (DMSO) or N,N-dimethylacetamide, halogenated hydrocarbons such as dichloromethane or trichloromethane, hydrocarbons such as cyclohexane, methyl cyclohexane, decaline, benzene, toluene, o-xylene, m-xylene or p-xylene, or a mixtures of the mentioned solvents. In the fifth step of the reaction, chloro compounds of formula VII are reacted with nucleophilic thiol R 3 SH or nucleophilic alcohol R 3 OH (both agents are commercially available or can be synthesized according to methods known from textbooks about organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure", 4 ed. John Wiley 8c Sons, to obtain the corresponding compound of formula VIII. The reaction is carried out in an appropriate solvent in the presence of a suitable base such as n-BuLi, sodium hydride, trialkylamine (e.g. trimethylamine or triethylamine), potassium carbonate, sodium carbonate, magnesium carbonate, calcium carbonate, preferably triethylamine, N-methyl morpholine or potassium carbonate. The reaction is conveniently carried out under an inert atmosphere such as nitrogen or argon atmosphere at a reaction temperature from 0°C to boiling temperature of the reaction mixture, preferably at a reaction temperature between about 10°C and about 60°C. Appropriate solvents for the reaction are ethers (e.g. tetrahydrofuran, diethyl ether, dibutyl ether or dioxane), polar aprotic solvents such as dimethylsulfoxide (DMSO) or N,N-dimethylacetamide, halogenated hydrocarbons such as dichloromethane or trichloromethane, hydrocarbons such as cyclohexane, methyl cyclohexane, decaline, benzene, toluene, o-xylene, m-xylene or p-xylene, or a mixtures of the mentioned solvents, preferably dichloromethane or trichloromethane. Also part of the present invention are novel compounds of formula Vlll-a wherein R 1 , R 2 and X are as defined in formula I and R 3 is C 7 -i 2 -alkyl, C 3 . 8 -cycloalkyl, optionally substituted phenyl or optionally substituted benzyl wherein phenyl or benzyl maybe substituted with 1-5 substituents selected from Ci- 4 -alkyl, Cι. 4 -alkoxy, hydroxy, fluorine, chlorine or bromine In the sixth step of the reaction, the aldehyde of formula VIII is reduced in the presence of a reducing agent to obtain the corresponding alcohol derivative of formula la. Reducing agents conveniently used for the reaction are preferably sodium borohydride or other reducing agents such as lithium borohydride, sodium triacetoxyborohydride, hydrogen over a catalyst or reducing agents known in the art applied according to known methods described in textbooks on organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4 th ed. John Wiley and Sons. The reduction reaction is conveniently carried out in an organic solvent for example alcoholic solvents such as methanol, ethanol, propanol, butanol, octanol or cyclohexanol, preferably methanol or ethanol or ethers such as tetrahydrofuran, diethyl ether, dibutyl ether, dioxane or diglyme, preferably tetrahydrofuran or a mixture of the mentioned solvents such as methanol and tetrahydrofuran or ethanol and tetrahydrofuran. The reaction is carried out at a reaction temperature between about -10°C and about 60°C, preferably at room temperature. The reduction reaction can also be carried out as described in textbooks about organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure", 4 th ed. John Wiley 8c Sons. In the seventh step of the reaction, the alcohol derivative of formula la is derivatized to the corresponding ether derivative of formula lb. The derivatisation reaction is conveniently carried out with an electophilic agent L-CH 2 -Z, wherein Z is as defined for compounds of formula I and L is a leaving group such as bromide, chloride, iodide, tosylate, triflate or any other according to methods known from textbooks on organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4 ed. John Wiley and Sons). The reaction is carried out as described in the literature, for example in the presence of a base such as sodium hydride, lithium hydride, potassium carbonate or triethylamine in an appropriate organic solvent such as tetrahydrofuran (THF) or polar aprotic solvents like dimethylsulfoxide (DMSO), N,N-dimethylacetamide or N,N-dimethylformamide (DMF), preferably DMF or THF, at a reaction temperature between about -10°C and about 60°C, preferably at room temperature. For the synthesis of compounds of formula la or lb wherein R 1 , R 3 , X and Z are as defined for compounds of formula I and R 2 is hydrogen, the corresponding compound of formula VI is N-protected with an appropriate protecting group for example 4-methoxybenzyl, benzyl or 3,4-dimethoxybenzyl and then further reacted according the reaction steps 4-6 (and optionally 7), and finally deprotected according to methods known from textbooks on protecting chemistry ('Protecting Groups in Organic Synthesis', second edition, Theodora W. Greene and Peter G. M. Wuts, Wiley-Interscience, 1991) for example in the presence of hydrogen and appropriate catalyst such as Pd/C or Pt/C. Compounds of formula la or lb wherein R 1 , R 3 , X and Z are as defined for compounds of formula I and R 2 is hydrogen are obtained. The protecting reaction is for example carried out in a polar aprotic solvents like dimethylsulfoxide (DMSO), dimethylacetamide or N,N- dimethylformamide (DMF), preferably dimethylformamide in the presence of a base such as lithium hydride or sodium hydride, preferably sodium hydride at a reaction temperature between about -10°C and about 60°C, preferably at room temperature. The reaction system is then treated with an appropriate protecting agent such as 4- methoxybenzyl chloride, 4-methoxybenzyl bromide, benzyl chloride, benzyl bromide, 3,4- dimethoxybenzyl chloride or 3,4-dimethoxybenzyl bromide at a reaction temperature between about -10°C and about 60°C, preferably at room temperature to obtain N- protected compound of formula VI. The deprotection reaction is carried out as described above. For the synthesis of compounds of formula la or lb wherein R 2 , R 3 , X and Z are as defined for compounds of formula I and R 1 is hydrogen, compound of formula III wherein R 1 is a N-protecting group known from the literature such as 4-methoxybenzyl, benzyl or 3,4-dimethoxybenzyl (commercially available or synthesized according to methods known from the literature) is reacted according reaction steps 1-6 (and optionally 7) and finally deprotected under conditions known from the literature. The protecting reaction is for example carried out in polar aprotic solvents like dimethylsulfoxide (DMSO), dimethylacetamide or N,N-dimethylformamide (DMF), preferably dimethylformamide in the presence of a base such as lithium hydride or sodium hydride, preferably sodium hydride at a reaction temperature between about -10°C and about 60°C, preferably at room temperature. The reaction system is then treated with an appropriate protecting agent such as 4-methoxybenzyl chloride , 4-methoxybenzyl bromide, benzyl chloride, benzyl bromide, 3,4-dimethoxybenzyl chloride or 3,4-dimethoxybenzyl bromide at a reaction temperature between about -10°C and about 60°C, preferably at room temperature to obtain N-protected compound of formula VI. The deprotecting reaction is carried out for example under hydrogen in the presence of a catalyst such as palladium on charcoal or platinum on charcoal (as described above). The corresponding compound of formula la or lb wherein R 2 , R 3 , X and Z are as defined for compounds of formula I and R is hydrogen is obtained. Optionally, compounds of formula la or lb wherein R 3 , X and Z are as defined for compounds of formula I, R 1 or R 2 is hydrogen and the other one of R 1 or R 2 is as defined for compounds of formula I, can also be converted to the corresponding compound of formula la or lb wherein R 1 , R 2 , R 3 , X and Z are as defined for compounds of formula I. The reaction is conveniently carried out with an electophilic agent R'-L or R 2 -L, wherein R 1 and R 2 is as defined for formula I but not hydrogen and L is a leaving group such as bromide, chloride, iodide, tosylate, triflate or any other according to methods known from textbooks on organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4 ed. John Wiley and Sons). The reaction is carried out as described in the literature, for example in the presence of a base such as sodium hydride, lithium hydride, potassium carbonate or triethylamine in an appropriate organic solvent such as tetrahydrofuran (THF) or polar aprotic solvents like dimethylsulfoxide (DMSO), N,N-dimethylacetamide or N,N- dimethylformamide (DMF), preferably DMF or THF at a reaction temperature between about -10°C and about 60°C, preferably at room temperature. Reaction scheme 2: VIII Ic Id wherein R 1 , R 2 , R 3 and X are as defined for compounds of formula I and R 4 is alkyl, aryl, optionally substituted phenyl or optionally substituted heterocyclyl as defined for compounds of formula I or Co- 3 -alkyl substituted with C -alkoxy, or heterocyclyl- oxy or R 4 together with the methyl group forms a optionally substituted C 2 - 4 -alkenyl as defined for compounds of formula I. In reaction scheme 2, the first reaction step is carried out in that the aldehydes of formula VIII are derivatised with a Grignard reagent of formula R 4 MgHal wherein R is alkyl, aryl, optionally substituted phenyl or optionally substituted heterocyclyl as defined for compounds of formula I or Co. 3 -alkyl substituted with C M -alkoxy, Ci-4-alkyl-carbonyl- oxy- or heterocyclyl-oxy or R 4 together with the methyl group forms a optionally substituted C 2 - 4 -alkenyl as defined for compounds of formula I, and Hal represents chlorine, bromine or iodine, preferably chlorine (commercially available or synthesised according to textbooks on organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4 th ed. John Wiley and Sons) to obtain the corresponding alcohol derivative of formula Ic. The derivatisation reaction is conveniently carried out in an inert solvent for example ethers such as tetrahydrofuran, diethyl ether, dibutyl ether, dioxane, diglyme or a mixture of the mentioned solvents, preferably tetrahydrofuran at a reaction temperature between about - 10°C and about 60°C, preferably at room temperature. In general, the derivatisation reaction can also be carried out as described in textbooks about organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure", 4 ed. John Wiley 8c Sons. In the second step of the reaction the methyl hydroxy group of alcohol derivative of formula Ic is converted via a deoxygenation reaction to the corresponding methylene group to obtain compound of formula Id. The reaction is conveniently carried out in the presence of trialkylsilane such as trimethylsilane, triethylsilane or tripropylsilane, preferably triethylsilane, dissolved in mineral acids such as trifluoroacetic acid (TFA) or in Lewis acids such as SnCl 4 (described in D. L. Comins et al, Tet. Lett., 1986, 27, 1869), preferably with trifluoroacetic acid at a reaction temperature from 0°C to 80°C, preferably at a reaction temperature between about 5°C and about 50°C. Alternatively, the reduction reaction can also be carried in the presence P2I4 as described in EP 0627423. For the synthesis of compounds of formula Ic or Id wherein the substituents are as defined above and R 2 is hydrogen, the corresponding compound of formula VI is N- protected as described for reaction scheme 1, further reacted according to reaction steps 4- 5 of reaction scheme 1, then reacted according to reaction scheme 2 and finally deprotected as described for reaction scheme 1. For the synthesis of compounds of formula Ic or Id wherein the substituents are as defined above and R 1 is hydrogen, compound of formula VIII wherein R 1 is a N-protecting group such as 4-methoxybenzyl (prepared according to reaction scheme 1) is reacted according reaction scheme 2 and finally deprotected as described for reaction scheme 1. Optionally, compounds of formula Ic or Id wherein the substituents are as defined above and R 1 or R 2 is hydrogen and the other one of R 1 or R 2 is as defined above, can also be converted to the corresponding compound of formula Ic or Id wherein R 1 , R 2 , R 3 , X and Z are as defined above. The reaction is carried out as described for reaction scheme 1. Reaction scheme 3: VIII wherein R, R 1 , R 2 , R 3 , X and Z are as defined for compounds of formula I. In reaction scheme 3, the first reaction step is carried out in that aldehyde of formula VIII is derivatised via a reductive amination reaction with a primary or secondary amine of formula RN(H)CH 2 -Z wherein R and Z are as defined for compounds of formula I to the corresponding amine compounds of formula Ie. The amines of formula RN(H)CH 2 -Z are commercially available or can be synthesized according to known methods from textbooks on organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4 th ed. John Wiley and Sons. The reductive amination reaction is known from textbooks about organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure", 4 th ed. John Wiley 8c Sons. The reaction may be carried out in an inert solvent such as hydrocarbons for example cyclohexane, methyl cyclohexane, decaline, benzene, toluene, o-xylene, m-xylene or p-xylene, preferably toluene at a reaction temperature between about 60°C and about boiling temperature of the organic solvent. After the reaction system has been cooled down, the organic solvent is evaporated and the residue is dissolved in an alcoholic solvent or ether for example methanol, ethanol, propanol, butanol, octanol or cyclohexanol, tetrahydrofuran, diethyl ether, dibutyl ether, dioxane or diglyme, preferably methanol, ethanol or tetrahydrofuran or a mixture of the mentioned solvents. The pH is adjusted in the range from 4.0 to 6.0, preferably in the range from 4.5 to 5.5 with inorganic acids, e.g. with hydrohalic acids such as hydrochloric acid, hydrobromic acid, sulphuric acid, nitric acid or phosphoric acid, and the like or with organic acids, e.g. with acetic acid, formic acid, tartaric acid, succinic acid, fumaric acid, maleic acid, malic acid, salicylic acid, citric acid, methanesulphonic acid and p-toluene sulphonic acid and the like. Subsequently, the system was reacted with a suitable reducing agent such as cyanoborohydride, sodium borohydride, NaBH 4 , BH 3 -THF, BH 3 -SMe 2 , catecholborane or other known in the art, preferably sodium cyanoborohydride or NaBH(OAc) 3 at a reaction temperature between about -10°C and about 60°C, preferably at room temperature. For the synthesis of compounds of formula Ie wherein the substituents are as defined above and R 2 is hydrogen, the corresponding compound of formula VI is N-protected with an appropriate protecting group as described for reaction scheme 1, further reacted according to reaction steps 4-5 of reaction scheme 1, then reacted according to reaction scheme 3 and finally deprotected as described for reaction scheme 1. For the synthesis of compounds of formula Ie wherein the substituents are as defined above and R 1 is hydrogen, compound of formula VIII wherein R 1 is a N-protecting group such as 4-methoxybenzyl (prepared according to reaction scheme 1) is reacted according to reaction scheme 3 and finally deprotected as described for reaction scheme 1. Optionally, compounds of formula Ie wherein the substituents are as defined for compounds of formula I and R 1 or R 2 is hydrogen and the other one of R or R is as defined for compounds of formula I, can also be converted to the corresponding compound of formula Ie wherein R l , R 2 , R 3 , X and Z are as defined for compounds of formula I. The reaction is carried out as described for reaction scheme 1. Reaction scheme 4: wherein R 1 , R 2 , R 3 and X are as defined for compounds of formula I and R 5 is hydrogen, alkyl, protected hydroxy-C 0 - 2 -alkyl or C 0 - 2 -alkyl substituted with optionally substituted phenyl or with optionally substituted heterocyclyl as defined for compounds of formula I or C 0 - 2 - alkyl substituted with Q-4-alkoxy, CM-alkyl-carbonyl-oxy- or heterocyclyl-oxy. In reaction scheme 4, the first reaction step is carried out in that the aldehyde function of compound of formula VIII reacted via a Wittig-Horner reaction with dialkyl phosphonate of formula (EtO) 2 P(=O)(CH 2 )R 5 wherein R 5 is as defined above (commercially available or synthesised according to known methods from textbooks on organic chemistry e.g. from J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4 l ed. John Wiley and Sons), to obtain olefmic compound of formula If. The reaction is carried out similar to the method described in the literature, for example in the presence of a strong base such as n-BuLi or preferably sodium hydride in an organic solvent for example anhydrous ethers such as diethyl ether, dibutyl ether, dioxane, preferably anhydrous tetrahydrofuran under inert atmosphere such as nitrogen or argon atmosphere at a reaction temperature from 0°C to 80°C, preferably at a reaction temperature between about 5°C and about 50°C. Optionally, olefinic compound of formula If can be obtained through other coupling reactions for example the Wittig reaction. In the second step of the reaction, the olefinic group of compound of formula If is hydrogenated to the corresponding compound of formula Ig. The reaction is carried out similar to methods described in the literature, for example under hydrogen in the presence of a hydrogenation catalyst in an appropriate solvent at a reaction temperature from 0°C to 80°C, preferably at a reaction temperature between about 5°C and about 50°C. The hydrogen pressure can be between about Oatm and about lOOatm, preferably between about Oatm and about 50atm and most preferred between about Oatm and about 20atm. The hydrogenation catalyst used for this reaction can be one of the commonly known catalysts such as noble metals (e.g. Pt, Pd or Rh) on supporting materials such as activated carbon or Al 2 O 3 , or generally as described in textbooks about organic chemistry e.g. J. March (1992), "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure", 4 ed. John Wiley 8c Sons. Preferred hydrogenation catalysts are Pd on activated carbon or Raney-Nickel. Appropriate solvents for the hydrogenation reaction are organic solvents such as alcohols (e.g. methanol, ethanol, propanol, butanol, octanol or cyclohexanol), ethers (e.g. tetrahydrofuran, diethyl ether, dibutyl ether or dioxane), polar aprotic solvents such as dimethylsulfoxide (DMSO) or N,N-dimethylacetamide, esters (e.g. ethyl acetate), halogenated hydrocarbons (e.g. dichloromethane or trichloromethane), hydrocarbons (e.g. cyclohexane, methyl cyclohexane, decaline, benzene, toluene, o-xylene, m-xylene or p-xylene) or a mixtures of the mentioned solvents. Preferred solvents are ester, most preferred solvent is ethyl acetate. For the synthesis of compounds of formula Ig wherein R 5 is unprotected hydroxy- C 0 . 2 -alkyl, the protected hydroxy group of compound of formula Ig is deprotected according to methods known from the art for example as described in 'Protecting Groups in Organic Synthesis', second edition, Theodora W. Greene and Peter G. M. Wuts, Wiley- Interscience, 1991. For the synthesis of compounds of formula Ig wherein the substituents are as defined above and R is hydrogen, the corresponding compound of formula VI is N-protected with an appropriate protecting group as described for reaction scheme 1, further reacted according to reaction steps 4-5 of reaction scheme 1, then reacted according reaction scheme 4 and finally deprotected as described for reaction scheme 1. For the synthesis of compounds of formula Ig wherein the substituents are as defined above and R 1 is hydrogen, compound of formula VIII wherein R 1 is a N-protecting group such as 4-methoxybenzyl (prepared according to reaction scheme 1) is reacted according to reaction scheme 4 and finally deprotected under conditions known from the literature for example under hydrogen in the presence of a catalyst such as palladium on charcoal or platinum on charcoal. Optionally, compounds of formula Ig wherein the substituents are as defined above and R 1 or R 2 is hydrogen and the other one of R 1 or R 2 is as defined above, can also be converted to the corresponding compound of formula Ig wherein the substituents are as defined above. The reaction is carried out as described for reaction scheme 1. Assay Method: HIV-1 reverse transcriptase assay: Inhibitor ICsn determination. HIV-1 RT assay was carried out in 96-well Millipore filtermat NOB50 plates using purified recombinant enzyme and a poly(rA)/oligo(dT)ι 6 template-primer in a total volume of 50 μL. The assay constituents were 50 mM Tris/HCl, 50 mM NaCl, 1 mM EDTA, 6 mM MgCl 2 , 5 μM dTTP, 0.1 μCi [ 3 H] dTTP, 5 μg/ml poly (rA) pre annealed to 2.5 μg/ml oligo (dT) 16 and a range of inhibitor concentrations in a final concentration of 10% DMSO. Reactions were initiated by adding 5 nM HIV-1 RT and after incubation at 37°C for 30 min, they were stopped by the addition of 50 μl ice cold 20%TCA and allowed to precipitate at 4 C for 30 min. The precipitates were collected by applying vacuum to the plate and sequentially washing with 2 x 200 μl of 10% TCA and 2 x 200 μl 70% ethanol. Finally the plates were dried and radioactivity counted in a Wallac Microbeta 1450 after the addition of 15 μl scintillation fluid per well. ICso' s were calculated by plotting % inhibition versus logι 0 inhibitor concentrations. Antiviral assay method Anti-HIV antiviral activity was assessed using an adaptation of the method of Pauwels et al. {Pauwels et al., 1988, J Virol Methods 20:309-321}. The method is based on the ability of compounds to protect HIV- infected T lymphoblastoid cells (MT4 cells) from cell-death mediated by the infection. The endpoint of the assay was calculated as the concentration of compound at which the cell viability of the culture was preserved by 50% ('50% inhibitory concentration', IC 50 ). The cell viability of a culture was determined by the uptake of soluble, yellow 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and its reduction to a purple insoluble formazan salt. After solubilization, spectrophotometric methods were employed to measure the amount of formazan product. MT4 cells were prepared to be in logarithmic-phase growth and a total of 2 x 10 cells infected with the HXB2-strain of HIV at a multiplicity of 0.0001 infectious units of virus per cell in a total volume of between 200-500 microlitres. The cells were incubated with virus for one h at 37°C before removal of virus. The cells are then washed in 0.01 M phosphate buffered saline, pH 7.2 before being resuspensed in culture medium for incubation in culture with serial dilutions of test compound. The culture medium used was RPMI 1640 without phenol red, supplemented with penicillin, streptomycin, L- glutamine and 10% fetal calf serum (GM10). Test compounds were prepared as 2 mM solutions in dimethyl sulphoxide (DMSO). Four replicate, serial 2-fold dilutions in GM10 were then prepared and 50 microlitres amounts placed in 96-well plates over a final nanomolar concentration range of 625 - 1.22. Fifty microlitres GM10 and 3.5 x 10 4 infected cells were then added to each well. Control cultures containing no cells (blank), uninfected cells (100% viability; 4 replicates) and infected cells without compound (total virus -mediated cell death; 4 replicates) were also prepared. The cultures were then incubated at 37 °C in a humidified atmosphere of 5% CO 2 in air for 5 s. A fresh solution of 5 mg/ml MTT was prepared in 0.01 M phosphate buffered saline, pH 7.2 and 20 microlitres added to each culture. The cultures were further incubated as before for 2 h. They were then mixed by pipetting up and down and 170 microlitres of Triton X-100 in acidified isopropanol (10% v/v Triton X-100 in 1:250 mixture of concentrated HCl in isopropanol). When the formazan deposit was fully solubilized by further mixing, the absorbance (OD) of the cultures was measured at 540nm and 690nm wavelength (690nm readings were used as blanks for artefacts between wells). The percent protection for each treated culture was then calculated from the equation: % Protection = (OD drug-treated cultures) - (OD untreated virus control cultures) ■ x l00% (OD uninfected cultures) - (OD untreated virus control cultures) The IC 5 Q was then obtained from graph plots of percent protection versus logio drug concentration. In the assay, compounds of formulas I range in activity from an HIV IC S Q of about 0.5 to about 5000 nM, with preferred compounds having a range of activity from about 0.5 to about 750 nM, more preferably about 0.5 to 300 nM, and most preferably about 0.5 to 50 nM. ND: not determined The imidazolone derivatives provided by the present invention can be used together with a therapeutically inert carrier as medicaments in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered enterally, such as orally, in the form of tablets, coated tablets, dragέes, hard and soft gelatine capsules, solutions, emulsions or suspensions, or nasally, e.g. in the form of nasal sprays. They can also be administered rectally, e.g. in the form of suppositories, or parenterally, (e.g. intramuscularly, intravenously, or subcutaneously), for example, in the form of injection solutions. For the manufacture of pharmaceutical preparations the imidazolone derivatives can be formulated with therapeutically inert, inorganic or organic carriers. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts can be used, for example, as such carriers for tablets, coated tablets, dragees and hard gelatine capsules. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like. Suitable carriers for the manufacture of injection solutions are, for example, water, saline, alcohols, polyols, glycerine, vegetable oils and the like. Natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like are suitable carriers for the manufacture of suppositories. The pharmaceutical preparations of the present invention may also be provided as sustained release formulations or other appropriate formulations. The pharmaceutical preparations can also contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavourants, salts for adjustment of the osmotic pressure, buffers, masking agents or antioxidants. The pharmaceutical preparations may also contain other therapeutically active agents such as those mentioned above. The imidazolone derivatives provided by the invention in the treatment of an immune mediated condition or disease, a viral disease, a bacterial disease, a parasitic disease, an inflammatory disease, a hyperproliferative vascular disease, a tumor, or cancer. The dosage can vary within wide limits and will, of course, be adjusted to the individual requirements in each particular case. Dosage levels of between about 0.01 and about 100 mg/kg body weight per day in monotherapy and/or in combination therapy are commonly administered from about 1 to 5 times per day. A typical preparation will contain from about 5% to 95% active compound (w/w) . The daily dosage can be administered as a single dosage or in divided dosages. The imidazolone derivatives provided by the present invention or the medicaments thereof may be for use in monotherapy and/or combination therapy, i.e. the treatment maybe in conjunction with the administration of one or more additional therapeutically active substance(s). When the treatment is combination therapy, such administration may be concurrent or sequential with respect to that of the imidazolone derivatives of the present invention. Thus, concurrent administration, as used herein, includes administration of the agents in conjunction or combination, together, or before or after each other. It will be understood that references herein to treatment extend to prophylaxis as well as to treatment of existing conditions. Treatment of a disease or condition, as used herein, also includes preventing, inhibiting, regressing, reversing, alleviating or relieving the disease or condition, or the clinical symptoms thereof. The term "subject" as used herein refers to animals, including humans and other mammals. In the following examples the abbreviations used have the following significations: MS mass spectroscopy ES electrospray El electron impact NMR nuclear magnetic r DMF N,N-dimethylforrri DMSO dimethylsulfoxide rt room temperature min minute(s) h hour(s) d day(s) All temperatures are given in degrees Celsius (°C). The described NMR spectra were recorded on a Bruker DRX 400 MHz spectrometer with the probe temperature set at 300 K. The mass spectra indicated by "(M+; El)", were recorded under electron impact conditions (El), on a THERMOQUEST MAT95 S with a source temperature of 200°C. Other mass spectra were recorded under electrospray ionization spectra (ESI) conditions, on one of the following machines: a) THERMOQUEST SSQ 7000 [Solvent 0.085% TFA in 90% Acetonitrile/water; flov rV rate 100 microliters/minute; capillary 250°C; spray voltage 5KV; sheath gas 80 psi], or b) LC-MS system (liquid chromatograph coupled to mass spectrum) THERMOQUEST TSQ 7000 ELECTROSPRAY or MICROMASS PLATFORM ELECTROSPRAY [Solvent 0.1% TFA in water or 0.085% TFA in 90% acetonitrile/ water or 0.085% TFA in acetonitrile] . With regard to the starting materials that are known compounds some of these may be purchased from commercial suppliers. Other starting materials that are known and their analogues can be prepared by methods well known in the art. Examples of compounds available from commercial suppliers, and citations to the synthesis of other compounds and their analogues are provided in the following: Compounds, whenever prepared by the processes of the present invention are also an object of the present invention. The following examples illustrate the present invention: Example 1 4-(3,5-Dichlorophenylthio)-5-(hydroxymethyl)-3-isopropyl-l-methyl-l,3-dihydro-2- imidazolone A mixture of 117mg of 5-(3,5-dichlorophenylthio)-l-isopropyl-3-methyl-l,3- dihydro-2-imidazolone-4-carboxaldehyde and 33mg of sodium borohydride in 4ml of tetrahydrofuran and 1ml of ethanol was stirred at rt for 3 h. The reaction mixture was reduced in volume and the residue was purified by flash chromatography on silica gel using ethyl acetate/hexane (1:1 then 2:1 then 100% ethyl acetate) for the elution to give 113mg of white crystals. Mass spectrum (ES) m/z 347 [M+H] + . The starting material was prepared as follows: Intermediate 1A 5-( ' 3,5-dichlorophenylthio)-l-isopropyl-3-methyl-l,3-dihydro-2-imidazolone-4- carboxaldehyde To a solution of 4.l6g of 5-chloro-l-isopropyl-3-methyl-l,3-dihydro-2- imidazolone-4-carboxaldehyde in 50ml of dichloromethane was added 4.4g of 3,5- dichlorothiophenol and 6.8ml of triethylamine. The mixture was stirred at rt under nitrogen for 18 h. The reaction mixture was concentrated and partitioned between ethyl acetate and 2N hydrochloric acid. The organic layer was washed with a further aliquot of 2N hydrochloric acid and brine then dried, filtered and evaporated to dryness. The residue crystallised on standing to provide a solid, which was triturated with diethyl ether to give 5g of a white solid. Mass spectrum (ES) m/z 344 [M+H] + . Intermediate IB 5-Chloro-l-isopropyl-3-methyl-l,3-dihydro-2-imidazoIone-4-carboxaldehyde A solution of 6.5g of 5-dimethylaminomethylene-3-isopropyl-l-methyl- imidazolidine-2,4-dione in 30ml of phosphorus oxychloride and 5ml of dimethylformamide was heated to 100°C for 2 h. After this time, the reaction mixture was cooled to rt, poured into ice water and extracted with ethyl acetate. The organic extract was dried, filtered and evaporated to give 4.16g as yellow needles. Mass spectrum (El) m/z 202 M + . Intermediate IC 5-Dimethylaminomethylene-3-isopropyl-l-methyl-imidazolidine-2,4-dione A mixture of 13.4g of 3-isopropyl-l-methyl-imidazolidine-2,4-dione and 13.6ml dimethylformamide dimethylacetal were heated at 100°C over the weekend. The reaction mixture was cooled to rt and purified by flash chromatography to give 9.9g of a golden oil. Mass spectrum (El) m/z 211 M + . Intermediate ID 3-Isopropyl-l-methylimidazolidine-2,4-dione A mixture of 14.9g of (3-isopropyl-l-methylureido)acetic acid in 50ml of water and 50ml of concentrated hydrochloric acid was refluxed for 2 h. On cooling the mixture was diluted with water and extracted with ethyl acetate to give 13.4g of a colourless oil. Mass spectrum (El) m/z 156 M + . Intermediate IE (3-Isopropyl-l-methylureido)acetic acid To a solution of 4g of sodium hydroxide in 75ml of water was added lOg of sarcosine portionwise. The solution was cooled and treated with 11.5ml of isopropyl isocyanate. After 2 h, the reaction mixture was washed with diethyl ether and the aqueous phase acidified with concentrated HCl to <pH 2. The product was extracted twice with ethyl acetate to give 10.45g of a white solid which was taken on to the next step. A further extraction of the aqueous phase after standing gave 5.5g of a colourless oil the next product. Example 2 5-(Benzyloxymethyl ' )-4-(3,5-dichlorophenylthio ' )-3-isopropyl-l-methyl-13-dihydro-2- imidazolone To 50mg of4-(3,5-dichlorophenylthio)-5-(hydroxymethyl)-3-isopropyl-l-methyl- l,3-dihydro-2-imidazolone in 1ml of dimethylformamide was added 7mg of sodium hydride (60% dispersion in oil). The reaction mixture was stirred at rt for 30 min until hydrogen gas evolution had ceased. The solution was then treated with 20μL of benzyl bromide and stirring continued for 1 h. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated, dried and evaporated to dryness to give 190mg of an oily residue. This residue was purified by flash chromatography on silica gel using ethyl acetate/hexane (1:1) for the elution to give 55mg of a colourless oil. Mass spectrum (ESI) m/z 437 [M+H] + . Example 3 5-(Benzyloxymethyl)-4-(3 t 5-dichlorophenoxy)-3-isopropyl-l-methyl- 3-dihydro-2- imidazolone To 115mg of4-(3,5-dichlorophenoxy)-5-hydroxymethyl-3-isopropyl-l-methyl-l,3- dihydro-2-imidazolone in 5ml of dimethylformamide was added 15mg of sodium hydride (60% dispersion in oil). The reaction mixture was stirred at rt for 30 min until hydrogen gas evolution had ceased. The solution was then treated with 45μL of benzyl bromide and stirring continued for 1 h. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated, dried and evaporated to dryness to give 190mg of an oily residue. This residue was purified by flash chromatography on silica gel using ethyl acetate/hexane (1:1) for the elution to give 41mg of a colourless oil. Mass spectrum (ESI) m/z 421 [M+H] + . The starting material was prepared as follows: Example 3A 4-(3,5-Dichlorophenoxy -5-hydroxymethyl-3-isopropyl-l-methyl-l,3-dihydro-2- imidazolone A mixture of lOOmg of 5-(3,5-dichlorophenoxy)-l-isopropyl-3-methyl-l,3-dihydro- 2-imidazolone-4-carboxaldehyde and 13mg of sodium borohydride in 5ml of methanol was stirred at rt for 2 h. The reaction mixture was reduced in volume then dissolved in ethyl acetate. The solution was washed with water, dried and evaporated to dryness to give 115mg of colourless needles. Mass spectrum (ESI) m/z 331 [M+H] + . Example 3B 5-( ' 3,5-Dichlorophenoxy -l-isopropyl-3-methyl-2,3-dihydro-2-imidazolone-4- carboxaldehyde To a solution of 163mg of 3,5-dichlorophenol in 3ml of dimethylformamide was added portionwise 26mg of sodium hydride (as a 60% dispersion in mineral oil). The reaction mixture was stirred until evolution of hydrogen gas has ceased then was treated with 200mg of 5-chloro-l-isopropyl-3-methyl-l,3-dihydro-2-imidazolone-4- carboxaldehyde. The mixture was stirred overnight at rt. The reaction mixture was diluted with ethyl acetate and washed with dilute sodium hydroxide solution. The organic phase was dried, filtered and evaporated to give 341mg of a buff solid. Mass spectrum (ESI) m/z 437, 438 [M+H] + . Example 4 4-(3,5-Dichlorophenylthio)-5-(hydroxymethyl)-3-isopropyl-l-(4-methoxybenzyl - 3- dihydro-2-imidazolone A mixture of 50mg of 5-(3,5-dichlorophenylthio)-l-isopropyl-3-(4-methoxybenzyl)- l,3-dihydro-2-imidazolone-4-carboxaldehyde and 5mg of sodium borohydride in 5ml of methanol was stirred at rt for 2 h. The reaction mixture was reduced in volume and dissolved in ethyl acetate, washed with water, dried and evaporated to give 50mg of a white solid. Mass spectrum (ESI) m/z 453 [M+H] + . The starting material was prepared as follows: Intermediate 4A 5-(3,5-Dichlorophenylthio)-l-isopropyl-3-(4-methoxybenzyl)- 3-dihydro-2- imidazolone-4-carboxaldehyde To a solution of 1.99g of 5-chloro-l-isopropyl-3-(4-methoxybenzyl)-l,3-dihydro-2- imidazolone-4-carbaldehyde in 25ml of dichloromethane was added 1.2g of 3,5- dichlorothiophenol and 2ml of triethylamine. The mixture was stirred at rt under nitrogen for 18 h. The reaction mixture was concentrated and partitioned between ethyl acetate and 2N hydrochloric acid. The organic layer was washed with a further aliquot of 2N hydrochloric acid and brine then dried, filtered and evaporated to dryness. The residue crystallised on standing to provide a solid, which was triturated with diethyl ether to give 1.4g of a white solid. Mass spectrum (ESI) m/z 451 [M+H] + . Intermediate 4B 5-Chloro-l-isopropyl-3-(4-methoxybenzyl -l,3-dihydro-2-imidazolone-4- carboxaldeh de A mixture of 1.99g of 5-dimethylaminomethylene-3-isopropyl-l-(4- methoxybenzyl)imidazolidine-2,4-dione, 10ml of phosphorus oxychloride and 2ml of dimethylformamide was heated at 100°C for 2 h. The reaction mixture was cooled to rt, poured onto ice water and extracted with ethyl acetate. After evaporation the crude product was purified by flash chromatography to give 2.2g of an oil. Mass spectrum (ESI) m/z 309 [M+H]+. Intermediate 4C 5-Dimethylaminomethylene-3-isopropyl-l-(4-methoxybenzyl ' )-imidazolidine-2,4-dione To a solution of lOOmg of 5-dimethylaminomethylene-3-isopropylimidazolidine- 2,4-dione in 2ml of dimethylformamide was added 425mg of sodium hydride (as a 60% dispersion in mineral oil). The mixture was stirred until evolution of hydrogen gas had ceased. The solution was then treated with 1.5ml of 4-methoxybenzyl chloride and stirring continued overnight at rt. The mixture was partitioned between ethyl acetate and water and the organic layer dried, filtered and concentrated. The residue was purified by flash chromatography eluting with 1:1 ethyl acetate: haxane to give 85mg of a colourless oil. 1H NMR (400MHz, deuteriochloroform): δ = 1.40 (6H, d, J = 7 Hz), 3.02 (6H, s), 3.72 (3H, s), 4.38 (IH, septet, J = 7 Hz), 4.60 (2H, s), 5.96 (IH, s), 6.80 (2H, d, J = 8 Hz), 7.05 (2H, d, J = 8 Hz). Intermediate 4D 5-Dimethylaminomethylene-3-isopropylimidazolidine-2,4-dione A mixture of 5g of 3-isopropylimidazolidine-2,4-dione and 5ml dimethylformamide dimethylacetal were heated at 100°C for 3 s. The reaction mixture was cooled to rt and purified by flash chromatography to give 2g of an orange solid. 1H NMR (400MHz, deuteriochloroform): δ = 1.42 (6H, d, J = 7 Hz), 3.11 (6H, s), 4.40 (IH, septet, J = 7 Hz), 6.64 (lH, s), 9.55 (lH, br s). Intermediate 4E 3-Isopropylimidazolidine-2,4-dione To a solution of 3.6g of sodium hydroxide in 75ml of water was added 7.5g of glycine. The solution was cooled to 5°C and treated with 9.8ml of isopropylisocyanate. After 5 h the reaction mixture was neutralised with 50ml concentrated hydrochloric acid added dropwise to the slurry. This mixture was refiuxed for 2 h then cooled to rt. The product was extracted with ethyl acetate to give 10.9g of a colourless oil. 1H NMR (400MHz, deuteriochloroform): 5 = 1.45 (6H, d, J = 7 Hz), 3.92 (2H, s), 4.35 (IH, septet, J = 7 Hz), 6.39 (lH, br s). Example 5 4-(3,5-Dichlorophenylthio)-5-(2-hydroxybenzyl)-3-isopropyl-l-methyl-l,3-dihydro -2- imidazolone To a solution of lOOmg of 4-(3,5-dichlorophenylthio)-5-(hydroxymethyl)-3- isopropyl-l-methyl-l,3-dihydro-2-imidazolone, 30mg of phenol and lOOmg of triphenylphosphine in 5mL of tetrahydrofuran at 0°C was added 70μL of diisopropylazodicarboxylate in 5mL of tetrahydrofuran over 20 min. The reaction was stirred overnight warming to room temperature. The mixture was then diluted with ethyl acetate and washed with 0.5N hydrochloric acid solution then 0.5N sodium hydroxide solution, dried, concentrated and purified by flash chromatography eluting with 3:1 hexane: ethyl acetate to give 16mg of a colourless oil. Mass spectrum (ES) m/z 423 [M+H] + . Examples 6-9 and 33-39 The compounds shown in table 2 were prepared in a manner analogous to that described for examples 1 to 5: Table 2 Example 10 4-(3,5-Dichlorophenylthio)-5-(alpha(RS)-hydroxybenzyl -3-isopropyl-l-methyl-l,3- dihydro-2-imidazolone A mixture of 345mg of 5-(3,5-dichlorophenoxy)-l-isopropyl-3-methyl-l,3-dihydro- 2-imidazolone-4-carboxaldehyde in 5ml of tetrahydrofuran was added to 0.4ml of a 3M solution of phenyl magnesium bromide also in 5ml of tetrahydrofuran under nitrogen. The reaction was stirred at rt for 2 h then quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The organic phase was washed with brine, dried and evaporated to give 490mg of a solid foam. Mass spectrum (ESI) m/z 423 [M+H] + . Example 11 4-(3,5-Dichlorophenylthio)-3-isopropyl-l-methyl-5-benzyl-l,3-dihydro-2-imidazolone To a mixture of 250mg of 4-(3,5-dichlorophenoxy)-5-( alpha(RS)-hydroxybenzyl)- 3-isopropyl-l-methyl-l,3-dihydro-2-imidazolone in 3ml of trifluoroacetic acid was added 90μL of triethylsilane and stirred under nitrogen for 0.5 h. The reaction mixture was evaporated then the residue was purified by flash chromatography to give 245mg of an amber oil. Mass spectrum (ES) m/z 407 [M+H] + . Examples 12 and 40-48 The compounds shown in table 3 were prepared in a manner analogous to that described for examples 10 to 11: Table 3 Example 13 4-(3,5-Dichlorophenylthio)-3-isopropyl-l-methyl-5-[[(4-pyridyl)methylamino]methyl1- 13-dihydro-2-imidazolone A mixture of lOOmg of 4-(3,5-dichlorophenylthio)-l-isopropyl-3-methyl-l,3- dihydro-2-imidazolone-4-carboxaldehyde and 34μL of 4-pyridylmethylamine in 10ml of toluene was azeotroped in a Dean-Stark apparatus for 2 h. The reaction was cooled to rt, evaporated and re-dissolved in 10ml of methanol. Bromocresol green was added and the pH adjusted to approximately 5 using 4N hydrochloric acid/ dioxane. The solution was treated portionwise with 30mg of sodium cyanoborohydride and the pH adjusted back to 5 using 4N hydrochloric acid/dioxane. This was repeated until the addition was complete. The reaction was evaporated and the residue was purified by flash chromatography on silica gel using ethyl acetate/hexane (2:1) followed by methanol/dichloromethane (1:19) for the elution to give 72mg of a colourless oil. Mass spectrum (ES) m/z 437, 438 [M+H] + . Example 14 4-(3,5-Dichlorophenylthio -3-isopropyl-l-(4-methoxybenzyl)-5-[[(4- pyridyl)methylamino]methyl1-l,3-dihydro-2-imidazolone A mixture of lg of 5-(3,5-dichlorophenylthio)-l-isopropyl-3-(4-methoxybenzyl)- dihydro-2-imidazolone-4-carboxaldehyde and 0.25ml of 4-pyridylmethylamine in 20ml of toluene was refluxed in a Dean-Stark apparatus for 2 h. The reaction was cooled to rt, evaporated and re-dissolved in 10ml of methanol. Bromocresol green was added and the pH adjusted to approximately 5 using 4N hydrochloric acid/dioxane. The solution was treated portionwise with 155mg of sodium cyanoborohydride and the pH adjusted back to 5 using 4N hydrochloric acid/dioxane. This was repeated until the addition was complete. The reaction was evaporated and the residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (2:1) followed by methanol/ dichloromethane (1:19) to give 1.07g of a golden solid. Mass spectrum (ES) m/z 543 [M+H] + . Examples 15-31 The compounds shown in table 4 were prepared in a manner analogous to that described for examples 13 to 14: Table 4 Ex. Structure Name MS (ES) (M + H)+ 15 5-(Benzylaminomethyl)-4-(3,5- 477 ((M+ dichlorophenylthio)-3-isopropyl-l- MeCN+ methyl-l,3-dihydro-2-imidazolone H) + ; ESI) 16 5-(Benzylaminomethyl)-3-isopropyl-l- 367 methyl-4-phenylthio-l,3-dihydro-2- imidazolone 17 3-Isopropyl-l-methyl-4-phenylthio-5- 369 {[(pyridin-4-ylmethyl)amino]methyl}-l,3- dihydro-2-imidazolone 18 5-(Benzylaminomethyl)-4-(3,5- 396 dimethylphenylthio)-3-isopropyl-l- methyl-l,3-dihydro-2-imidazolone 19 4-Cyclohexylthio-3-isopropyl-l-methyl-5- 375 {[(pyridin-4-ylmethyl)amino]methyl}-l,3- dihydro-2-imidazolone 4-(3,5-Dimethylphenythio)-3-isopropyl-l- 397 methyl-5-{ [(pyridin-4- ylmethyl)amino] methyl}- l,3-dihydro-2- imidazolone 4-Benzylthio-3-isopropyl-l-methyl-5- 383 {[(pyridin-4-ylmethyl)amino]methyl}-l,3- dihydro-2-imidazolone 4-(3-Chlorophenylthio)-3-isopropyl-l- 403 methyl-5-{ [(pyridin-4- ylmethyl)amino]methyl}-l,3-dihydro-2- imidazolone 3-Isopropyl-4-isopropylthio-l-methyl-5- 355 {[(pyridin-4-ylmethyl)amino]methyl}-l,3- dihydro-2-imidazolone 4-Isobutylthio-3-isopropyl-l-methyl-5- 349 {[(pyridin-4-ylmethyl)amino]methyl}-l,3- dihydro-2-imidazolone 25 3-Benzyl-4-(3,5-dichlorophenylthio)-l- 485 methyl-5-{ [(pyridin-4- ylmethyl) amino] methyl} - 1 ,3 - dihydr o -2 - imidazolone 26 l,3-Dibenzyl-4-(3,5-dichlorophenylthio)- 561 5-{ [ (pyridin-4-ylmethyl) amino] methyl}- l,3-dihydro-2-imidazolone 27 l-Benzyl-4-(3,5-dichlorophenylthio)-3- 513 isoproρyl-5-{ [(pyridin-4- ylmethyl)amino]methyl}-l,3-dihydro-2- imidazolone 28 l-Benzyl-4-(3,5-dichlorophenylthio)-3- 513 propyl-5-{ [(pyridin-4- ylmethyl)amino]methyl}-l,3-dihydro-2- imidazolone 29 4-(3,5-Dichlorophenoxy)-3-isopropyl-l- 421 methyl-5-{[(pyridin-4- ylmethyl)amino] methyl}- l,3-dihydro-2- imidazolone 30 4-sec-Butylthio-3-isopropyl-l-methyl-5- 349 { [ (pyridin-4-ylmethyl)amino] methyl} - 1,3- dihydro-2-imidazolone 31 l-Isopropyl-5-(3-methoxyphenylthio)-3- 399 methyl-4- { [ (pyridin-4- ylmethyl)amino] methyl}- l,3-dihydro-2- imidazolone Example 32 4-( " 3,5-Dichlorophenylthio)-3-isopropyl-l-methyl-5-(2-phenylethyl)-l,3-dihydro -2- imidazolone A solution of 50mg of 4-(3,5-dichlorophenylthio)-5-styryl-3-isopropyl-l-methyl- 1,3 -dihydr o-2 -imidazolone was hydrogenated over a catalytic amount of 5% Pd on carbon for 4 h. The reaction mixture was filtered and evaporated then purified by flash chromatography eluting with 3:1 hexane/ ethyl acetate to give 5mg of a colourless oil. Mass spectrum (ES) m/z 421 [M+H] + . The starting material was prepared as follows: Intermediate 32 A 4-(3,5-Dichlorophenylthio -5-styryl-3-isopropyl-l-methyl-l,3-dihydro-2-imidazolone Polymer supported triphenylphosphine (lg, 3mmol) and 713μL of benzyl bromide were refluxed in 20ml of toluene for 3 h. The mixture was allowed to cool to rt and the toluene decanted. The resulting salt was stirred in 10ml of tetrahydrofuran at 0°C and treated with potassium tert.-butoxide. This mixture was stirred for 30 min at 0°C then 345mg of5-(3,5-dichlorophenylthio)-2,3-dihydro-l-isopropyl-3-methyl-2-oxo-lH- imidazole-4-carboxaldehyde was added. The mixture was stirred at rt for 3 s then filtered and evaporated. The residue was purified by flash chromatography eluting with 3:2 hexane/ethyl acetate to give 140mg of a colourless oil. Mass spectrum (ES) m/z 419 [M+H] + . Examples 49-52 The compounds shown in table 5 were prepared in a manner analogous to that described for examples 13 to 14: Table 5 Ex. Structure Name MS (ES) (M + H)+ 49 [E]-3-[5-(3,5-Dichloro- 416 phenylsulfanyl)-l-isopropyl-3-methyl- 2-oxo-2,3-dihydro-lH-imidazol-4-yl]- acrylic acid ethyl ester 50 3-[5-(3,5-Dichloro-phenylsulfanyl)-l- 369 isopropyl-3-methyl-2-oxo-2,3-dihydro- lH-imidazol-4-yl] -acrylonitrile 51 3-[5-(3,5-Dichloro-phenylsulfanyl)-l- 387 isopropyl-3-methyl-2-oxo-2,3-dihydro- lH-imidazol-4-yl] -acrylamide 52 l-Benzyl-5-(3,5-dichloro- 392 phenylsulfanyl)-3-methyl-4-vinyl-l,3- dihydro-imidazol-2-one Example 53 4-(3,5-Dichloro-phenylsulfanyl -3-isopropyl-l-methyl-5-pyridin-4-ylmethyl-l,3-dihydro- imidazol-2-one A solution of 160mg of phosphorus tetraiodide in 15mL of toluene was heated in the dark at 80°C for 20 min. To this solution was added dropwise a solution of 150mg of 4- (3,5-dichloro-phenylsulfanyl)-3-isopropyl-l-methyl-5-[l-hydroxy-l-pyridin-4-ylmethyl]- l,3-dihydro-imidazol-2-one in 5mL of toluene. The mixture was then heated at 80°C for 1 h then allowed to cool to room temperature. Then 8mL of 10% aqueous sodium bisulphite solution was added and the biphasic mixture stirred for 1 h. The aqueous phase was extracted three times with 30mL of ethyl acetate and combined extracts were washed with brine, dried, filtered and evaporated to give a yellow residue which was purified by flash chromatography on silica gel using ethyl acetate/methanol (19:1) for the elution to give 50mg as a pale yellow oil. Mass spectrum (ES) m/z 408 [M+H] + . The starting material 4-(3,5-dichloro-phenylsulfanyl)-3-isopropyl-l-methyl-5-[l- hydroxy- l-pyridin-4-ylmethyl] -l,3-dihydro-imidazol-2-one was prepared as follows: 560mg of 4-Bromopyridine.hydrobromide was treated with 15mL of 5% aqueous sodium hydrogen carbonate and extracted three times with 20mL of diethyl ether and combined extracts were washed with brine, dried, filtered and evaporated to give a colourless oil which was dissolved in 3mL of tetrahydrofuran. To this solution, under nitrogen at room temperature, was added 1.45mL of a 3.0M solution of isopropyl magnesium chloride in diethyl ether. The reaction mixture was stirred at room temperature for 1.5 h then a solution of l.Og of 5-(3,5-dichlorophenylthio)-l-isopropyl-3- methyl-l,3-dihydro-2-imidazolone-4-carboxaldehyde in lOmL of tetrahydrofuran was added. The reaction mixture was stirred at room temperature overnight then 20mL of water added. The aqueous phase was extracted three times with lOmL of dichloromethane and combined extracts were washed with brine, dried, filtered and evaporated to give a yellow oil which was purified by flash chromatography on silica gel using ethyl acetate/hexane (2:1 then 4:1) for the elution to give 250mg of a pale yellow solid. Mass spectrum (ES) m/z 424 [M+H] + .

Claims: Claims 1. Compounds of formula I wherein R 1 is hydrogen, alkyl, cycloalkyl, aryl or alkyl substituted with optionally substituted phenyl; R 2 is hydrogen, alkenyl, alkyl or alkyl substituted with optionally substituted phenyl; R 3 is alkyl, cycloalkyl, optionally substituted phenyl, optionally substituted benzyl or heterocyclyl; A is alkyl, hydroxy-alkyl, alkenyl, substituted alkenyl, aryl-CH(OH)-, substituted alkyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or alkyl and Z represents heterocyclyl or optionally substituted aryl; X represents S or O; with the provisos that (i) only one of R 1 and R 2 is hydrogen; (ii) when X is O, then R 1 cannot be aryl; as well as hydrolyzable esters or ethers of compounds of formula I and pharmaceutically acceptable salts thereof. 2. Compounds as claimed in claim 1 wherein R 1 is hydrogen, Ci- -alkyl, C 3 .s-cycloalkyl, aryl or Ci- 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from C M -alkyl, Cι- 4 -alkoxy, hydroxy, fluorine, chlorine and bromine; R 2 is hydrogen, C 2 -4-alkenyl, Cι-ι 2 -alkyl or Cι. 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from C M -alkyl, C M -alkoxy, hydroxy, fluorine, chlorine and bromine; R 3 is .π-alkyl, C 3 - 8 -cycloalkyl, phenyl, benzyl or heterocyclyl, wherein a phenyl ring maybe substituted with 1-5 substituents selected from CM-alkyl, CM-alkoxy, hydroxy, fluorine, chlorine, bromine and cyano; A is .π-alkyl, hydroxy- . 4 -alkyl, C 2 . 4 -alkenyl, substituted C 2 - 4 - alkenyl, aryl- CH(OH)-, Ci-4-alkyl substituted with C M -alkoxy, Cι. 4 -alkyl-carbonyl-oxy-, heterocyclyl-oxy or A is Cι. 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents or with heterocyclyl optionally substituted with 1-4 substituents selected from C M -alkyl, C M -alkoxy, hydroxy, fluorine, chlorine and bromine, wherein substituted C 2 _ 4 -alkenyl is substituted with 1-2 substituents selected from cyano, amino-carbonyl and or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Cι-4-alkyl and Z represents heterocyclyl or optionally substituted aryl with 1-3 benzyl-oxy groups; X represents S or O; with the proviso that only one of R 1 and R 2 is hydrogen. Compounds as claimed in claim 1 or 2 wherein R 1 is .π-alkyl, aryl or Cι. 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from C M -alkyl, C M -alkoxy, hydroxy, fluorine, chlorine and bromine; R 2 is C 2 - 4 -alkenyl, .π-alkyl or C M -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from C M -alkyl, Cι. -alkoxy, hydroxy, fluorine, chlorine and bromine; R 3 is .^-alkyl, C 3 . 8 -cycloalkyl, phenyl, benzyl or heterocyclyl, wherein a phenyl ring maybe substituted with 1-5 substituents selected from Cι_ 4 -alkyl, C M -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano; A is - 7 -alkyl, hydroxy-Cι. 4 -alkyl, C 2 - 4 -alkenyl, substituted C 2 _ 4 -alkenyl, aryl- CH(OH)-, -4-alkyl substituted with C M -alkoxy, C -alkyl-carbonyl-oxy-, heterocyclyl-oxy or A is C M -alkyl substituted with phenyl optionally substituted with 1-5 substituents or with heterocyclyl optionally substituted with 1-4 substituents selected from Cι- 4 -alkyl, Cι. 4 -alkoxy, hydroxy, fluorine, chlorine and bromine, wherein substituted C 2 . 4 -alkenyl is substituted with 1-2 substituents selected from cyano, amino-carbonyl and C -alkyl-oxy-carbonyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Cι_ 4 -alkyl and Z represents heterocyclyl or optionally substituted aryl with 1-3 benzyl-oxy groups; X represents S or O. Compounds as claimed in any one of claims 1 to 3 wherein R 1 is Ci. 7 -alkyl, phenyl or Ci- -alkyl substituted with phenyl; R 2 is C 2 - 4 -alkenyl, Cι- 7 -alkyl or d- 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from C M -alkyl, C M -alkoxy, hydroxy, fluorine, chlorine and bromine; R 3 is Ci- 7 -alkyl, C 3 . 6 -cycloalkyl, phenyl, benzyl or heterocyclyl, wherein a phenyl ring may be substituted with 1-5 substituents selected from - 4 -alkyl, C M -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano; A is Cι. 7 -alkyl, hydroxy-C M -alkyl, C 2 - 4 -alkenyl, substituted C 2 . 4 -alkenyl, phenyl- CH(OH)-, Ci- 4 -alkyl substituted with - 4 -alkoxy, d^-alkyl-carbonyl-oxy-, heterocyclyl-oxy or A is Cι- 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents or with pyridyl optionally substituted with 1-4 substituents selected from C M -alkyl, Cι. 4 -alkoxy, hydroxy, fluorine, chlorine and bromine, wherein substituted C 2 - 4 -alkenyl is substituted with 1-2 substituents selected from cyano, amino-carbonyl and Cι. 4 -alkyl-oxy-carbonyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or - 4 -alkyl and Z represents pyridyl or optionally substituted phenyl with 1-3 benzyl-oxy groups; X represents S or O. 5. Compounds as claimed in any one of claims 1 to 4 wherein R 1 is Ci- 7 -alkyl or Ci- 4 -alkyl substituted with phenyl; R 2 is C 2 . 4 -alkenyl, Cι. 7 -alkyl or Cι-4-alkyl substituted with phenyl; R 3 is Cι. 4 -alkyl, C 3 . 6 -cycloalkyl or optionally substituted phenyl, wherein phenyl may be substituted with 1-5 substituents selected from C - alkyl, C M -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano; A is Cι- 7 -alkyl, C 2 - 4 -alkenyl, substituted C 2 - 4 -alkenyl, Ci- 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents or with pyridyl optionally substituted with 1-4 substituents selected from Cι- 4 -alkyl, C M -alkoxy, hydroxy, fluorine, chlorine and bromine, wherein substituted C 2 . 4 -alkenyl is substituted with 1-2 substituents selected from cyano, amino-carbonyl and Cι. 4 -alkyl-oxy-carbonyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or . -alkyl and Z represents pyridyl or optionally substituted phenyl with 1-3 benzyl-oxy groups; X represents S or O. 6. Compounds as claimed in any one of claims 1 to 5 wherein R 1 is Ci.7-alk l; R 2 is Ci- 7 -alkyl; R 3 is optionally substituted phenyl, wherein phenyl may be substituted with 1-5 substituents selected from C1-4- alkyl, Cι_ 4 -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano; A is Cι- 4 -alkyl substituted with phenyl optionally substituted with 1-3 substituents or with pyridyl optionally substituted with 1-2 substituents selected from C M -alkyl, Cι. -alkoxy, hydroxy, fluorine, chlorine and bromine, or A signifies a group of formula Z-CH2-Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Cι. 4 -alkyl and Z represents pyridyl or phenyl; X represents S or O. . Compounds as claimed in any one of claims 1 to 6 wherein R 1 is C M -alkyl; R 2 is C M -alkyl; R 3 is optionally substituted phenyl, wherein phenyl maybe substituted with 1-3 substituents selected from Cι- 2 - alkyl, Cι. 2 -alkoxy, hydroxy, fluorine, chlorine, bromine and cyano; A is Cι- 2 -alkyl substituted with phenyl optionally substituted with 1-3 substituents or with pyridyl optionally substituted with 1-2 substituents selected from C M -alkyl, C M -alkoxy, hydroxy, fluorine, chlorine and bromine, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or ^-alkyl and Z represents pyridyl or phenyl; X represents S or O. 8. Compounds as claimed in any one of claims 1 to 7 wherein R 1 is isopropyl; R 2 is methyl or ethyl; R 3 is optionally substituted phenyl, wherein phenyl maybe substituted with 1-3 chlorine substituents; A is Cι- 2 -alkyl substituted with phenyl or pyridyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Cι. 2 -alkyl and Z represents pyridyl or phenyl; X represents S or O. 9. Compounds as claimed in any one of claims 1 to 8 wherein R 1 is isopropyl; R 2 is methyl; R 3 is optionally substituted phenyl, wherein phenyl may be substituted with 1-2 chlorine substituents; A is Ci- 2 -alkyl substituted with pyridyl, or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Cι. 2 -alkyl and Z represents pyridyl; X represents S or O. 10. Compounds of formula I wherein R 1 is hydrogen, - 12 -alkyl, C 3 . 8 -cycloalkyl, aryl or Cι. 4 -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from C 1 . 4 -alkyl, Cι. 4 -alkoxy, hydroxy, fluorine, chlorine and bromine; R 2 is hydrogen, Cι-ι 2 -alkyl or C M -alkyl substituted with phenyl optionally substituted with 1-5 substituents selected from C M -alkyl, C M -alkoxy, hydroxy, fluorine, chlorine and bromine; R 3 is Cι.i2-alkyl, C 3 .8-cycloalkyl, phenyl or benzyl, wherein a phenyl ring may be substituted with 1-5 substituents selected from Ci-4-alkyl, C M -alkoxy, hydroxy, fluorine, chlorine and bromine; A is hydroxy-C -alkyl or aryl-CH(OH)-; or A signifies a group of formula Z-CH 2 -Y-CH 2 -, wherein Y represents O or NR wherein R is hydrogen or Cι- 4 -alkyl and Z represents aryl or heterocyclyl; or A signifies C M -alkyl substituted with phenyl optionally substituted with 1-5 substituents or with heterocyclyl optionally substituted with 1-4 substituents selected from C M -alkyl, Cι- 4 -alkoxy, hydroxy, fluorine, chlorine and bromine; X represents S or O; with the proviso that only one of R 1 and R 2 is hydrogen; as well as hydrolyzable esters or ethers of compounds of formula I and pharmaceutically acceptable salts thereof. 11. Compounds as claimed in any one of claims 1 to 10 wherein X represents S. 12. Compounds as claimed in claims 1 or 10 which compounds are selected from: 4-(3,5-dichlorophenylthio)-5-hydroxymethyl-3-isopropyl-l-methyl-l,3-dihydro-2- imidazolone, 5-(benzylaminomethyl)-4-(3,5-dichlorophenylthio)-3-isopropyl-l-methyl-l,3-dihydro -2- imidazolone, 4-(3,5-dichlorophenylthio)-5-(alpha(RS)-hydroxybenzyl)-3-isopropyl-l-methyl-l,3- dihydro -2-imidazolone, 4-(3,5-dichlorophenylthio)-5-hydroxymethyl-l-methyl-3-phenyl-l,3-dihydro-2- imidazolone, 5-benzyloxymethyl-4-(3,5-dichlorophenylthio)-3-isopropyl-l-methyl-l,3-dihydro-2- imidazolone, 4-(3,5-dichlorophenylthio)-3-isopropyl-l-methyl-5-{[(pyridin-4- ylmethyl)amino]methyl}-l,3-dihydro-2-imidazolone, 5-(benzylamino-methyl)-3-isopropyl-l-methyl-4-phenylthio-l,3-dihydro-2-imidazolone, 3-isopropyl-l-methyl-4-phenylthio-5-{[(pyridin-4-ylmethyl)amino]methyl}-l,3-dihydro- 2-imidazolone, 5-benzyloxymethyl-4-(3,5-dichlorophenoxy)-3-isopropyl-l-methyl-l,3-dihydro-2- imidazolone, 5-benzyloxymethyl-4-(3,5-dichlorophenylthio)-l-methyl-3-phenyl-l,3-dihydro-2- imidazolone, 4-(3,5-dichlorothio)-3-isopropyl-l-methyl-5-(pyridin-4-ylmethoxymethyl)-l,3-dihydro- 2-imidazolone, 5-(benzylaminomethyl)-4-(3,5-dimethylphenylthio)-3-isopropyl-l-methyl-l,3-dihydro-2- imidazolone, 4-cyclohexylthio-3-isopropyl-l-methyl-5-{[(pyridin-4-ylmethyl)amino]methyl}-l,3- dihydro-2-imidazolone, 4-(3,5-dimethylphenythio)-3-isopropyl-l-methyl-5-{[(pyridin-4- ylmethyl)amino]methyl}-l,3-dihydro-2-imidazolone, 4-benzylthio-3-isopropyl-l-methyl-5-{[(pyridin-4-ylmethyl)-amino]-methyl}-l,3- dihydro-2-imidazolone, 4-(3-chlorophenylthio)-3-isopropyl-l-methyl-5-{[(pyridin-4-ylmethyl)amino]methyl}- l,3-dihydro-2-imidazolone, 3-isopropyl-4-isopropylthio-l-methyl-5-{[(pyridin-4-ylmethyl)amino]methyl}-l,3- dihydro-2-imidazolone, 4-isobutylthio-3-isopropyl-l-methyl-5-{[(pyridin-4-ylmethyl)amino]methyl}-l,3- dihydro-2-imidazolone, 4-(3,5-dichlorophenylthio)-3-isopropyl-l-(4-methoxybenzyl)-5-{[(pyridin-4- ylmethyl)amino]methyl}-l,3-dihydro-2-imidazolone, 4-(3,5-dichlorophenylthio)-5-hydroxymethyl-3-isopropyl-l-(4-methoxybenzyl)-l,3- dihydro-2-imidazolone, 4-(3,5-dichlorophenylthio)-3-isopropyl-l-methyl-5-phenethyl-l,3-dihydro-2- imidazolone, 4-(3,5-dichlorophenylthio)-5-(2-hydroxybenzyl)-3-isopropyl-l-methyl-l,3-dihydro-2- imidazolone, 3-benzyl-4-(3,5-dichlorophenylthio)-l-methyl-5-{[(pyridin-4-ylmethyl)amino]methyl}- l,3-dihydro-2-imidazolone, l,3-dibenzyl-4-(3,5-dichlorophenylthio)-5-{[(pyridin-4-ylmethyl)amino]methyl}-l,3- dihydro-2-imidazolone, l-benzyl-4-(3,5-dichlorophenylthio)-3-isopropyl-5-{[(pyridin-4- ylmethyl)amino] methyl}- l,3-dihydro-2-imidazolone, l-benzyl-4-(3,5-dichlorophenylthio)-3-propyl-5-{[(pyridin-4-ylmethyl)amino]methyl}- l,3-dihydro-2-imidazolone, 5-benzyl-4-(3,5-dichlorophenylthio)-3-isopropyl-l-methyl-l,3-dihydro-2-imidazolone, 3-benzyl-4-(3,5-dichlorophenylthio)-5-hydroxymethyl-l-methyl-l,3-dihydro-2- imidazolone, 4-(3,5-dichlorophenoxy)-3-isopropyl-l-methyl-5-{[(pyridin-4-ylmethyl)amino]methyl}- l,3-dihydro-2-imidazolone, 4-sec-butylthio-3-isopropyl-l-methyl-5-{[(pyridin-4-ylmethyl)amino]methyl}-l,3- dihydro-2-imidazolone, 3-isopropyl-4-(3-methoxyphenylthio)-l-methyl-5-{[(pyridin-4-ylmethyl)amino]methyl}- l,3-dihydro-2-imidazolone, 3-benzyl-4-(3,5-dichlorophenylthio)-5-(l-hydroxyethyl)-l-methyl-l,3-dihydro-2- imidazolone. 13. Compounds as claimed in claim 1 which compounds are selected from: 4-(3,5-Dichloro-phenylsulfanyl)-3-isopropyl-5-methoxymethyl-l-methyl-l,3-dihydro- imidazol-2-one, 4-Hydroxymethyl-3-methyl-l-phenyl-5-(pyridin-4-ylsulfanyl)-l,3-dihydro-imidazol-2- one, l-Benzyl-4-hydroxymethyl-3-methyl-5-(pyridin-4-ylsulfanyl)-l,3-dihydro-imidazol-2- one; hydrochloric acid, 4-(3,5-Dichloro-phenylsulfanyl)-3-isopropyl-l-methyl-5-(pyridin-3-ylmethoxymethyl)- l,3-dihydro-imidazol-2-one, 4-(4-Benzyloxy-benzyloxymethyl)-5-(3,5-dichloro-phenylsulfanyl)-l-isopropyl-3-methyl- l,3-dihydro-imidazol-2-one, Acetic acid 5-(3,5-dichloro-phenylsulfanyl)-l-isopropyl-3-methyl-2-oxo-2,3-dihydro-lH- imidazol-4-ylmethyl ester, 4-(3,5-Dichloro-phenylsulfanyl)-3-isopropyl-l-methyl-5-(pyridin-4-yloxymethyl)-l,3- dihydro-imidazol-2-one, 3-(5-Benzyl-3-isopropyl-l-methyl-2-oxo-2,3-dihydro-lH-imidazol-4-ylsulfanyl)- benzonitrile, 4-Benzyl-5-isobutylsulfanyl-l-isopropyl-3-methyl-l,3-dihydro-imidazol-2-one, 4-Benzyl-l-isopropyl-5-isopropylsulfanyl-3-methyl-l,3-dihydro-imidazol-2-one, 4-Benzyl-l-isopropyl-3-methyl-5-methylsulfanyl-l,3-dihydro-imidazol-2-one, 4-(3,5-Dichloro-phenylsulfanyl)-5-isobutyl-3-isopropyl-l-methyl-l,3-dihydro-imidazol- 2-one, 4-Benzyl-5-(3,5-dichloro-phenylsulfanyl)-3-ethyl-l-isopropyl-l,3-dihydro-imidazol-2- one, l-Allyl-5-benzyl-4-(3,5-dichloro-phenylsulfanyl)-3-isopropyl-l,3-dihydro-imidazol-2- one, 4-(3,5-Dichloro-phenylsulfanyl)-l-ethyl-3-isopropyl-5-pyridin-4-ylmethyl-l,3-dihydro- imidazol-2-one, l-Allyl-4-(3,5-dichloro-phenylsulfanyl)-3-isopropyl-5-pyridin-4-ylmethyl-l,3-dihydro- imidazol-2-one, [E]-3-[5-(3,5-Dichloro-phenylsulfanyl)-l-isopropyl-3-methyl-2-oxo-2,3-dihydro-lH- imidazol-4-yl] -acrylic acid ethyl ester, 3-[5-(3,5-Dichloro-phenylsulfanyl)-l-isopropyl-3-methyl-2-oxo-2,3-dihydro-lH- imidazol-4-yl] -acrylonitrile, 3-[5-(3,5-Dichloro-phenylsulfanyl)-l-isopropyl-3-methyl-2-oxo-2,3-dihydro-lH- imidazol-4-yl] -acrylamide, l-Benzyl-5-(3,5-dichloro-phenylsulfanyl)-3-methyl-4-vinyl-l,3-dihydro-imidazol-2-one, or 4-(3,5-Dichloro-phenylsulfanyl)-3-isopropyl-l-methyl-5-pyridin-4-ylmethyl-l,3-dihydro- imidazol-2-one. 14. A process for the preparation of compounds of formula wherein R 1 , R 2 , R 3 and X are as defined in formula I; comprises reacting chloro compound of formula VII wherein R 1 and R 2 are as defined in formula I with nucleophilic agent R 3 XH wherein R 3 and X are as defined in formula I. 15. Compounds of formula VTII-a wherein R , R and X are as defined in formula I and R 3 is C 7 .ι 2 -alkyl, C 3 . 8 -cycloalkyl, optionally substituted phenyl or optionally substituted benzyl wherein phenyl or benzyl maybe substituted with 1-5 substituents selected from CM-alkyl, Ci. -alkoxy, hydroxy, fluorine, chlorine or bromine. 16. A compound of formula I, or hydrolyzable ester, ether or pharmaceutically acceptable salt thereof, or a composition containing a compound of formula I, as claimed in any one of claims 1 to 13 for use as medicament. 17. Use of a compound of formula I; or hydrolyzable ester, ether or pharmaceutically acceptable salt thereof, or a composition containing a compound of formula I, as defined in any one of claims 1 to 13 for the preparation of a medicament for the treatment of diseases mediated by the human immunodeficiency virus (HIV). 18. A compound of formula I, or hydrolyzable ester, ether or pharmaceutically acceptable salt thereof, or a composition containing a compound of formula I as claimed in any one of claims 1 to 13 for its use in the treatment of a disease mediated by the human immunodeficiency virus (HIV). 19. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of formula I, or hydrolyzable ester, ether or pharmaceutically acceptable salt thereof, as defined in any one of claims 1 to 13 and, if desired, a pharmaceutical inert carrier. 20. A pharmaceutical composition according to claim 19 for its use in the treatment of diseases mediated by the human immunodeficiency virus (HIV). 21. The invention as hereinbefore described.

Inventors: DYMOCK BRIAN WILLIAM, JONES PHILIP STEPHEN, MERRETT JOHN HERBERT, PARKES KEVIN EDWARD BURDON, PARRATT MARTIN JOHN, WALTER DARYL SIMON, DYMOCK, BRIAN, WILLIAM, JONES, PHILIP, STEPHEN, MERRETT, JOHN, HERBERT, PARKES, KEVIN, EDWARD, BURDON, PARRATT, MARTIN, JOHN, WALTER, DARYL, SIMON
Applicants: HOFFMANN LA ROCHE, F. HOFFMANN-LA ROCHE AG
Application year: 2001
Main classification: C07D233
IPC codes: A61K31, A61P31, C07D233, C07D401