COMPOUNDS AND THEIR USE AS CYSTEINE PROTEASE INHIBITORS

Abstract: A compound of formula (I) as a cysteine protease (for example a Cathepsin) inhibitor.

Description: COMPOUNDS AND THEIR USE AS CYSTEINE PROTEASE INHIBITORS The present invention relates to compounds that are cysteine protease inhibitors and in particular compounds that are Cathepsin L inhibitors and or Cathepsin S inhibitors especially Cathepsin S inhibitors. The invention further relates to processes for their preparation, to intermediates useful in their preparation, to their use as therapeutic agents, to pharmaceutical compositions containing them and to a method of treating a Cathepsin L or Cathepsin S mediated disease state. Cysteine proteases are enzymes important in normal cell physiology, but they are also associated with several disease states including autoimmunity, inflammation, metastasis, tissue damage following myocardial infarction, bone resorption and muscle wasting in dystrophic diseases. Cathepsins B, H, K, L, N, P, W and S are cysteinyl proteases involved in normal protein degradation and are normally located in the lysosomes of cells. However, when these enzymes are found outside the lysosomes they have been implicated as playing a causative role in a number of disease states including bone resorption disease such as osteoporosis. The number of people living to an old age has increased dramatically in recent years. This has been marked by an increase in the number of people having osteoporosis and other diseases associated with old age. Osteoporosis is accompanied by a high incidence of bone fracture resulting in many aged patients being confined to their beds. There is therefore a great need for a pharmaceutical composition to treat or prevent this disease. Living bone is continuously being remodelled and replenished by the process of resorption and deposition of the protein matrix and calcium minerals. These events are facilitated by the osteoclast, which has the ability to degrade and demineralise the bone, and the osteoblast which is responsible for new bone generation. In normal situations these processes are intimately linked resulting in little alteration of bone mass. However, pathological conditions exist in which there is an imbalance between their activities resulting in increased degradation and demineralisation (resorption) of bone and the development of fragile and/or brittle bone structure, as seen during osteoporosis. While the exact mechanism for this resorption is not known, increased osteoclast activity, as realised by increased proteolytic activity, is a contributing factor, and selective inhibition of proteolytic action may result in the arrest or reversal of bone loss. The lysosomal cysteine proteinases, Cathepsins B, H, K, L, N, P, W and S have been postulated as the proteinases that are responsible for osteoclast bone resoφtion, because of their ability to degrade insoluble type I collagens at low pH. Cathepsins B, H, K, L, N, P, W and S have been further implicated as playing a causative role in other diseases such as rheumatoid arthritis, osteoarthritis, tumour metastasis, pneumocystitis, Crithidia fusiculata, malaria, trypanosoma brucei brucei, schistosomiasis, periodontal disease, metachromatic leukodystrophy and muscular dystrophy. Cathepsins B, H, K, L, N, P, W and S, either alone or together, have also been implicated as playing a causative role in chronic obstructive pulmonary disease (COPD). Many autoimmune diseases are incurable, chronic and progressive. Rheumatoid arthritis is one of the commonest of these affecting about 0.5 % of the world's population causing significant morbidity and mortality. Within 5 years of diagnosis 60-70% of patients will experience difficulty with mobility. Rheumatoid arthritis patients die earlier than age and gender matched individuals in the general population. In recent years a number of synthetic inhibitors of cysteine proteases have been disclosed. US 5,055,451 discloses a series of peptidyl methyl ketones as thiol protease inhibitors; WO 95/15749 discloses peptidyl ketones with heterocyclic leaving groups as cysteine protease inhibitors; the in vivo inhibition of Cathepsin B by peptidyl (acyloxy) methyl ketones was discussed in J. Med. Chem. 1994, 37, 1833-40 and these types of compounds as inhibitors of cysteine protease inhibitors were also discussed in J. Am. Chem. Soc, 1988, 110, 4429-4431 ; peptidyl diazomethyl ketones as specific inactivators of thiol proteinases was discussed in J. Biol. Chem., 1981, 256, 4, 1923-8 and in Methods in Enzymology, 1981, 80, 820-5; the inhibiting activities of l-peptidyl-2-haloacetyl hydrazines towards Cathepsin B and calpains was discussed in Eur. J. Med. Chem., 1993, 28 297-31 1 and peptidyl fluoromethyl ketones as inhibitors of Cathepsin B and the implication for treatment of Rheumatoid arthritis was discussed in Biochemical Pharmacology, 1992, 44, 6, 1201-7. Thus, there is a great need for a specific cysteine protease inhibitor, especially a Cathepsin L inhibitor or a Cathepsin S inhibitor. The present invention discloses compounds with inhibitory activity of cysteine proteases and in particular of Cathepsin L and or Cathepsin S. The compounds of the invention are also useful in the treatment of chronic obstructive pulmonary disease (COPD). Accordingly the present invention provides a compound of formula (I): (I) wherein: R 1 and R 2 are independently selected from hydrogen, phenyl, naphthyl, heteroaryl, heterocycle, C 3 . 12 cycloalkyl or C 1-6 alkyl (wherein said Cι -6 alkyl is optionally substituted with one or more phenyl, naphthyl, C 3-12 cycloalkyl, heterocycle or heteroaryl) or R 1 and R 2 together with the nitrogen to which they are attached form Het; and wherein any phenyl, naphthyl, heteroaryl, heterocycle, C 3 _ι 2 cycloalkyl or Het is optionally substituted with one or more R ; R 3 is hydrogen, C 1-6 alkyl (wherein said Cj-βalkyl is optionally substituted with one or more phenyl, naphthyl, heteroaryl, heterocycle, C 3-12 cycloalkyl, -NHR 8 , -SR 8 or -OR 8 ), hydroxy, -OR 8 , -NHCOR 9 , -NHSO 2 R 9 , phenyl, naphthyl, C 3- ι 2 cycloalkyl, heterocycle or heteroaryl; and wherein any phenyl, naphthyl, heterocycle, heteroaryl or C 3 _ J2 cycloalkyl is optionally substituted with one or more R 7 ; R 4 is hydrogen or a group of formula (la): (la) wherein X is C]. 6 alkyl, phenyl, naphthyl, heteroaryl, C 3 _ ]2 cycloalkyl or heterocycle wherein said Cι -6 alkyl, phenyl, naphthyl, heteroaryl, C 3- ι 2 cycloalkyl or heterocycle are optionally substituted with one or more R ; M is -O-, -S-, -SO-, -SO 2 -, -NH-, -N(C 1-4 alkyl)- or M is a direct bond; n is 0-3; m is 0-3; R 5 is hydrogen, Cι- 6 alkyl, Cι -6 alkylsulphanyl, Cι. 6 alkoxy, phenyl or heteroaryl wherein said Cι_ alkyl, Ci_ 6 alkylsulphanyl, Cι_ 6 alkoxy, phenyl or heteroaryl are optionally substituted with one or more R 1 ' ; R 6 is hydrogen or Cι_ 6 alkyl; R is hydrogen, Cι- alkyl (wherein said C 1-6 alkyl is optionally substituted with one or more phenyl, naphthyl, C 3 _ι 2 cycloalkyl, heterocycle or heteroaryl), phenyl, naphthyl, C 3 . ι 2 cycloalkyl, heterocycle or heteroaryl; and wherein any phenyl, naphthyl, heteroaryl, heterocycle or C 3- ι 2 cycloalkyl is optionally substituted with one or more R ; R 9 is Cι_ 6 alkyl (wherein said Cι_ 6 alkyl is optionally substituted with one or more phenyl, naphthyl, C 3- ι 2 cycloalkyl, heterocycle or heteroaryl), phenyl, naphthyl, C 3 _ ι 2 cycloalkyl, heterocycle or heteroaryl; and wherein any phenyl, naphthyl, heterocycle, heteroaryl or C 3-12 cycloalkyl is optionally substituted with one or more R 13 ; R 7 , R 10 , R π , R 12 and R 13 are, independently, Cι_ 6 alkyl, C 2 . 6 alkenyl, C 2-6 alkynyl, halo, trifluoromethyl, hydroxy, trifluoromethoxy, cyano, C 1-6 alkoxy, C 1-6 alkanoyl, C 1-6 alkanoyloxy, amino, . ό alkylamino, N,N-(Cι. 6 alkyl) 2 amino, Cι_ 6 alkanoylamino, nitro, carboxy, carbamoyl, N-(Cι -6 alkyl)carbamoyl, N,N-(Cι_ 6 alkyl) 2 carbamoyl, Cι. 6 alkoxycarbonyl, mercapto, Ci -6 alkylsulphanyl, C]. 6 alkylsulphinyl, C 1-6 alkylsulphonyl, C]. 6 alkylsulphonylamino, sulphamoyl, N-(Cι_ 6 alkyl)sulphamoyl or N,7V-(Cι -6 alkyl) 2 sulphamoyl; or a pharmaceutically acceptable salt thereof. In one particular aspect the present invention provides a compound of formula (I), wherein: R 1 and R 2 are independently selected from hydrogen, phenyl, naphthyl, heteroaryl, heterocycle, C 3 . 12 cycloalkyl or C]. alkyl (wherein said Cι_ 6 alkyl is optionally substituted with one or more phenyl, naphthyl, C 3 .ι 2 cycloalkyl, heterocycle or heteroaryl) or R 1 and R 2 together with the nitrogen to which they are attached form Het; and wherein any phenyl, naphthyl, heteroaryl, heterocycle, C _ι 2 cycloalkyl or Het is optionally substituted with one or more R 7 ; R is hydrogen, Cι_ 6 alkyl (wherein said is optionally substituted with one or more phenyl, naphthyl, heteroaryl, heterocycle, C 3 _i 2 cycloalkyl, -ΝHR 8 , -SR 8 or -OR 8 ), hydroxy, -OR 8 , -ΝHCOR 9 , -ΝHSO 2 R 9 , phenyl, naphthyl, C 3- ι 2 cycloalkyl, heterocycle or heteroaryl; and wherein any phenyl, naphthyl, heterocycle, heteroaryl or C 3 _ι cycloalkyl is optionally substituted with one or more R 7 ; R is hydrogen or a group of formula (la): (la) wherein X is Cι_ 6 alkyl, phenyl, naphthyl, heteroaryl, C 3 _ι 2 cycloalkyl or heterocycle wherein said Cι_ alkyl, phenyl, naphthyl, heteroaryl, C 3 . 12 cycloalkyl or heterocycle are optionally substituted with one or more R 10 ; M is -O-, -S-, -SO-, -SO 2 -, -NH-, -N(Cι -4 alkyl)- or M is a direct bond; n is 0-3; m is 0-3; R 5 is hydrogen, Cι -6 alkyl, C]_ 6 alkylsulphanyl, C]. 6 alkoxy, phenyl or heteroaryl wherein said C 1- alkyl, Cι- 6 alkylsulphanyl, phenyl or heteroaryl are optionally substituted with one or more R 11 ; R 6 is hydrogen or Cι_ 6 alkyl; R 7 is Cι_ 6 alkyl, C 2-6 alkenyl, C 2 . 6 alkynyl, halo, trifluoromethyl, hydroxy, trifluoromethoxy, cyano, Cι. 6 alkoxy, Cι_ 6 alkanoyl, Cι- alkanoyloxy, amino, Cι- 6 alkylamino, NN-(Cι- alkyl) 2 amino, Cι_ 6 alkanoylamino, nitro, carboxy, carbamoyl, N-(Cι- 6 alkyl)carbamoyl, NN-(Cι. alkyl) 2 carbamoyl, Cι_ 6 alkoxycarbonyl, mercapto, C 1- alkylsulphanyl, Cι_ 6 alkylsulphinyl, Cι- 6 alkylsulphonyl, sulphamoyl, A/-(C]. 6 alkyl)sulphamoyl or N,N-(C ] -6 alkyl) 2 sulphamoyl; R 8 is hydrogen, Cι -6 alkyl (wherein said Cι -6 alkyl is optionally substituted with one or more phenyl, naphthyl, C 3 _ι 2 cycloalkyl, heterocycle or heteroaryl), phenyl, naphthyl, C 3 _ ι 2 cycloalkyl, heterocycle or heteroaryl; and wherein any phenyl, naphthyl, heteroaryl, heterocycle or C -ι 2 cycloalkyl is optionally substituted with one or more R 12 ; R 9 is Cι_ 6 alkyl (wherein said Cι -6 alkyl is optionally substituted with one or more phenyl, naphthyl, C 3 . 12 cycloalkyl, heterocycle or heteroaryl), phenyl, naphthyl, C 3 _ 12 cycloalkyl, heterocycle or heteroaryl; and wherein any phenyl, naphthyl, heterocycle, heteroaryl or C _ι 2 cycloalkyl is optionally substituted with one or more R 1 ^ ; R 10 is Cι- 6 alkyl, C 2 _ alkenyl, C 2 . 6 alkynyl, halo, trifluoromethyl, hydroxy, trifluoromethoxy, cyano, C ]-6 alkoxy, C]. 6 alkanoyl, Cj-βalkanoyloxy, amino, Cι. 6 alkylamino, N,N-(Cι -6 alkyl) 2 amino, Cι_ 6 alkanoylamino, nitro, carboxy, carbamoyl, N-(Cι_ 6 alkyl)carbamoyl, Λ/,Λ/-(Cι_ 6 alkyl) 2 carbamoyl, Ci- 6 alkoxycarbonyl, mercapto, Cι -6 alkylsulphanyl, Cj- 6 alkylsulphinyl, Cι- 6 alkylsulphonyl, Cι_ 6 alkylsulphonylamino, sulphamoyl, N-(C]. alkyl)sulphamoyl or N,N-(Cι. 6 alkyl) sulphamoyl; R u Cι_ 6 alkyl, C 2 -6alkenyl, C 2-6 alkynyl, halo, trifluoromethyl, hydroxy, trifluoromethoxy, cyano, Cι_ alkoxy, Cι_ 6 alkanoyl, Cι. 6 alkanoyloxy, amino, Cι_ 6 alkylamino, N,A/-(Cι -6 alkyl) 2 amino, -ealkanoylamino, nitro, carboxy, carbamoyl, N,N-(C 1 . 6 alkyl) 2 carbamoyl, Cι -6 alkoxycarbonyl, mercapto, d^alkylsulphanyl, Cι -6 alkylsulphinyl, C ]-6 alkylsulphonyl, sulphamoyl, N-(Cι_ 6 alkyl)sulphamoyl or N,N-(C 1 . 6 alkyl) 2 sulphamoyl; R 12 is Cι. 6 alkyl, C 2 . 6 alkenyl, C 2 . 6 alkynyl, halo, trifluoromethyl, hydroxy, trifluoromethoxy, cyano, C 1-6 alkoxy, Cι -6 alkanoyl, Cι. 6 alkanoyloxy, amino, Cι_ 6 alkylamino, N,N-(C 1-6 alkyl) 2 amino, Cι_ 6 alkanoylamino, nitro, carboxy, carbamoyl, A/-(C 1-6 alkyl)carbamoyl, N,N-(C]. alkyl) 2 carbamoyl, Cι_ 6 alkoxycarbonyl, mercapto, Cι_ 6 alkylsulphanyl, Cι. 6 alkylsulphinyl, Ci- ό alkylsulphonyl, sulphamoyl, N-(Cι -6 alkyl)sulphamoyl or N,N-(Cι. 6 alkyl) sulphamoyl; R 13 is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo, trifluoromethyl, hydroxy, trifluoromethoxy, cyano, Cι_ 6 alkoxy, Cι -6 alkanoyl, Cι -6 alkanoyloxy, amino, Cι. 6 alkylamino, N,N-(Cι- alkyl) 2 amino, C]- 6 alkanoylamino, nitro, carboxy, carbamoyl, N-(Cι -6 alkyl)carbamoyl, N,N-(Cι -6 alkyl) 2 carbamoyl, Cι- alkoxycarbonyl, mercapto, Cj -6 alkylsulphanyl, Cι_ alkylsulphinyl, C ]-6 alkylsulphonyl, sulphamoyl, N-(C 1-6 alkyl)sulphamoyl or NΛ/-(C]. 6 alkyl) 2 sulphamoyl; or a pharmaceutically acceptable salt thereof. In this specification the term 'alkyl' includes straight chained and branched structures. For example, Cι. 6 alkyl includes propyl, isopropyl and t- butyl. However, references to individual alkyl groups such as 'propyl' are specific for the straight chained version only and references to individual branched chain alkyl groups such as 'isopropyl' are specific for the branched chain version only. A similar convention applies to other radicals, for example "hydroxyCι. 6 alkyl" includes 1 -hydroxyethyl and 2-hydroxyethyl. The term "halo" refers to fluoro, chloro, bromo and iodo. "Het" is a saturated, partially saturated or fully unsaturated, mono or bicyclic ring that contains 4-12 atoms, one atom of which is the nitrogen atom to which R 1 and R 2 are attached to, and the other atoms are either all carbon atoms or they are carbon atoms and 1 -3 heteroatoms chosen from nitrogen, sulphur or oxygen, wherein a -CH 2 - group can optionally be replaced by a -C(O)-, and a ring sulphur atom may be optionally oxidised to form S-oxide(s). It will be appreciated that where R 1 and R together with the nitrogen atom to which they are attached form a group Het this nitrogen atom is not quatemised, i.e. a neutral compound is formed. Suitable values for "Het" include moφholino, piperidyl, piperazinyl, pyrrolidinyl, thiomoφholino, pyrrolinyl, homopiperazinyl, pyrrolyl, pyrazolyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolidinyl and triazolyl. Preferably "Het" is moφholino, piperidyl, piperazinyl, pyrrolidinyl, thiomoφholino, pyrrolinyl or homopiperazinyl. "Heterocycle" is a fully saturated, mono or bicyclic ring that contains 4-12 atoms, at least one of which is selected from nitrogen, sulphur or oxygen, wherein a -CH 2 - group can optionally be replaced by a -C(O)-, and a ring sulphur atom may be optionally oxidised to form S-oxide(s). Suitable values for "heteroaryl" include moφholino, piperidyl, piperazinyl, pyrrolidinyl, thiomoφholino, homopiperazinyl, imidazolyl, imidazolidinyl, pyrazolidinyl, dioxanyl and dioxolanyl. Preferably "heterocycle" is moφholino, piperidyl, piperazinyl, pyrrolidinyl, thiomoφholino or homopiperazinyl. "Heteroaryl" is a partially unsaturated or fully unsaturated, mono or bicyclic ring that contains 4-12 atoms, at least one of which is selected from nitrogen, sulphur or oxygen, wherein a -CH 2 - group can optionally be replaced by a -C(O)-, and a ring sulphur and/or nitrogen atom may be optionally oxidised to form S-oxide(s) and/or an N-oxide. Suitable values for "heteroaryl" include thienyl, furyl, imidazolyl, thiazolyl, thiadiazolyl, pyrimidinyl, pyridinyl, pyrazinyl, pyridazinyl, triazinyl, pyrrolyl and pyrazolyl. Preferably "heteroaryl" is thienyl, furyl, imidazolyl, thiazolyl, pyrimidinyl, pyridinyl, pyrrolyl and pyrazolyl. Examples of "Cι_ 6 alkanoyloxy" are acetoxy and propionyloxy. Examples of "Cι -6 alkoxycarbonyl" include methoxycarbonyl, ethoxycarbonyl, n- and t-butoxycarbonyl. Examples of "C]. alkoxy" include methoxy, ethoxy and propoxy. Examples of "C 1-6 alkanoylamino" include formamido, acetamido and propionylamino. Examples of include methylsulphinyl and ethylsulphinyl. Examples of "C]. 6 alkylsulphonyl" include mesyl and ethylsulphonyl. Examples of "Cι_ 6 alkanoyl" include acetyl and propionyl. Examples of "C] -6 alkylamino" include methylamino and ethylamino. Examples of "Λ/,N-(Cι_ 6 alkyl) 2 amino" include N,N-dimefhylamino, Λ/N-diethylamino and A/-ethyl-A/-methylamino. Examples of "C 2 . 6 alkenyl" are vinyl, allyl and 1-propenyl. Examples of "C 2 - 6 alkynyl" are ethynyl, 1-propynyl and 2-propynyl. Examples of "Λ/-(Cι_ 6 alkyl)carbamoyl" are Λ/-methylaminocarbonyl and /V-ethylaminocarbonyl. Examples of "NΛ/-(Cι. 6 alkyl) 2 carbamoyl" are N,N-dimethylaminocarbonyl and N-methyl-N- ethylaminocarbonyl. Examples of "N-(C]_ 6 alkyl)sulphamoyl" are N-methylsulphamoyl and N-ethylsulphamoyl. Examples of "N,N-(C 1- 6alkyl) 2 sulphamoyl" are N,Λ/-dimethylsulphamoyl and NΛ/-diethylsulphamoyl. Examples of "C 3 _ι 2 cycloalkyl" are cyclopropyl, cyclopentyl and cyclohexyl. Where optional substituents are chosen from "one or more" groups it is to be understood that this definition includes all substituents being chosen from one of the specified groups or the substituents being chosen from two or more of the specified groups. For example where optional substituents are chosen from one or more halo, Cι_ 6 alkoxy and Cι_ 6 alkyl, examples of possible combinations of substituents include 1) a bromo group, 2) two chloro groups, 3) a methoxy, ethoxy and propoxy substituent, 4) a fluoro and a methoxy group, 5) a methoxy, a methyl and an ethyl group, and 6) a chloro, a methoxy and an ethyl group. Preferred values of R 1 , R 2 , R 3 and R 4 are as follows. Such values may be used where appropriate with any of the definitions, claims or embodiments defined hereinbefore or hereinafter. Preferably R 1 and R 2 together with the nitrogen to which they are attached form Het. More preferably R 1 and R 2 together with the nitrogen to which they are attached form moφholino. Preferably R 3 is hydrogen. Preferably R 4 is a group of formula (la) as depicted above wherein X is Cι_ alkyl or phenyl, M is a direct bond, n is 0-3 and m is 0-3. More preferably R 4 is isobutyl, pentyl or 3-phenylpropyl. In a further aspect R 5 is hydrogen or heteroaryl. In one aspect of the invention, preferably R is hydrogen. In another aspect of the invention, preferably R 5 is heteroaryl. Preferably R is hydrogen. Therefore in a preferred aspect of the invention, there is provided a compound of formula (I) wherein: R 1 and R 2 together with the nitrogen to which they are attached form Het; R is hydrogen; R 4 is a group of formula (la) as depicted above wherein X is Cι_ 6 alkyl or phenyl, M is a direct bond, n is 0-3 and m is 0-3; R 5 is hydrogen; and R is hydrogen; or a pharmaceutically acceptable salt thereof. Therefore in a more preferred aspect of the invention, there is provided a compound of formula (I) wherein: R 1 and R 2 together with the nitrogen to which they are attached form moφholino; R 3 is hydrogen; R 4 is isobutyl, pentyl or 3-phenylpropyl; R is hydrogen; and R 6 is hydrogen; or a pharmaceutically acceptable salt thereof. A preferred aspect of the invention relates to any one of the Examples or a pharmaceutically acceptable salt thereof. Suitable pharmaceutically acceptable salts include acid addition salts such as the methanesulphonate, fumarate, hydrochloride, hydrobromide, citrate and maleate salts and salts formed with phosphoric and sulphuric acid. In another aspect suitable salts are base salts such as an alkali metal salt for example a sodium salt, an alkaline earth metal salt for example a calcium or a magnesium salt, an organic amine salt for example a salt with triethylamine, moφholine, N-methylpiperidine, Λ/-ethylpiperidine, procaine, dibenzylamine, N,N-dibenzylethylamine or an amino acid for example a lysine salt. There may be more than one cation or anion depending on the number of charged functions and the valency of the cations or anions. A preferred pharmaceutically acceptable salt is a sodium salt. Some compounds of formula (I) may possess chiral centres. It is to be understood that the invention encompasses all such optical isomers and diasteroisomers of compounds of formula (I) which possess cysteine protease inhibitory activity, and mixtures thereof in all proportions. The invention further relates to all tautomeric forms of the compounds of formula (I). It is also to be understood that certain compounds of the formula (I) can exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It is to be understood that the invention encompasses all such solvated forms. Another aspect of the present invention provides a process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof According to this aspect of the invention there is provided a process (in which variable groups are as defined for formula (I) unless otherwise stated) which comprises: a) reacting an acid of formula (II): (II) (or an activated derivative thereof) with an amine of formula (III): R? -R 6 H 2 N X ^ CN (HI) b) reacting an acid of formula (IV): (IV) (or an activated derivative thereof) with an amine of formula (V): R 1 I NH 2/ R (V) c) dehydrating an amide of formula (VI): (VI) and thereafter if necessary: i) converting a compound of the formula (I) into another compound of the formula (I); ii) removing any protecting groups; iii) forming a pharmaceutically acceptable salt. Specific reaction conditions for the above reactions are as follows: a) and b) Acids and amines may be coupled together in the presence of a suitable coupling reagent. Standard peptide coupling reagents known in the art can be employed as suitable coupling reagents, or for example carbonyldiimidazole and dicyclohexyl-carbodiimide, optionally in the presence of a catalyst such as dimethylaminopyridine or 4-pyrrolidinopyridine, optionally in the presence of a base for example triethylamine, pyridine, or 2,6-di-α/fcy/-pyridines such as 2,6-lutidine or 2,6-di-tert-butylpyridine. Suitable solvents include dimethylacetamide, dichloromethane, benzene, tetrahydrofuran and dimethylformamide. The coupling reaction may conveniently be performed at a temperature in the range of -40 to 40°C. Suitable activated acid derivatives include acid halides, for example acid chlorides, and active esters, for example pentafluorophenyl esters. The reaction of these types of compounds with amines is well known in the art, for example they may be reacted in the presence of a base, such as those described above, and in a suitable solvent, such as those described above. The reaction may conveniently be performed at a temperature in the range of -40 to 40°C. Compounds of formula (II) may be prepared according to the following scheme: i) Standard peptide coupling conditions + (V) ii) De-esterificat ~ion (II > (Ila) Compounds of formula (IV) may be prepared according to the following scheme: (IVa) Compounds of formula (Ha), (III), (IVa) and (V) are commercially available compounds, or they are known in the literature, or they are prepared by standard processes known in the art. For example compounds of formula (Ha) and (IVa) may be prepared by analogy with the syntheses described in Synlett, 1993, 155 (for R 3 = H) and WO 98/07742 and WO 98/43959 (for R 3 ≠ H). Compounds of formula (III) may also be prepared according to the following scheme: M KCN, NH 1 6/ R 5 Aq Et 2 O *" (III) (Ilia) Compounds of formula (Ilia) are commercially available compounds, or they are known in the literature, or they are prepared by standard processes known in the art. c) Amides of formula (VI) may be dehydrated by standard processes known in the art. For example this process may be carried out with thionyl chloride in the presence of a base for example triethylamine, pyridine, or 2,6-di-α/&y/-pyridines such as 2,6-lutidine or 2,6-di-tert-butylpyridine or by treatment with oxalyl chloride and pyridine in DMF. The reaction may conveniently be carried out at a temperature at or below room temperature. Amides of formula (VI) may be prepared according to the following scheme: R5 p6 Standard peptide (II) ' + ~ H 2 N XT/ NH 2 coupling conditio ^ ns (VI) O (Via) Compounds of formula (Via) are commercially available compounds, or they are known in the literature, or they are prepared by standard processes known in the art. If not commercially available, the necessary starting materials for the procedures described above may be made by procedures which are selected from standard organic chemical techniques, techniques which are analogous to the synthesis of known, structurally similar compounds, by techniques which are analogous to the above described procedures or by techniques which are analogous to the procedures described in the examples. It will be appreciated that certain of the optional substituents on a phenyl or naphthyl or a heteroaryl ring in the compounds of the present invention may be introduced by standard aromatic substitution reactions or generated by conventional functional group modifications either prior to or immediately following the processes mentioned above, and as such are included in the process aspect of the invention. Such reactions and modifications include, for example, introduction of a substituent by means of an aromatic substitution reaction, reduction of substituents, alkylation of substituents and oxidation of substituents. The reagents and reaction conditions for such procedures are well known in the chemical art. Particular examples of aromatic substitution reactions include the introduction of a nitro group using concentrated nitric acid, the introduction of an acyl group using, for example, an acyl halide and a Lewis acid (such as aluminium trichloride) under Friedel Crafts conditions; the introduction of an alkyl group using an alkyl halide and Lewis acid (such as aluminium trichloride) under Friedel Crafts conditions; and the introduction of a halogeno group. Particular examples of modifications include the reduction of a nitro group to an amino group by, for example, catalytic hydrogenation with a nickel catalyst or treatment with iron in the presence of hydrochloric acid with heating; oxidation of alkylthio to alkylsulphinyl or alkylsulphonyl. It will also be appreciated that in some of the reactions mentioned herein it may be necessary/desirable to protect any sensitive groups in the compounds. The instances where protection is necessary or desirable and suitable methods for protection are known to those skilled in the art. Thus, if reactants include groups such as amino, carboxy or hydroxy it may be desirable to protect the group in some of the reactions mentioned herein. A suitable protecting group for an amino or alkylamino group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an alkoxycarbonyl group, for example a methoxycarbonyl, ethoxycarbonyl or tert-butoxycarbonyl group, an arylmethoxycarbonyl group, for example benzyloxycarbonyl, or an aroyl group, for example benzoyl. The deprotection conditions for the above protecting groups necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or alkoxycarbonyl group or an aroyl group may be removed for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an acyl group such as a tert-butoxycarbonyl group may be removed, for example, by treatment with a suitable acid as hydrochloric, sulphuric or phosphoric acid or trifluoroacetic acid and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon, or by treatment with a Lewis acid for example boron tris(trifluoroacetate). A suitable alternative protecting group for a primary amino group is, for example, a phthaloyl group which may be removed by treatment with an alkylamine, for example dimethylaminopropylamine, or with hydrazine. A suitable protecting group for a hydroxy group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an aroyl group, for example benzoyl, or an arylmethyl group, for example benzyl. The deprotection conditions for the above protecting groups will necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or an aroyl group may be removed, for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an arylmethyl group such as a benzyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon. A suitable protecting group for a carboxy group is, for example, an esterifying group, for example a methyl or an ethyl group which may be removed, for example, by hydrolysis with a base such as sodium hydroxide, or for example a tert-butyl group which may be removed, for example, by treatment with an acid, for example an organic acid such as trifluoroacetic acid, or for example a benzyl group which may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon. The protecting groups may be removed at any convenient stage in the synthesis using conventional techniques well known in the chemical art. In a still further aspect the present invention provides an intermediate compound of formula (VI). According to a further feature of the invention there is provided a compound of the formula (I), or a pharmaceutically acceptable salt thereof, for use in a method of treatment of the human or animal body by therapy. According to a further feature of the present invention there is provided a method for producing inhibition of a cysteine protease in a warm blooded animal, such as man, in need of such treatment, which comprises administering to said animal an effective amount of a compound of the present invention, or a pharmaceutically acceptable salt thereof The invention also provides a compound of the formula (I), or a pharmaceutically acceptable salt thereof, for use as a medicament; and the use of a compound of the formula (I) of the present invention, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the inhibition of a cysteine protease in a warm blooded animal, such as man. In particular the invention provides the use of a compound of the formula (I) of the present invention, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the inhibition of Cathepsin S in a warm blooded animal, such as man. In order to use a compound of the formula (I) or a pharmaceutically acceptable salt thereof for the therapeutic treatment of mammals including humans, in particular in the inhibition of a cysteine protease, it is normally formulated in accordance with standard pharmaceutical practice as a pharmaceutical composition. Therefore in another aspect the present invention provides a pharmaceutical composition which comprises a compound of the formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier. The pharmaceutical compositions of this invention may be administered in standard manner for the disease condition that it is desired to treat, for example by oral, rectal or parenteral administration. For these puφoses the compounds of this invention may be formulated by means known in the art into the form of, for example, tablets, capsules, aqueous or oily solutions or suspensions, (lipid) emulsions, dispersible powders, suppositories, ointments, creams, drops and sterile injectable aqueous or oily solutions or suspensions. A suitable pharmaceutical composition of this invention is one suitable for oral administration in unit dosage form, for example a tablet or capsule which contains between 100 mg and 1 g of the compound of this invention. In another aspect a pharmaceutical composition of the invention is one suitable for intravenous, subcutaneous or intramuscular injection. Each patient may receive, for example, an intravenous, subcutaneous or intramuscular dose of 1 mgkg "1 to 100 mgkg "1 of the compound, preferably in the range of 5 mgkg "1 to 20 mgkg "1 of this invention, the composition being administered 1 to 4 times per day. The intravenous, subcutaneous and intramuscular dose may be given by means of a bolus injection. Alternatively the intravenous dose may be given by continuous infusion over a period of time. Alternatively each patient will receive a daily oral dose which is approximately equivalent to the daily parenteral dose, the composition being administered 1 to 4 times per day. The following illustrate representative pharmaceutical dosage forms containing the compound of formula (I), or a pharmaceutically-acceptable salt thereof (hereafter compound X), for therapeutic or prophylactic use in humans: (e) Buffers, pharmaceutically-acceptable cosolvents such as polyethylene glycol, polypropylene glycol, glycerol or ethanol or complexing agents such as hydroxy-propyl β cyclodextrin may be used to aid formulation. Note The above formulations may be obtained by conventional procedures well known in the pharmaceutical art. The tablets (a)-(c) may be enteric coated by conventional means, for example to provide a coating of cellulose acetate phthalate. Inhibition of Cathepsin S. The pharmaceutically-acceptable compounds of the present invention are useful in the inhibition of Cathepsin S, having a good activity in vitro against human Cathepsin S. Cathepsin S assay. Cloning and Expression of human Cathepsin S. Recombinant human Cathepsin S was cloned and expressed in Baculovirus, by the following method. The cDNA sequence for human Cathepsin S is available in the EMBL database Accession Number M90696. This database sequence was used to prepare, by PCR on mRNA from human tissues, a recombinant plasmid carrying an insert with a DNA sequence identical to that of Cathepsin S in the EMBL database (Ace No M90696). The techniques for mRNA isolation, PCR and cloning are standard techniques known by those skilled in the art. Sequence determination of the recombinant insert was carried out using established DNA sequencing techniques. The PCR was done so as to introduce an EcoRI cloning site 5' of the 'ATG' of Cathepsin S and an Xbal cloning site 3' of the 'Stop' codon. The PCR product was cloned between the EcoRI and Xbal sites of the baculovirus transfer vector pFASTBAC-1 (Bac-to- Bac Expression System commercially available from Gibco BRL -Life Technologies ( cat no 10359-016)). This recombinant construct was used to generate, by standard techniques, a recombinant baculovirus capable of expressing preprocathepsin S. Expression of recombinant Cathepsin S was tested for the baculoviral constructs by infection of two insect cell lines : Sf9 cells (ATCC No CRL-171 1) and T.ni cells (Invitrogen, Cat No B855-02). Purification of Cathepsin S Method 1. Procathepsin S was found in the insect cell medium and acid activated. The medium was mixed with an equal volume of lOOmM Sodium Acetate buffer pH 4.5, 5mM dithiothreitol (DTT) and 5mM EDTA and incubated for one hour at 37°C method of Maubach et al (Eur. J. Biochem., 250, 745-750, 1997). Method 2. The pH of insect cell medium (10ml) containing procathepsin S was adjusted to 4.5 with glacial acetic acid and DTT and EDTA added to 5mM. The sample was then incubated at 37°C for 150min to enable conversion to the active enzyme. Ammonium sulphate was then added to 80% saturation and a pellet obtained by centrifugation. This pellet was redissolved in 2ml buffer A (lOOmM Tris, 500mM NaCl, ImM EDTA, pH7.5) and mixed in a batchwise fashion with lOOμl thiopropyl-Sepharose for 15min at 4°C. The non bound fraction was removed by a brief centrifugation and the gel washed with 2x1 ml buffer A. Cathepsin S was then eluted by batch mixing with 0.4ml 20mM DTT in buffer A for 15min at 4°C. Measurement of Cathepsin S Activity. Cathepsin S activity was measured based on the method of Maubach et al (Eur. J. Biochem., 250, 745-750, 1997), using the fluorogenic substrate Z-Val-Val-Arg-NHMec. Inhibitors were identified by their ability to decrease the generation of the fluorescent leaving group (NHMec). Briefly the assay was as follows: rHuman Cathepsin S (1.5 nmoles) was pre-incubated with or without compounds in 50mM Potassium phosphate buffer pH 6.0-6.2, 20mM Na 2 EDTA, 0.1 % Brij at 25°C for 5 minutes in a solid black 96 well plate. Synthetic substrate, 20μM Z-Val-Val-Arg-NHMec, was added and the mixture incubated at 30°C for 20 minutes. The reaction was stopped by the addition of 0.1M sodium chloroacetate pH 4.3. Fluorescence was determined using a Fluoroskan II plate reader; excitation 355nm, emission 460nm. Compound potency was determined from the raw fluorescence data by calculating the IC 50 against Cathepsin S using a PC graph drawing software package. When tested in the above in-vitro tests the compounds of this invention give IC 50 S in the range 1-10,000 nM. The invention will now be illustrated by the following non-limiting examples in which, unless stated otherwise: (i) temperatures are given in degrees Celsius (°C); operations were carried out at room or ambient temperature, that is, at a temperature in the range of 18-25°C; (ii) organic solutions were dried over anhydrous magnesium sulphate; evaporation of solvent was carried out using a rotary evaporator under reduced pressure (600-4000 Pascals; 4.5-30 mm Hg) with a bath temperature of up to 60°C; (iii) chromatography means flash chromatography on silica gel; thin layer chromatography (TLC) was carried out on silica gel plates, where a silica Mega Bond Elut column is referred to, this means a column containing lOg or 20g of silica of 40 micron particle size, the silica being contained in a 60ml disposable syringe and supported by a porous disc, obtained from Varian, Harbor City, California, USA under the name "Mega Bond Elut SI"; "Mega Bond Elut" is a trademark; (iv) in general, the course of reactions was followed by TLC and reaction times are given for illustration only; (v) final products had satisfactory proton nuclear magnetic resonance (NMR) spectra; (vi) yields are given for illustration only and are not necessarily those which can be obtained by diligent process development; preparations were repeated if more material was required; (vii) when given, NMR data is in the form of delta values for major diagnostic protons, given in parts per million (ppm) relative to tetramethylsilane (TMS) as an internal standard, determined at 250 MHz using perdeuterio dimethyl sulphoxide (DMSO-δ 6 ) as the solvent unless otherwise stated; (viii) chemical symbols have their usual meanings; SI units and symbols are used; (ix) solvent ratios are given in percentage by volume; (x) mass spectra (MS) were run with an electron energy of 70 electron volts in the chemical ionisation (CI) mode using a direct exposure probe; where indicated ionisation was effected by electron impact (El) or fast atom bombardment (FAB); where values for m/z are given, generally only ions which indicate the parent mass are reported; and (xi) The following abbreviations are used: DMF NN-dimethylformamide; and THF tetrahydrofuran. Example 1 A/-rR-2-(Moφholιnocarbonylmethyl)heptanoyllamιnoacetonιtπle Iso-buty\ chloroformate (0 136 ml) was added dropwise to a solution of R-2- (moφhohnocarbonylmethyl)heptanoιc acid (Method 1 ) (0 35 g) and A/-methylmoφhohne (0.165 ml) in THF (20 ml) at -15°C under argon and the mixture was stirred at -15°C for 20 minutes then tπethylamine (0 21 ml) was added followed by a solution of aminoacetonitπle (0.138g) in anhydrous DMF (3 ml). The mixture was allowed to warm to room temperature and stirring was continued for 20 hours. The reaction mixture was evaporated to dryness under high vac and the residue obtained was partitioned between water (30 ml) and ethyl acetate (30 ml). The aqueous layer was collected and extracted with ethyl acetate (3 x 30 ml). The combined ethyl acetate extracts were washed with brine and dried The residue obtained on removal of the solvent was triturated with diethyl ether to give the title compound. NMR (CDC1 3 ): 7.9 (m, IH), 4.0-4.3 (m, 2H), 3.3-3.8 (m, 8H), 2.7-2 9 (m, 2H), 2.3-2.5 (m, IH), 1.7- 1.9 (m, IH), 1.2-1.6 (m, 8H), 0.8-1.0 (m, 3H); m z (M+H) 296.5 Example 2 Following the procedure of Example 1 and using the appropriate starting mateπals there was obtained- Preparation of Starting Materials The starting materials for the Examples above are either commercially available or are readily prepared by standard methods from known materials For example the following reactions are illustrations but not limitations of the preparation of some of the starting materials used in the above reactions Method 1 R-2-(Moφholιnocarbonylmethyl)heptanoιc acid Methyl R-2-(moφhohnocarbonylmethyl)heptanoate (Method 3) (0.37g) was dissolved in THF (10 ml) and 1 0M lithium hydroxide (6.8 ml) was added and the mixture was stirred for 20 hours. The residue obtained on removal of the solvent was diluted with water (20 ml) and washed with ethyl acetate (2 x 20 ml) The aqueous extract was acidified with 2M HC1 and extracted with ethyl acetate (3 x 20 ml) The combined ethyl acetate extracts were washed with brine and dried. Removal of the solvent gave the title compound as an oil, yield 0.35g, (M+H) 258. Methods 2-3 Following the procedure of Method 1 and using the appropriate starting materials there was obtained: Method 4 Methyl R-2-rmoφholιnocarbonylmethyllheptanoate /sσ-butyl chloroformate (0 225 ml) was added dropwise to a solution of R-2- pentylsuccmic acid- 1 -methyl ester (0 5 g) and N-methylmoφhohne (0 27 ml) in THF (20 ml) at -15°C under argon and the mixture was stirred at -15°C for 20 minutes then moφho ne (0.216 ml) was added The mixture was allowed to warm to room temperature and stirring was continued for 20 hours The reaction mixture was evaporated to dryness and the residue obtained was partitioned between water (30 ml) and ethyl acetate (30 ml) The aqueous layer was collected and extracted with ethyl acetate (3 x 30 ml) The combined ethyl acetate extracts were washed with brine and dried. The residue obtained on removal of the solvent was passed down a 20g Mega Bond Elut column eluting with dichloromethane, then 1% methanol in dichloromethane and finally 2% methanol in dichloromethane to give the title compound (M+H) 272. Methods 5-6 Following the procedure of Method 4 and using the appropriate starting materials there was obtained:

Claims: CLAIMS A compound of formula (I): (I) wherein: R 1 and R 2 are independently selected from hydrogen, phenyl, naphthyl, heteroaryl, heterocycle, C 3 .ι cycloalkyl or Cι -6 alkyl (wherein said Cι_ 6 alkyl is optionally substituted with one or more phenyl, naphthyl, C 3 .ι 2 cycloalkyl, heterocycle or heteroaryl) or R 1 and R 2 together with the nitrogen to which they are attached form Het; and wherein any phenyl, naphthyl, heteroaryl, heterocycle, C 3-12 cycloalkyl or Het is optionally substituted with one or more R 7 ; R 3 is hydrogen, Cι_ 6 alkyl (wherein said Cι_ 6 alkyl is optionally substituted with one or more phenyl, naphthyl, heteroaryl, heterocycle, C 3 _ι 2 cycloalkyl, -NHR , -SR or -OR ), hydroxy, -OR 8 , -NHCOR 9 , -NHSO 2 R 9 , phenyl, naphthyl, C 3 -ι 2 cycloalkyl, heterocycle or heteroaryl; and wherein any phenyl, naphthyl, heterocycle, heteroaryl or C 3- ι cycloalkyl is optionally substituted with one or more R ; R 4 is hydrogen or a group of formula (la): (la) wherein X is Cι_ 6 alkyl, phenyl, naphthyl, heteroaryl, C 3 . 12 cycloalkyl or heterocycle wherein said Cι_ alkyl, phenyl, naphthyl, heteroaryl, C 3 .ι cycloalkyl or heterocycle are optionally substituted with one or more R 10 ; M is -O-, -S-, -SO-, -SO 2 -, -NH-, -N(C alkyl)- or M is a direct bond; n is 0-3; m is 0-3; R 5 is hydrogen, Cι -6 alkylsulphanyl, phenyl or heteroaryl wherein said Cι_ 6 alkyl, Ci-βalkylsulphanyl, Cι -6 alkoxy, phenyl or heteroaryl are optionally substituted with one or more R 11 ; R 6 is hydrogen or Cι_ 6 alkyl; R 8 is hydrogen, Cι. 6 alkyl (wherein said Cι_ 6 alkyl is optionally substituted with one or more phenyl, naphthyl, C 3 .ι 2 cycloalkyl, heterocycle or heteroaryl), phenyl, naphthyl, C 3 _ι 2 cycloalkyl, heterocycle or heteroaryl; and wherein any phenyl, naphthyl, heteroaryl, heterocycle or C 3 _ι 2 cycloalkyl is optionally substituted with one or more R 12 ; R 9 is Cι- 6 alkyl (wherein said Cι- alkyl is optionally substituted with one or more phenyl, naphthyl, C 3 .ι 2 cycloalkyl, heterocycle or heteroaryl), phenyl, naphthyl, C 3- ι 2 cycloalkyl, heterocycle or heteroaryl; and wherein any phenyl, naphthyl, heterocycle, heteroaryl or C 3- ι 2 cycloalkyl is optionally substituted with one or more R 13 ; R 7 , R 10 , R 11 , R 12 and R 13 are, independently, Cι -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo, trifluoromethyl, hydroxy, trifluoromethoxy, cyano, Cι -6 alkoxy, Cι_ 6 alkanoyl, Cι -6 alkanoyloxy, amino, Cι_ 6 alkylamino, N,N-(Cι- 6 alkyl) 2 amino, Cι_ 6 alkanoylamino, nitro, carboxy, carbamoyl, A/-(Ci- alkyl)carbamoyl, NN-(Cι. 6 alkyl) 2 carbamoyl, Cι -6 alkoxycarbonyl, mercapto, Cι -6 alkylsulphanyl, Cι_ alkylsulphinyl, Cι -6 alkylsulphonyl, Cι -6 alkylsulphonylamino, sulphamoyl, A/-(Cι. 6 alkyl)sulphamoyl or N, A/-(C i _ 6 alkyl) 2 sulphamoy 1 ; or a pharmaceutically acceptable salt thereof. 2. A compound of formula (I) as claimed in claim 1 wherein R 1 and R 2 together with the nitrogen to which they are attached form Het; wherein Het is a saturated, partially saturated or fully unsaturated, mono or bicyclic ring that contains 4-12 atoms, one atom of which is the nitrogen atom to which R 1 and R 2 are attached to, and the other atoms are either all carbon atoms or they are carbon atoms and 1 -3 heteroatoms chosen from nitrogen, sulphur or oxygen, wherein a -CH 2 - group can optionally be replaced by a -C(O)-, and a ring sulphur atom may be optionally oxidised to form S-oxide(s). 3. A compound of formula (I) as claimed in claim 1 or 2 wherein R 3 is hydrogen. 4. A compound of formula (I) as claimed in claim 1 , 2 or 3 wherein R 4 is a group of formula (la) wherein X is C|. 6 alkyl or phenyl, M is a direct bond, n is 0-3 and m is 0-3. 5. A compound of formula (I) as claimed in claim 1 , 2, 3 or 4 wherein R 5 is hydrogen or heteroaryl. A compound of formula (I) as claimed in claim 1, 2, 3, 4 or 5 wherein R 6 i •s hydrogen. 7. A process for preparing a compound of formula (I) as claimed in claim 1 comprising: a) reacting an acid of formula (II): (or an activated derivative thereof) with an amine of formula (III): R 5 R 6 H 2 N X CN <' » > b) reacting an acid of formula (IV): (or an activated derivative thereof) with an amine of formula (V): R 1 , NH (V) 2/ R c) dehydrating an amide of formula (VI): and thereafter if necessary: i) converting a compound of the formula (I) into another compound of the formula (I); ii) removing any protecting groups; or, iii) forming a pharmaceutically acceptable salt. 8. An intermediate compound of formula (VI): wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in claim 1. 9. A pharmaceutical composition which comprises a compound of formula (I) as claimed in claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier. 10. A compound of formula (I) as claimed in claim 1 , or a pharmaceutically acceptable salt thereof, for use in a method of treatment of the human or animal body by therapy. 11. A method for producing inhibition of a cysteine protease in a warm blooded animal in need of such treatment, which comprises administering to said animal an effective amount of a compound of formula (I) as claimed in claim 1 , or a pharmaceutically acceptable salt thereof. 12. The use of a compound of the formula (I) as claimed in claim 1 , or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in the inhibition of a cysteine protease in a warm blooded animal.

Inventors: EDWARDS PHILIP NEIL, JOHNSTONE CRAIG, LARGE MICHAEL STEWART, OLDFIELD JOHN, TUCKER HOWARD, EDWARDS, PHILIP, NEIL, JOHNSTONE, CRAIG, LARGE, MICHAEL, STEWART, OLDFIELD, JOHN, TUCKER, HOWARD
Applicants: ASTRAZENECA AB, ASTRAZENECA UK LTD, EDWARDS PHILIP NEIL, JOHNSTONE CRAIG, LARGE MICHAEL STEWART, OLDFIELD JOHN, TUCKER HOWARD, ASTRAZENECA UK LIMITED, EDWARDS, PHILIP, NEIL, JOHNSTONE, CRAIG, LARGE, MICHAEL, STEWART, OLDFIELD, JOHN, TUCKER, HOWARD
Application year: 2000
Main classification: C07D295
IPC codes: A61K31, A61P1, A61P3, A61P9, A61P11, A61P19, A61P21, A61P29, A61P33, A61P35, A61P37, A61P43, C07D295