7,7-DISUBSTITUTED CEPHEM-4-KETONES

Abstract: The present invention provides compounds of formulae (Ia) and (Ib) and pharmaceutically or veterinarily salts thereof; wherein A, R1, R2 and R3 are hydrogen, halogen or an organic group; Q and W are appropriate substituents and X is either oxygen or sulphur or NR, wherein R is either hydrogen or an organic group. A process for their preparation is also described. The compounds of formulae (Ia) and (Ib) and the pharmaceutically and veterinarily acceptable salts thereof are elastase inhibitors.

Description: 7.7-DISUBSTITUTED CEPHEM-4-KETONES The present invention relates to new 7, 7-disubstituted cephem-4-ketones, to a process for their preparation and to pharmaceutical and veterinary compositions containing them. The compounds according to the invention are useful as protease inhibitors, especially human leukocyte elastase (HLE) inhibitors, and for the prevention, control and treatment of diseases involving the uncontrolled release of proteolytic enzymes, in particular emphysema, metastasis, cystic fibrosis, adult respiratory distress syndrome, rheumatoid arthritis, osteoarthritis, periodontal diseases, septic and traumatic shock, infectious arthritis, rheumatic fever, spondylitis, gout, lupus and psoriasis. The invention provides a compound of the formula (la) or (lb) or a pharmaceutically acceptable salt thereof: wherein A is an organic radical which is optionally substituted and is selected from Cj . -C 12 straight or branched alkyl , C 2 -C 12 alkenyl , C 2 -C 12 alkynyl , C 6 -C 14 aryl , C 3 -C 8 cycloalkyl , C 3 -C 8 cycloalkenyl C 7 -C 22 alkaryl , C 7 -C 22 aralkyl , C 8 -C 14 alkenylaryl , C 8 -C 14 aralkenyl , C 8 -C 14 alkynylaryl , C 8 - C 14 aralkynyl , ( cycloalkyl ) alkyl , ( cycloalkyl ) alkenyl , heterocyclyl , (heterocyclyl ) alkyl , (heterocyclyl ) alkenyl ; Q and W, each independently, represent (1) chloro, fluoro, bromo or iodo; (2) A as defined above (3) hydroxy or an ether OA wherein A is as defined above (4) a thioether, sulfoxide or sulfone -S(0),„A wherein m is either zero, one or two and A is as defined above,- (5) a selenoether, selenoxide or selenone -Se (0) i wherein m is either zero, one or two and A is as defined above; (6) acyl -C(0)A wherein A is as defined above,- (7) formyloxy -OC(0)H or acyloxy -OC(0)A wherein A is as defined above; (8) sulfonyloxy -OS(0) 2 A wherein A is as defined above,- (9) formamido - HC(0)H or an acylamino group -NHC(0)A wherein A is as defined above or acylamino - H-Z wherein Z is a mono, di- or tripeptide composed of D or L α-aminoacids chosen from Ala, Gly, Val, Leu, lie, Phe and with the terminal amino group either free or acylated by a group -C(0)A or -C(0))A wherein A is as defined above; (10) azido, nitro or cyano; or Q and taken together constitute an oxo group (=0) or a group of formula =CHA, =CHC(0)A, =CHC(0)0A or =CHS(0) 2 A wherein A is as defined above; or Q and taken together with the carbon atom to which they are attached constitute an oxylane or cyclopropyl group,- with the proviso that in the compounds of formula (la) Q and do not both represent chloro or fluoro atoms; and where appropriate Q and W are optionally substituted; R_ is either hydrogen or an optionally substituted straight or branched C-.-C 12 alkyl or a C 2 -C 12 alkenyl group, or a C 7 -C 14 aralkyl group, or a (heterocyclyl)alkyl group; R 2 represents: (1) hydrogen; (2) A as defined above; ( 3 ) halo ; (4) a sulfenyl, sulfinyl or sulfonyl group -S(0) m A wherein A and m are as defined above; (5) an acyloxy group -OC(0)A wherein A is as defined above; or R_ and R 2 taken together constitute a methylene group or a group of formula =CHA, =CHC(0)A or =CHC(0)OA wherein A is as defined above,- or R_ and R 2 taken together with the carbon atom to which they are attached constitute a carbocyclic or heterocyclic group; where approprite R 1 and/or R 2 are optionally substituted; R 3 represents : (1) A as defined above; (2) chloro or fluoro or hydrogen,- (3) a sulfenyl, sulfinyl or sulfonyl group -S(0) m A wherein A and m are as defined above; (4) hydroxy or an oxy group -0-A wherein A is as defined above; (5) formyl -C(0)H, carboxy -C0 2 H, or an acyl group -C(0)A or C(0)0A wherein A is as defined above,- (6) on oxymethyl group -CH 2 -OA wherein A is as defined above; (7) a thiomethyl group or a derivative thereof of formula -CH 2 S(0) m A wherein m and A are as defined above; (8) formyloxymethyl -CH 2 OC(0)H or an acyloxymethyl group - CH 2 OC(0)A or -CH 2 0-Z wherein A and Z are as defined above; (9) an acylthiomethyl group -CH 2 SC(0)A wherein A is as defined above; (10) an aminomethyl group -CH 2 -N(A)A ' wherein A is as defined above and A ' , being the same or different, is as defined above for A; or A and A ' taken together with the nitrogen atom to which they are attached represent a heterocyclic ring; (11) ammoniomethyl -CH 2 N + (A) (AJ A " wherein A and A ' are as defined above and A " , being the same or different, is as defined for A; or A is alkyl and A' and A" together with the nitrogen atom to which they are attached represent a heterocyclic ring, or A and A' and A" together with the nitrogen atom to which they are attached represent a heterocyclic ring; (12) formamidomethyl -CH 2 NHC(0)H or an acylaminomethyl group -CH 2 NH-C(0)A or -CH 2 NH-Z wherein A and Z are as defined above,- where appropriate R 3 is optionally substituted; and X represents 0, NR or S, wherein R is hydrogen or straight or branched C^-C^ alkyl, C 3 - C 8 cycloalkyl, C 6 -C 14 aryl or C 7 -C 22 aralkyl group; or an isomer thereof which is a stereoisomer, diastereoisomer, epimer, geometrical isomer or tautomer, or a mixture of any of these isomers. The Ci-C 12 alkyl group is a straight or branched alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl. The C 2 -C 12 alkenyl group is a straight or branched alkenyl group such as vinyl, allyl, crotyl, 2-methyl-1-propenyl, 1-methyl-1-propenyl, butenyl, pentenyl. The C 2 -C 12 alkynyl group is a straight or branched alkynyl group such as ethynyl, propargyl, l-propynyl, 1-butynyl, 2-butynyl. The C 6 -C 14 aryl group is a monocyclic, bicyclic or tricyclic aromatic hydrocarbon group of 6 to 14 carbon atoms, such as phenyl, naphthyl, phenanthryl or anthryl. The C 3 -C 8 cycloalkyl group is a saturated carbocyclic group of 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. The C 5 -C 8 cycloalkenyl group is an unsaturated carbocyclic group such as cyclopentenyl, cyclohexenyl. The C 7 -C 22 aralkyl group is an alkyl group of 1 to 4 carbon atoms linked to one , two or three monocyclic aromatic hydrocarbon groups of 6 carbon atoms or to a bicyclic aromatic hydrocarbon group of 10 carbon atoms. Examples of aralkyl groups are benzyl, phenylethyl, naphthylmethyl, benzhydryl or trityl. The C 8 -C 14 aralkenyl group is an alkenyl group of 2 to 4 carbon atoms linked to a monocyclic or bicyclic aromatic hydrocarbon group of 6 to 10 carbon atoms. Examples of aralkenyl groups are styryl, 2-phenyl-1-propenyl, 3-phenyl-2-butenyl, 2-naphthylethenyl. The C 8 -C 14 aralkynyl group is an alkynyl group of 2 to 4 carbon atoms linked to a monocyclic or bicyclic aromatic hydrocarbon group of 6 to 10 carbon atoms. Examples of aralkynyl groups are 2-phenylethynyl, 2-naphthylethynyl. The (cycloalkyl)alkyl group is an alkyl group of 1 to 4 carbon atoms linked to a cycloalkyl group. The (cycloalkyl)alkenyl group is an alkenyl group of 2 to 4 carbon atoms linked to a C 3 -C 8 cycloalkyl group as defined above. The heterocyclyl group is a 3- to 6-membered , saturated or unsaturated heterocyclyl ring, containing at least one heteroatom selected from 0, S and N, which is optionally fused to a second 5- or 6-membered , saturated or unsaturated heterocyclyl group or to a cycloalkyl group or to an aryl group. Examples of heterocyclyl groups are pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, thienyl, furyl, aziridinyl, oxiranyl, azetidinyl, pyridinyl, pyrazinyl, pyrimidinyl, pyranyl, pyridazinyl, benzothienyl, benzothiazolyl, benzoxazolyl, isobenzofuranyl, benzofuranyl, chromenyl, indolyl, indolizinyl, isoindolyl, cinnolinyl, indazolyl, purinyl. The (heterocyclyl)alkyl group is an alkyl group of 1 to 4 carbon atoms linked to a heterocyclyl group. The (heterocyclyl)alkenyl group is an alkenyl group of 2 to 4 carbon atoms linked to a heterocyclic group. The term halogen (or halo) preferably encompasses fluorine, chlorine, bromine or iodine. The above said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, aralkyl, aralkenyl, aralkynyl, (cycloalkyl)alkyl, (cycloalkyl)alkenyl, heterocyclyl, (heterocyclyl)alkyl, (heterocyclyl)alkenyl, oxirane and cyclopropyl groups can be either unsubstituted or substituted by one or more substituents selected from the following ones: halo (i.e., fluoro, bromo, chloro or iodo) ; hydroxy; nitro; - azido; mercapto (-SH) ; amino (i.e., -NH 2 , or -NHR' or -NR'R'') wherein R' and R' ' , which are the same or different, are C^C- ,; , straight or branched alkyl groups or phenyl or benzyl; - formyl (i.e., -CHO) ; cyano; carboxy(alkyl) (i.e., (CH 2 ) t C00H or (CH 2 ) t COOR') wherein R' is as defined above and t is 0, 1, 2 or 3; sulfo (i.e. , -S0 3 H) ; - acyl (i.e., -C(O)R') wherein R' is as defined above or trifluoroacetyl (i.e., -C(0)CF 3 ); carbamoyl (i.e., -C0NH 2 ) ; N-methylcarbamoyl (i.e., -C0NHCH 3 ) or N-carboxymethylcarbamoyl (i.e., -CONHCH 2 COOH) ; - carbamoyloxy (i.e., -0C0NH 2 ) ; acyloxy (i.e., -OC(O)R') wherein R' is as defined above or formyloxy (-OC(O)H); alkoxycarbonyl or benzyloxycarbonyl (i.e., -C(O)OR') wherein R' is as defined above,- - alkoxycarbonyloxy or benzyloxycarbonyloxy (i.e., -OC(O)OR') wherein R' is as defined above,- alkoxy, phenoxy or benzyloxy (i.e., -OR') wherein R' is as defined above; alkylthio, phenylthio or benzylthio (i.e., -SR' ) wherein R' is as defined above; alkylsulfinyl, phenylsulfinyl or benzylsulfinyl (i.e., -S(O)R') wherein R' is as defined above; alkylsulfonyl, phenylsulfonyl or benzylsulfonyl (i.e., -S(0) 2 R') wherein R' is as defined above; acylamino (i.e., -NHC(0)R''' or -NHC(O)OR' ' ' ) wherein R' ' ' is Ci-Cij straight or branched alkyl, phenyl, benzyl, CH 2 CH 2 COOH or CH 2 CH 2 CH 2 COOH; sulfonamido (i.e., -NHS0 2 R' ) wherein R' is as defined above; guanidino (i.e., -NHC(=NH)NH 2 ) ; C 1 -C 4 alkyl, C 2 -C 4 alkenyl or alkynyl; - C 3 -C 6 cycloalkyl; phenyl substituted methyl selected from chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, aminomethyl, N,N-dimethylaminomethyl, azidomethyl, cyanomethyl, carboxymethyl, sulfomethyl, carbamoylmethyl, carbamoyloxymethyl, hydroxymethyl, C 1 -C 4 alkoxycarbonylmethyl, guanidinomethyl. The carboxy, amino, hydroxy and mercapto groups may optionally be protected. The carboxyl-protecting group may, for example, be a lower alkyl group such as methyl, ethyl, propyl, isopropyl or tert-butyl; a halogenated lower alkyl group such as a 2,2,2-trichloroethyl or a 2,2,2-trifluoroethyl; a lower alkanoyloxyalkyl group such as acetoxymethyl, propionyloxymethyl, pivaloyloxymethyl, 1-acetoxyetyl, 1-propionyloxyethyl; a lower alkoxycarbonyloxyalkyl group such as 1- (methoxycarbonyloxy)ethyl, 1- (ethoxycarbonyloxy)ethyl, 1- (isopropoxycarbonyloxy)ethyl,• a lower alkenyl group such as 2-propenyl, 2-chloro-2-propenyl, 3-methoxycarbonyl-2-propenyl, 2-methyl-2-propenyl, 2-butenyl, cinnamyl; an aralkyl group such as benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, benzhydryl, bis(p-methoxyphenyl)methyl; a (5-substituted 2-oxo-l,3-dioxol-4-yl)methyl group such as (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl; a silyl group such as trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, triphenylsilyl; or an indanyl group; a phthalidyl group,- a pyranyl group; a methoxymethyl or methylthiomethyl group; a 2-methoxyethoxymethyl group. Particularly preferred are a tert-butyl group, a p-nitrobenzyl group, a p-methoxybenzyl group, a benzhydryl group, a tert-butyldimethylsilyl, tert-butyldiphenylsilyl group or a propenyl group. The amino, hydroxy or mercapto protecting groups possibly present may be those usually employed in the chemistry of penicillins and cephalosporins for this kind of functions. They may be, for instance, optionally substituted, especially halo-substituted, acyl groups, e.g. acetyl, monochloroacetyl, dichloroacetyl, trifluoroacetyl, benzoyl or p-bromophenacyl,- triarylmethylgroups, e.g. triphenylmethyl,- silyl groups, in particular trimethylsilyl, dimethyl-tert-butylsilyl, diphenyl-tert-butylsilyl, ; or also groups such as tert-butoxycarbonyl, p-nitrobenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, benzyl and pyranyl. Preferred protecting groups of the hydroxy function are p-nitrobenzyloxycarbonyl; allyloxycarbonyl; dimethyl-tert-butylsilyl; diphenyl-tert-butylsilyl; trimethylsilyl,- 2,2,2-trichloroethoxycarbonyl,- benzyl; dimethoxybenzyl,- p-methoxybenzyloxycarbonyl; p-bromophenacyl; triphenylmethyl, pyranyl, methoxymethyl, benzhydryl, 2-methoxyethoxymethyl, formyl, acetyl, trichloroacetyl. The present invention provides the salts of those compounds of formula (la) or (lb) that have salt-forming groups, especially the salts of the compounds having a carboxylic group, a basic group (e.g. an amino or guanidino group) , or a quaternary ammonium group. The salts are especially physiologically tolerable salts, for example alkali metal and alkaline earth metal salts (e.g. sodium, potassium, lithium, calcium and magnesium salts) , ammonium salts and salts with an appropriate organic amine or amino acid (e.g. arginine, procaine salts), and the addition salts formed with suitable organic or inorganic acids, for example hydrochloric acid, sulfuric acid, carboxylic and sulfonic organic acids (e.g. acetic, trifluoroacetic, p- toluenesulfonic acid) . Some compounds of formula (I) which contain a carboxylate and an ammonium group may exist as zwitterions; such salts are also part of the present invention. The present invention encompasses all the possible stereoisomers as well as their racemic or optically active mixtures. Furthermore, physiologically hydrolyzable ester, hydrates and solvates of compounds of formula (la) or (lb) are included within the scope of the present invention. The physiologically hydrolyzable esters of the compounds (la) or (lb) may include, for example, methoxycarbonyl ethyl, 1-methoxycarbonyloxy-1-ethyl, indanyl, phtalidyl, methoxymethyl, pivaloyloxymethyl, glycyloxymethyl, phenylglycyloxymethyl or 5-methyl-2-oxo- 1,3-dioxolan-4-yl esters, and other physiologically hydrolyzable esters which have been widely used in the technical fields of penicillin and cephalosporin antibiotics: more preferably, methoxycarbonyloxymethyl, 1- methoxycarbonyloxy-1-ethyl, methoxymethyl or pivaloyloxymethyl; and most preferably, methoxycarbonyloxymethyl or methoxymethyl. Typical solvates of the cephalosporin compounds of formula (I) may include solvates with water miscible solvents, e.g. methanol, ethanol, acetone or acetonitrile or acetonitrile; and more preferably, ethanol. The compounds of formula (la) or (lb) are particularly preferred when A is selected from C^C- . ;, straight or branched alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 6 -C 10 aryl, C 7 -C 13 aralkyl, C 7 -C 13 alkaryl, C 3 -C 8 cycloalkyl and heterocycyl, and is optionally substituted by one or more of halo, sulfo, carboxy, ^C- alkylcarbonyloxy, C_-C 5 alkoxy, C_-C 3 alkoxycarbonyl, carbamoyl, sulfamoyl, C_- C 5 carbamoyl oxy, haloalkyl carboxamido, nitro, cyano, diazo, hydroxy, benzhydryloxy, amino, C 6 -C 10 arylcarbonyl, C 6 -C 10 aryloxy, C 7 -C 13 aralkyloxy, C 7 -C 13 alkaryloxy, C^G- alkanoyl, Q-C 3 alkanoyloxy, alkylsulfonyl, C 6 -C 10 aryl carbonyl oxy, C e - C 10 aryl carboxy, C 7 -C 13 aralkanoyloxy, C 7 -C 13 alkaryl carboxy, C 7 -C 13 aralkyl carboxy, C 7 -C 13 alkaryl carbonyl oxy, C 7 -C 13 aralkyl carbonyl oxy, G-Cg halocarbamoyl C^C- alkyl carboxy, Ci-Cg alkanoyl amido,- Q and , each independently, are (1') chloro, fluoro or bromo; (2') straight or branched G-Cg alkyl or d-Cg alkenyl; (3') Ci-Cj alkyloxy, C- . -C S alkenyloxy, C 6 -C 10 aryloxy, C 7 -C 10 aralkyloxy, heterocyclyl oxy; (4') Ci-C 3 alkylthio, C 2 -C 5 alkenylthio, C ε -C 10 arylthio, C 7 - C 10 aralkyl thio, heterocyclyl thio; (5') Ci-C j alkylsulf inyl, C 2 -C 3 alkenylsulf inyl, C 6 -C 10 arylsulf inyl, C 7 -C 10 aralkylsulf inyl, heterocyclylsulf inyl; (6') Ci-Cg alkylsulfonyl, C 2 -C 5 alkenylsulf onyl, C 6 -C 10 arylsulf onyl, C 7 -C 10 aralkylsulf onyl, heterocyclylsulf onyl, • (7') phenylselenyl, phenylseleninyl, phenylselenonyl; (8') Ci-Cj alkylcarbonyl, C 2 -C 5 alkenylcarbonyl, C 6 -C 10 arylcarbonyl, C 7 -C 10 aralkylcarbonyl, heterocyclylcarbonyl; (9') Ci-Cj alkylcarbonyloxy, C 2 -C 3 alkenylcarbonyloxy, C 6 -C 10 arylcarbonyloxy, C 7 -C 10 aralkylcarbonyloxy, heterocyclylcarbonyloxy,- (10') Ci-Cg alkylsulfonyloxy, C 2 -C 5 alkenylsulfonyloxy, C 6 - C 10 arylsulfonyloxy, C 7 -C 10 aralkylsulfonyloxy, heterocyclylsulfonyloxy; (11') Ci-Cg alkylcarboxamido, C 2 -C 5 alkenylcarboxamido, C 6 - C 10 arylcarboxamido, C 7 -C 10 aralkylcarboxamido, heterocyclylcarboxamido,- (12') nitro, azido, cyano, formyloxy, formamido; or Q and taken together constitute an oxo group, or a methylene group, or an optionally substituted cyclopropyl or oxirane group, or a group of formula =CHY or =CHC(0)Y or =CHC(0)OY or =CHS(0) 2 Y, wherein Y is C^C- alkyl, d-C*. alkenyl, C β -C 10 aryl, C 7 -C 10 aralkyl or heterocyclyl; and, where appropriate, are optionally substituted by one or more substituents for the groups defined under (1')- (11') being selected from halo, sulfo, carboxy, d-C 5 alkylcarbonyloxy, Ci-Cg alkoxy, d-G alkoxycarbonyl, d-C 3 carbamoyl, sulfamoyl, d-C E carbamoyloxy, d-C 5 alkyl carboxamido, Ci-Cg haloalkylcarboxamido, nitro, cyano, diazo, hydroxy, benzhydryloxy, amino, C 6 -C 10 arylcarbonyl, C 6 -C 10 aryloxy, C 7 -C ι3 aralkyloxy, C 7 -C 13 alkaroloxy, Ci-C 5 alkanoyl, -G alkanoyloxy, Ci-C 5 alkylsulfonyl, C 6 -C 10 aryl carbonyl oxy, C 6 -G 0 arylcarboxy, C 7 -C 13 alkaryl carboxy, C 7 -C 13 aralkyl carbonyl oxy, C 7 -C 13 aralkyl carboxy, C 7 -C 13 alkaryl carbonyloxy, C 7 -C 13 aralkanoyloxy, Ci-C 5 halocarbamoyl , G-G alkylcarboxy, C ι -C E alkanoyl ami do, C 7 - C 13 alkaryl carbonyl, C 7 -C 13 aralkyl carbonyl, d-C 5 alkyl thio, C 6 -C 10 arylthio, Ci-Cg alkylsulfonyl, C 6 -C 10 arylsulf onyl , sulfo Ci-Cg alkyl, carboxy C ι -C 5 alkyl thio, G-C 5 alkylcarbonyloxy Ci-C 3 alkylthio, C 2 -C 10 secondary amino, C 3 - Ci 5 tertiary amino, di-C ι -C 5 alkylamino, di-Ci-C 3 -alkylamino Ci-Cg alkyl, oxo, halo d-G alkanoyl, straight or branched Ci-Cg alkyl and straight or branched C 2 -C 3 alkenyl; Ri is either hydrogen or halogen, or an optionally substituted straight or branched C 2 -C 3 alkyl or G-G alkenyl, or an optionally substituted C,-G 0 aralkyl or (heterocyclyl) alkyl; optional substituents being selected from nitro, cyano, carbamoyl, hydroxy, carboxy, amino, methoxycarbonyl , benzhydryl oxycarbonyl , tert-butoxycarbonyl , acetyl , acetoxy, formamido, methoxy, sulfonyl, methylthio, phenoxy, halogen ,- R 2 is either (1' ) hydrogen,- (2') halogen (3') an optionally substituted straight or branched - alkyl, Ci-Cg alkenyl or C 7 -C 10 aralkyl; (4') optionally substituted C 3 -C 10 arylthio, or heterocyclylthio; (5') a group OC(0)R 4 wherein R 4 is hydrogen, or an optionally substituted G-C 3 straight or branched alkyl or alkenyl or an optionally substituted C 3 -C 6 cycloalkyl, C 6 -G 4 aryl C 7 -C 14 aralkyl, heterocyclyl; the optional substituents being selected from halo, sulfo, carboxy, G-C 5 alkylcarbonyloxy, C ι -C 3 alkoxy, G-C 5 alkoxycarbonyl, C ι -C E carbamoyl, sulfamoyl, G-C 5 carbamoyloxy, Ci-C 5 alkylcarboxamide, G-C 5 haloalkylcarboxamido, nitro, cyano, diazo, hydroxy, benzhydryloxy, amino, C 6 -G 0 arylcarbonyl, C 6 -C ι0 aryloxy, C 7 -C 13 aralkyloxy, C 7 -C ι3 alkaryloxy, C ι -C B alkanoyl, Ci-C 5 alkanoyloxy, C ι -C 5 alkylsulfonyl, C 6 -C 10 arylcarbonyloxy, C 6 - C 10 arylcarboxy, C 7 -C 13 alkarylcarboxy, C 7 -C 13 aralkylcarbonyloxy, C 7 -C 13 aralkylcarboxy, C 7 -C 13 alkarylcarbonyloxy, C 7 -C ι3 aralkanoyloxy, Ci-C 5 halocarbanoyl, -G alkylcarboxy, C ι -C 3 alkanoylamido, C 7 - C ι3 alkarylcarbonyl, C 7 -C 13 aralkylcarbonyl, C ι -C 5 alkylthio, C 6 -C 10 arylthio, C ι -C 3 alkylsulfonyl, C 6 -C 10 arylsulfonyl, sulfo G-G alkyl, carboxy C ι -C B alkylthio, C 2 -G 0 secondary amino, C 3 -C 1S tertiary amino, di-G-C 3 -alkylamino, di-C ι -C 5 - alkyla ino-Ci-Cg alkyl, oxo, -G haloalkanoyl, straight or branched G-C 3 alkyl and straight or branched C 2 -C 5 alkenyl; R 3 is either hydrogen or (1') methyl, chloromethyl, bromomethyl, benzyl, ethyl, propyl, phenyl (2') chloro (3') methoxy or benzyloxy (4') methyl hio (5') formyl, acetyl, benzoyl, carboxy, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl or benzy1oxycarbonyl,- (6') methoxymethyl, ethoxymethyl, isopropoxymethyl; or benzyloxymethyl, phenoxymethyl, 3-pyridyloxymethyl wherein the phenyl and pyridyl rings are either unsubstituted or substituted by one group or two equal or different groups chosen from hydroxy, carboxy, amino, halogen and G-C 4 alkoxycarbonyl • (7') a heterocyclylthiomethyl group wherein the heterocyclyl ring either unsubstituted or substituted by one group or two equal or different groups chosen from the following: hydroxy, carboxy, amino, sulfo, dimethylaminomethyl, carboxymethyl, carboxymethylthio, cyano, cyanomethyl, nitro, methoxy, methylthio, acetoxy, halogen or d-C 4 alkyl or alkenyl; (8') acetoxymethyl, benzoyloxymethyl, phenylacetoxymethyl or C 3 -C 6 alkanoyloxymethyl wherein the above groups are either unsubstituted or substituted by one or more groups selected from carboxy, hydroxy, G-C 3 alkoxy; (9') trialkylammoniomethyl wherein the alkyl group is chosen from methyl, ethyl or propyl,- N- methylpyrrolidiniomethyl, N-methylpiperidimiomethyl, N- methylmorpholiniomethyl; (10') pyridiniomethyl which is either unsubstituted or substituted on the heterocyclic ring by fluoro, clhoro, methoxy, hydroxy, carboxy or carbamoyl; (11') carbamoyloxymethyl; (12' ) carboxy; and X represents 0, S or NR, wherein R is as defined above. A further preferred class of compounds of formula (la) and (lb) is when A is a group selected from methyl, tert- butyl, 2-phenyl-2-propyl, benzyl and diphenylmethyl, which groups are optionally substituted by one or more substituents selected from carboxy, carbamoyl, methanesulfonyl, methoxy, ethoxy, tert-butoxy, benzyloxy, acetoxy, pivaloyoxy, benzoxy, carboxymethyl, -C 6 H 4 -COOH, GHgCOO-, -CH 2 -C 6 H 4 -COOH, CH 3 -C 6 H 4 -COO-, C 6 H 5 -CH 2 - COO-, -C 6 H 4 -CH 2 C00H, benzoyl, pivaloyl, formamido, acetamido, trifluoroacetamido and pivalamido; Q and , which are as defined above, are independently each optionally substituted, where appropriate, by one or more substituents selected from fluoro, chloro, bromo, carboxy, tetrazolyl, carbamoyl, methanesulfonyl, benzyloxy, benzoxy, acetoxy, pivaloyloxy, methylthio, phenylthio, benzenesulfonyl, sulfomethyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxymethylthio, -C 6 H 4 -COOH, C 6 H s COO-, -CH 2 - C 6 H 4 -C00H, CH 3 -C 6 H 4 -COO-, C 6 H B -CH 2 -COO-, -C 6 H 4 CH 2 COOH, acetyl, trifluoroacetyl, benzoyl, pivaloyl, dimethylamino, diethylamino, dimethylaminoethyl, formamido, acetamido, trifluoroacetamido, pivalamido, vinyl and allyl; and R 2 , which is as defined above, is optionally substituted where appropriate by one or more substituents selected from fluoro, chloro, bromo, carboxy, tetrazolyl, carbamoyl, methanesulfonyl, benzyloxy, benzoxy, acetoxy, pivaloyloxy, methylthio, phenylthio, benzenesulfonyl, sulfomethyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxymethylthio, -C 3 H 4 -COOH, C 6 H 5 COO-, -CH 2 -C 6 H 4 -COOH, CH 3 - C 6 H 4 -COO-, -OCOCH 2 C ε H 5 , HOCOCH 2 C 6 H 4 ., acetyl, trifluoroacetyl, benzoyl, pivaloyl, dimethylamino, diethylamino, dimethylaminoethyl, formamido, acetamido, trifluoroacetamido, pivalamido, vinyl and allyl. Compounds of formula (la) and (lb) and their pharmaceutically and veterinarily acceptable salts are particularly preferred when they are of formula (lc) and (Id) respectively: Specific examples of the preferred compounds of the present invention are those listed in Tables l - 6. Table 1 # Q W Ri R 2 R 3 1 H H CH- 3 8 12 13 14 15 2268 16 Table 1 continued 41 H 42 OCOPh CH. 43 Table 3. # *1 R< *3 46 H N-N 7 CH 3 N-N CH 3 8 CH 2 -S'^ N ^ CH 9 H 2 H 3 OCOPh CH. 4 H CH 2 OCOPh - 19 Table 4. u CH- N-N CH 3 N-N 59 CH -S N ' CH 5 60 H 63 H 64 OCOPh CH 65 H OAOCOPh Table 5. 66 t-Bu N-N H CH 3 S-^ S ^CH 3 N-N 67 CH 2 -S CH 68 H CH, 1 H 4 H 5 OCOPh CH. 6 H CH.OCOPh Table 6. # Q W R< R 2 OCH H H O s NH 80 81 82 83 84 85 CH 2 CH 2 CH CH 2 CH 2 CH 86 Ph CH 2 CH 2 CH 3 OCH 3 87 88 89 90 91 CHoCHoCH-i. CHoCH 2C^ H Strategies for the preparation of compounds of formula (I) can vary depending on the nature of the substituents of the cephem nucleus. For example cephem-4-carboxylic acids which bear the suitable substituents at C-7 can be synthesized according to or by analogy with known procedures and then converted to the desired cephem-4- ketones. The conversion cephem-4-carboxylic acid/cephem-4- ketone can be carried out for example as described in EP- A-0337704 (18.10.89) and may precede or follow the oxidation of the thiazolidine sulfur to sulfone. Alternatively the proper C-7 substituents can be introduced by modifying cephem derivatives already bearing the ketone group at C-4 and prepared according to literature methods. For example compounds of formula (I) wherein and W constitute a methylene or substituted methylene group can be prepared by reaction of 7-oxocephems with the suitable Grignard or ittig-Horner reagent (see e.g.: Heterocycles 24 (1986) 289) . A particularly preferred process for the preparation of compounds of formula (la) and (lb) comprises: (i) reacting a compound of formula (II) wherein A, R 1 , R 2 and R 3 are as defined above with either (i a ) a reagent of formula (III) Q-W (III) wherein Q and W, being the same or different, are as defined above,- or (i b ) reagents of formulae (IV) and (V) Q-H (IV) W-L (V) wherein Q and W are as defined above and L is a leaving group (ii) if needed, subjecting a compound of formula (la) , wherein A, Q, , R 1# R 2 and R 3 are as defined above, to known processes and/or conventional reactions which entail the transformation of any of the groups A, Q, , R l f R 2 and R 3 of a compound of formula (la) to afford a different compound of formula (la) wherein A, Q, W, R lf R 2 and R 3 are as defined above or a compound of the formula (Ib) ■ (iii) if desired, converting the resulting compound of formula (la) or (Ib) into a pharmaceutical or veterinarily acceptable salt thereof. The reaction of a diazocephe of formula (II) [step (i a )] with a compound of formula (III) is usually performed in an aprotic solvent such as dichloromethane, chloroform, benzene, toluene, xylenes, cyclohexane, n-hexane, diethyl ether, ethyl acetate, dioxane, acetonitrile, tetrahydrofurane, dimethoxyethane and so on. Reaction temperatures range between -50° and 140 °C, preferably between -20 °C and +110 °C. The presence of a catalyst can sometimes have a beneficial effect enhancing the reativity of diazo-derivatives. Said catalyst can be either an acid, preferably a Lewis acid such as boron trifluoride, aluminum trichloride, tin tetrachloride and the like, or a metal reagent such as rhodium acetate. In some instances the reaction between diazo-derivatives of formula (II) and reagents of formula (III) can be advantageously performed under photochemical conditions (i.e. irradiation with UV light) . In step (ib) the leaving group L is typically a halogen, preferably bromine, chlorine or iodine, or an imido group, preferably succinimido or phthalimido. The reagent W-L (V) is usually used in stoichiometric amount or a slight excess thereof, while the reagent Q-H (IV) can sometimes be used in large molar excess. Suitable solvents for the reaction (i b ) are the same as those of the reaction (i a ) and reaction temperatures usually range between -30 °C and +110 °C. As above mentioned, it is understood that compounds of formula (Ia) and (Ib) can be prepared from compounds of formula (Ia) by way of known chemical reactions or in analogy with known processes, i.e. the groups A, Q, W, R 1( R 2 and R 3 can be converted by conventional methods into different groups included within those previously defined, if desired, at the end or at any stage of the process above. For example, a compound of the formula (Ia) , wherein R 3 is a substituted methyl group, may be converted into a compound of the formula (Ib) as described in PCT/EP94/01643. For example compounds of formula (Ia) or (Ib) wherein Q and/or W are bromine can be transformed into compounds of formula (Ia) or (Ib) wherein Q and/or are alkenyl groups by reaction with the suitable alkenylstannane reagent under radical conditions according to a procedure already applied to penicillins (Tetrahedron, 45 (1989) , 941) . In some instances a bromine atom at C-7 (e.g. compounds of formula (Ia) or (Ib) wherein Q is bromine and is alkoxy) can be displaced by suitable nucleophiles (e.g.: thiolates, carboxylates... ) providing different compounds of formula (I) . Modifications of the R 1# R 2 and R 3 groups of compounds of formula (Ia) can be performed for example as described in EP-A-0337704 (18.10.89), O-A-91/09036 (27.06.91), European Patent Application No. 9304440 (04.03.93), British Patent Application No. 93103904 (25.06.92) . Compounds of formula (II) can be prepared by a process which comprises: (i) converting the carboxy group -C0 2 H at the 4- position of a compound of formula (VI) wherein R 1 , R 2 and R 3 are as defined above, and R 5 is an amino protecting group, into a carbonyl group -C(0)-A wherein A is as defined above, and oxidizing the sulfur atom at the 1-position to give a compound of formula (VII wherein A, R 1 , R 2 , R 3 and R 5 are as defined above; and (ii) if needed, subjecting a compound of formula (VII) wherein A, R 1 , R 2 , R 3 and R 5 are as defined above, to known reactions which entail the conversion of any of the groups A, R 1 , R 2 , R 3 and R 5 of a compound of formula (VII) to afford a different compound of formula (VII) wherein A, R 1 , R 2 , R 3 and R 5 are as defined above; and (iii) converting the resulting compounds of formula (VII) into diazo-cephems of formula (II) wherein A, R 1 , R 2 , and R 3 are as defined above. In the conversion step referred to under (i) , the carboxylic moiety is typically activated as the halide, anhydride, mixed anhydride, thioester or ester thereof, and then reacted with a synthetic equivalent of AJ wherein A is as defined above. Suitable synthetic equivalents of A " include the following organometallic derivatives of A: A-MgX (Grignard reagents) ,• A-Li(organolitium reagents e.g.phenyl1ithium) ; A 2 CuLi(lithium dialkylcopper reagents); A(PhS)CuLi (lithium phenylsulphenyl (alkyl) copper reagents) ; A 2 CuMgX (magnesium diorganocopper reagents) ACu(CN)ZnX (copper-zinc reagents) A-Cu (cuprous reagents; e.g. cuprous acetylides) ; A 2 Cd (organocadmium reagents) ; AZnX (organozinc reagents) ,- AMnX (organomanganese reagents) ,- A 3 T1 (organothallium reagents) ; and A n SnX^. n , (organotin reagents, wherein X is C 1 -C 12 alkyl, chloro, phenyl, and n may be 0,1,2,3) . Sometimes these reagents are conveniently prepared in situ starting from suitable precursors and according to customary methods. The conditions of the above-stated reactions are described or referred to in major textbooks (see among others, J. March, "Advanced Organic Chemistry", McGraw-Hill) and can vary widely according to the individual substrate and group A. Typical reaction solvents are non-protic solvents such as tetrahydrofuran, diethyl ether, dichloromethane, benzene, toluene, hexamethylphosphoramide, dimethoxyethane, dioxane, dichloroethane, xylene, chloroform, n-hexane or mixtures thereof. Suitable reaction temperatures can vary from -100 °C to +120 °C, preferably between -80 °C and +60 °C. The addition of inorganic or organometal derivatives (e.g. copper salts such as cuprous iodide, iron derivatives such as tris[acetylacetonato]iron(III) , palladium derivatives such as bis [triphenylphosphine]benzyl- palladium chloride, aluminum derivatives such as aluminum trichloride, titanium derivatives such as titanium tetrachloride and so on) , in amount ranging from catalytic to equimolecular, has sometimes led to milder reaction conditions, decreased formation of by-products, improved yields and easier work-ups. In the oxidation step referred to under (i) the compounds are oxidized to the corresponding sulphones. Preferred oxidizing agents are inorganic or organic peracids or salts thereof in an inert organic solvent or in a mixture of water and an organic solvent. Suitable peracids are, for example, peracetic acid, m- chloroperoxybenzoic acid (MCPBA) , monoperphthalic acid, alkaline monoperoxysulfate, tetrabutylammoniu peroxydisulfate; suitable solvents are chloroform, dichloromethane, tetrahydrofuran (THF) , acetonitrile, ethanol, acetic acid, ethyl acetate or mixtures thereof. The oxidation is usually carried out at a temperature of from -20 °C to +80 °C. As above referred to under (ii) , it is understood that the groups A, R 1 , R 2 , R 3 and R 5 of compounds of formula (VII) can be converted by conventional methods into different groups A, R 1 , R 2 , R 3 and R 5 included within those previously defined. These conversions are well known on cephems of formula (VII) or analogues thereof. The conversion of compounds of formula (VII) to compound of formula (II) referred to under (iii) is generally realized either by nitrosation followed by rearrangement of the intermediate N-nitroso derivatives or by prior removal of the R 5 group and diazotization of the intermediate 7-amino derivatives. Typical nitrosating agents are nitrosyl chloride, dinitrogen tetroxide, dinitrogen trioxide. Suitable solvents are protic or aprotic organic solvents such as chloroform, dichlorometane, tetrahydrofuran, ethyl acetate, acetic acid, acetic anhydide, acetonitrile or mixtures thereof. The rearrangement of N-nitroso derivatives generally takes place in aprotic solvents under thermal conditions or under acid- or base-catalyzed conditions. Removal of the R 5 group (i.e. unmasking the amino function) from compounds of formula (VII) is carried out under conditions dependent on the nature of the amino protecting group R 5 . Typical R 5 groups are groups which withstand the tranformations referred to under (ii) annd (iii) and still can be removed under selective and mild conditions. Typical R 5 groups are acid sensitive groups such as tert-butoxycarbonyl, p-methoxybenzyloxycarbonyl, trityl, 1-adamantyloxycarbonyl and so on (which can be removed under mild conditions in the presence of organic or inorganic acids e.g. formic acid, trifluoroacetic acid, p- toluensulfonic acid, methansulfonic acid, aluminum trichloride, boron trifluoride...) or groups that can be removed under neutral conditions such as p- nitrobenzylox carbonyl, benzyloxycarbonyl (removable by hydrogenolysis) ; allyloxycarbonyl (removable in the presence of palladium catalysts or equivalent catalysts) . The diazotation reaction can usually be carried out either in an aprotic organic solvent (e.g. ethyl acetate, dichloromethane, chloroform, tetrahydrofuran, acetonitrile...) in the presence of organic nitrites (e.g. alkyl nitrites such as butyl nitrite, tert-butylnitrite, amyl nitrite, propyl nitrite and so on) with or without an acid catalyst (e.g.formic acid, trifluoroacetic acid, p- toluensulfonic acid, acetic acid, methanesulfonic acid) or in a biphasic system in the presence of nitrous acid (usually in situ generated by interaction of an inorganic nitrite (e.g. alkaline metal, alkaline-earth metal or ammonium nitite) and an organic or inorganic acid (e.g. p- toluenesulfonic acid, methanesulfonic acid, sulfuric acid, perchloric acid, hydrochloric acid and the like) . Compounds of formulae (III) , (IV) and (V) are known compounds or can be prepared from known compounds by known processes. The potentialities of protease inhibitor therapy in the treatment of conditions resulting from the destruction of connective tissues have recently received particular attention. Much effort has been devoted to the search for inhibitors of human leukocyte elastase (HLE) , which is the primary destructive agent in pulmonary emphysema and is probably involved in rheumatoid arthritis (J.C. Power, Am. Rev. Resp. Diseases 127, S54-S58, 1983; CH. Hassal et al, FEBS Letters, 183, n. 2, 201, 1985, G. Weinbaum and V.V. Damiano, TIPS, 8, 6, 1987; M. Velvart, Rheumatol. Int. 1, 121, 1981) . Low molecular weight inhibitors appear to have a number of advantages over natural high molecular weight protease inhibitors from either plant or animal sources: 1) they can be obtained in quantities; 2) they can be rationally designed or optimised; 3) they are not antigenic,- and 4) they may be used orally or in aerosols. Many low molecular weight elastase inhibitors discovered so far contain reactive functional groups (chloromethyl ketones, isocyanates, etc) ,- they may react with functional groups of proteins, and therefore they may be quite toxic. In this respect, jβ-lactam compounds are of potential interest because, though reactive towards serine protease, they are, as it is known, non-toxic at very high concentrations. The compounds of the present invention are characterized by high inhibitory activity on elastases, especially human leukocyte elastase (HLE) and in particular can possess improved chemical and/or biological stability, making them suitable for systemic (i.v. or oral) administration. When tested as inhibitors of human leukocyte elastase (HLE) , representative compounds of formula (I) showed good "potency" (low value of apparent dissociation constant of the HLE-inhibitor complex at steady state, K x ss ) and "efficiency" (high value of rate of formation of the HLE- inhibitor complex, k 5 /K : -> ES -> E + P + E + wherein E = enzyme (HLE ) S = substrate (see Protocol) P = product (see Protocol) I = inhibitor El = Michaelis complex EI*= covalent complex (inactivated enzyme) I*= inactivated inhibitor Protocol Kinetic parameters of HLE (Calbiochem) were determined at 37° C, 0.027M pH 7.4 phosphate buffer, 1% DMSO, 1% MeCN, NaCl (1=0.15), by monitoring the release of 7-amino- 4-methylcoumarin (fluorescence detection) from N- methoxysuccinyl-alanyl-prolyl-valyl-7-amido-4- methylcoumarin as the substrate, according to the equations : V -V 9 [P] = s t+—^μ- (l-e* fc ) , = , . [J] /K x κ~κ& +Ks 1+ [S] /K m + [I] /K x wherein [P] , [ I] , [S] =product , inhibitor , and substrate concentration V s =steady state rate V z =zero time rate V 0 =rate at [I] =0 K m =Michaelis constant for the enzyme substrate pair (independently determined under the same experimental conditions) . Full details of the Experimental Protocol are reported in M. Alpegiani et al. , Eur. J. Med. Chem. 1992, 27, 875- 890. For example, the compounds prepared respectively in examples 5 and 8 have a K on of 3000 and 3400 M "1 sec "1 , K_ BS 0.1 and 6μM. Moreover the compound of example 8 showed a chemical stability, expressed as half-life in aqueous buffer at 37°C, of 410 hours at pH 7.4 and of 3000 hours at pH 1.2. Owing to their high elastase-inhibiting activity and their quite negligible toxicity, (the orientative acute toxicity by i.v., oral or aerosol route is almost always greater than 500 mg/kg in rat) the compounds of the present invention can be used in the treatment of inflammatory and degenerative diseases caused by proteolytic enzymes in mammals including humans. The compounds can be used to make medicaments useful to prevent or arrest the progression of diseases caused by proteolytic degradation of lungs and connective tissues, reduce inflammation and fever, and relieve pain. Such diseases are emphysema, acute respiratory distress syndrome, bronchial inflammation, rheumatoid arthritis, osteoarthritis, infectious arthritis, rheumatic fever, spondylitis, gout, lupus, psoriasis, or in the control of tumour invasion and the like. Accordingly, the present invention also provides pharmaceutical and veterinary compositions containing a suitable carrier and/or diluent and, as an active principle, a 4-alk(en)ylcephem sulfone of formula (I) or a pharmaceutically or veterinarily acceptable salt thereof. The pharmaceutical or veterinary compositions containing a compound of formula I or salt thereof may be prepared in a conventional way by employing conventional non-toxic pharmaceutical carriers or diluents in a variety of dosage forms and ways of administration. In particular, the compounds of formula I can be administered: A) Orally, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Compositions intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preserving agents in order to provide pharmaceutically elegant and palatable preparations. Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets. These excipients may be for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, maize starch, or alginic acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by known techniques to delay disintegration and adsorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed. Formulation for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example, peanut oil, liquid paraffin, or olive oil. Aqueous suspensions contain the active materials in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents, for example, sodium carboxymethylcellulose, methylcellulose, hydroxy propylmethylcellulose, sodium alginate, polyvinylpyrrolidone gum tragacanth and gum acacia,- dispersing or wetting agents may be naturally-occurring phosphatides, for example lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyoxyethylene sorbitan monooleate. The said aqueous suspensions may also contain one or more preservatives, for example, ethyl or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, or one or more sweetening agents, such as sucrose or saccharin. Oily suspension may be formulated by suspending the active ingredient in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. The oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents, such as those set forth above, and flavouring agents may be added to provide a palatable oral preparation. These compositions may be preserved by the addition of an antioxidant such as ascorbic acid. Dispersible powders and granules suitable for peparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, a suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above. Additional excipients, for example sweetening, flavoring and coloring agents, may also be present. The pharmaceutical compositions of the invention may also be in the form of oil-in-water emulsions. The oily phase may be a vegetable oil, for example olive oil or arachis oils, or a mineral oil, for example liquid paraffin or mixtures of these. Suitable emulsifying agents may be naturally-occurring gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol anhydrides, for example sorbitan mono-oleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsion may also contain sweetening and flavoring agents. Syrups and elixirs may be formulated with sweetening agents, for example glycerol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative and flavoring and coloring agents. B) Parenterally, either subcutaneously, or intravenously, or intramuscularly, or intrasternally, or by infusion techniques, in the form of sterile injectable aqueous or olagenous suspensions. The pharmaceutical compositions may be in the form of a sterile injectable aqueous or olagenous suspension. This suspension may be formulated according to the known art using those suitable dispersing of wetting agents and suspending agents which have been mentioned above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example as a solution in 1,3-butane diol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or diglycerides. In addition fatty acids such as oleic acid find use in the preparation of injectables,- C) By inhalation, in the form of aerosols or solutions for nebulizers; D) Rectally, in the form of suppositories prepared by mixing the drug with a suitable non-irratating excipient which is solid at ordinary temperature but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Such materials are cocoa butter and poly-ethylene glycols; E) Topically, in the form of creams ointments, jellies, solutions or suspensions. Still a further object of the present invention is to provide a method fo controlling inflammatory and degenerative diseases by administering a therapeutically effective amount of one or more of the active compounds encompassed by the formula I in humans or mammalians in need of such treatment. Daily dose are in the range of about 0.1 to about 50 mg per kg of body weight, according to the activity of the specific compound, the age, weight and conditions of the subject to be treated, the type and severity of the disease, and the frequency and route of administration; preferably, daily dosage levels for humans are in the range of 20 mg to 2 g. The amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. For example, a formulation intended for the oral administration to humans, may contain from 5 mg to 2 g of active agent compounded with an appropriate and convenient amount of carrier material which may vary from about 5 to about 95 percent of the total composition. Dosage unit forms will generally contain between from about 5 mg to about 500 mg of active ingredien . Compounds of formula (VI) are known compounds or can be prepared from known compounds by known methods. The following preparations and examples illustrate but do not limit the invention. PREPARATION 1 7β - tert - Butoxycarbonylamino - 3 - desacetoxy cephalosporanic acid Trietylamine (56 ml) was added dropwise to a mixture of 7?-amino-3-deacetoxy cephalosporanic acid (42.8 g) in dioxane (800 ml) and water (400 ml) . tert - Butylpercarbonate (66 g) was then added and the resulting mixture was vigorously stirred at room temperature for 6 hours, thence poured into water/diethyl ether (ratio 3:1; 800 ml) . The aqueous phase was acidified with 8% hydrochloric acid (300 ml) and extracted twice with ethyl acetate. Following drying over Na 2 S0 4 and evaporation of the solvent, a foamy solid was obtained which upon treatment with petroleum ether turned into a white powder (53 g) . IR (KBr) v max 3600-2500, 1780, 1710 cmA NMR (200 MHz, DMSO-d 6 ) δ 2.00 (3H, s) , 3.33 (IH, d, J= 17.8 Hz), 3.49 (IH, d, J= 17.8 Hz), 4.98 (IH, d, J= 4.6 Hz), 5.34 (IH, dd, J= 4.6 and 8.9 Hz), 7.95 (IH, d, J= 8.9 Hz, exch. D 2 0) . PREPARATION 2 73-tert-Butoxycarbonylamino-4-tert-butylcarbonyl-3-methyl- 3-cephem 1.1-dioxide Step A. 7β-tert-Butoxycarbonylamino-3-desacetoxy cephalosporanyl chloride A solution of 7/3-tert-butylamino-3-desacetoxy cephalosporanic acid (40.8 g) in dry tetrahydrofuran (400 ml) was cooled to 0°C. Under nitrogen, oxalyl chloride (16.8 ml) was added, soon followed by 0.7 ml of N,N- dimethylformamide. The resulting solution was stirred for 2 hours at 0-5°C, then it was rotoevaporated to dryness. Dry toluene (60 ml) was added and the mixture was evaporated again to dryness, giving a brownish solid (42.34 g) , used as such in the following step. Step B. 7θ-tert-Butoxycarbonyl amino-4- ert-butyl carbonyl- 3-methyl-3-cephem To a solution of copper (I) iodide (31.5 g) and lithium chloride (140.2 g) in dry THF (200 ml) cooled to - 70°C and, under nitrogen atmosphere, a IM solution of tert- butyl magnesium chloride (165 ml) was added dropwise . To this mixture, a solution of crude 7β- tert- butoxycarbonylamino-3-deacetoxy cephalosporanyl chloride (42.34 g) in dry THF (400 ml), was dropped slowly always keeping the temperature at -70°C. The reaction mixture was stirred till temperature rose to 20°C, then was poured into diethyl ether (600 ml) and 20% aqueous NH 4 C1 (600 ml) . The etheral extracts were collected, washed with aqueous NaHC0 3 and brine, dried over Na 2 S0 4 and evaporated. The crude residue was purified by silica gel chromatography to yield the title compound as a white powder (41.89 g) IR (KBr) v max 3320, 1780, 1725 (sh) , 1695 cm "1 NMR (CDC1 3 , 200 MHz) δ 1.21 (9H,s), 1.45 (9H, s) , 1.75 (3H, d, J= 0.5 Hz), 3.09 (IH, d, J= 17.5 Hz), 3.52 (IH, br.d, J= 17.5 Hz), 4.97 (IH, d, J= 4.6 Hz), 5.20 (IH, d, J= 9.1 Hz, exch. D 2 0) , 5.51 (IH, dd, J= 4.6 and 9.2 H z ) . Step C. 7θ-tert-Butoxycarbonylamino-4-tert-butylcarbonyl- 3--methyl-3-cephem 1.1-dioxide 73-tert-Butoxycarbonylamino-4-tert-butylcarbonyl-3- methyl-3-cephem (41.89 g) was dissolved in methylene chloride (600 ml) . The solution was cooled to -10°C and 55% 3-chloroperbenzoic acid (92.7 g) was added portionwise. The resulting mixture was stirred for 4 hours at room temperature. The precipitated 3-chlorobenzoic acid was filtered off and the filtrate was sequentially washed with IM aqueous NaHS0 3 and saturated aqueous NaHC0 3 . Upon drying over Na 2 S0 4 , the solvent was rotoevaporated. Treatment of the residue with dichloromethane/diethyl ether gave the title product as a white solid (39.3 g) . IR (KBr) v max 3400, 1780, 1700 cm "1 NMR (200 MH Z , CDC1-J δ 1.23 (9H, s) , 1.45 (9H, s) , 1.72 (3H,s) , 3.54 (IH, d, J= 18.2 Hz) , 3.88 (IH, br . d, J= 18.2 Hz) , 4.79 (IH, br.d, J= 3.7 Hz) , 5.81 (2H, ) . PREPARATION 3 7 β-Amino-4- ert-butylcarbonyl-3-methyl-3-cephem 1.1-dioxide To a suspension of 24 g of 7/3-tert- butoxycarbonylamino-4-tert-butylcarbonyl-3-methyl-3-cephem 1,1-dioxide in methylene chloride (50 ml) were added 2 ml of anisole and 140 ml of trifluoroacetic acid. After stirring for 0.5 h, the TFA was evaporated in vacuo. The residue was taken up in ethyl acetate and washed with saturated aqueous NaHC0 3 and eventually with brine. Upon drying over Na 2 S0 4 , the solvent was rotoevaporated and treatment of the residue with a mixture of dichloromethane/diisopropyl ether gave the title product as a white powder (13.9 g) . IR (KBr) υ max 1785, 1690 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.23 (9H, s) , 1.7 1 (3H, s) , 3.48 (IH, d, J= 18.2 Hz), 3.87 (IH, br.d, J= 18.2 Hz), 4.71 (IH, br.d, J= 4.7 Hz), 4.80 (IH, br.d. J= 4.7 Hz). PREPARATION 4 4- ert-Butylcarbonyl-7-diazo-3-methyl-3-cephem 1.l-dioxide To a solution of 13.9 g of 7β-amino-4- tert- butylcarbonyl-3-methyl-3-cephem 1,1 dioxide in methylene chloride (700 ml) were added acetic acid (1ml) and tert- butylnitrite (11 ml) . The reaction mixture was stirred for 0.5 h at room temperature, thence poured into a IM solution of aqueous NaHC0 3 . The organic layer was separated, washed with water and dried over Na 2 S0 4 . Removal of the solvent in vacuo, left an oily residue which upon treatment with petroleum ether turned into a yellow powder (14.1 g) . IR (CHC1 3 ) υ max 2100, 1790, 1700 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.25 (9H, s) , 1.78 (3H, s) , 3.66 (IH, d, J= 17.1 Hz), 3.86 (IH, br.d, J= 17.1 Hz), 5.50 (IH, s) . PREPARATION 5 3-bromomethyl-7i8-tert-butoxycarbonylamino-4-tert- butylcarbonyl-3-methyl-3-cephem 1.1-dioxide A solution of 7β- tert-butoxycarbonylamino-4- ert- butylcarbonyl-3-methyl-3-cephem 1,1-dioxide (2.7 g) in carbon tetrachloride (150 ml) and methylene chloride (100 ml) was refluxed for 4 h in the presence of N- bromosuccinimide (NBS; 1.5 g) and α, a' -azoisobutyronitrile (AIBN; 100 mg) . Removal of the solvent and silica gel chromatography of the residue afforded the title compound (2.8 g,- plus 0.4 g of 2-bromo derivative) as a white solid. IR (KBr) υ max 1805, 1725, 1685 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.27 (9H, s) , 1.46 (9H, s) , 3.57 (IH, d, J= 18 Hz), 4.26 (IH, br.d, J= 18 Hz) , 3.77 (IH, d, J= 11.4 Hz), 4.02 (IH, d, J= 11.4 Hz), 4.88 (IH, br.d, J= 4.6 Hz) , 5.85 (2H, m) . PREPARATION 6 7β- ert-Butoxycarbonylamino-4- ert-butylcarbonyl-3- (5- methyl-1.3 ,4-thiadiazol-2-yl) thiomethyl-3-cephem 1.1- dioxide. A solution of 3-bromomethyl 73-tert- butoxycarbonylamino-4- ert-butylcarbonyl-3-cephem 1, 1- dioxide (2.8 g) was treated, in dry acetonitrile (150 ml), with triethylamine (1 ml) and 2-mercapto-5-methyl-l, 3,4- thiadiazole (1.05 g) . After 30 min the reaction mixture was diluted with ethyl acetate, washed with brine and dried over Na 2 S0 4 . Removal of the solvent and flash chromatography of the residue afforded the title product as a white powder (3.1 g) . IR (KBr) υ max 1800, 1730, 1700 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.24 (9H, s) , 1.46 (9H, s) , 3.81 (IH, d, J= 14.5 Hz) , 4.15 (IH, d, J= 14.5 Hz), 3.96 (IH, d, J= 18.3 Hz) , 4.20 (IH, br.d, J= 18.3 Hz) , 4.87 (IH, m) , 5.85 (2H, m) . PREPARATION 7 73-Amino-4- ert-butylcarbonyl-3- (5-methyl-l.3,4-thiadiazol- 2-yl)thiomethyl-3-cephem 1,1-dioxide To a suspension of 7/3-tert-butoxycarbonylamino-4-tert- butylcarbonyl-3- (5-methyl-l,3,4-thiadiazol-2-yl)thiomethyl- 3-cephem l,l-dioxide (3.1 g) in methylene chloride (15 ml) were added anisole (0.15 ml) and trifluoroacetic acid (10 ml) . In about 10 min the reaction was over. TFA was completely removed in vacuo and the residue taken up in ethyl acetate and washed with aqueous NaHC0 3 . Upon drying over NA 2 S0 4 , the solvent was rotoevaporated and the residue taken up in methylene chloride/isopropyl ether (1/2) . Collection of the precipitate by filtration afforded the pure title product as a light yellow powder (2 g) . IR (KBr) υ max 1780, 1690 cm "1 NMR (200 MHz, DMSO-d 6 ) δ 1.14 (9H, s) , 2.45 (2H, m) , 2.67 (3H, s) , 3.80 (IH, d, J= 13.3 Hz), 3.95 (IH, d, J= 13.3 Hz), 3.98 (IH, d, J= 17.5 Hz), 4.39 (IH, br.d, J= 17.5 Hz), 5.01 (IH, m) , 5.27 (IH, d, J= 4.6 Hz) . PREPARATION 8 4- ert-Butylcarbonyl-7-diazo-3- (5-methyl-1.3.4-thiadiazol- 2-yl)thiomethyl-3-cephem 1.1-dioxide To a suspension of 7/3-amino-4-tert-butylcarbonyl-3- (5- methyl-1,3,4-thyadiazol-2-yl)thiomethyl-3-cephem 1,1- dioxide (2 g) in methylene chloride (60 ml) were added tert-butylnitrite (1.1 ml) and a catalytic amount of acetic acid (0.06 ml) . The reaction mixture was stirred for 4 h at room temperature ( clear and yellow solution) , thence poured into a IM solution of NaHC0 3 . The organic layer was collected, washed with water and dried over Na 2 S0 4 . Removal of the solvent and flash chromatography of the crude product left an oily residue which, upon treatment with petroleum ether, turned into a yellow solid (1.22 g) . IR (CHC1 3 ) υ max 2100, 1790, 1700 cm '1 NMR (200 MHz, CDC1 3 ) δ 1.27 (9H, s) , 2.75 (3H, s) , 3.83 (IH, d, J= 14.2 Hz) , 4.17 (IH, d, J= 14.2 Hz) , 4.05 (IH, d, J= 17.4 Hz) , 4.21 (IH, br.d, J= 17.4 Hz) , 5.58 (IH, br.s) . PREPARATION 9 7i5-tβrt-Butoxycarbonylamino-3-methyl-4-phenylcarbonyl- cephem 1,1-dioxide Step A. 73- ert-butoxycarbonylamino-3-methyl-4- phenylcarbonyl-3-cephem To a solution of copper (I) iodide (22.2 g) and lithium chloride (9.9 g) in dry THF (150 ml), cooled to - 50°C and under nitrogen atmosphere, a 1.9M solution of phenyl magnesium chloride (61.5 ml) was added dropwise. To this mixture, a solution of crude 7/3-tert- butoxycarbonylamino-3-deacetoxy cephalosporanyl chloride (30 g, prepared according to the procedure described in PREPARATION 2, step A) in dry THF (150 ml) and diglyme (90 ml) , was dropped slowly always keeping the temperature at - 50°C. After stirring for 1 h at the same temperature, the reaction mixture was poured into diethyl ether (1 1) and 20% aqueous NH 4 C1 (1.6 1). The organic layer was separated, washed twice with aqueous NH 4 C1 and eventually wiyh brine. Upon drying over NaS0 4 , the solvent was removed in vacuo and the resultant crude residue was passed through a silica gel column to give the purified title compound as a light yellow solid (12.3 g) . IR (KBr) υ max 1770, 1700, 1670 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.45 (9H, s) , 1.77 (3H, s) , 3.22 (IH, d, J= 18 Hz), 3.60 (IH, br.d, J= 18Hz) , 5.08 (IH, d, J= 4.6 Hz), 5.24 (IH, br.d, J= 9.5 Hz), 5.52 (IH, dd, J= 4.6 and 9.5 Hz), 7.30-8.00 (5H, m) . Step B. 73-tert-butoxycarbonylamino-3-methyl-4- phenylcarbonyl-3-cephem 1,1-dioxide To a solution of 7/3- ert-butoxycarbonylamino-3-methyl- 3-cephem (12.3 g) in ethyl acetate (500 ml), cooled to - 10°C, 55% 3-chloroperbenzoic acid (25.7 g) was added portionwise. The resulting mixture was stirred for 6 h at room temperature and then sequentially washed with IM aqueous NaHS0 3 and saturated aqueous NaHC0 3 . Upon drying over NaS0 4 , the solvent was rotoevaporated to a small volume. Following addition of cyclohexane gave the title compound which was collected by filtration as white crystals (11.7 g) . IR (KBr) υ max 1770, 1720, 1670 cm "1 NMR (200 MHz, DMSO-d δ 1.38 (9H, s) , 1.64 (3H, s) , 4.11 (IH, d, J= 18.2 Hz), 4.36 (IH br.d, J= 18.2 Hz), 5.44 (IH, d, J= 4.6 Hz), 5.65 (IH, dd, J= 4.6 and 9.7 Hz), 7.20 (IH, d, J= 9.7 Hz), 7.4-7.9 (5H, m) . PREPARATION 10 7/3-Amino-3-methyl-4-phenylcarbonyl-3-cephem 1.1-dioxide To a suspension of 7/3-tert-butoxycarbonylamino-3- methyl-4-phenylcarbonyl-3-cephem 1,1-dioxide (11.7 g) in methylene chloride (40 ml) , trifluoroacetic acid (45 ml) and a catalytic amount of anisole (1 ml) were added. After stirring for 30 min., TFA was evaporated in vacuo and the residue taken up in ethyl acetate. Following washing with saturated aqueous NaHC0 3 afforded the precipitation of the a white solid from the organic layer. The aqueous phase was discarded and the precipitate was collected by filtration, washed with a mixture of ethyl acetate/hexane and eventually dried in vacuo to give the title compound as a white powder (8.4 g) . IR (KBr) υ max 1770, 1670 cm "1 NMR (200 MHz, DMSO-d 6 ) δ 1.62 (3H, s) , 4.03 (IH, d, J= 18.2 Hz), 4.31 (IH, br.d, J= 18.2 Hz), 4.83 (IH, m) , 5.27 (IH, d, J= 4.2 Hz), 7.5-8.0 (5H, m) . PREPARATION 11 7-Diazo-3-methyl-4-phenylcarbonyl-3-cephem 1, 1-dioxide A suspension of 7/S-amino-3-methyl-4-phenylcarbonyl-3- cephem 1,1-dioxide (8.4 g) in methylene chloride (400 ml) was treated with tert-butylnitrite (6.5 ml) and a catalytic amount of acetic acid. The reaction mixture was stirred for 0.5 h at room temperature thence poured into a IM solution of aqueous NaHC0 3 . The organic layer was separated, washed with water and dried over NaS0 4 . Removal of the solvent in vacuo left an oily residue which upon treatment with petroleum ether turned into a yellow solid (6.5 g) . IR (CHC1 3 ) υ max 2090, 1790, 1670 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.66 (3H, s) , 3.66 (IH, d, J= 17.8 Hz) , 4.02 (IH, br.d, J= 17.8 Hz) , 5.66 (IH, s) , 7.4-8.0 (5H, m) . EXAMPLE 1 7.7-Dibromo-4-tert-butylcarbonyl-3-methyl-3-cephem 1.1- dioxide To a solution of 4-tert-butylcarbonyl-7-diazo-3- methyl-3-cephem 1,1-dioxide (4.6 g) in methylene chloride (400 ml) at -20°C was added bromine (15.2 ml) . In the reaction mixture was let rise to 0°C and after about 30 min. the reaction was over (TLC monitoring) . The solvent was rotoevaporated and the residue was taken up in CH 2 CL 2 /ET 2 0 (1/1) . Collection by filtration of the precipitate afforded the title product as a light yellow powder (4.7 g) . IR (CHCI 3 ) υ max 1820, 1700 cm "1 NMR (200MHz, CDC1 3 ) δ 1.26 (9H, s) , 1.75 (3H, s) , 3.56 (IH, d, J= 17.8 Hz) , 3.92 (IH, d, J= 17.8 Hz), 5.14 (IH, s) . EXAMPLE 2 7,7-Diallyl-4-tert-butylcarbonyl-3-methyl-3-cephem 1.1- dioxide To a solution of 4.3 g of 7, 7-dibromo-4-tert- butylcarbonyl-3-methyl-3-cephem 1,1-dioxide in acetonitrile (150 ml) , prepared as described in example 1, were added a;,Qf-azoisobutyronitrile (100 mg) and allyltributyltin (9.3 ml) . The reaction mixture was let stand at reflux for 2 h, then poured into water-ethyl acetate. The organic layer was collected, dried over Na 2 S0 4 and concentrated in vacuo. Flash chromatography of the residue gave the pure title product as a white solid (2.46 g) . IR (KBr) υ max 1760, 1690 cm _1 NMR (200 MHz, CDC1 3 ) δ 1.26 (9H, s) , 1.68 (3H, s) , 2.55 (2H, m) , 2.8-3.1 (2H, m) , 3.39 (IH, d, J= 17.6 Hz), 3.90 (IH, br.d, J= 17.6 Hz), 4.45 (IH, br.s), 5.1-5.3 (4H, m) , 5.7-6.0 (2H, m) . EXAMPLE 3 7.7-Diallyl-2-bromo-4-tert-butylcarbonyl-3-methyl-3-cephem 1.1-dioxide To a solution of 2 g of 7,7-diallyl-4-tert- butylcarbonyl-3-methyl-3-cephem 1,1-dioxide in acetonitrile (40 ml) were added trietylamine (0.87 ml) and N- bromosuccinimide (1.22 g) . After 30 min. the reaction mixture was poured into ethyl acetate / 4% aqueous HaHS0 3 . The organic layer was collected and sequentially washed with saturated NaHC0 3 and water. After drying over Na 2 S0 4 , removal of the solvent left a crude residue which was then purified by flash chromatography affording the pure title product as a white solid (2.2 g) . IR (KBr) υ max 1795, 1705 cm "1 NMR (200 NMR, CDC1 3 ) δ 1.23 (9H, s) , 1.80 (3H, s) , 2.59 (2H, m) , 2.8-3.1 (2H, m) , 4.86 (IH, s) , 5.17 (IH, s) , 5.2-5.4 (4H, m) , 5.6-6.0 (2H, m) . EXAMPLE 4 7.7-Diallyl-4-tert-butylcarbonyl-3-methyl-2- (1-methyl- 1,2,3,4-tetrazol-5-yl)thio-3-cephem l, 1-dioxide Procedure A To a solution of 215 mg of 7,7-diallyl-2-bromo-4-tert- butylcarbonyl-3-methyl-3-cephem 1,1-dioxide, prepared as described in example 3, in dimethylformamide (2ml) was added sodium 1-methyl-l,2,3,4-tetrazolyl-5-mercaptide (160 mg) . After 15 min. the reaction mixture was diluted with ethyl acetate and sequentially washed with saturated NaHC0 3 and brine. Upon drying over Na 2 S0 4 and removal of the organic solvent in vacuo, the crude residue was passed through a silica gel column affording the pure title product as a white powder (180 mg) . Procedure B A solution of 350 mg of 7,7-diallyl-4-tert- butylcarbonyl-3-methyl-3-cephem 1,1-dioxide in acetonitrile (6 ml) was sequentially treated with toluene-4-thiosulfonic acid S- (1-methyl-lH-tetrazol-5-yl) ester (300 mg) and 1,5- diazabicyclo [4.3.0]non-5-ene (0.25 ml). The reaction mixture was stirred for 1 h at room temperature and then poured into ethyl acetate / 2% aqueous HC1. The organic phase was washed with brine, dried over Na 2 S0 4 and concentrated. Flash chromatography of the residue gave the title product as a white solid (300 mg) . IR (KBr) υ max 1785, 1700 cm "1 NMR (200MHz, CDC1 3 ) δ 1.25 (9H, s) , 1.94 (3H, s) , 2.6 (2H, m) , 2.8-3.1 (2H, m) , 4.09 (3H, s) , 4.87 (IH, s) , 4.98 (IH, s) , 5.1-5.4 (4H, m) , 5.7-5.9 (2H, m) . EXAMPLE 5 7.7-Diallyl-4-tert-butylcarbonyl-3-methyl-2- (5-methyl- 1.3,4-thiadiazol-2-yl) hio-3-cephem 1,1-dioxide 215 mg of 7,7-diallyl-2-bromo-4-tert-butylcarbonyl-3- methyl-3-cephem 1,1-dioxide, prepared according the procedure described in example 3, were dissolved in dimethylformamide (2ml) and treated with triethylamine (0.07 ml) and 2-mercapto-5-methyl-l,3,4 thiadiazole (70 mg) . After 15 min. the reaction mixture was diluted with ethyl acetate then sequentially washed with saturated NaHC0 3 and brine and eventually dried over Na 2 S0 4 . The organic layer was concentrated in vacuo and the resulting residue was chromatographed on a flash column affording the pure title product as a white powder (185 mg) . IR (KBr) υ max 1790, 1700 cm _1 NMR (200 MHz, CDC1 3 ) δ 1.22 (9H, s) , 1.91 (3H, s) , 2.58 (2H, m) , 2.79 (3H, s) , 2.7-3.1 (2H, m) , 5.01 (IH, s) , 5.1-5.4 (4H, m) , 5.2 (IH, s) , 5.7-5.9 (2H, m) . EXAMPLE 6 7.7-Diallyl-4-tert-butylcarbonyl-2- (4-carboxybenzoyl)oxy-3- methyl-3-cephem 1.1 dioxide 430 mg of 7,7-diallyl-2-bromo-4-tert-butylcarbonyl-3- methyl-3-cephem 1,1-dioxide were dissolved in acetonitrile (25 ml) and treated with silver (4- methoxybenzyloxycarbonyl) -4-benzoate (400 mg) . The reaction mixture was let stir at room temperature for 2 h. Solid AgBr was removed by filtration and the remaining solution was diluted with ethyl acetate, washed with saturated brine and eventually dried over Na 2 S0 4 . Flash chromatography of the concentrated residue afforded the pure protected compound (390 mg) which was then dissolved in dichloromethane (5 ml) and treated with anisole (0.0050 ml) and trifluoroacetic acid (2 ml) . After 20 min., TFA was removed in vacuo and the resulting residue taken up in dichloromethane (2 ml) . Addition of isopropylether afforded the title compound as a white powder (250 mg) . IR (KBr) υ max 1790, 1745, 1705 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.31 (9H, s) , 1.77 (3H, s) , 2.59 (2H, m) , 2.8-3.1 (2H, m) , 4.64 (IH, s) , 5.2-5.4 (4H, m) , 5.7-5.9 (2H, m) . EXAMPLE 7 7oj-Allyl-7i3-bromo-4-tert-butylcarbonyl-3-methyl-cephem 1, 1- dioxide To a solution of 2.1 g of 7,7-dibromo-4-tert- butylcarbonyl-3-methyl-3-cephem 1,1-dioxide in acetonitrile (70 ml) , prepared as described in example 1, were added o;,α-azoisobutyronitrile (50 mg) and allyltributyltin (2,1 ml) . The reaction mixture was let stand at reflux for 1 h, then was allowed to warm to room temperature and poured into water/ethyl acetate. The organic layer was collected, dried over Na 2 S0 4 and concentrated in vacuo. The residue was chromatographed a on a flash column to yield the title compound as a white powder (1.5 g) . IR (KBz) υ 1800, 1700 cm "1 NMR (200 MH 2 , CDC1 3 ) δ 1.27 (9H, s) , 1.73 (3H, s) , 2.95- 3.00 (2H, m) , 3.51 (IH, d, J= 17.4 Hz) , 3.86 (IH, br.d, J= 17.4 Hz), 4.65 (3H, s) , 5.3-5.4 (2H, m) , 5.7- 5.9 (IH, m) . EXAMPLE 8 7/3-Bromo-4-tert-butylcarbonyl-7α?-methoxy-3-methyl-3-cephem 1.l-dioxide To a solution of 4.6 g of 4-tert-butylcarbonyl-7- diazo-3-methyl-3-cephem 1,1-dioxide in methylene chloride (100 ml) was added methanol (70 ml) and then solid N- bromosuccinimide (2.75 g) in small portions to control N 2 evolution. After stirring for 1.5 h at room temperature, the reaction mixture was diluted with CH 2 C1 2 . The organic layer was washed with brine and dried over Na 2 S0 4 . Removal of the solvent in vacuo left a residue which was purified by flash chromatography (n-hexane/EtOAc 2/1) affording the title product as a light yellow solid (4.45 g) . IR (KBr) υ max 17800, 1690 cm "1 NMR (200 NHz, CDC1 3 ) δ 1.27 (9H, s) , 1.78 (3H, s) , 3.60 (IH, d, J= 17.1 Hz), 3.85 (IH, br.d, J= 17.1 Hz), 3.66 (3H, s) , 4.76 (IH, br.s) . EXAMPLE 9 7 oι-Allyl-4-tert-butylcarbonyl-7/3-methoxy-3-methyl-3-cephem 1.1-dioxide To a solution of 4.4 g 7-bromo-4-tert-butylcarbonyl-7- methoxy-3-methyl-3-cephem 1,1-dioxide in acetonitrile (160 ml) were added oι, o>' -azoisobutyronitrile (100 mg) and allyltributyltin (7.7 ml) . The reaction mixture was let stand at reflux for 4 h, then poured into water/ethyl acetate. The organic layer was collected, dried over Na 2 S0 4 and concentrated in vacuo. Flash chromatography of the residue gave the purified title product as a white solid (2.9 g) . IR (CHC1 3 ) υ max 1790, 1700 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.25 (9H, s) , 1.72 (3H, s) , 2.6-2.9 (2H, m) , 3.43 (IH, d, J= 17.7 Hz) , 3.83 (IH, br.d, J= 17.7 Hz), 3.63 (3H, s) , 4.50 (IH, br.s), 4.3-5.4 (2H, m) , 5.7-5.9 (IH, m) . EXAMPLE 10 7 oi-Allyl-4-tert-butylcarbonyl-7/3-methoxy-3-methyl-2- (5- methyl-1.3 ,4-thiadiazol-2-yl) thio-3-cephem 1.1-dioxide To a solution of 7α-allyl-2-bromo-4-tert- butylcarbonyl-7/3-methoxy-3-methyl-3-cephem 1,1-dioxide (160 mg) prepared as described in Example 3, starting from the compound of example 9, were added triethylamine (0.07 ml) and 2-mercapto-5-methyl-1,3,4 thiadiazole (70 mg) . In about 15 min. the reaction was over. The reaction mixture was diluted with ethyl acetate, sequentially washed with saturated NaHC0 3 and brine and dried over Na 2 S0 4 . Removal of the solvent in vacuo left the crude product which was obtained pure as a white solid by silica gel chromatography (120 mg) . IR (KBr) υ max 1810, 1700 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.20 (9H, s) , 1.92 (3H, s) , 2.79 (3H, S) , 2.7-2.9 (2H, m) , 3.61 (3H, s) , 5.11 (IH, s) , 5.12 (IH, S) , 5.35 (2H, m) , 5.8-5.9 (IH, m) . EXAMPLE 11 7 a.-Allyl-4-tert-butylcarbonyl-7/3-methoxy-3-methyl-2- (1- methyl-1.2.3.4-tetrazol-5-yl) thio-3-cephem 1. l-dioxide Following the procedure described in Example 10 and using 2-mercapto-1-methyl-1, 2 , 3, 4-tetrazole instead of 2- mercapto-5-methyl-l, 3, 4-thiadiazole the title product was obtained as a white powder. IR (KBr) v max 1790, 1700 cm "1 EXAMPLE 12 7α-Allyl-2- (6-hydroxy-2-methyl-5-oxo-2.5-dihydro-l,2.4-triazin- 3-yl) thio-4-tert-butylcarbonyl-73-methoxy-3-methyl-3-cephem 1. l-dioxide A solution of 7α-allyl-4-tert-butylcarbonyl-7/3- methoxy-3-methyl-3-cephem 1, l-dioxide (130 mg) in acetonitrile (5 ml) was sequentially treated with N- bromosuccinimide (100 mg) and triethylamine (0.06 ml) . After 5 minutes at room temperature a solution of 6-benzhydryloxy-3-mercapto-2-methyl-5-oxo-2, 5-dihydro-l, 2, 4 -triazine (140 mg) and triethylamine (0.06 ml) in DMF (1 ml) was added. The reaction mixture was stirred for 15 minutes, then partitioned between EtOAc and water. The organic layer was sequentially washed with 2% aqueous HC1, 4% aqueous NaHC0 3 and brine, then dried over Na 2 S0 4 and concentrated under reduced pressure. The residue was dissolved in dichloromethane (1 ml) and treated with anisole (0.2 ml) and trifluoroacetic acid (1 ml) . After 30 minutes, TFA was removed in vacuo; the residue was dissoved in EtOAc and extracted with saturated aqueous NaHC0 3 . Upon careful acidification with concentrated hydrochloric acid, the aqueous phase was back extracted with EtOAc. Following drying (Na 2 S0 4 ) and removal of the solvent, a waxy solid was obtained which was treated with diisopropyl ether to afford the title compound as a white powder IR (KBr) υ max 1790, 1700, 1620-1660 cm "1 NMR (200 MHz, CDC1 3 ) 6 1.25 (9H, s) , 1.85 (3H, s) , 2.79 (3H, s) , 2.6-3.0 (2H, m) , 3.62 (3H, s) , 3.82 (3H, s) , 4.73 (IH, S) , 5.2-5.5 (2H, m) , 5.7-5.9 (IH, m) , 5.94 (IH, s) . EXAMPLE 13 7α?-Allyl-2-benzoyloxy-4-tert-butylcarbonyl-7/3-methoxy-3- methyl-3-cephem 1.l-dioxide 7 oi-allyl-2-bromo-4-tert-butylcarbonyl-7/3-methoxy-3- methyl-3-cephem 1,l-dioxide (200 mg) , prepared as described in Example 3, starting from the compound of example 9, was dissolved in dry acetonitrile (5 ml) and treated with silver benzoate (210 mg) . After stirring for 30 min. at room temperature, the reaction mixture was partitioned between ethyl acetate and water. Following drying over Na 2 S0 4 , the organic phase was rotoevaporated. The residue was passed through a silica gel column affording the pure title product as a white solid (140 mg) IR (KBr) υ max 1815, 1785, 1740, 1705 cm "1 NMR (200 NHz, CDC1 3 ) δ 1.30 (9H, s) , 1.76 (3H, s) , 2.7-2.9 (2H, m) , 3.63 (3H, s) , 4.67 (IH, s) , 5.35 (2H, m) , 5.8-5.9 (IH, m) , 6.03 (IH, s) . EXAMPLE 14 4-tert-Butylcarbonyl-7-methoxy-3-methyl-7- (1-methyl- 1.2.3.4-tetrazol-5-yl)thio-3-cephem 1. l-dioxide To a solution of 7/3-bromo-4-tert-butylcarbonyl-7α- methoxy-3-methyl-3-cephem 1,l-dioxide (200 mg) in acetonitrile (5 ml) was added sodium 1-methyl 1,2,3,4- tetrazolyl-5-mercaptide (200 mg) . After stirring for 5 h at room temperature, the reaction mixture was partitioned between ethyl acetate/saturated NaHC0 3 . The organic phase was collected, washed with water and dried over Na 2 S0 4 . Removal of the solvent in vacuo left a residue which was taken up in dichloromethane. Because of its poor solubility in such a solvent, the residue was first triturated and eventually filtered to give the title product as a light yellow powder (170 mg) . IR (KBr) υ max 1800, 1700 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.23 (9H, s) , 1.73 (3H, s) , 3.47 (IH, d, J= 18 Hz), 3.97 (IH, br.d, J= 18 Hz), 3.81 (3H, s) , 4.12 (3H, s) , 5.48 (IH, s) . EXAMPLE 15 7/3-Bromo-7α?-methoxy-3-methyl-4-phenylcarbonyl-3-cephem 1.1- dioxide To a solution of 7-diazo-3-methyl-4-phenylcarbonyl-3- cephem 1, l-dioxide (2.1 g) in methylene chloride (50 ml) was added methanol (30 ml) and then solid N- bromosuccinimide (NBS; 1.41 g) in small portions to control N 2 evolution. After stirring for 1.5 h at room temperature, the reaction mixture was diluted with CH 2 C1 2 . The organic layer was washed with brine and dried over Na 2 S0 4 . Removal of the solvent in vacuo left a residue which was chromatographed on a flash column (n-hexane/ethyl acetate 2/1) affording the title product as a yellow solid (2.12 g) . IR (KB r ) υ max 1790, 1670 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.69 (3H, s) , 3.61 (3H, s) , 3.59 (IH, d, J= 17.7 Hz), 3.99 (IH br.d, J= 17.7 Hz) , 4.95 (IH, br.s) , 7.5-8.0 (5H, m) . EXAMPLE 16 7α;-Allyl- 7β-methoxy-3-methyl-4-phenylcarbonyl-3-cephem 1,1- dioxide To a solution of 7-bromo-7-methoxy-3-methyl-4- phenylcarbonyl-3-cephem 1, l-dioxide (1.1 g) in acetonitrile (40 ml) were added α,c' -azoisobutyronitrile (AIBN; 30 mg) and allyl tributyltin (1.8 ml) . The reaction mixture was let stand at reflux for 4 h, then poured into water/ethyl acetate. The collected organic layer was dried over Na 2 S0 4 and concentrated in vacuo . Flash chromatography of the residue gave the purified title compound as a light yellow solid (645 mg) . IR (KB r ) υ max 1780, 1670 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.68 (3H, s) , 2.6-2.9 (2H, m) , 3.61 (3H, s), 3.50 (IH, d, J= 17.9 Hz) , 3.88 (IH, br.d, J= 17.9 Hz) , 4.62 (IH, br.s), 5.2-5.4 (2H, m) , 5.6-5.8 (IH, m) , 7.4-8.0 (5H, ) . EXAMPLE 17 7α--Allyl-7/3-methoxy-3-methyl-2- (1-methyl-l.2.3.4-tetrazol- 5-yl) thio-4-phenylcarbonyl-3-cephem l. l-dioxide A solution of 7α-allyl-7/3-methoxy-3-methyl-4- phenylcarbonyl-3-cephem 1, l-dioxide (480 mg) in acetonitrile (10 ml) was sequentially treated with toluene- 4-thiosulfonic acid S- (1-methyl-lH-tetrazol-5-yl) ester (395 mg) and 1, 5-diazabicyclo [4.3.0]non-5-ene (DBN; 0.32 ml) . The reaction mixture was stirred for 0.5 h at room temperature, then poured into ethyl acetate/2% aqueous HC1. The organic layer was collected, washed with brine, dried over Na 2 S0 4 and concentrated to dryness . Flash chromatography of the residue gave the title product as a light yellow solid (380 mg) . IR (KB r ) υ max 1790, 1675 cm "1 NMR (200 MHz, CDC1 3 ) 6 1.93 (3H, s) , 2.6-2.9 (2H, m) , 3.58 (3H, S) , 4.10 (3H, s) , 5.01 (IH, s) , 5.09 (IH, s) , 5.3-5.4 (2H, m) , 5.6-5.8 (IH, m) , 7.5- 8.0 (5H, m) . EXAMPLE 18 4-tert-Butylcarbonyl- 7β-methoxy-3-methyl-7o?-propyl-3-cephem 1. l-dioxide A mixture of 7α-allyl-4-tert-butylcarbonyl-7/3-methoxy- 3-methyl-3-cephem 1, l-dioxide (1.02 g) , cyclohexadiene (3 ml) and 10% Pd/C (250 mg) was heated at reflux for 90 minutes. Upon removal of the catalyst by filtration, the filtrate was partitioned between EtOAc and water and the organic layer was dried (Na 2 S0 4 ) and concentrated in vacuo. The residue was purified by flash chromatography affording the title product as a white solid (835 mg) . IR (CHCI 3 ) υ max 1780, 1695 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.02 (3H, t, J= 7.2 Hz), 1.25 (9H, s) , 1.4-1.7 (2H, m) , 1.72 (3H, s) , 1.8-2.1 (2H, m) , 3.47 (IH, d, J= 17.5 Hz) , 3.59 (3H, s) , 3.81 (IH, br.d, J= 17.5 Hz), 4.45 (IH, m) . EXAMPLE 19 4-tert-Butylcarbonyl-73-methoxy-3-methyl-2- (1-methyl- l,2,3,4-tetrazol-5-yl) thio-7α-propyl-3-cephem 1. l-dioxide A solution of 4-tert-butylcarbonyl-7 / 3-methoxy-3- methyl-7α"-propyl-3-cephem 1, l-dioxide (50 mg) and toluene- 4-thiosulfonic acid S- (1-methyl-IH-tetrazol-5-yl) ester (45 mg) was treated with 1, 5-diazabicyclo[4, 3, 0]non-5-ene (0.045 ml) and left stand at room temperature for 15 minutes. The reaction mixture was partitioned between EtOAc and water. The upper layer was sequentially washed with 2% aqueous HC1, 4% aqueous NaHC0 3 and brine. Drying over Na 2 S0 4 , removal of the solvent and purification of the residue by flash chromatography allowed the isolation of the title product as a white powder (39 mg) IR (KBr) υ max 1785, 1695 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.04 (3H, t, J= 7.2 Hz) , 1.24 (9H, s) , 1.4-1.8 (2H, m) , 1.8-2.2 (2H, m) , 1.94 (3H, s) , 3.57 (3H, s) , 4.10 (3H, s) , 4.90 (IH, s) , 4.92 (IH, s) . EXAMPLE 20 2-Bromo-3-bromomethyl-4-tert-butylcarbonyl-7/3-methoxy-7α?- propyl-3-cephem 1. l-dioxide and 3-bromomethyl-4-tert- butylcarbonyl-73-methoxy-7o , -propyl-3-cephem 1. l-dioxide A solution of 4-tert-butylcarbonyl-7/3-methoxy-3- methyl-7α-propyl-3-cephem 1, l-dioxide (800 mg) in dichloromethane/carbon tetrachloride 1:4 (100 ml) was treated with NBS (1.3 g) and AIBN (70 mg) . The mixture was heated at reflux for 2 hours then concentrated under vacuum. The residue was flash chromatographed over Si0 2 (eluting with EtOAc/n-hexane mixtures) . The first eluted product was shown to be the 2,3'- dibromocephem derivative (600 mg) : IR (CHCI υ max 1800, 1705 cm XL NMR (200 MHz, CDC1 3 ) δ 1.04 (3H, t, J= 7.2 Hz) , 1.31 (9H, s) , 1.3-1.7 (2H, m) , 1.8-2.2 (2H, m) , 3.60 (3H, s), 3.79 (IH, d, J= 11.7 Hz), 4.10 (IH, dd, J= 0.5 and 11.7 Hz), 5.17 (IH, d, J= 0.5 Hz) , 5.44 (IH, s) . The second eluted product was the 3' -bromo cephem derivative (250 mg) : IR (KBr) υ max 1785, 1695 cm "1 . NMR (200 MHz, CDC1 3 ) δ 1.03 (3H, t, J= 7.2 Hz), 1.29 (9H, s) , 1.3-1.7 (2H, m) , 1.8-2.2 (2H, m) , 3.50 (IH, dd, J= 0.8 and 17.7 Hz), 3.59 (3H, s) , 3.81 and 3.95 (2H, ABq, J= 11.3 Hz), 4.18 (IH, dd, J= 1.5 and 17.7 Hz), 4.57 (IH, dd, J= 0.8 and 1.5 Hz) . EXAMPLE 21 4-tert-Butylcarbonyl-7 β-methoxy-3- (1-methyl-1.2,3.4- tetrazol-5-yl) thiomethyl-7α-propyl-3-cephem 1. l-dioxide A solution of 3-bromomethyl-4-tert-butylcarbonyl-7/3- methoxy-7α-propyl-3-cephem 1, l-dioxide (120 mg) in CH 3 CN (12 ml) was treated with sodium 1-methyl-1,2,3,4- tetrazolyl-5-mercaptide (120 mg) and stirred for 15 minutes at room temperature, then poured into EtOAc/4% aqueous NaHC0 3 . The organic layer was dried (Na 2 S0 4 ) and rotoevaporated. The residue was purified by flash crhomatography yielding the title product as a white powder (100 mg) . IR (KBr) υ max 1790, 1695 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.03 (3H, t, J= 7.2 Hz) , 1.25 (9H, s) , 1.4-1.6 (2H, m) , 1.8-2.2 (2H, m) , 3.59 (3H, s) , 3.77 and 4.07 (2H, ABq, J= 13.3 Hz), 3.82 (IH, dd, J= 0.5 and 17.5 Hz), 3.95 (3H, s) , 4.10 (IH, dd, J= 1.4 and 17.5 Hz) , 4.55 (IH, dd, J= 0.5 and 1.4 Hz) . EXAMPLE 22 4-tert-Butylcarbonyl-7/3-methoxy-3- (6-hydroxy-2-methyl-5-oxo -2,5-dihydro-l.2.4-triazin-3-yl)thiomethyl-7α-propyl-3- cephem 1, l-dioxide Starting from 3-bromomethyl-4-tert-butylcarbonyl-7/3- methoxy-7α-propyl-3-cephem 1,l-dioxide and following a procedure similar to that described in Example 12 the title product was obtained as a light pink powder. IR (KBr) υ max 1790, 1695, 1620-1660 cm '1 EXAMPLE 23 4-tert-Butylcarbonyl-7ι3-methoxy-2- (l-methyl-l.2.3.4- tetrazol-5-yl)thio-3- (1-methyl-l.2.3.4-tetrazol-5- yl)thiomethyl-7o?-propyl-3-cephem 1.l-dioxide A solution of 2-bromo-3-bromomethyl-4-tert- butylcarbonyl-7/3-methoxy-7α-propyl-3-cephem 1,l-dioxide (100 mg) in CH 3 CN (10 ml) was treated with sodium l-methyl-l,2,3,4-tetrazolyl-5- mercaptide (150 mg) and stirred at room temperature for 30 minutes, then partitioned between EtOAc and water. The upper phase was washed with brine, then dried (Na 2 S0 4 ) and rotoevaporated. Following purification by flash chromatography, the title product was obtained as a white powder (80 mg) . IR (KBr) υ max 1795, 1695 cm "1 NMR (200 MHz, CDC1 3 ) δ 1.03 (3H, t, J= 7.2 Hz), 1.25 (9H, s) , 1.3-1.8 (2H, m) , 1.8-2.2 (2H, m) , 3.57 (3H, s) , 3.70 and 4.33 (2H, ABq, J= 14.0 Hz), 3.96 (3H, S) , 4.14 (3H, s) , 4.91 (IH, s) , 5.41 (IH, s, exch. D 2 0) . EXAMPLE 24 4' -tert-Butyl-7ι8-methoxy-7o?-propyl-furo[3,4-cl cephem 1,1- dioxide A solution of 3-bromomethyl-4-tert-butylcarbonyl-7/3- ethoxy-7α-propyl-3-cephem 1,l-dioxide (125 mg) in acetonitrile (10 ml) was treated with triethylamine (0.08 ml) and let stand at room temperature for 1 hour. The reaction mixture was partitioned between EtOAc and 1% aqueous HC1; the organic layer was dried (Na 2 S0 4 ) and rotoevaporated. The residue was passed through a short pad of Si0 2 eluting with n-hexane/EtOAc 3:1. The title product was obtained as a whitish powder. IR (KBr) υ max 1790 cm "1 . NMR (200 MHz, CDC1 3 ) δ 1.03 (3H, t, J= 7.2 Hz), 1.37 (9H, s) , 1.4-1.7 (2H, ) , 1.9-2.2 (2H, m) , 3.64 (3H, S) , 4.14 (2H, m) , 4.57 (IH, s) , 7.14 (IH, t, J= 1.4 Hz) . EXAMPLE 25 Pharmaceutical composition for intramuscular injection: Ingredients Per ml Per liter 1. Active ingredient 10.0 mg 10 g Cpd of Form Ia or Ib 2. Isotonic buffer q.s. q.s. solution pH 4.0. Procedure: Step 1. Dissolve the active ingredient in the buffer solution. Step 2. Aseptically filter the solution from step 1. Step 3. The sterile solution is aseptically filled into sterile ampoules Step 4. The ampoules are sealed under aseptic conditions

Claims: CLAIMS 1. A compound of formula (Ia) or (Ib) or a pharmaceutically or veterinarily acceptable salt thereof wherein A is an organic radical which is optionally substituted and is selected from straight or branched C 1 -C 12 alkyl , C 2 -C 12 alkenyl , C 2 -C 12 alkynyl , C 6 -C 14 aryl , C 3 -C β cycloalkyl , C 5 -C 8 cycloalkenyl , C 7 -C 22 alkaryl , C 7 -C 22 aralkyl , C 8 -C 14 alkenylaryl , C 8 -C 14 aralkenyl , C 8 -C 14 alkynylaryl , C 8 -C 14 aralkynyl , ( cycloalkyl ) alkyl , ( cycloalkyl ) alkenyl , heterocyclyl , (heterocyclyl ) alkyl , (heterocyclyl ) alkenyl ,- Q and W, each independently, represent (1) chloro, fluoro, bromo or iodo; (2) A as defined above (3) hydroxy or an ether OA wherein A is as defined above (4) a thioether, sulfoxide or sulfone -S(0) m A wherein m is either zero, one or two and A is as defined above,- (5) a selenoether, selenoxide or selenone -Se(0) m A wherein m is either zero, one or two and A is as defined above,- (6) acyl -C(0)A wherein A is as defined above,- (7) formyloxy -0C(0)H or acyloxy -0C(0)A wherein A is as defined above,- (8) sulfonyloxy -0S(0) 2 A wherein A is as defined above,- (9) formamido -NHC(0)H or an acylamino group -NHC(0)A wherein A is as defined above or acylamino -NH-Z wherein Z is a mono, di- or tripeptide composed of D or L α-aminoacids chosen from Ala, Gly, Val, Leu, lie, Phe and with the terminal amino group either free or acylated by a group -C(0)A or -C(0)0A wherein A is as defined above,- (10) azido, nitro or cyano,- or Q and W taken together constitute an oxo group (=0) or a group of formula =CHA, =CHC(0)A, =CHC(0)0A or =CHS(0) 2 A wherein A is as defined above,- or Q and W taken together with the carbon atom to which they are attached constitute an oxirane or cyclopropyl group,- and where appropriate Q and W are optionally substituted; with the proviso that in the compounds of formula (Ia) Q and W do not both represent chloro or fluoro atoms,- R_ is either hydrogen or an optionally substituted straight or branched C^-C^ alkyl or a C 2 -C 12 alkenyl group, or a C 7 - C 14 aralkyl group, or a (heterocyclyl) alkyl group,- R 2 represents: (1) hydrogen; (2) A as defined above,- (3) halo,- (4) a sulfenyl, sulfinyl or sulfonyl group -S(0),„A wherein A and m are as defined above,- (5) an acyloxy group -0C(0)A wherein A is as defined above,- or R_ and R 2 taken together constitute a methylene group or a group of formula =CHA, =CHC(0)A or =CHC(0)0A wherein A is as defined above; or R_ and R 2 taken together with the carbon atom to which they are attached constitute a carbocyclic or heterocyclic group,- where appropriate R 1 and/or R 2 are optionally substituted; R 3 represents : (1) A as defined above,- (2) chloro or fluoro or hydrogen; (3) a sulfenyl, sulfinyl or sulfonyl group -S(0) m A wherein A and m are as defined above; (4) hydroxy or an oxy group -O-A wherein A is as defined above; (5) formyl -C(0)H, carboxy -C0 2 H, or an acyl group -C(0)A or C(0)OA wherein A is as defined above,- (6) on oxymethyl group -CH 2 -OA wherein A is as defined above,- (7) a thiomethyl group or a derivative thereof of formula -CH 2 S(0) m A wherein m and A are as defined above,- (8) formyloxymethyl -CH 2 0C(0)H or an acyloxymethyl group - CH 2 OC(0)A or -CH 2 0-Z wherein A and Z are as defined above,- (9) an acylthiomethyl group -CH 2 SC(0)A wherein A is as defined above,- (10) an aminomethyl group -CH 2 -N(A)A ' wherein A is as defined above and A ' , being the same or different, is as defined above for A; or A and A ' taken together with the nitrogen atom to which they are attached represent a heterocyclic ring; (11) ammoniomethyl -CH 2 N + (A) (AJ A " wherein A and A' are as defined above and A " , being the same or different, is as defined for A,- or A is alkyl and A' and A" together with the nitrogen atom to which they are attached represent a heterocyclic ring, or A and A' and A" together with the nitrogen atom to which they are attached represent a heterocyclic ring; (12) formamidomethyl -CH 2 NHC(0)H or an acylaminomethyl group -CH 2 NH-C(0)A or -CH 2 NH-Z wherein A and Z are as defined above,- where appropriate R 3 is optionally substituted; and X represents 0, NR or S, wherein R is hydrogen or straight or branched C^C^ alkyl, C 3 -C 8 cycloalkyl, C 6 - C 14 aryl or C 7 -C 22 aralkyl group; or an isomer thereof which is a stereoisomer, diastereoisomer, epimer, geometrical isomer or tautomer, or a mixture of any of these isomers . 2. A compound or salt according to claim 1 wherein A is selected from straight or branched C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 6 -C 10 aryl, C 7 -C α3 aralkyl, C 7 -C 13 alkaryl, C 3 -C 8 cycloalkyl and heterocyclyl, and is optionally substituted by one or more of halo, sulfo, carboxy, C ι -C 5 alkylcarbonyloxy, C^C,- alkoxy, Ci-C B alkoxycarbonyl, C^C,- carbamoyl, sulfamoyl, C ι -C 5 carbamoyloxy, C._-C 5 alkyl carboxamido, C ι -C 5 haloalkyl carboxamido, nitro, cyano, diazo, hydroxy, benzhydryl oxy, amino, C 6 -C 10 arylcarbonyl, C 3 -C 10 aryloxy, C 7 -C 13 aralkyloxy, C 7 -C 13 alkaryloxy, C ι -C 5 alkanoyl, Ci-Cg alkanoyloxy, Ci-Cg alkylsulfonyl, C 6 -C ι0 aryl carbonyl oxy, C 6 - C 10 aryl carboxy, C 7 -C 13 alkaryl carboxy, C 7 -C ι3 aralkyl carbonyl oxy, C 7 -C 13 aralkanoyloxy, C 7 -C 13 alkaryl carbonyl oxy, C 7 -C 13 aralkyl carboxy, Ci-Cg halocarbamoyl, alkylcarboxy, C ι -C 3 alkanoyl amido,- Q and W, each independently, are (1') chloro, fluoro or bromo; (2') straight or branched alkenyl; (3') Ci-Cg alkyloxy, C ι -C 5 alkenyloxy, C 6 -C ι0 aryloxy, C 7 -C 10 aralkyloxy, heterocyclyl oxy,- (4') Ci-Cg alkylthio, C 2 -C 3 alkenylthio, C 6 -C 10 arylthio, C 7 - Ci o aralkyl thio, heterocyclyl thio ; (5') Ci-Cg alkyl sulf inyl, C 2 -C 5 alkenylsulf inyl, C 6 -C ι0 arylsulf inyl, C 7 -C ι0 aralkylsulf inyl, heterocyclylsulf inyl; (6') Ci-Cg alkylsulfonyl, C 2 -C 5 alkenyl sulf onyl, C 6 -C 10 arylsulf onyl, C 7 -C ι0 aralkylsulf onyl, heterocyclyl sulf onyl; (7') phenyl selenyl, phenylseleninyl, phenyl selenonyl; (8') Ci-Cg alkyl carbonyl, C 2 -C 5 alkenyl carbonyl, C 6 -C 10 arylcarbonyl, C 7 -C 10 aralkyl carbonyl, heterocyclyl carbonyl; (9') C ι -C 3 alkylcarbonyloxy, C 2 -C 5 alkenyl carbonyl oxy, C 3 -C ι0 aryl carbonyloxy, C 7 -C ι0 aralkylcarbonyloxy, heterocyclylcarbonyloxy,- (10') Ci-Cg alkyl sulfonyloxy, C 2 -C 5 alkenyl sulfonyloxy, C 6 - C 10 arylsulfonyloxy, C 7 -C ι0 aralkylsulf onyloxy, heterocyclylsulf onyloxy; (11') Ci-Cg alkyl carboxamido, C 2 -C 3 alkenyl carboxamido, C 6 - C 10 aryl carboxamido, C 7 -C 10 aralkyl carboxamido, heterocyclyl carboxamido ,- (12') nitro, azido, cyano, formyloxy, formamido,- or Q and W taken together constitute an oxo group, or a methylene group, or an optionally substituted cyclopropyl or oxirane group, or a group of formula =CHY or =CHC(0)Y or =CHC(0)0Y or alkenyl, C 6 -C 10 aryl, C 7 -C 10 aralkyl or heterocyclyl; and, where appropriate, are optionally substituted by one or more substituents for the groups defined under (1')- (11') being selected from halo, sulfo, carboxy, C ι -C 3 alkylcarbonyloxy, Ci-C 5 alkoxy, C ι -C 5 alkoxycarbonyl, C ι -C 5 carbamoyl, sulfamoyl, C ι -C 5 carbamoyloxy, C ι -C 5 alkylcarboxamido, C ι -C 5 haloalkyl carboxamido, nitro, cyano, diazo, hydroxy, benzhydryl oxy, amino, C 6 -C ι0 arylcarbonyl, C 6 -C 10 aryloxy, C 7 -C ι3 aralkyloxy, C 7 -C 13 alkaroloxy, alkanoyl, Ci-Cg alkanoyloxy, C ι -C 5 alkylsulfonyl, C 6 -C 10 aryl carbonyl oxy, C 6 -C 10 arylcarboxy, C 7 -C 13 alkaryl carboxy, C 7 -C 13 aralkyl carbonyl oxy, C 7 -C 13 alkaryl carbonyloxy, C 7 -C 13 aralkanoyloxy, C 7 -C 13 aralkyl carboxy, Ci-Cg halocarbamoyl, Ci-Cg alkylcarboxy, alkanoyl ami do, C 7 -C 13 alkaryl carbonyl, C 7 -C 13 aralkyl carbonyl, C. . -C 5 alkylthio, C 6 -C 10 arylthio, alkylsulfonyl, C 6 -C 10 arylsulf onyl, sulfo alkyl, carboxy C 3 .-C 5 alkylthio, Ci- Cg alkylcarbonyloxy Ci-Cg alkylthio, C 2 -C 10 secondary amino, C 3 -C 1B tertiary amino, di-Ci-Cg alkylamino, alkylamino alkyl, oxo, halo Ci-Cg alkanoyl, straight or branched C ι -C 5 alkyl and straight or branched C 2 -C 5 alkenyl ; Ri is either hydrogen or halogen, or an optionally substituted straight or branched C 2 -C 5 alkyl or alkenyl, or an optionally substituted C 7 -C 10 aralkyl or (heterocyclyl) alkyl ,- optional substituents being selected from nitro, cyano, carbamoyl, hydroxy, carboxy, amino, methoxycarbonyl , benzhydryloxycarbonyl, tert-butoxycarbonyl, acetyl, acetoxy, formamido, methoxy, sulfonyl, methylthio, phenoxy, halogen; R 2 is either ( 1 ' ) hydrogen • (2') halogen (3') an optionally substituted straight or branched C ι -C 5 alkyl, Ci-Cg alkenyl or C 7 -C 10 aralkyl; (4') optionally substituted C 6 -C 10 arylthio, or heterocyclyl thio ; (5') a group 0C(0)R 4 wherein R 4 is hydrogen, or an optionally substituted C ι -C 5 straight or branched alkyl or alkenyl or an optionally substituted C 3 -C 6 cycloalkyl, C 6 -C 14 aryl C 7 -C 14 aralkyl, heterocyclyl; the optional substituents being selected from halo, sulfo, carboxy, Ci-Cg alkylcarbonyloxy, C_-C 3 alkoxy, Ci-C 5 alkoxycarbonyl, C ι -C 3 carbamoyl, sulfamoyl, C ι -C 5 carbamoyl oxy, C ι -C 5 alkyl carboxamide, Ci-Cg haloalkylcarboxamido, nitro, cyano, diazo, hydroxy, benzhydryl oxy, amino, C 6 -C ι0 arylcarbonyl, C 6 -C 10 aryloxy, C 7 -C 13 aralkyloxy, C 7 -C 13 alkaryloxy, Ci-Cg alkanoyl, C- . -C 5 alkanoyloxy, Ci-Cg alkylsulfonyl, C 6 -C 10 aryl carbonyl oxy, C 6 - C 10 aryl carboxy, C 7 -C 13 alkaryl carboxy, C 7 -C 13 aralkyl carbonyloxy, C 7 -C 13 aralkyl carboxy, C 7 -C 13 alkaryl carbonyl oxy, C 7 -C 13 aralkanoyloxy, C^-C 3 halocarbanoyl, Ci-Cg alkylcarboxy, C ι -C 5 alkanoyl amido, C 7 - C 13 alkaryl carbonyl, C 7 -C 13 aralkyl carbonyl, alkylthio, C 6 -C 10 arylthio, alkylsulfonyl, C 6 -C 10 arylsulf onyl, sulfo C jL -Cg alkyl, carboxy Ci-Cg alkylthio, C 2 -C 10 secondary amino, C 3 -C 15 tertiary amino, di-Ci-Cg-alkylamino, alkylamino- Ci-Cg alkyl, oxo, Ci-C 5 haloalkanoyl, straight or branched C ι -C E alkyl and straight or branched C 2 -C 5 alkenyl; R 3 is either hydrogen or (1') methyl, chloromethyl, bromomethyl, benzyl, ethyl, propyl, phenyl (2' ) chloro (3') methoxy or benzyloxy (4') methylthio (5') formyl, acetyl, benzoyl, carboxy, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl or benzyloxycarbonyl; (6') methoxymethyl, ethoxymethyl, isopropoxymethyl,- or benzyloxymethyl, phenoxymethyl, 3-pyridyloxymethyl wherein the phenyl and pyridyl rings are either unsubstituted or substituted by one group or two equal or different groups chosen from hydroxy, carboxy, amino, halogen and C 1 -C 4 alkoxycarbonyl,- (7') a heterocyclylthiomethyl group wherein the heterocyclyl ring either unsubstituted or substituted by one group or two equal or different groups chosen from the following: hydroxy, carboxy, amino, sulfo, dimethylaminomethyl, carboxymethyl, carboxymethylthio, cyano, cyanomethyl, nitro, methoxy, methylthio, acetoxy, halogen or C^C j alkyl or alkenyl; (8') acetoxymethyl, benzoyloxymethyl, phenylacetoxymethyl or C 3 -C 6 alkanoyloxymethyl wherein the above groups are either unsubstituted or substituted by one or more groups selected from carboxy, hydroxy, C 1 -C 3 alkoxy,- (9') trialkylammoniomethyl wherein the alkyl group is chosen from methyl, ethyl or propyl; N- methylpyrrolidiniomethyl, N-methylpiperidimiomethyl, N- methylmorpholiniomethyl; (10') pyridiniomethyl which is either unsubstituted or substituted on the heterocyclic ring by fluoro, clhoro, methoxy, hydroxy, carboxy or carbamoyl; (11' ) carbamoyloxymethyl; (12' ) carboxy; and X represents 0, S or NR, wherein R is as defined in claim 1. 3. A compound or salt according to claim 1 or 2 wherein A is a group selected from methyl, tert-butyl, 2- phenyl-2-propyl, benzyl and diphenylmethyl, which groups are optionally substituted by one or more substituents selected from carboxy, carbamoyl, methanesulfonyl, methoxy, ethoxy, tert-butoxy, benzyloxy, acetoxy, pivaloyoxy, benzoxy, carboxymethyl, -C 6 H 4 -C00H, C 6 H 5 C00-, -CH 2 -C 6 H 4 -COOH, CH 3 -C 6 H 4 -C00-, C 6 H S -CH 2 - COO-, -C 6 H 4 -CH 2 COOH, benzoyl, pivaloyl, formamido, acetamido, trifluoroacetamido and pivalamido; Q and W, which are as defined in claim 1 or 2, are independently each optionally substituted, where appropriate, by one or more substituents selected from fluoro, chloro, bromo, carboxy, tetrazolyl, carbamoyl, methanesulfonyl, benzyloxy, benzoxy, acetoxy, pivaloyloxy, methylthio, phenylthio, benzenesulfonyl, sulfomethyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxymethylthio, -C 6 H 4 -COOH, C 6 H 5 COO-, -CH 2 -C 6 H 4 -COOH, CH 3 - C 6 H 4 -C00-, C 6 H s -CH 2 -C00-, -C 6 H 4 CH 2 COOH, acetyl, trifluoroacetyl, benzoyl, pivaloyl, dimethylamino, diethylamino, dimethylaminoethyl, formamido, acetamido, trifluoroacetamido, pivalamido, vinyl and allyl; and R 2 , which is as defined in claim 1 or 2, is optionally substituted where appropriate by one or more substituents selected from fluoro, chloro, bromo, carboxy, tetrazolyl, carbamoyl, methanesulfonyl, benzyloxy, benzoxy, acetoxy, pivaloyloxy, methylthio, phenylthio, benzenesulfonyl, sulfomethyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxymethylthio, -C 6 H 4 -COOH, C 6 H 5 C00-, -CH 2 -C 6 H 4 -COOH, CH 3 - C 6 H 4 -COO-, -OCOCH 2 C 6 H s , HOCOCH 2 C 6 H 4- , acetyl, trifluoroacetyl, benzoyl, pivaloyl, dimethylamino, diethylamino, dimethylaminoethyl, formamido, acetamido, trifluoroacetamido, pivalamido, vinyl and allyl. 4. A compound selected from 7, 7-Dibromo-4-tert-butylcarbonyl-3-methyl-3-cephem 1,1- dioxide 7,7-Diallyl-4-tert-butylcarbonyl-3-methyl-3-cephem 1,1- dioxide 7, 7-Diallyl-2-bromo-4-tert-butylcarbonyl-3-methyl-3-cephem l, l-dioxide 7, 7-Diallyl-4-tert-butylcarbonyl-3-methyl-2- (1-methyl- 1,2,3,4-tetrazol-5-yl) thio-3-cephem 1, l-dioxide 7, 7-Diallyl-4-tert-butylcarbonyl-3-methyl-2- (5-methyl- 1,3, 4-thiadiazol-2-yl) thio-3-cephem 1, l-dioxide 7, 7-Diallyl-4-tert-butylcarbonyl-2- (4-carboxybenzoyl) oxy-3- methyl-3-cephem 1,1 dioxide 7α-Allyl-73-bromo-4-tert-butylcarbonyl-3-methyl-cephem 1,1- dioxide 7/3-Bromo-4-tert-butylcarbonyl-7α-methoxy-3-methyl-3-cephem 1, l-dioxide 7ot-Allyl-4-tert-butylcarbonyl-7/3-methoxy-3-methyl-3-cephem 1, l-dioxide 7 a-Allyl-4-tert-butylcarbonyl- 7β-methoxy-3-methyl-2- (5- methyl-1, 3,4-thiadiazol-2-yl) thio-3-cephem 1, l-dioxide 7α-Allyl-4-tert-butylcarbonyl-7/3-methoxy-3-methyl-2- (1- methyl-1, 2,3, 4-tetrazol-5-yl) thio-3-cephem 1, l-dioxide 7c-Allyl-2- (6-hydroxy-2-methyl-5-oxo-2, 5-dihydro-l, 2, 4-1riazin-3-yl) thio-4-tert-butylcarbonyl-7/3-methoxy-3- methyl-3-cephem 1, l-dioxide 7 a-Allyl-2-benzoyloxy-4-tert-butylcarbonyl-7/3-methoxy-3- methyl-3-cephem 1, l-dioxide 4-tert-Butylcarbonyl-7-methoxy-3-methyl-7- (1-methyl- 1,2,3, 4-tetrazol-5-yl) thio-3-cephem 1, l-dioxide 7jβ-Bromo-7o'-methoxy-3-methyl-4-phenylcarbonyl-3-cephem 1, 1- dioxide 7α-Allyl-7/3-methoxy-3-methyl-4-phenylcarbonyl-3-cephem 1, 1- dioxide 7o!-Allyl-7/3-methoxy-3-methyl-2- (l-methyl-l, 2,3, 4-tetrazol- 5-yl) thio-4-phenylcarbonyl-3-cephem 1, l-dioxide 4-tert-Butylcarbonyl-7/3-methoxy-3-methyl-7cϋ-propyl-3-cephem 1, l-dioxide 4-tert-Butylcarbonyl-7/3-methoxy-3-methyl-2- (1-methyl- 1, 2, 3,4-tetrazol-5-yl) thio-7cϋ-propyl-3-cephem 1, l-dioxide 2-Bromo-3-bromomethyl-4-tert-butylcarbonyl-7,3-methoxy-7α- propyl-3-cephem l, l-dioxide and 3-bromomethyl-4-tert- butylcarbonyl-7/3-methoxy-7α-propyl-3-cephem l, l-dioxide 4-tert-Butylcarbonyl-7/3-methoxy-3- (l-methyl-l, 2, 3,4- tetrazol-5-yl)thiomethyl-7α-propyl-3-cephem 1,l-dioxide 4-tert-Butylcarbonyl- β-methoxy-3- (6-hydroxy-2-methyl-5-oxo -2,5-dihydro-l,2,4-triazin-3-yl)thiomethyl-7α-propyl-3- cephem l, l-dioxide 4-tert-Butylcarbonyl-73-methoxy-2- (l-methyl-l,2,3,4- tetrazol-5-yl)thio-3- (l-methyl-l,2,3,4-tetrazol-5- yl)thiomethyl-7α-propyl-3-cephem l,l-dioxide 4' -tert-Butyl-7/3-methoxy-7α-propyl-furo[3,4-c] cephem 1,1- dioxide,- and pharmaceutically or veterinarily acceptable salts thereof; and the stereoisomers, diastereoisomers, geometrical isomers, and tautomers thereof, and their mixtures. 5. A compound according to any one of the preceding claims, or a pharmaceutically or veterinarily acceptable salt thereof, of the formula (lc) or (Id) ,- 6. A process for preparing a compound as defined in claim 1, or a pharmaceutically or veterinarily acceptable salt thereof, which process comprises: (i) reacting a compound of formula (II) wherein A, R 1( R 2 and R 3 are as defined in claim 1 with either (i a ) a reagent of formula (III) Q-W (III) wherein Q and W, being the same or different, are as defined in claim 1; or (i b ) reagents of formulae (IV) and (V) Q-H (IV) W-L (V) wherein Q and W are as defined above and L is a leaving group (ii) if needed, subjecting a compound of formula (Ia) , wherein A, Q, W, R_ and R 3 are as above defined, to known processes and/or conventional reactions which entail the transformation of any of the groups A,Q,W,R 1( R 2 and R 3 of a compound of formula (Ia) to afford a different compound of formula (Ia) wherein A, Q, W, R lf R 2 and R 3 are as above defined or a compound of the formula (Ib) , (iii) if desired, converting the resulting compound of formula (Ia) or (Ib) into a pharmaceutical or veterinarily acceptable salt thereof. 7. A pharmaceutical or veterinary composition comprising a suitable carrier and/or diluent and, as an active principle, a compound according to any one of claims 1 to 5 or a pharmaceutically or veterinarily acceptable salt thereof. 8. A compound or salt as defined in any one of claims 1 to 5 for use in a method of treatment of the human or animal body by therapy. 9. A compound or salt as claimed in claim 8, for use in the treatment of inflammatory or degenerative diseases caused by proteolytic enzymes in mammals including humans. 10. A compound or salt as claimed in claim 8 for use in the treatment of emphysema, adult respiratory distress syndrome, rheumatic fever, spondylitis, gout, lupus or psoriasis, or in the control of tumor invasion.

Inventors: ALPEGIANI MARCO, BISSOLINO PIERLUIGI, CORIGLI RICCARDO, PERRONE ETTORE, ALPEGIANI, MARCO, BISSOLINO, PIERLUIGI, CORIGLI, RICCARDO, PERRONE, ETTORE
Applicants: PHARMACIA & UPJOHN SPA, PHARMACIA & UPJOHN S.P.A.
Application year: 1996
Main classification: C07D501
IPC codes: A61K31, A61P43, C07D501