MXPA99011694A - Reverse hydroxamate inhibitors of matrix metalloproteinases - Google Patents

Abstract

Compounds having formula (I) are matrix metalloproteinase inhibitors. Also disclosed are matrix metalloproteinase-inhibiting compositions and methods of inhibiting matrix metalloproteinase in a mammal.

Description

INHIBITORS OF INVERSE HYDROXAMATES OF METAL OPROTEI NASAS D E MAT R I Z Technical Field This invention relates to compounds having activity to inhibit matrix metalloproteinases, to pharmaceutical compositions comprising these compounds and to a medical method of treatment. More particularly, this invention concerns compounds containing reverse hydroxamate, which inhibit matrix metalloproteinases, pharmaceutical compositions comprising these compounds, and a method for inhibiting matrix metalloproteinases.

BACKGROUND ART Matrix metalloproteinases (MMPs) are a class of extracellular enzymes that include collagenase, stromelysin and gelatinase, which are believed to be involved in the destruction of tissue, which accompanies a large number of disease states ranging from arthritis until cancer. Normal connective tissue cells are embedded within an extracellular matrix of glycoproteins and high molecular weight proteins. In healthy tissue, there is a continuous and delicately balanced series of processes, which include cell division, matrix synthesis and matrix degradation. In certain pathological conditions, an imbalance of these three processes can lead to restructuring of inappropriate tissue. In arthritis, for example, mobility of the joints can be lost when there is inadequate remodeling of load-bearing joint cartilage. With cancer, the lack of coordination of cell division and the two processes of matrix synthesis and degradation can lead to the conversion of transformed cells to invasive phenotypes, in which an increased matrix disorder allows tumor cells to penetrate Basement membranes surrounding capillaries which, in turn, can lead to subsequent metastasis. Interest in discovering therapeutic agents which bind to and inhibit MMP's has increased. The discovery of new therapeutic agents possessing this activity will lead to new drugs having a novel mechanism of action to combat disease states involving tissue degenerative processes that include, for example, rheumatoid arthritis, osteoarthritis, osteopenias, such as, osteoporosis, periodontitis. , gingivitis, corneal, epidermal or gastric ulceration, and tumor growth and metastasis or invasion.

BRIEF DESCRIPTION OF THE INVENTION In its main embodiment, the present invention provides a matrix metalloproteinase inhibitor compound of formula (I), (I), or a pharmaceutically acceptable salt or prodrug thereof, wherein A is hydrogen; n is zero; Rf and R3 are independently selected from the group consisting of (1) hydrogen and (2) alkyl of one to six carbon atoms; R2 and R4 are independently selected from the group consisting of (1) hydrogen; (2) alkyl of one to six carbon atoms; (3) alkenyl of one to six carbon atoms; (4) alkynyl of one to six carbon atoms; (5) alkoxyalkyl; (6) alkoxycarbonylalkyl, wherein the alkylene and alkyl groups are independently from one to six carbon atoms; (7) halogalkyl of one to six carbon atoms; (8) hydroxyalkyl, wherein the alkylene group is from one to six carbon atoms; (9) - (alkylene) -S (0) p-alkyl, wherein the alkylene is from one to six carbon atoms, and the alkyl is from one to six carbon atoms; (10) phenyl; (11) phenylalkoxyalkyl, wherein the alkylene and alkyl groups are independently from one to six carbon atoms; (12) phenylalkyl, wherein the alkylene group is from one to six carbon atoms; (13) phenoxyalkyl, wherein the alkylene group is from one to six carbon atoms; (14) - (alkylene) -N (R5) SO2-phenyl, wherein the alkylene is from one to six carbon atoms, and wherein R5 is selected from the group consisting of (a) hydrogen and (b) one to six carbon atoms; (1 5) (heterocycle) oxyalkyl, wherein the alkylene group is from one to six carbon atoms; (16) - (alkylene) -S (O) p-heterocycle, wherein the alkylene group is from one to six carbon atoms; (17) - (alkylene) -heterocycle, wherein the alkylene group is from one to six carbon atoms; and (1 8) - (alkylene) -NR 6 R 7, wherein the alkylene group is from one to six carbon atoms, wherein for (1 5) - (1 7), the heterocycle is selected from the group consisting of (a ) pyridyl, (b) pyrazinyl, (c) pyridazinyl, (d) furyl, (e) thienyl, (f) isoxazolyl, (g) oxazolyl, (h) thiazoyl and (i) isothiazolyl, and wherein for (1) ) - (17), phenyl, phenyl parts of phenylalkoxyalkyl, phenylalkyl, - (alkylene) -N (R 5) SO 2 -phenyl, phenoxyalkyl, and - (alkylene) -S (O) p-phenyl, and heterocycle, the heterocycle portions of (heterocycle) oxyalkyl, - (alkylene) -heterocycle and - (alkylene) -S (O) p-heterocycle are optionally substituted with one, two or three substituents independently selected from the group consisting of (a ) alkyl of one to six carbon atoms; (b) alkoxy of one to six carbon atoms; (c) alkoxyalkyl, wherein the alkyl group and the alkylene group are independently from one to six carbon atoms; (d) halo; (e) haloalkyl of one to six carbon atoms; (f) hydroxy; (g) hydroxyalkyl of one to six carbon atoms; (h) - (alkylene) -heterocycle, (i) - (alkylene) -phenyl, (j) -N (R5) SO2-alkyl, (k) phenyl, wherein the phenyl is optionally substituted with 1, 2, 3 , 4 o substituents independently selected from the group consisting of (i) cyano, (ii) nitro, and (iii) halo, (1) -C ()) R R5; and (m) -C (0) NRxRy, wherein Rx and Ry are independently selected from the group consisting of (i) alkyl of one to six carbon atoms, (ii) phenyl and (iii) phenylalkyl, wherein para ( ii) and (iii), the phenyl and the phenyl portion of phenylalkyl are optionally substituted with substituents independently selected from the group consisting of halo and alkoxy of one to six carbon atoms, and wherein for (1 8), R 1 and R-? are independently selected from the group consisting of (a) hydrogen; (b) alkyl of one to six carbon atoms; (c) cycloalkyl of three to eight carbon atoms; (d) cycloalkylalkyl, wherein the cycloalkyl group is from three to eight carbon atoms, and the alkylene group is from one to ten carbon atoms; (e) alkanoyl of one to ten carbon atoms; (f) phenyl and (g) phenylalkyl, wherein the alkylene group is from three to ten carbon atoms, wherein for (f) and (g), the phenyl and phenyl portion of phenylalkyl are optionally substituted with one or two substituents independently selected from the group consisting of (i) alkyl of one to six carbon atoms; (ii) alkoxy of one to six carbon atoms; (iii) perfluoroalkyl of one to six carbon atoms; (iv) halo; (v) haloalkyl of one to six carbon atoms and (vi) alkanoyl of one to six carbon atoms; or R6 and R7, taken together with the nitrogen atom to which they are attached, define a group selected from the group consisting of (1) morpholinyl; (2) thiomorpholinyl; (3) thiomorpholinyl sulfone; (4) pyrrolidinyl; (5) piperazinyl; (6) piperidinyl; (7) succinimidyl; (8) maleimidyl; (9) glutarimidyl; (10) phthalimidyl; (11) naphthalimidyl; wherein for (1) - (23), the groups defined by R6 and R7, together with the nitrogen atom to which they are attached, are optionally substituted with one or two substituents independently selected from the group consisting of (a) halo, (b) alkyl, (c) alkoxy, (d) phenoxy, (e) phenylalkyl and (f) benzyloxy; or Rt and R2, taken together with the carbon atom to which they are attached form a ring selected from the group consisting of (1) spiroalkyl of three to eight carbon atoms and (2) tetrahydropyranyl; or R3 and R, taken together with the carbon atom to which they are attached, form a spiroalkyl group of three to eight carbon atoms; or R-i and R3 taken together with the carbon atoms to which they are attached are a carbocyclic ring of 5, 6 or 7 members; X is selected from the group consisting of (1) -O-; (2) -NR5SO2-; (3) -S (O) p-; and (4) -C (O) -; where each group is drawn with its end to the left, being the end that joins the alkylene group and its end on the right hand, being the end to which it joins Ar-i; Ar-i is phenyl, which is optionally substituted with one or two substituents independently selected from the group consisting of (a) alkyl of one to six carbon atoms; (b) perfluoroalkyl of one to six carbon atoms; (c) halo; (d) haloalkyl of one to six carbon atoms; (e) alkoxy of one to six carbon atoms; (f) hydroxy; (g) hydroxyalkyl of one to six carbon atoms; (h) alkoxyalkyl, wherein the alkyl and alkylene groups are independently from one to six carbon atoms; e (i) n itro; Y is selected from the group consisting of (1) a covalent bond, (2) -O-, (3) alkylene of two to four carbon atoms, (4) piperidinyl, (5) alkylene of two carbon atoms, ( 6) alkynylene of two carbon atoms, (7) -S (O) p- and (8) -C (O) -; and Ar2 is an aryl group selected from the group consisting of (1) phenyl; (2) pyridyl; (3) pyrazinyl; (4) pyridazinyl; (5) furyl; (6) thienyl; (7) isoxazolyl; (8) oxazolyl; (9) thiazolyl e (10) isothiazolyl, wherein the aryl group is optionally substituted with one, two or three substituents independently selected from the group consisting of (a) alkyl of one to six carbon atoms; (b) alkoxy of one to six carbon atoms; (c) alkoxy of one to six carbon atoms substituted with alkoxy of one to six carbon atoms; (d) -alkyl-C02R5; (e) -alkyl-NRxRy; (f) alkoxyalkyl, wherein the alkyl group is from one to six carbon atoms, and the alkylene group is from one to six carbon atoms; (g) cyano; (h) cyanoalkyl of one to six carbon atoms; (i) halo; (j) haloalkyl of one to six carbon atoms; (k) hydroxy; (I) hydroxyalkyl of one to six carbon atoms; (m) hydroxyalkyl, wherein the alkyl group is from one to six carbon atoms; (n) thioalkoxy of one to six carbon atoms; (o) thioalkoxyalkyl, wherein the alkyl group is from one to six carbon atoms, and the alkylene group is from one to six carbon atoms; (p) phenylalkoxy, wherein the alkylene group is from one to six carbon atoms; (q) phenoxy; (r) phenoxyalkyl, wherein the alkylene group is from one to six carbon atoms; (s) (heterocycle) oxy; (t) (heterocycle) oxyalkyl, wherein the alkylene group is from one to six carbon atoms; (u) perfluoroalkyl of one to six carbon atoms; (v) perfluoroalkoxy, wherein the perfluoroalkyl part is from one to six carbon atoms; (w) sulfinylalkyl, wherein the alkyl part is from one to six carbon atoms; (x) sulfonylalkyl, wherein the alkyl part is from one to six carbon atoms; (y) wherein X is selected from -CH2-, -CH2O- and -O-, and Y is selected from -C (O) - and - (C (R ") 2) V-, where R" is hydrogen or alkyl from one to four carbons, and v is 1 -3; (z) -N (R5) S02R5-, wherein R5 is as previously defined and R5- is selected from the group consisting of (i) hydrogen and (ii) alkyl of one to six carbon atoms; and (aa) -SO2N (R5) (R5.). where for (s) and (t), the heterocycle part of (heterocycle) oxy and (heterocycle) oxyalkyl are selected from the group consisting of (i) pyridyl; (ii) pyrazinyl; (iii) pyridazinyl; (iv) furyl; (v) thienyl; (vi) isoxazolyl; (vii) oxazolyl; (viii) thiazolyl e (ix) isothiazolyl, and wherein for (s) and (t), the heterocycle part of (heterocycle) oxy and (heterocycle) oxyalkyl are optionally substituted with one or two substituents independently selected from the group consisting of (i) alkyl of one to six carbon atoms; (ii) alkoxy of one to six carbon atoms; (iii) perfluoroalkyl of one to six carbon atoms; (iv) halo; (v) cyano; (vi) cyanoalkyl; (vii) haloalkyl of one to six carbon atoms, and (viii) alkanoyl of one to six carbon atoms, and wherein for (q) and (r), the phenyl part of phenoxy and phenoxyalkyl are optionally substituted with one or two substituents independently selected from the group consisting of (i) alkyl of one to six carbon atoms; (ii) alkoxy of one to six carbon atoms; (iii) perfluoroalkyl of one to six carbon atoms; (iv) halo; (v) cyano; (vi) cyanoalkyl; (vii) haloalkyl of one to six carbon atoms and (viii) alkanoyl of one to six carbon atoms.

In another aspect, the present invention provides pharmaceutical compositions, which comprise a therapeutically effective amount of compound of formula I in combination with a pharmaceutically acceptable carrier. In yet another aspect, the present invention provides a method for inhibiting matrix metalloproteinases in a host mammal in need of such treatment, which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula I.

DETAILED DESCRIPTION OF THE INVENTION Definition of terms As used throughout this specification and the appended claims, the following terms have the specified meanings: The term "alkyl", as used herein, represents a monovalent group derived of a straight or branched chain saturated hydrocarbon by the removal of a simple hydrogen atom, and is exemplified by methyl, ethyl, n- and iso-propyl, n-, sec-, ε- and tert-butyl, neopentyl and the like. The term "alkanoyl", as used herein, represents an alkyl group, as defined above, attached to the parent molecular group through a carbonyl group and exemplified by formyl, acetyl, propionyl, butanoyl, and the like. The term "alkenyl", as used herein, represents straight or branched chain monovalent groups containing a double carbon-carbon lane derived from an alkene by the removal of a hydrogen atom, and is exemplified by ethenyl, 1- propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl and the like. The term "alkoxy", as used herein, represents an alkyl group attached to the parent molecular group through an oxygen atom and is exemplified by methoxy, isopropoxy, tert-butoxy and the like. The term "alkoxyalkyl", as used herein, represents an alkyl group to which an alkoxy group is attached. The term "alkoxycarbonyl", as used herein, represents an ester group, that is, an alkoxy group attached to the parent molecular group through a carbonyl group, and is exemplified by methoxycarbonyl, ethoxycarbonyl, and the like. The term "alkoxycarbonylalkyl", as used herein, represents an alkyl group, as defined above, substituted by an alkoxycarbonyl group. The term "alkylene", as used herein, represents a saturated divalent hydrocarbon group derived from a saturated straight-chain or branched hydrocarbon by the removal of two hydrogen atoms and is exemplified by methylene, ethylene, isopropylene and the like. The term "alkynyl", as used herein, represents straight or branched chain monovalent groups of two to six carbon atoms containing a carbon-carbon triple bond derived from an alkyne by the removal of a hydrogen atom and is exemplified by ethynyl, 1-propynyl and the like. The term "benzyloxy", as used herein, represents phenyl- (CH2) -O-. The term "cyano", as used herein, represents a -CN group. The term "cyanoalkyl," as used herein, represents a cyano group attached to the parent molecular moiety through an alkyl group. The term "cycloalkyl", as used herein, represents a monovalent saturated cyclic hydrocarbon group and is exemplified by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo [2.2. 1] heptyl and similes. The term "cycloalkylalkyl", as used herein, represents a cycloalkyl group attached to the parent molecular group through an alkylene group. The term "halo", as used herein, represents F, Cl, Br and I. The term "haloalkyl", as used herein, represents an alkyl group substituted by one, two, three or four halogen atoms and is exemplified by chloromethyl, bromoethyl, chlorodifluoromethyl, and the like. The term "heterocycle", as used herein, represents a ring of five, six or seven members containing one, two or three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. The five-member ring has zero to two double bonds and the six- and seven-member rings have zero to three double bonds. The heterocycles include indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, benzothienyl, pyrrolyl, pyrroliniin, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl. , isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiomorpholino sulfone, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, oxadiazolyl, tladiazolyl, pyrimidyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothioquinolyl, pyranyl, dihydropyranyl, dithiazolyl, benzofuranyl, benzothienyl, succinimidyl, maleic idyl, glutarimidyl, phthalimidyl, naphthalimidyl and the like.

The heterocycles also include ° ¥ xr -fr r and similar.

The term "(heterocycle) oxy", as used herein, represents a heterocycle group attached to the parent molecular moiety through oxygen. The term "(heterocycle) oxyalkyl", as used herein, represents a group (heterocycle) oxy linked to the parent molecular group through an alkyl group. The term "hydroxy", as used herein, represents an -OH group. The term "hydroxyalkyl", as used herein, represents an alkyl group, as defined above, substituted by one to three hydroxy groups, with the proviso that not more than one hydroxy group may be attached to a carbon atom simple of the alkyl group and is exemplified by hydroxymethyl, dihydroxypropyl and the like. The term "nitro", as used herein, refers to -N02. The term "perfluoroalkyl", as used herein, represents an alkyl group, as defined herein, wherein each hydrogen radical attached to the alkyl group has been replaced by a fluoride radical. Perfluoroalkyl groups are exemplified by trifluoromethyl, pentafluoroethyl and the like.

The term "perfluoroalkoxy", as used herein, refers to a perfluoroalkyl group, as defined herein, attached to the parent molecular group through an oxygen atom. The term "pharmaceutically acceptable salt", as used herein, represents those salts which are, within the scope of the correct medical judgment, suitable for use in contact with the tissues of human and lower animals without undue toxicity, irritation, response allergic and the like, and they are coextensive with a reasonable risk / benefit ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M Berge, et al. , describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1 977, 66: 1 -1 9. The salts can be prepared in situ during the isolation and final purification of the compounds of the invention, or separately by reacting the free base group with a suitable organic acid. Representative acid addition salts include salts of acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorrate, canfersulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate , pectinate, persulfate, 3-phenylprpionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, valerate and the like. Representative alkaline or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium and the like, as well as non-toxic ammonium, quaternary ammonium ammonium cations, including, but not limited to, ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine , trimethylamine, triethylamine, ethylamine and the like.

The term "phenoxy", as used herein, represents a phenyl group attached to the parent molecular group through an oxygen atom. The term "phenoxyalkyl", as used herein, represents a phenoxy group attached to the parent molecular group through an alkyl group. The term "phenyl", as used herein, represents an aromatic, monocyclic, 6-membered carbocyclic ring. The term "phenylalkyl", as used herein, represents a phenyl group attached to the parent molecular group through an alkylene group and is exemplified by benzyl, phenethyl and the like. The term "phenylalkoxy", as used herein, represents a phenyl group attached to the parent molecular group through an alkoxy group. The term "phenylalkoxyalkyl" as used herein, represents a phenylalkoxy group, as defined above, attached to the parent molecular group through an alkyl group. The term "prodrug", as used herein, represents compounds that are rapidly transformed in vivo to the parent compound of the above formula, for example, by hydrolysis in the blood. A thorough discussion is provided in T. Higuchi and V. Stella, Prodrugs as Novel Delivery Systems, (Vol. 14 of A. C.S. Symposium Series, and in Edward B.

Roche, ed. , Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1 987, both incorporated herein by reference. The average levels of the compounds of the present invention are, within the scope of the correct medical judgment, suitable for use in contact with the tissues of humans and lower animals with undue toxicity, irritation, allergic response and the like, coextensive with a risk / risk ratio. reasonable profit, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. The term "spiroalkyl", as used herein, represents an alkylene di-radical, the two ends of which are attached to the same carbon atom of the parent group to form a spirocyclic group. The term "sulfinyl", as used herein, refers to a group -S (O) -. The term "sulfinylalkyl", as used herein, refers to an alkyl group, as defined herein, attached to the parent molecular group through a sulfinyl group. The term "sulfonyl", as used herein, refers to a group -SO2-. The term "thioalkoxy", as used herein, represents an alkyl group attached to the parent molecular group through a sulfur atom. The compounds of the present invention can exist as stereoisomers, wherein asymmetric or chiral centers are present.

These compounds are designated by the symbols "R" or "S", depending on the configuration of the substituents around the chiral carbon atom. The present invention contemplates various stereoisomers and mixtures thereof. Stereoisomers include enantiomers and diastereomers, and mixtures of enantiomers or diastereomers are designated (±). The individual stereoisomers of compounds of the present invention can be prepared synthetically from commercially available starting materials, which contain asymmetric or chiral centers, or by the preparation of racemic mixtures followed by the well-known resolution for those of ordinary skill in The technique. These resolution methods are exemplified by (1) attachment of a mixture of enantiomers to a chiral auxiliary, separation of the resulting mixture of diastereomers by recrystallization or chromatography and release of the optically pure product from the auxiliary, or (2) direct separation of the mixture. of optical enantiomers in chiral chromatographic columns.

Preferred Modes The preferred compounds of the present invention have the formula (I), wherein A is hydrogen; Ri. 3 and they are H; X is selected from the group consisting of (1) -O-; (2) -C (O) -; (3) -S (O) p-, where p is 2, and (4) -NR5S02-; Ar! it is phenyl; And it is selected from the group consisting of one (1) covalent bond and (2) -O-; and n is zero; the most preferred compounds of the present invention have the formula (I), wherein A is hydrogen, X is -O-; Ar! it is phenyl; And it is a covalent bond; and N is zero.

Preferred compounds that fall within the scope of formula (I) include, but are not limited to: (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-il ) oxy] methyl] -2-phenoxyethyl] -N-hydroxyformamide, (+) - N- [1 - [[(4'-cyano- [1,1'-biphenl] -4-yl) ox]] methyl] -2- (phenylthio) ethyl] -N-hydroxyformamide, (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] - 2- (2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl) ethyl] -N-hydroxyformamide, (+) - N- [1 - [[(4'-cyano- [1, 1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (±) -N- [ 1 - [[(4'-Cyano- [1,1'-biphenyl] -4-yl) oxl] methyl] -3- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) propyl ] -N-hydroxyformamide, (±) -N- [1 - [[[3 '- (cyanomethyl) - [1,1'-biphenyl] -4-yl] ox]] methyl] pentyl-N-hydroxyformamide , (+) - N- [1 - [[(4'-cyano- [1,1, -biphenyl] -yl) oxy] methyl] -3-methylbutyl] -N-hydroxyformamide, (±) -N- [ 1 - [[(4, -cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2-methylbutyl] -N-hydroxyformamide, (±) -N- [1 - [[(4 '-cyano- [1,1'-biphenyl nyl] -4-yl) oxy] m ethyl] pentyl] -N-hydroxy f orma mida, (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4-methylphenyl) ethyl] -N-hydroxyformamide, ( ±) -N- [1 - [[(4'cyano- [1,1'-biphenl] -4-yl) oxy] -1- (4-fluorophenyl) ethyl] -N-hydroxyformamide, (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4-fluorophenyl) ethyl] -N-hydroxyformamide, (±) - N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] ethyl] -N-hydroxy ormamide, N- [2 - [(4'-cyano- [1,1'-bifenyl] -4-y!) Oxy] ethyl] -Nh id roxy acetamide, N- [2 - [(4'-cyano - [1,1'-biphenyl] -4-yl) oxy] ethyl] -N-hydroxyf ormamide, (+) - N- [1- [4- [2E-phenylethenyl) phenoxy] methyl] -2- (3 , 4,4-trimethyl-2,5-dioxo-1-imidazole id inyl) ethyl] -N-hydroxyform amide, (±) -N- [1 - [[4- (2-furanyl) phenoxy] methyl] - 2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (±) -N- [1 - [[(4'-butoxy [1,1'- biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (±) -N- [1- [ [(4'-Fluoro [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazole id inyl) ethyl] - N-hydroxy-ormamide, (+) - N- [1 - [[(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifluoromethyl) [ 1,1'-biphenyl] -4-yl] oxy] ethyl] -N-hydroxyl ormamide, (±) -N- [1 - [[(4'-methoxy [1,1'-biphenyl] -4-yl] ) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-ylidazole id inyl) ethyl] -N-hydroxy-ormamide, (±) -N- [1 - [[(4 '-methyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazole idin) ethyl] -N-hi droxif ormamide, (±) -N- [1 - [[(4'-butoxy [1, 1'-biphenyl] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazole id inyl) ethyl] -N-hydroxy-ormamide, (±) - N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [(4'-ethoxy [1,1'-biphenyl] -4-yl) oxy] ] ethyl] -N-hydroxyformamide, (±) -N- [1 - [[4- (1,3-benzodioxol-5-yl) phenoxy] methyl] -2- (4,4-dimethyl-2,5- dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (±) -N- [1 - [[(4'-butoxy [1,1'-biphenyl] -4-yl) oxy] methyl] -2- ( 3-methy-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (±) -N- [1 - [[4- (3-thienyl) phenoxy] methyl] -2- (3,4 , 4-trimethyl-2,5-dioxo-1-imidazole idin i I) eti I] - N-hydroxyl ormamide, (±) -N- [1 - [[([1,1'-biphenyl] -4- il) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazole id inyl) ethyl] -N-hydroxy-ormamide, (±) -N- [1 - [[( 3'-Chloro-4'-fluoro [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxy ormamide, ±) -N- [1 - [[(2'-methyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-tr! methyl-2,5-dioxo-1-midazole idinyl) ethyl] -N-hydroxyform amide, +) - N- [1 - [[(4'-cyanol [1,1'-biphenyl] -yl) oxy] methyl ] -2- (2,5-dioxo-1-midazolidinyl) ethyl] -N-hydroxyform amide, ±) -N- [1 - [[(4'-cyanol [1,1'-biphenyl] 4-yl) oxy] methyl] -2- (1,1-dioxido-3-oxo-1,2-benzisothiazol-2 (3H) -yl) ethyl] -N-hydroxyformamide, +) - N- [1 - [(4, 4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'-trifluoro-methoxy) [1,1'-biphenyl] -4-yl] oxy] ethyl] -N-hydroxyformamide, +) - N- [1 - [[4- (4-pheny! -1-piperidinium) phenoxy] methyl] -2 ~ (3,4,4-trimethyl-2,5-d-oxo-1-midazole id inyl) ethyl] -N-hydroxyl ormamide, ±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'-trifluoromethyl] [1 , 1'-biphenyl] -4-yl] oxy] ethyl] -N-hydroxyformamide, ±) -N- [1 - [[(3'-cyano [1,1'-biefnil] -4-yl) oxy] methyl] -2- [methyl [(4-methylphenyl) sulfonyl] amino] ethyl] -N-hydroxyformamide, +) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4- il) oxy] methyl] -2- [4,4-dimethyl-2,5-dioxo-3- (3-pi ridin i I meti I) -1-m-idazol idin il] ethyl] -N-hydroxyl ormamide , ±) -N- [1 - [(4'-cyano [1,1'-bif en il] -4-yl) oxy] -1-meti I propiI] -Nh id roxif ormamide, ±) -N- [1 - [[(3'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo- 1- midazolidinyl) ethyl] -N-hydroxyformamide, ±) -N- [1 - [[[4 '- (methylthio) [1,1'-biefnyl] -4-yl] oxy] methyl] -2- (3 , 4,4-trimethyl-2,5-dioxo-imidazolidinyl) ethyl] -N-hydroxyformamide, +) - N - [1- [4 - [[4- (trifluoromethyl-phenoxy] phenoxy] methyl] -2- (3 , 4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) etl] -N-hydroxyl ormamide, (±) -N- [1 - [[[4 '- (trifluoromethoxy) [1, 1'-biphenyl] -4-yl] oxy] methi]] - 2- (3,4,4, -trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -2-N-hydroxyformamide, (+) -N- [1 - [[[4 '- (methylsulfonyl) [1,1'-biphenyl] -4-yl] oxy] methyl-2- (3,4,4-trimethyl-2,5-dioxo-1 -imidazole id inyl) ethyl] -N-hydroxyformamide ida, (±) -N- [1 - [[[3 '- (cyanomethyl) -4'-methoxy [1,1'-biphenyl] -4-yl] oxy ] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (+) - N- [1 - [[[3 '- (cyanomethyl)] l) [1,1'-biphenyl] -4-yl] oxy] methyl] -3- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) propyl]] - N-hydroxyformamide, (± ) -N- [1 - [[(4'-Butoxy [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (4,4-dimethyl-2, 5-dioxo-1-imidazole id inyl) ethyl] -Nh id roxiformam ida, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] met L] -3- (4,4-dimethyl-2,5-dioxo-1-imidazole id inyl) propyl] -N-hydroxyl ormamide, (±) -N- [1 - [[[4 '- (methylsulfonyl ) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazole id inyl) ethyl] -N-hydroxyl ormamide, (± ) -N- [1 - [[(3'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (2,5-dioxo-1-pyrrolidinyl) ethyl] -N- hydroxyl ormamide, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,6- dioxo-1-piperidinyl) ethyl] -N-hydroxy-ormamide, N- [1S - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (2,5 -dioxo-1-pyrrolidinyl) ethyl] -N-hydroxyformamide, N- [1R - [[(4'-cyano [1,1'-bifenii] -4-yl) oxy] methyl] -2- (2, 5-dioxo-1-pyrrolidinyl) ethyl] -Nh id roxiformam ida, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl ] -2- (3-ethyl-3-methyl-2,5-dioxo-1-pyrroldiinyl) ethyl] -N-hydroxyformamide, (±) -N- [4- [4 - [[(4-chlorophenoxy) phenyl] ] sulfonyl] methyl] tetrahydro-2H-pyran-4-yl] -N-hydroxyformamide, (±) -N- [1 - [[[4'-cyan or [1,1'-biphenyl] -4-yl) oxy] methyl] -2 - [[(2-methoxycarbonyl) -phenyl] thio] ethyl] -N-hydroxy-ormamide, (±) -N- [1- [[(4'-cyano [1,1, -biphenyl] -4-yl) oxy] methyl] -5 - [(4-methyl-2-oxo-2H-1-be nzo piran-6-yl ) oxy] pent il] -Nh id roxiformam da, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] 4-yl) oxy] methyl] -4 - [( 4-meth1l-2-oxo-2H-1-benzopyran-6-yl) oxy] butyl] -N-hydroxyformamide, (±) -N- [1 - [[(4'-cyano [1, 1'-biphenyl] -4-yl) oxy] methyl] -4 - [(4-methyl-2-oxo-2H-1-benzo-pi-ran-7-yl) oxy] butyl] -Nh'droxif Orma measure, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] meth]] - 5 - [(4-methylene-2 -oxo-2H-1-benzopy n-7-i I) oxy] pent i lN-hydroxyl ormamide, (±) -N- [1 - [[(4'-cyano [1,1'-b] Phenyl] -4-yl) oxy] methylene] -2- (5,5-dimethyl-2,4-d-oxo-3-oxazolidinyl) ethyl] -N-hydroxyformamide, (±) -N- [ 1 - [[(4'-cyano [1,1'-biphenl] -4-yl) sulfonyl] methyl] -2- (3,4,4-methyl-2,5) -d -oxo-1-α-dazol-din-yl) ethyl] -N-hydroxy-amide, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4- L) oxy] methylene] -2- (3-methyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo [Beta] -amidazolidinyl) ethyl] -N-hydroxyformamide, (+) - N- [1 - [[(4'-chloro- [1,1'-b-phenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazole idyl) ethyl] -N-hydroxyformamide, (±) -N- [1 - [[(3 '-cyanomethyl- [1,1'-biphenyl] -4-y) oxy] methyl] -2- (3,5,5-trimethyl-2,4-dioxo-1-ylamdazolyl) propyl] -N-hydroxyformamide, (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-i) oxy] meth] -2-isopropylthioethyl] - Nh id roxiformam da, (+) - N- [1 - [[(3'-cyanomethyl- [1,1'-b-phenyl] -4i) oxy] methyl] -2- (3,4,4 -trιmethyl-2,5-dioxo-1-imidazole id inyl) etl] -N-hydroxyl ormamide, (±) -N- [1 - [[(4'-cyano- [1 , 1'-biphenyl] -4-yl) oxy] methyl] -2- (3-ethyl-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (±) - N- [1 - [[(4'-cyano- [1,1'-biphenyl) -4-yl) oxy] methyl] -2- (3-benzyl-4,4-dimethyl-2,5-dioxo- 1-imidazolidinyl) ethyl] -N-hydroxyformamide, (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-i) oxy] methyl] -2- ( 3,5,5-trimethyl-2,4-dioxo-1-imidazole idin il) etll] -N- hydroxyl ormamide, (±) -N- [1 - [[4'-methoxy [1,1'-biphenyl] -4-yl) sulfonyl] methyl] ethyl] -N-hydroxyformamide, (±) -N- [1 - [[(4'-chloro [1,1'-bipheni] -4-yl) sulfonyl] methyl] ethyl] -N-hydroxyformamide ida, (±) -N- [1 - [[4- (1,3-benzodioxol-5-yl) phenyl] sulfonyl] methyl] ethyl] -N-hydroxyformamide, (±) -N- [1 - [[[ 4- (4-chlorophenoxy) phenyl] sulfonyl] methyl] ethyl] -N-hydroxyformamide, (+) - N- [1 - [[(4'-methoxy [1,1'-biphenyl] -4-yl) sulfonyl] methyl] propyl] -N-hydroxyformamide, (±) -N- [1 - [1,1-dimethyl-2 - [(4 '- (trifluoromethyl) [1,1'-biphenyl] -4-yl] sulfonyl] ethyl] -N-hydroxyformamide, (±) -N- [1- [(phenylmethoxy) methyl] -2 - [[4 '- (trifluoromethyl) [1,1'-biphenyl] -4-yl] sulfonyl] ethyl] -Nh id roxiformam ida, (±) -N- [1- [ hydroxymethyl) -2 - [[(4 '- (trifluoromethyl) [1,1'-biphenyl] -4-yl] sulfonyl] ethyl] -N-hydroxyformamide, (±) -N- [1 - [(4.4 -dimeti-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifluoromethyl) [1,1'-biphenl] -4-yl] t] o] ethyl] -N- hydroxyformamide, (±) -N- [1 - [(4-4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifluoromethyl) [1, 1'- biphenyl] -4-yl] sulfonyl] ethyl] -N-hydroxyl ormamide, (+) - N- [1 - [(2,5-dioxo-1-imidazole idinyl) methyl] -2 - [[4 '- ( trif luoromethoxy) [1,1'-biphenyl] -4-yl) oxy] ethyl] -N-hydroxyformamide, (±) -N- [1 - [[[4 '- (trifluoromethyl) [1,1'-biphenyl] ] -4-yl] sulfonyl] methyl] -2- (3,4,4-trimethyl-2, 5-dioxo-1-imidazolidinyl) ethyl] -Nh id roxiformam ida, (+) - N- [1- [ [(4'-Butyl [1,1'-biphenyl] -4-yl) oxy] useful] -2- (3-methyl-2,5-dioxo-1-imidazole id inyl) ethyl] -N-hydroxyl ormamide, (±) -N- [1 - [(3-methyl-2,5-dioxo -1-imidazolidinyl) methyl] -2 - [[4'- (trifluo rom ethoxy) [1,1'-biphenyl] -4-yl] oxy] ethyl] -N-hydroxyformamide, (+) - N- [1 - [4- [4 - [(4'-chloro [1,1'-b-phenyl] -4-M) sulfonyl] methyl] tetrahydro-2H-pyran-4-yl] -Nh id roxiformam ida, (+ ) -N- [1 - [[[4- (4-chlorophenoxy) phenyl] sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyl ormamide , (±) -N- [1 - [[[4- (4-chlorophenoxy) f eni] sulfonyl] methyl] -2- (3,4,4-trimethyl-2, 5-dioxo-1 - imidazolidinyl) ethyl] -N-hydroxyformamide, (±) -N- [1 - [[(4-butyl [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (3,4,4 -trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyl ormamide, (±) -N- [1 - [[(4'-butyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazo I idinyl) ethyl] -N-hydroxyl ormamide, (±) -N- [1 - [[[3 '- ( cyanomethyl) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (+) - N- [1- [4- (2-thienyl) phenoxy] methyl] -2- [1- (3,4,4-tr imethyl-2,5-dioxo-1-imidazole id inyl) ethyl] -N-hydroxyl ormamide, (±) -N- [1 - [[(3-nitro [1,1'-biphenyl] -4-yl) oxy] meth] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (±) -N- [1 - [[(4 '-methyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2 - [[3- (methylsulfonyl) amino] phenyl] ethyl] -N-hydroxy-ormamide, (±) -N- [ 1 - [[[3- (diethylamino) carbonyl] phenyl] methyl] -2 - [(4'-methyl [1,1'-biphenyl] -4-i I) oxy] ethyl] -Nh id roxiformam id a, (±) -N- [1 - [[(4, -cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2 - [(4'-cyano [1,1'-biphenyl]] -4-yl) oxy] ethyl] -Nh id roxiformam id a, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolindinyl) ethyl] -N-hydroxyl ormamide, (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1- imidazolidinyl) methyl] -2 - [[4 '- (2-methoxyethoxy) [1, 1'-bif in 1] -4-yl] oxy] ethyl] -Nh'droxif ormamide, (+) - N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [(4'-propoxy [1,1'-bif in il] -4-i I) oxy] et ii] - -hydroxy ormamide, (+) - N- [1 - [(4,4-dimethyl-2, 5-dioxo-1-im idazole idin) methyl] -2 - [( 4'-pentyloxy [1,1'-bif en yl] -4-i I) oxy] et il] -N-hydroxyl ormamide, (±) -N- [1 - [[[3 '- (cyanomethyl)] [1,1'-biphenyl] -4-yl] sulfonyl] methyl] -3- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) propyl] -N-hydroxyformamide, (±) -N- [1 - [[[4 '- (trifluoromethoxy] [1,1'-biphenyl] -4-yl] sulfonyl] methyl] -2- (3,4,4-tri-methyl-2,5-dioxo-1) -imidazolidinyl) ethyl] -N-hydroxyformamide ida, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (3- methy-2,5-dioxo-1-im idazo I idin il) ethyl] -Nh id roxiformam ida, (+) - N- [1 - [[[3 '- (cyanomethyl) [1,1'-biphenyl] -4-yl] sulfonyl] methyl] -2- (3,4,4-trimethyl-2, 5-di oxo-1-imidazo I idin il) ethyl] -N-hid roxiformam ida, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxyl] methyl] -2- (1,6-dihydro-3-methyl-6-oxo-1-pyrazidazin) ethyl] -Nh id roxiformam id a, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (4, 4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, (±) -N- [1 - [[[4- (4-fluorophenoxy) phenyl] sulfonyl] methyl] -2- (4,4-di-methyl-2, 5-dioxo-1-imidazoIidinyl) ethyl] -Nh id roxiformam ida, (+) - N- [1 - [[4- (4-pyridinyl) phenoxy] met] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -Nh id roxiformam ida, (S) -N- [1 - [(4,4-dimeti-2,5 -dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trif I uoro m ethoxy) [1, 1 '-bif en il] -4-i I] oxy] et il] -N-hydroxyl orma mida, (R) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifluoromethoxy) [1,1'-biphenyl] -4-yl] oxy] ethyl] -N-hydroxyformamide, N- [1 - [[[4 '- (trifluoromethoxy)) [1,1'-biphenyl] -4-yl] oxy] methyl] -3- ( 4,4-dimethyl-2,5-di oxo-1-imidazole id i nyl) propyl] -Nh id roxiformam ida, N- [1- [4 - [(4-pyridinylthio) phenoxy] methyl] -2 - (4,4-Di methyl-2,5-di-oxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, N- [1 - [[[4-chlorophenoxy] phenyl] sulfonyl] methyl] -3- (4,4-dimethyl-2,5-dioxo-1-imidazo lid inyl) propyl] -N-hydroxyformamide ida, N- [1 - [[(4'-cyano [1,1'-biphenyl] -4- l) oxyl] methyl] -2-81,6-dihydro-6-oxo-1-pyridine (I)) i-Nh id roxiformam ida, N- [1 - [[[4 '- (aminosulfonyl)] [1,1'-biphenyl] -4-yl [oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide, N- [1 - [[[4 '- (trifluoromethoxy) [1, 1' -biphenyl] -4-yl] sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] - N-hydroxyformamide, N- [1 - [4 - [(4-pyridinyloxy) phenyl] sulfonyl] ethyl] -N-hydroxyformamide, N- [1 - [[(4-cyanophenoxy) phenyl] sulfonyl] methyl] -2 - (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxy-ormamide, N- [1 - [[4 - [[4- (trifluoromethoxy) phenoxy] phenyl] sulfonyl] methyl] -3- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) propyl] -N-hydroxyl ormamide, and N- [1 - [[4 - [[4- (trifluoromethoxy) phenoxy] phenyl] sulfonyl ] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide.

Pharmaceutical Compositions The present invention also provides pharmaceutical compositions, which comprise compounds of the present invention formulated together with one or more pharmaceutically acceptable, non-toxic carriers. The pharmaceutical compositions can be formulated especially for oral administration in solid or liquid form, for parenteral injection or for rectal administration. The pharmaceutical compositions of this invention can be administered to humans and other animals, orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally or topically (such as powders, ointments or drops), buccally or as an oral or nasal lifting atom. The term "parenteral" administration, as used herein, refers to modes of administration, which include infusion and intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection.

The pharmaceutical compositions of this invention for parenteral injection comprise sterile, pharmaceutically acceptable aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution in sterile injectable solutions or dispersions just before use. Examples of suitable carriers, diluents, solvents or aqueous and non-aqueous vehicles include water, ethanol, polyols (such as, glycerol, propylene glycol, polyethylene glycol and the like), and suitable mixtures thereof, vegetable oils (such as, olive oil). and injectable organic esters, such as ethyl oleate. The proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. These compositions may also contain auxiliaries, such as preservatives, wetting agents, emulsifying agents and dispersing agents. The prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutane, phenol sorbic acid and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be caused by the inclusion of agents (such as aluminum monostearate and gelatin) that retard absorption.

In some cases, in order to prolong the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be achieved by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of drug absorption then depends on its rate of dissolution which, in turn, may depend on the crystal size and crystalline form. Alternatively, the delayed absorption of a parenterally administered drug form is achieved by dissolving or suspending the medicament in an oily vehicle. Injectable depot forms are made by forming microencapsulated drug matrices in biodegradable polymers, such as polylactide-polyglycolide. Depending on the ratio of drug to polymer and the particular polymer nature employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly (orthoesters) and poly (anhydrides). Injectable depot formulas are also prepared by trapping the drug in liposomes or microemulsions, which are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacteria retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions, which can be dissolved or dispersed in sterile water or other sterile injectable medium. before use.

Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is mixed with at least one pharmaceutically acceptable, inert carrier or excipient, such as, sodium citrate or dicalcium phosphate and / or) fillers or extenders, such as, starches, lactose, sucrose , glucose, mannitol and silicic acid; b) binders, such as, carboxymethyl cellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and acacia; c) humectants, such as glycerol; d) disintegrating agents, such as, agar-agar, calcium carbonate, potato or tapioca starch, algic acid, certain silicates and sodium carbonate; e) solution retarding agents, such as paraffin; f) absorption accelerators, such as quaternary ammonium compounds; g) wetting agents, such as cetyl alcohol and glycerol monostearate; h) absorbents, such as kaolin and bentonite clay, and i) lubricants, such as, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures of the same. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type can also be employed as fillings in hard and soft filled gelatin capsules, using excipients such as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, "dragees", capsules, pills and granules can be prepared with coatings and shells, such as, enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and may also be of such composition that they release the active ingredient (s) only, or preferably, in a certain part of the intestinal tract, optionally or in a delayed manner. Examples of crimped compositions that may be used include polymeric substances and waxes. The active compounds may also be in microencapsulated form, if appropriate, with one or more of the aforementioned excipients. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and ices. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate. , benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, peanut, corn, germ, olive, castor bean and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and esters of sorbitan fatty acids and mixtures thereof. In addition to the inert diluents, the oral compositions may also include auxiliaries, such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and flavoring agents.

The suspensions, in addition to the active compounds, may contain suspending agents, such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, tragacanth and mixtures thereof. Compositions for rectal or vaginal administration are preferably suppositories, which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers, such as cocoa butter, polyethylene glycol or a suppository wax, which are solids at room temperature, but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. The compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. The liposomes are formed by mono- or multi-lamellar hydrated liquid crystals, which are dispersed in an aqueous medium. Any lipid metabolizable and physiologically acetable, non-toxic, capable of forming liposomes can be used. The present compositions in liposome form may contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients and the like. The preferred lipids are phospholipids and phosphatidyl cholines (lecithins), both natural and synthetic. Methods for forming liposomes are known in the art. See, for example, Prescott, E., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1 976), p. 33 et seq. Dosage forms for topical administration of a compound of this invention include powders, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any necessary preservative, buffer or propellant, which may be required. Ophthalmic formulations, ointments, powders and eye solutions are also contemplated as being within the scope of this invention. The current dosage levels of active ingredients in the pharmaceutical compositions of this invention can be varied so as to obtain an amount of the active compound (s) that is effective to achieve the desired therapeutic response for a particular patient, compositions and mode of administration. The selected dosage level will depend on the activity of the particular compound, the route of administration, the severity of the condition being treated and the condition and prior medical history of the patient being treated. However, it is within the skill of the art to start with doses of the compound at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. Generally, dosage levels of from about 1 to about 50, more preferably from about 5 to about 20 mg, of active compound per kilogram of body weight per day, when administered orally to a mammalian patient.

If desired, the effective daily dose can be divided into multiple doses for administration purposes, for example, two to four separate doses per day.

Determination of stromelysin inhibition The efficacy of the compounds of this invention as inhibitors of matrix metalloproteinase was determined by measuring the inhibition of stromelysin. The inhibition of stromelysin by the compounds of this invention was determined as follows: recombinant truncated stromelysin (human sequence) produced in E. coli was prepared by expression and purification of the protein as described by Ye et al. (Biochemistry, 1 992, 31, 1 1231-1 1235, which is incorporated herein by reference). The enzyme was assayed by cleaving the thiopide ester substrate Ac-Pro-Leu-Gly- [2-mercapto-4-methyl-pentanoyl] -Leu-Gly-OEt as described by Weingarten and Feder (Anal. Biochem. 1 985, 147, 437-440 (1988), which is incorporated herein by reference) as a vertebrate collagenase substrate. The reported conditions were modified to allow the tests to be performed on a microtiter plate. Upon hydrolysis of the thioester linkage, the liberated thiol group reacted rapidly with 5,5'-dithio-bis (2-nitrobenzoic acid) (DTNB) to produce a yellow color, which was measured by a microtiter plate reader assembly. at 405 nm. The cutting ratios of the substrate by stromelysin in the presence or absence of inhibitors were measured in a 30 minute test at room temperature. Solutions of the compounds were prepared in DMSO, and these were diluted to various concentrations in the assay buffer (M ES 50 mM / NaOH pH 6.5 with 10 mM CaCl2 and 0.2% Pluronic F-68), which was used for dilution of the enzyme and substrate. The potency of the compounds [IC50] was calculated from the inhibition / inhibitor concentration data. The compounds of this invention inhibited stromelysin as shown by the data of representative examples in Table 1.

Table 1 Preparation of compounds of this invention The compounds and processes of the present invention will be better understood in connection with the following synthetic schemes, which are merely illustrative of the methods, by which the compounds of the invention can be prepared and are not intended to limit the scope of the invention as defined in the appended claims. The representative procedures are indicated in the following Schemes 1-5.

Abbreviations The abbreviations, which have been used in the descriptions of the schemes and the examples that follow are: THF for tetrahydrofuran and DMF for N, N-dimethylformamide.

As shown in Scheme 1, deprotonation of the phenolic portion of 1 with a base, preferably, sodium or potassium hydride; and alkylation of the resulting anion with an excess, preferably a two to four times excess, of an electrophilic, preferably, epibromohydrin or epichlorohydrin, provided the alkylated epoxide 2. An excess of a second nucleophile, preferably, an excess of two to four times, it was deprotonated with a base, such as sodium or potassium hydride, and condensed with 2 to provide alcohol 3, which was treated with bis-Boc-hydroxylamine under Mitsunobu conditions to provide the protected hydroxylamine bis -Boc 6. Removal of the Boc-protective groups with acid, preferably HCl in dioxane or trifluoroacetic acid in methylene chloride, and neutralization of the amine salt with a base, preferably sodium bicarbonate, provided a portion of hydroxylamine exposed, which was treated with a formulating agent, preferably, formicacetyl anhydride, in solvents such as THF or dichloromethane, to provide hydroxamic acid 7.

Alternatively, 2 was converted to the corresponding iodo ketone 4 by a two-step procedure, which comprised (a) treatment of the epoxide with triphenylphosphine and a iodinating agent, preferably iodine, in an inert solvent, such as dichloromethane, for providing the corresponding iodoalcohol followed by (b) oxidation of the corresponding iodo ketone 4 with a mild oxidizing agent, preferably, Dess-Martin periodinane (Dess, DB; Martin, J. C, J. Am. Chem. Soc. 1 991, 1 1 3, 7277-7287, which is incorporated herein by reference). The introduction of RA was achieved by alkylation of the desired phenol or benzenetriol derivative with 4 in the presence of a base, preferably potassium carbonate, in a polar solvent, such as, DMF. The resulting ketone was converted to the corresponding oxime by treatment with hydroxylamine hydrochloride in a hydroxylic solvent, preferably ethanol, with a catalytic amount of base, preferably pyridine. When R * contained sulfur, the alcohol was oxidized to the corresponding ketone using Dess-Martin periodinane in an inert solvent, such as, dichloromethane was then converted to 5 as described above. Treatment of 5 with a reducing agent, preferably borane pyridine complex, in a hydroxylic solvent, preferably ethanol, and adding excess aqueous hydrochloric acid provided the corresponding hydroxylamine, which was formed as described above to provide 7. Depending on the nature of the R1 group: protection and subsequent deprotection of other reactive groups was required to successfully complete the synthetic sequences described. Commonly used protective groups are described in Greene, "Protective Groups In Organic Synthesis," (John Wiley &Sons, New York (1981)), which is incorporated herein by reference.

Esguema 1 Scheme 2 shows an alternate preparation of intermediate 5. Alkylation of 1 with ethyl bromoacetate was achieved in the presence of a base, preferably potassium carbonate, in a polar solvent, preferably DMF, to provide 8, which was subsequently hydrolyzed to 9 by treatment with an aqueous base, preferably lithium hydroxide in a mixture of solvents, preferably water and dioxane. Amide 10 was prepared by coupling N, 0-dimethylhydroxylamine hydrochloride 9 with a coupling agent, preferably bis (2-oxo-3-oxazolidinyl) phosphinic chloride (BOP-CI). Treatment of 10 with Ri-MgX, where X is Br or Cl, at reduced temperature, preferably -78 ° C in an inert solvent, preferably THF, gave ketone 1 1, which was converted to 5, and finally to 7, as described in Scheme 1.

Esguema 2 HQ, N .O. Ar2-Y-Arí 5 Scheme 3 shows the synthesis of compounds where the introduction of the phenolic groups and R < It was inverted. This route intersects with the route described in Scheme 1 in epoxide 14, and the chemistry described in Scheme 1 can be used to convert 14 to hydroxamic acid by using HO-A ^ -Y-ARa instead of R < -H The heterocyclic Ri-derivatives, preferably those having appropriate pKa's, such as hydantoin in this scheme, were condensed with the desired olefinic alcohol under Mitsunobu conditions to provide the corresponding N-alkenylheterocycle 12. The treatment of with an alkylating agent, preferably methyl iodide, in the presence of a base, preferably sodium hydride, provided N-methyl alkenylheterocycle 1 3, which was epoxidized with methachloroperbenzoic acid (MCPBA) in dichloromethane to provide 14. The reaction sequence described in Scheme 1 was then used to convert 14 to hydroxamic acid 5.

Scheme 3 13 14 wherein the alkylene group is from one to six carbon atoms, n is 1, and R6 and R7 together with the nitrogen atom to which they are attached form Scheme 4 shows an alternate synthesis of the substituted hydantoin compounds 22 and 23. The alkylation of 16 with a substituted hydantoin 1 7 in the presence of a base, preferably potassium carbonate, provides enol ether 1 8. The treatment of 1 8 with a brominating agent, such as NBS in acetone, provides bromoketone 1 9, which can then be alkylated with either aryl thiols (20, X = S) or substituted phenols (20, X = 0) for give the ketones 21. Ketones 21, where Y is a covalent bond, could also be prepared from 1 9 in a two-step procedure, first to be rented either with bromine thiophenols (20a, X = S) or bromophenols (20a, H = 0), then coupling the 1 0a aryl bromides with an appropriate aryl boronic acid following the Suzuki protocol, or an appropriate aryl stannane. The reaction sequence described in scheme 1 can be used to convert 21 to hydroxamic acids 22. Compounds wherein X = S can be converted to sulfones 23 via oxidation with an appropriate oxidant, such as oxone or m-chloroperbenzoic acid .

Esguema 4 19a 22 23 Scheme 5 shows an alternate synthesis of the sulfones 29. The deprotonation of the sulfone with a base, such as, LDA followed by addition to a ketone or aldehyde 24 gives an alcohol, which can be dehydrated either by reaction with acid , such as, toluene sulfonic acid, or by a stepwise 2-step procedure: first convert the alcohol into a leaving group, such as, mesylate via treatment with mesyl chloride and triethylamine, then remove with a base, preferably 1 , 8-diazabicyclo [5.4.0] undec-7-ene. Reaction of the olefin with a preferably O-protected hydroxylamine, O-benzyl gives the adduct 28. The formylation as previously described in Scheme 1, followed by removal of the protecting group, preferably under hydrogenation conditions for the compounds wherein P is benzyl, provides the sulfone 29. The sulfone 28 can also be prepared directly via the deprotonation of sulfone 25, with a base, such as n-BuLi and the subsequent addition, preferably in the presence of trifluoride etherate boron, to an O-protected oxime 30.

Scheme 5 24 25 26 2S The foregoing can be better understood by reference to the following examples, which illustrate the methods by which the compounds of the invention can be prepared, and are not intended to limit the scope of the invention as defined in the appended claims.

Example 1 (+) - N-p -rr (4'-cyano- [1,1 '-bifeniH-1-yl) oxy-1-methyl-2-phenoxyethyl-H-N-hydroxyformamide Example 1 A (+) - 3-phenoxypropan-ri, 21-oxirane A suspension of sodium hydride (0.47 g, 1 1 .7 mmol) in THF (20 ml) was treated sequentially with a phenol solution (1.00 g). , 0.6 mmol) in THF (20 ml), then with epibromohydrin (2.73 ml, 31.8 mmol) in a single portion, refluxed for 2 hours, cooled, treated with 20% aqueous potassium hydrogen sulfate. %, then separated between ethyl acetate and brine. The organic layer was washed sequentially with saturated aqueous sodium bicarbonate and brine, dried (Na2SO4) and concentrated to give 1.65 g of a golden oil, which was purified on silica gel with 1.0% ethyl acetate. hexanes (500 mL) and 20% ethyl acetate / hexanes to give 1.1.1 g (75%) of the title compound. MS (DCI / NH3) m / e 168 (M + N H4) + and 1.85 (M + NH4 + N H3) +.

Example 1 B (+) - 1 - (4- (4'-carbonitrilofeni-phenoxy) -3-phenoxy-2-propanol A suspension of sodium hydride (0.1-8 g, 4.39 mmol) in THF (4 ml) was treated sequentially with a solution of 4'-hydroxy-4-biphenylcarbonitrile (0.78 g, 3.99 mmol) in THF (4 mL), Example 1 A (0.60 g, 3.99 mmol) in THF (2 mL), then DMF (6 mL), was added. refluxed for 1 hour, cooled, treated with 20% aqueous potassium hydrogen sulfate and separated between ethyl acetate and brine The organic layer was washed with saturated aqueous sodium bicarbonate, 1% aqueous sodium hydroxide. % and brine, dried (Na2SO4) and concentrated to give 1.04 g of a yellow oil, which was purified on silica gel with 25-30% ethyl acetate / hexanes to give 0.42 g (22%) of the compound of title MS (DCI / NH3) m / e 363 (M + N H4) + and 380 (M + NH4 + NH3) +.

Example 1 C (±) -NO-bis (t-butyloxycarbonyl) -1 - (4- (4'-carbonitrilophenyl) phenoxy) -3-phenoxy-prop-2-yl-N-hydroxylamine A solution of Example 1 B ( 0.41 g, 1-1.1 mmol), triphenylphosphine (0.40 g, 1.54 mmol) and di-Boc-hydroxylamine (0.33 g, 1.42 mmol) in THF (5 mL) was treated with diethyl azodicarboxylate (0.24 mL, 1 mL). .54 mmol) in the form of drops, stirred at room temperature for 1 hour and concentrated. The resulting oil was redissolved in dichloromethane (30 ml) and concentrated in vacuo (2 cycles) to remove any excess THF, then purified on silica gel with 1 5% ethyl acetate / hexanes to give 0.50 g (75 mL). %) of the title compound as a colorless foam. MS (CDI / N H3) m / e 578 (M + NH4) +.

Example 1 D (+) - 1 - (4- (4'-carbonyltriphenyl) phenoxy) -3-phenoxy-prop-2-yl-N-hydroxylamine A solution of Example 1 C (0.45 g, 0.80 mmol) in dichloromethane (3 ml) was treated with trifluoroacetic acid (6 ml), stirred for 1 5 minutes at room temperature, drained in excess of saturated aqueous sodium bicarbonate and extracted into ethyl acetate. The resulting organic extracts were washed with brine, dried (Na2SO4) and concentrated to give 0.70 g of a brown oil, which was purified on silica gel with 50% ethyl acetate / hexanes to give 0.23 g (81%). of deprotected hydroxylamine as a light yellow foam.

Example 1 E (±) -N-ri -rr (4, -cyano-ri, 1 '-bifeniH-4-yl) oxpmetin-2-phenoxyetin-N-hydroxyformamide A solution of Example 1 D (0.1 5 g, 0.41 mmol) in dichloromethane (2 ml) was cooled to -10 ° C and treated with a solution of formicacetyl anhydride (38 mg, 0.43 mmol) in dichloromethane (1 ml), stirred for minutes, it was diluted with ether and washed sequentially with saturated aqueous sodium bicarbonate, 10% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and brine, dried (Na S04) and concentrated to give 0.17 g of an oil glassy, coffee, which was purified on silica gel with 97.5% (40% ethyl acetate / hexanes) / 2.5% methanol to provide 67 mg (42%) of light brown foam, which was recrystallized from acetate of ethyl / hexanes / acetone to provide the title compound as piled, light pink crystals.

Mp 133-135 ° C; 1 H NMR (300 MHz, CDCl 3) d 8.15 (br s; 1H), 8.07 (s; 1H), 7.69 (AB; 1H, J = 9 Hz), 7.62 (AB; 1H; J = 9 Hz), 7.54 ( d; 1H, J = 9 Hz), 7.32 (dd; 1H, J = 6.5, 8.0 Hz), 6.97-7.06 (m; 3H), 6.92 (d; 2H, J = 7.5 Hz), 4.24-4.47 (m; 5H); MS (DCI / NH3) m / e 345 (M + NH4-HCONHOH) +; Anal, caled for C23H20N2O4: C, 71.12; H, 5.19; N, 7.21. Found: C, 71.04; H, 5.16; N, 7.01.

Example 2 (±) -N-f1-rf (4'-cyano-ri.1'-biphenyl-4-yl) oxymethyl-2- (phenylthio) etn-N-hydroxyformamide Example 2A (+) - 3- (4- (4'-carbon) trufen i Dfen oxy) pro pa n-f 1, 2-1 oxirane The title compound was prepared following the procedure of Example 1A but using 4'-hydroxy-4-biphenylcarbonitrile (10.0 g, 51.2 mmol) in place of phenol. Purification by trituration with ether afforded 9.13 g (71%) of the title compound as a cretaceous solid. Mp 115-116 ° C; MS (DCI / NH3) m / e 269 (M + NH4) + and 286 (M + NH4 + NH3) +.

Example 2B (±) -1- (4- (4'-carbonyltriphenyl) phenoxy) -3-thiophenoxy-2-propanol A solution of Example 2A (0.90 g), triethylamine (1.75 ml) and benzenethiol (1.10 ml) in ethanol The residue (14 ml) was heated at reflux for 1 hour, cooled and partitioned between ethyl acetate and aqueous sodium hydroxide at 10%. The organic layer was washed sequentially with 10% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and brine, dried (Na 2 SO) and concentrated to give 1.27 g of a thick golden oil, which was purified by recrystallization from ethyl acetate / hexanes / methanol to provide the title compound as stacked, colorless crystals. Pf 1 05-1 05 ° C; MS (DCI / NH3) m / e 379 (M + NH4) +.

Example 2C (+) - 1 - (4- (4'-carbonitrilophenol) phenoxy) -3-thiophenoxy-2-propanone A suspension of Dess-Martin periodinane in dichloromethane (25 ml) was treated with Example 2B (2.02 g) in dichloromethane (1.5 ml), stirred at room temperature for 0.5 hour and separated between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was washed sequentially with saturated aqueous sodium thiosulfate, saturated aqueous sodium bicarbonate and brine, dried (Na2SO4) and concentrated to provide 2.27 g of an orange solid, pooled, which was purified on silica gel with 30 g. % ethyl acetate / hexanes to give 1.90 g of the title compound as a pale yellow cretaceous solid. MS (DCI / N H3) m / e 377 (M + NH4) +.

Example 2D (+) - 1 - (4- (4'-carbonitrilophenyl) phenoxy) -3-thiophenoxy-2-propanone oxime A solution of Example 2C (2.02 g) in methanol (20 ml) and THF (10 ml) it was treated sequentially with 10 drops of pyridine, then with hydroxylamine hydrochloride (0.78 g), heated to reflux for 1 hour, cooled and separated between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was washed sequentially with water and brine, dried (Na2SO4) and concentrated to give 1.90 g of the title compound as a yellow cretaceous solid, which was used without further purification. MS (DCI / NH3) m / e 375 (M + H) + and 392 (M + NH4) +.

Example 2E (+) - N- (4- (4'-carbonyltrilophenyl) phenoxy) -3-thiophenoxyprop-2-yl) hydroxylamine A solution of Example 2D (1.90 g) in THF (10 ml) was treated sequentially with absolute ethanol (20 ml), borane pyridine (1.5 ml), then in the form of drops with 6N aqueous hydrochloric acid, stirred for 1 hour at room temperature, poured into excess saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The combined organic extracts were washed with slurry, dried (Na2SO) and concentrated to provide 2.25 g of an orange oil, which was purified on silica gel with 30% ethyl acetate / hexanes to provide 1.26 g of the compound of the title as a light gold oil. MS (DCI / N H3) m / e 377 (M + H) + and 394 (M + NH4) +.

Example 2F (+) - Np-rr (4'-cyano-ri.1'-biphenyl-4-yl) oxy-methyl-2- (phenylthio) ethyl-N-hydroxyformamide A solution of compound 2E (1.24 g) in THF (10 mL) was cooled to -23 ° C and treated with a solution of formicacetyl anhydride (280 μL) in THF (2 mL)., stirred for 15 minutes, diluted with ether and washed sequentially with saturated aqueous sodium bicarbonate, 10% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and brine, dried (Na2SO4) and concentrated to provide 1.27 g of a glassy orange oil, which was purified on silica gel with 97.5% (40% ethyl acetate / hexanes) / 2.5% methanol to provide 300 mg of the title compound as a light orange foam. 1H NMR (300 MHz, CDCI3) d 7.95 (br s; 1H), 7.90 (s, 1H), 7.70 (AB, 1H, J = 7.5 Hz), 7.62 (AB, 1H, J = 7.5 Hz), 7.51 (d; 1H; J = 9 Hz), 7.20-7.43 (AB; m; 5H), 6.95 (d; 2H, J = 9 Hz), 4.33 (dd; 1H, J = 8.5, 10.5 Hz), 4.17 (dd; 1H, J = 4.5, 10.5 Hz), 4.0 (m; 1H ), 3.36 (dd; 1H, J = 8.5, 14 Hz), 3.28 (dd; 1H, J = 6.14 Hz); MS (DCI / NH3) m / e 422 (M + NH4) +. Anal, caled for C23H2oN2? 3S: C, 68.30; H, 4.98; N, 6.73. Found: C, 68.19; H, 4.86; N, 6.73.

Example 3 (±) -N-ri-rr (4'-cyano-ri.1'-biphenin-4-yl) oxylmethyl-2- (2,3-dihydro-1,3-dioxo-1-H, isoindol-2 -il) etip-N-hydroxyformamide Example 3A (+) - 3- (4- (4'-carbonitrilophenyl) phenoxa-3-vodo-2-propanol A solution of iodine (1.54 g, 6.0 mmol) in dichloromethane (20 ml) was treated with triphenylphosphine ( 1.58 g, 6.0 mmol), stirred for 5 minutes, treated with 3- (4'-carbonitrilophenyl) phenoxy) propan- (1,2) oxirane (1.0 g, 4.0 mmol) in a single portion, it was stirred at room temperature for 30 minutes, treated with water and separated between ethyl acetate and brine. The organic layer was dried (Na2SO4) and concentrated to provide 3 g of crude product, which was purified on silica gel with 30% ethyl acetate / hexanes to provide 1.38 g (91%) of the title compound. MS (DCI / NH3) m / e 397 (M + NH4) + and 414 (M + NH4 + NH3) +.

Example 3B 3- (4- (4'-carbonitrilofen il) phenoxy) -1-vidopropan-2-one The title compound was prepared as in Example 2C, but using Example 3A (1.0 g, 2.63 mmol ) instead of 3- (4- (4'-carbonitrilophenol) phenoxy) -1-thiophenoxypropan-2-ol. Purification on silica gel with 20% ethyl acetate / hexanes gave 0.65 g (66%) of the title compound. MS (DCI / NH3) m / e 395 (M + NH4) + and 412 (M + NH4 + NH3) +.

Example 3C 1 - (4- (4'-carbonitrilophenyl) phenoxy) -3-phthaloylpropan-2-one A solution of Example 3B (1.38 g, 3.66 mmol) in DMF (20 ml) was treated with potassium phthalimide (1.02 g, 5.50 mmol) was stirred at room temperature for 10 minutes, treated with water and separated between ethyl acetate and brine. The organic layer was dried (Na2SO4) and concentrated to give 0.98 g (67%) of the title compound. MS (DCI / NH3) m / e 414 (M + NH4) +.

Example 3D (+) - N-ri-rr (4'-cyano-ri.1'-biphenin-4-yl) oxy-1-methyl-2- (2,3-dihydro-1,3-dioxo-1H-iso in do l- 2-yl) ethill-Nh id roxiformam ida The title compound was prepared according to Example 2D, but using Example 3C (0.56 g, 1.41 mmol) instead of 1- (4- (4'-carbonitrilophenyl) phenoxy) -3-thiophenoxypropan-2-one to provide the corresponding oxime, which was reduced according to example 2E using 1- (4- (4'-carbonitrilophenyl) phenoxy) -3-phthaloylpropan-2-one oxime instead of 1 - (4- (4'-carbonitrilophenyl) phenoxy) -3-thiophenoxypropan-2-one oxime. The resulting hydroxylamine was formed according to Example 2F, but using 1- (4- (4'-carbontirtylphenyl) phenoxy) -3-phthaloyl-2-propylhydroxylamine instead of 1- (4- (4'-carbonitrilophenyl) phenoxy) -3-thiophenoxy-2-propyl hydroxylamine. Purification on silica gel with 60% ethyl acetate / hexanes provided 0. 185 g (30%) of the title compound. Mp 199-202 ° C; 1 H NMR (300 MHz, CDCl 3) d 10.06 (s; 0.5H), 9.67 (s; 0.5H), 8.32 (s; 0.5H), 7. 99 (s; 0.5H), 7.88 (m; 8H), 7.72 (m, 2H), 7.02 (m; 3H), 4.96 (m; 0.5H), 4. 52 (m; 0.5H), 4.25 (m; 2H), 3.78-4.00 (m; 2H); MS (DCI / NH3) m / e 459 (M + NH4) +; Anal, caled for C25H19N305: C, 67.96; H, 4.304; N, 9.52. Found: C, 67.43; H, 4.34; N, 9.04.

Example 4 (+) - N-1 -rr (4'-cyano-p. 1 '-bifenyl-4-yl) oxylmethyl-2- (3,4,4-trimethyl-2,5-dioxoim idazolidin-1-yl) etill-N hydroxyformamide Example 4A (±) -1 - (4- (4'-carbonitrilophenyl) phenoxy) -3 - ((5,5-dimethyl) hydantoin-3-yl) -2-propanol A solution of 5,5-dimethylhydantoin (0.26) g, 1.99 mmol) in THF (20 ml) was treated with potassium tert-butoxide (1.99 ml, 1.99 mmol), stirred for 5 minutes, treated with 3- (4'-carbonitrilophenyl) phenoxy) - (1,2) oxirane (0.50 g, 1.99 mmol) in a single portion, stirred at 70 ° C for 6 hours, treated with excess saturated aqueous ammonium chloride and separated between ethyl acetate and brine. The organic layer was dried (Na2SO4) and concentrated to give a yellow solid, which was purified on silica gel with ethyl acetate to give 0.70 g (93%) of the title compound. MS (DCI / NH3) m / e 397 (M + NH4) \ Example 4B (+) - 1 - (4- (4'-carbonitrilophenyl) phenoxy) -3- (3- (5,5-dimethyl) hydantoin) -2- (t-butyldimethylsilyloxy) propane A solution of Example 4A (0.40 g, 1.06 mmol) in dichloromethane (20 ml) was treated with tert-butyldimethylsilyl chloride (0.24 g, 1.60 mmol) and imidazole (0.1 g, 1.6 mmol), stirred at room temperature for 30 minutes, it was treated with water and separated between ethyl acetate and brine. The organic layer was dried (Na2SO) and concentrated to provide a solid, which was purified on silica gel with 50% ethyl acetate / hexanes to give 0.50 g (95%) of the title compound. MS (DCI / NH3) m / e 51 1 (M + NH4) +.

Example 4C (±) -1 - (4'-cyano-ri, 1'-biphenyl-4-yl) oxy) -3- (3,4,4-trimethyl-2,5-dioxo-1-midazolidin- 1 -yl) -2-t-butyldimethylsilyloxypropane A solution of 4B (0.60 g, 1.20 mmol) in THF (20 ml) was treated with sodium hydride (0.035 g, 1.40 mmol), then with iodomethane (0.26 g, 1.8 mmol) in a single portion, stirred at 70 ° C for 30 minutes, treated with saturated aqueous ammonium chloride and separated between ethyl acetate and brine. The organic layer was dried (Na2SO) and concentrated to provide the title compound as white crystals.

Example 4D (+) - 1 - (4'-cyano-ri. 1 '-bifenyl-4-yl) oxy) -3- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidin-1) -il) -2-propanol A solution of Example 4C in THF (30 ml) was treated with tetrabutylammonium fluoride (1 M in THF, 2.0 ml, 2.0 mmol), stirred at room temperature for 30 minutes, treated with water and separated between ethyl acetate and brine. The organic layer was dried (Na2SO) and concentrated to provide crude product, which was purified on silica gel with ethyl acetate to provide 0.47 g (1 00%) of the title compound.

MS (DCI / NH3) m / e 411 (M + NH4) +.

Example 4E 1- (4'-cyano-M, 1 '-biphenyl -yl) oxy) -3- (3,4,4-trimethyl-2,5-dioxoimidazole id in-1-yl) -2-propanone Example 4D (0.59 g, 1.50 mmol) was processed according to the procedure in Example 2C. Purification of the crude product on silica gel with 50% ethyl acetate / hexanes gave 0.58 g (98%) of the title compound. MS (DCI / NH3) m / e 409 (M + NH4) +.

Example 4F (+) - ri- (4'-cyano-ri, 1'-biphenip-4-yl) oxy) -3- (3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl) prop-3 illhydroxylamine Example 4E (0.57 g, 1.46 mmol) was processed according to the procedures in Examples 2D and 2E. Purification of the crude product on silica gel with 60% ethyl acetate / hexanes provide 0.31 g (52% >) of the title compound. MS (DCI / NH3) m / e 409 (M + NH4) +.

Example 4G (+) - N-ri-rr (4'-cyano-p.1'-biphenin-4-yl) oxy] methyl-2- (3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl) ) ethip-N-hydroxyformamide Example 4F was processed according to the procedure in Example 2F. Purification of the crude product on silica gel with 60% ethyl acetate / hexanes gave 0.19 g (60%) of the title compound. Mp 65-67 ° C; MS (DCI / NH3) m / e 437 (M + H) + and 454 (M + NH4) +. 1 H NMR (300 MHz, CDCl 3) d 9.90 (s; 0.5H), 9.58 (s; 0.5H), 8.32 (s; 0.5H), 7.92 (s; 0.5H), 7.85 (m; 4H), 7.72 (s; d; 2H, J = 5.6 Hz), 7.02 (dd; 2H, J = 5.5, 2.5 Hz), 4.86 (m; 0.5H), 4.42 (m; 0.5H), 4.08-4.02 (m; 2H), 3.82 -3.70 (m; 1H), 3.55-4.05 (m; 1H), 2.8 (s; 1.5 H), 2.78 (s; 1.5H), 1.5 (s; 3H), 1.48 (s; 3H); Anal, caled for C23H2 N4O5: C, 63.23; H, 5.50; N, 12.83. Found: C, 62.96; H, 5.55; N, 12.45.

Example 5 (+) - N-f1-rf (4'-cyano-p, 1'-bipheniip-4-yl) oxymethyl-3- (3,4,4-trimethyl-2,5-d-oxoamidezolid) N-1-yl) propyl-N-hydroxyformamide Example 5A 1- (prop-2-enyl) -4,4-dimethyl-2,5-dioxoimidazolidine A solution of 3-buten-1-ol (1 g, 13.9 mmol), triphenylphosphine (4.73 g, 18 mmol) and 5,5-dimethylhydantoin (2.1 g, 16.7 mmol) in THF (50 ml) was treated dropwise with diethylazodicarboxylate (3.13 g, 18.0 mmol), stirred at room temperature for 1 hour, treated with water and separated between ethyl acetate and brine. The organic layer was dried (Na2SO4) and concentrated to give crude product, which was purified on silica gel with 50% ethyl acetate / hexanes to give 2.5 g (100%) of the title compound.

Example 5B 1 - (prop-2-enyl) -3,4,4-trimethyl-2,5-dioxoimidazolidine A solution of Example 5A (2.3 g, 1 2.6 mmol) in THF (50 ml) was treated with hydride of sodium (0.45 g, 1 8.9 mmol), then with iodomethane (2.7 g, 18.9 mmol) in a single portion, refluxed for 2 hours, cooled, treated with water, and separated between ethyl acetate and salm outside. The organic layer was dried (Na2SO4) and concentrated to give 3.5 g of a yellow solid, which was purified on silica gel with 50% ethyl acetate / hexanes to give 2.4 g (98%) of the title compound. MS (DCI / NH3) m / e 214 (M + N H4) +.

Example 5C (+) - 1 - ((1 ', 2'-oxyranyl) propyl) -3,4,4-trimethyl-2, 5-dioxoimidazolidine A solution of Example 5B (3.0 g, 15.3 mmol) in dichloromethane (50 ml ) was treated with m-chloroperbenzoic acid (4.4 g), stirred at room temperature for 2 hours, treated with saturated aqueous sodium carbonate and separated between ethyl acetate and saline. The organic layer was dried (Na2SO4) and concentrated to a solid, which was purified on silica gel with 70% ethyl acetate / hexanes to provide 1.5 g (46%) of the title compound. MS (DCI / N H3) m / e 21 3 (M + 1) + and 230 (M + NH 4) +.

Example 5D (±) -1 - (2-hydroxy-3-iodo-propyl) -3,4,4-trimethyl-2-l 5-dioxoimidazolidine A solution of iodine (0.29 g, 1.88 mmol) in dichloromethane (20 ml. ) was treated with triphenylphosphine (0.3 g, 1.88 mmol), stirred for 5 minutes, treated with Example 5C (0.2 g, 0.94 mmol) in a single portion, stirred at room temperature for 30 minutes, treated with water and separated between ethyl acetate and brine. The organic layer was dried (Na2SO) and concentrated to give a yellow solid, which was purified on silica gel, with 75% ethyl acetate / hexanes to give 0.26 g (80%) of the title compound. MS (DCI / NH3) m / e 342 (M + H) + and 358 (M + NH4) +.

Example 5E 1 - (3-Vido-propan-2-onyl) -3,4,4-trimethyl-2,5-dioxoimidazolidine Example 5D was processed according to the procedure in Example 2C. Purification of the crude product on silica gel with 60% ethyl acetate / hexanes gave 0.3 g (96%) of the title compound. MS (DCI / N H3) m / e 339 (M + H) + and 356 (M + NH4) +.

Example 5F (±) -1 - (3-r (4'-c'ano-ri. 1 '-bifenip-4-yl) oxyl-propan-2-on-1-yl) -3,4,4-trimethyl- 2,5-dioxoimidazolidine A solution of 4'-hydroxy-4-biphenylcarbonitrile (0.38 g, 1.9 mmol) in THF (50 ml) was treated with potassium carbonate (0.5 g), then with Example 5E (0.44 g). , 1.30 mmol), refluxed for 7 hours, cooled, treated with 10% aqueous HCl and separated between ethyl acetate and brine. The organic layer was dried (Na2SO4) and concentrated to give a yellow solid, which was purified on silica gel with 75% ethyl acetate / hexanes to give 0.52 g (99%) of the title compound. MS (DCI / NH3) m / e 423 (M + NH4) +.

Example 5G (+) - 1 - (3-r (4'-cyano-p. 1 '-bifenill-4-yl) oxyl-propan-2-oxymeno-1-yl) -3,4,4- trimethyl-2,5-dioxyimidazolidine Example 5F was processed according to the procedure in Example 2D. The crude product was purified on silica gel with 75% ethyl acetate / hexanes to give 0.68 g (1.60 mmol, 100%) of the title compound. MS (DCI / N H3) m / e 439 (M + NH4) +.

Example 5H (±) -N-ri -rf (4'-c'ano-ri. 1 '-bifenin-4-yl) oxymethyl-3- (3,4,4-trimethyl-2,5-dioxo- 1 - im id azo l id in il) propi HNh id roxiformam id a Example 5G was processed according to the procedures in Examples 2E and 2F. Purification of the crude product on silica gel with 75% ethyl acetate / hexanes gave 0.408 g (56%) of the title compound. Mp 68-70 ° C; 1 H NMR (300 MHz, CDCl 3) d 9.99 (s; 0.5H), 9.46 (s; 0.5 H), 8.35 (s; 0.5H), 7.92 (s; 0.5H), 7.092 (d; 2H, J = 5.6 Hz), 7.85 (d; 2H, J = 5.6Hz), 7.70 (d; 2H, J-5.6 Hz), 7.05 (d; 2H, J = 5.6Hz), 4.52 (m; 0.5H), 4.18-3.95 (m; 3.5H), 3.46 (m; 2H), 2.82 (s; 1.5H), 2.79 (s; 1.5H), 2.02-1.72 (m; 1H), 1.32 (s; 6H); MS (DCI / NH3) m / e 468 (M + NH4) +; Anal, caled for C2 H26N405: C, 63.93; H, 5.77; N, 12.43. Found: C, 63.38; H, 5.99; N, 11.97.

Example 6 (+) - N-ri-rrr3 '- (Cyanomethyl) -ri, 1'-bifeniH-4-yl-1-oxo-1-methynthlori-N-hydroxyformamide Example 6A 4 - ((t-Butyldimethyl) silyloxy) phenyl boronic acid A solution of (4-bromophenoxy) trimethylsilane (60 g, 20.9 mmol) in THF (60 ml) was treated with n-butyllithium at -78 ° C, stirred for 15 minutes, treated with trisopropyl borate, stirred at -78 ° C for 10 minutes, warmed to room temperature, stirred for another 30 minutes, it was treated with water and separated between ethyl acetate and brine. The organic layer was dried (MgSO4) and concentrated to provide 4.79 g (91%) of the title compound.

Example 6B 4'-Hydroxy-3-biphenylcarbonitrilomethane A mixture of Example 6A (4.8 g, 1 9.0 mmol), 3-bromo phenyl acetonitrile (3.1 g, 1 6.0 mmol), cesium carbonate (7.8 g, 24.0 mmol) and tetrakis (triphenylphosphine) palladium (0) (0.55 g, 0.48 mmol) was treated via syringe with DMF (30 ml) under positive nitrogen pressure, stirred at 1000 ° C for 10 h, treated with water and separated between ethyl acetate and brine. The organic layer was dried (MgSO4) and concentrated to give a brown oil, which was purified on silica gel with 50% ethyl acetate / hexanes to give 3.3 g (82%) of the title compound. MS (DCI / NH3) m / e 227 (M + NH4) +.

Example 6C 2- (4- (3'-carbonitrilomethylphenyl) phenoxy) ethyl acetate A solutof 6B (0.5 g, 2.4 mmol) in THF (20 ml) was treated with potassium carbonate (0.5 g) and ethyl bromoacetate ( 0.6 g, 3.6 mmol), refluxed for 3 hours, cooled, treated with 10% aqueous HCl and separated between ethyl acetate and brine. The organic layer was dried (Na2SO4) and concentrated to give a yellow solid, which was purified on silica gel with 50% ethyl acetate / hexanes to give 0.48 g (68%) of the title compound. 1 H NMR (300 MHz, CDCl 3) d 7.52 (m; 4H), 7.40 (m; 1 H), 7.36 (m; 1 H), 7.0 (m; 2H), 4.65 (s; 2H), 4.30 (q;; 2H, J = 4.8 Hz), 3.80 (s; 2H), 1.32 (t; 3H, J = 4.8 Hz).

EXAMPLE 6D 2- (4- (3'-carbohydrate itri lom et i IfeniDf in oxy) acetic acid A solutof 6C (0.47 g, 1.6 mmol) in 1,4-dioxane (20 ml) and water (10 ml) ) was treated with lithium hydroxide (0.5 g), stirred at room temperature for 30 minutes, treated with 10% aqueous HCl and separated between ethyl acetate and brine.The organic layer was dried (Na 2 SO 4) and Concentrate to give a yellow solid, which was purified on silica gel with 50% ethyl acetate / hexanes to give 0.37 g (83%) of the title compound.1 H NMR (300 MHz, CDCl 3) d 7.60 (m; 4H), 7.46 (m; 1 H9, 7.32 (m; 1 H), 7.02 (m; 2H), 4.72 (s; 2H), 4.08 (s; 2H).

Example 6E N, 0-dimethyl-2- (4- (3'-carbonitriomethylphenyl) phenoxy) acetyl hydroxylamine A solutof 6D (0.35 g, 1.3 mmol), triethylamine (0.5 ml) and bis (2-) chloride oxo-3-oxazolidinyl) -phosphinic acid (0.78 g, 2.6 mmol) in dichloromethane (20 ml) was treated with NO-dimethyl-hydroxylamine hydrochloride (0.25 g, 2.6 mmol), stirred at room temperature for 2 hours, treated with water and separated between ethyl acetate and brine. The organic layer was dried (Na2SO4) and concentrated to give a yellow solid, which was purified on silica gel with 50% ethyl acetate / hexanes to give 0.28 g (69%) of the title compound. 1 H NMR (300 MHz, CDCl 3) d 7.59 (m; 4H), 7.46 (m; 1 H), 7.32 (m; 1 H), 7.02 (m; 2H), 4.96 (s; 2H), 4.08 (s); 2H), 3.78 (2; 3H), 3.1 5 (s; 3H).

Example 6F 1- (4- (3'-carbonitrilomethylphenyl) phenoxy) -2-hexanone A solutof 6E (0.27 g, 0.85 mmol) in THF (10 ml) was treated with n-butylmagnesium bromide (1 ml, 2.0 mmol ) at -78 ° C, stirred at -78 ° C for 1 h, treated with water and separated between ethyl acetate and brine. The organic layer was dried (Na2SO4) and concentrated to give a yellow solid, which was purified on silica gel with 25% ethyl acetate / hexanes to give 0.15 g (59%) of the title compound. 1 H NMR (300 MHz, CDCl 3) d 7.52 (m; 4 H), 7.42 (m; 1 H), 7.28 (m; 1 H), 6.98 (m; 2 H), 4.60 (s; 2 H), 3.82 (s; 2 H) , 2.62 (t; 2H, J = 5.5 Hz), 1.64 (m; 2H); 1.38 (m, 2H), 0.92 (t; 3H; J = 4.8 Hz).

Example 6G (+) - N-ri-rrr3 '- (cyanomethyl) -p, 1'-biphenin-4-ynyloxymethylpentyl-N-hydroxyformamide Example 6F (0.15 g, 0.50 mmol) was processed according to the procedures described in Examples 2D-F (even). Purificatof the crude final product on silica gel with 40% ethyl acetate / hexanes gave 0.07 g (41%) of the title compound. Mp 99-101 ° C; MS (DCI / NH3) m / e 352 (M + NH4) +. H NMR (300 MHz, CDCl 3) d 8.58 (brs; 0.5H), 8.04 (brs; 0.5H), 8.0 (s; 1H), 7.48 (m; 4H), 7.42 (m; 1H9, 7.26 (m; 1H ), 6.98 (m; 2H), 4.05 (t; 1H, J = 5.6 Hz), 3.8-4.0 (m; 2H), 3.80 (s; 2H), 1.92 (m; 1H), 1.60 (m; 2h) , 1.38 (m; 3H), 0.98 (t; 3H, J = 4.8 Hz).

Anal, caled for C2? H24N2O3: C, 71.50; H, 6.81; N, 7.94. Found: C, 71.44; H, 6.90; N, 7.80.

Example 7 (+) - Np-rr (4'-cyano-p.1'-b-phenyl-4-yl) oxymethyl-3-methylbutyl-N-hydroxyformamide 4'-hydroxy-4-biphenylcarbonitrile (1.0 g , 5.12 mmol) was processed according to the procedures described in Examples 6C-G (even), but substituting isobutylmagnesium bromide for the n-butylmagnesium bromide used in Example 6F. Purificatof the crude final product on silica gel with 30% ethyl acetate / hexanes provided 0. 036 g of the title compound. Mp 112-113 ° C; MS (DCI / NH3) m / e 356 (M + NH4) +. 1 H NMR (300 MHz, CDCl 3) d 7.95 (s; 1 H), 7.70 (d; 2 H, J = 5.6 Hz), 7.62 (d; 2H, J = 5.8), 7.52 (d; 2H; J = 5.8 Hz), 6.98 (d; 2H; J = 5.8Hz), 4.25 (m; 1H), 3. 92-4.05 (m; 2H), 1.95 (m; 1H), 1.75 (m; 1H), 1.35 (m; 1H), 1.00 (d; 3H, J = 4.8 Hz), 0.98 (d; 3H; J = 4.8 Hz). Anal, caled for C20H22N2O3: C, 70.92; H, 6.50; N, 8.27. Found: C, 70.91; H, 6.68; N, 8.13.

Example 8 (+) - Np-rr (4'-c'ano-ri.1'-b'fenin-4-yl) oxymethyl-2-methylbutyl-1-N-hydroxyformamide The title compound was prepared following the sequence of steps described in Example 7, but substituting sec-butylmagnesium chloride for isobutylgnesium bromide. Purification of the crude final product on silica gel with 30% ethyl acetate / hexanes gave 0.10 g of the title compound. Mp 96-98 ° C; MS (DCI / NH3) m / e 356 (M + NH4) +. 1 H NMR (300 MHz, CDCl 3) d 7.95 (s; 1H), 7.70 (d; 2H; J = 5.6 Hz), 7.62 (d; 2H, J = 5.8), 7.52 (d; 2H; J = 5.8 Hz) 6.98 (d; 2H; J = 5.8 Hz), 4.32 (m; 1H), 4.15 (m; 2H); 3.65 (m; 1H), 1.98 (m; 1H), 1.62 (m; 1H), 1.02 (m; 3H), 0.98 (m, 3H). Anal, caled for 0.8 H2O + C20H22N2O3: C, 68.03; H, 6.69; N, 7.90. Found: C, 68.60; H, 6.58; N, 7.23.

Example 9 (+) - N-f1-rr (4'-cyano- |, 1,1'-b-phenyl-4-yl) oxy] methinpentyl-1-N-hydroxyformamide The title compound was prepared following the sequence of steps described in Example 7, but substituting n-butylmagnesium bromide for isobutylmagnesium bromide. Purification of the crude final product on silica gel with 30% ethyl acetate / hexanes gave 0.210 g of the title compound. Mp 105-108 ° C; MS (DCI / NH3) m / e 356 (M + NH4) +. 1 H NMR (300 MHz, CDCl 3) d 7.95 (s; 1H), 7.70 (d; 2H, J = 5.6 Hz), 7.62 (d; 2H; J = 5.8), 7.52 (d; 2H, J = 5.8 Hz) , 6.98 (d; 2H, J = 5.8Hz), 4.25 (m; 1H), 3.99-3.82 (m; 2H), 1.92 (m; 1H), 1.60 (m; 2H), 1.40 (m; 3H), 0.98 (t; 3H, J = 4.3Hz). Anal, caled for 0.5C6H6 + C2oH22N2? 3: C, 73.13; H, 6.62; N, 7.42.

Found: C, 73.18; H, 6.65; N, 7.39.

Example 10 (±) -N-ri-rr (4'-cyano-p.1'-biphenin-4-yl) oxpmethyl-2- (4-methylphenyl) etin-N-hydroxyformamide The title compound was prepared following the sequence of steps described in Example 7, but substituting 4-methylbenzylmagnesium bromide for isobutylmagnesium bromide. Purification of the final crude product on silica gel with 30% ethyl acetate / hexanes gave 0.24 g of the title compound. Mp 173-175 ° C; MS (DCI / NH3) m / e 404 (M + NH4) +. 1 H NMR (300 MHz, CDCl 3) d 7.70 (d; 2 H, J = 5.6 Hz), 7.68 (s; 1 H), 7.62 (d; 2H; J5.8), 7.52 (d; 2H, J = 5.8 Hz), 7.12 (s; 4H), 6.98 (d; 2H; J = 5.8 Hz), 4.35 (m; 1H, 4.12-3.98 (m; 2H), 3.15 (m; 1H), 2.94 (m; 1H), 1.35 (s; 3H). Anal, caled for C24H22N2O3: C, 74.52; H, 5.69; N , 7.24 Found: C, 73.95; H, 5.79; N, 7.06.

Example 11 (±) -N-r2-y (4'-cyano-ri, 1'-biphenyl-4-yl) oxyl-1- (4-fluorophenyl) ethyn-N-hydroxyformamide The title compound was prepared following the sequence of steps described in Example 7, but replacing 4-fluorophenylmagnesium bromide with isobutylmagnesium bromide. Purification of the crude final product on silica gel with 30% ethyl acetate / hexanes gave 0.285 g of the title compound. Mp 194-196 ° C; MS (DCI / NH3) m / e 394 (M + NH4) +. 1 H NMR (300 MHz, CDCl 3) d 9.70 (brs; 1H), 8.42 (s; 0.5H), 8.28 (s; 0.5H), 7.86 (m; 4H), 7.72 (d; 2H, J = 5.6 Hz) , 7.55 (m; 2H), 7.25 (m; 2H), 7.12 (d; 2H; J = 5.8 Hz), 5.72 (brs; 0.5H), 5.35 (brs; 0.5H), 4.60 (m; 1H), 4.36 (m; 1H). Anal, caled for C22H17N2O3: C, 70.14; H, 4.45; N, 7.44. Found: C, 70.19; H, 4.25; N, 7.30.

Example 12 (±) -Np-rr (4'-cyano-ri.1'-bifeniH-4-yl) oxylmetin-2- (4-fluorophenyl) ethyp-N-hydroxyformamide The title compound was prepared following the sequence of steps described in Example 7, but replacing 4-fluorobenzylmagnesium bromide with isobutylmagnesium bromide. Purification of the crude final product on silica gel with 30% ethyl acetate / hexanes gave 0.22 g of the title compound. MS (DCI / NH3) m / e 408 (M + NH4) +. 1 H NMR (300 MHz, CDCl 3) d 8.35 (brs; 1 H), 7.65 (m; 5 H), 7.52 (2 H, J = 5.6 Hz), 7.20 (m; 2 H), 6.98 (m; 4 H), 4.35 (m; 1H), 4.15-3.98 (m; 2H), 3.18 (dd; 1H, J = 6.0, 9.0 Hz), 2.95 (dd; 1H, J = 3.0, 9.0 Hz). Anal, caled for C23H19N2? 3: C, 70.69; H, 4.87; N, 7.17. Found: C, 70.38; H, 4.96; N, 6.98.

Example 13 (±) -N-p-rr (4'-cyano- [1,1'-biphenyl-1,4-yl) oxymethyl-p-N-hydroxyformamide Example 13A (4- (4'-carbonitrilophenyl) phenoxy) propan-2-one A solution of 4- (4'-carbonitrilophenyl) phenol (4.86 g, 24.9 mmol) in DMF (100 ml) was treated with potassium carbonate ( 13.8 g, 99.6 mmol), heated at 50 ° C for 10 minutes, treated in a single portion with chloroacetone (2.48 ml, 30 mmol), stirred for 4 hours at room temperature and separated between 3: 1 ethexexanes and saturated aqueous sodium carbonate. The organic layer was dried (MgSO4) and concentrated under vacuum 1/3 of its original volume to cause precipitation of solution product. The solution was treated with more ether and stored at -20 ° C for 17 hours. The title compound (2.01 g, 32%) was collected by filtration and dried under vacuum. MS (DCI / NH3) m / e 251 (M) +, 269 (M + NH4) + and 286 (M + NH4 + NH3) +.

Example 13B (±) -N-1-yl (4'-cyano-1,1'-biphenin-4-yl) oxylmethylletin-N-hydroxyformamide The title compound was obtained following the procedures in Examples 2D-F (even), but substituting Example 13A (2.00 g, 7.96 mmol) for Example 2C. Purification of the crude final product on silica gel with 5% methanol / dichloromethane gave 325 mg of the title compound. Mp 141-144 ° C; 1 H NMR (300 MHz, d6-DMSO) d 9.88 and 9.45 (br s; 1 H), 8.02 and 8.33 (s; 1 H), 7.90 (AB; 2H, J = 7.5 Hz), 7.84 (AB; 2H) , J = 7.5 Hz), 7.61 (d; 2H, J = 9 Hz), 7.06 (d; 2H; J = 9 Hz), 4.67 (m; 0.32 H), 3.92-4.25 (m; 2.68H), 1 .23 and 1 .18 (d; 3H; J = 6 Hz); MS (DCI / NH3) m / e 314 (M + N H4) +. Anal, caled for C17H16N2O3: C, 68.90; H, 5.44; N, 9.45. Found: C, 68. 61; H, 5.55; N, 9.21.

Example 14 N-2-r (4'-cia no-p, 1 '-bif en il] -4-i I) oxy-II-N-hydroxy acetamide Example 14A 2- (4- (4'-carbonyltriphenyl) phenoxy) -bromoethane A solution of 4- (4'-carbonitrilophenyl) phenol (3.00 g, 24.8 mmol) in DMF (20 ml) was treated with potassium carbonate (8.24 g, 99.4 mmol) and 1,2-dibromoethane (6.42 ml, 124 mmol), heated at 50 ° C for 1 9 hours and separated between 3: 1 ether : hexanes and water. The organic layer was separated and the aqueous layer was extracted with 3: 1 ether hexanes. The combined organic layers were dried (MgSO4) and concentrated. Purification of the crude product on silica gel with 50% dichloromethane / hexanes provided a white solid which was recrystallized from ether / pentane to provide 1.25 g (17%) of the title compound as colorless needles. MS (DCI / N H3) m / e 301/303 (M) +, 31 9/321 (M + N H4) + and 336- / 338 (M + N H4 + N H3) +.

Example 14B N, O-bis (t-butyloxycarbonyl) -2-y (4- (4'-carbonitrilophenyl) phenoxy) ethyl-N-hydroxylamine A solution of N, O-bis (t-butyloxycarbonyl) -N-hydroxylamine ( 443 mg, 1.9 mmol) in DMF (15 mL) was treated with a 60% oil dispersion of sodium hydride (76 mg, 1.9 mmol), stirred at room temperature for 15 minutes, treated with Example 1 3A (0.54 g, 1.79 mmol), stirred for 4 hours at room temperature and separated between 1: 1 ethexexanes and saturated aqueous ammonium chloride. The organic layer was separated, and the aqueous layer was extracted with 1: 1 ether hexanes. The combined organic layers were dried (MgSO4) and concentrated. Purification on silica gel with 10% ethyl acetate / hexanes gave 0.65 g (80%) of the title compound as a colorless viscous oil. MS (DCI / NH3) m / e 472 (M + N H4) +.

Example 14C 2-R (4- (4'-carbonitrilophenyl) phenoxy) ethyl-N-hydroxylamine hydrochloride Example 14B (0.64 g, 1.41 mmol) was treated with 4N hydrochloric acid in dioxane (10 ml) and stirred at room temperature for 2.5 hours, during which time a colorless precipitate formed. The precipitate was collected by filtration, washed with dioxane and dried to give the HCl salt of the title compound as a colorless solid (0.22 g, 56%).

Example 14D NQ-bis (acetyl) -2-r (4- (4'-carbonitrilophenyl) phenoxy) ethyl-N-hydroxylamine A solution of Example 14C (27 mg, 0.093 mmol) in THF at 0 ° C was treated with triethylamine (32 μl, 0.23 mmol), stirred for 1 hour at 0 ° C, treated as drops with acetyl chloride (16 μl), stirred for 1 hour at 0 ° C and 18 hours at room temperature and separated between 1 N aqueous hydrochloric acid and ether. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried (MgSO4) and concentrated. Purification of the residue on silica gel with 2% acetone / dichloromethane gave 29 mg (83%) of the title compound. MS (DCI / NH3) m / e (M + NH4) +.

Example 14D N-r 2 - (r 4'-cyano-f 1,1 '-bifen-p-4-iDoxi] ethyl 1-N-hydroxyacetam ida A solution of Example 14D (29 mg, 0.077 mmol) in THF (5 ml) and ethanol (2 ml) was cooled to 0 ° C, treated with aqueous lithium hydroxide (0.31 ml of 1.0 N lithium hydroxide), stirred at 0 ° C for 10 minutes at room temperature for 1.5 hours. The organic layer was separated and the aqueous layer was extracted with ether.The combined organic layers were washed with 1N aqueous hydrochloric acid, dried (MgSO4) and concentrated to a solid, which was purified by trituration with ethyl acetate to provide 19.7 mg (86%) of the title compound, as a colorless solid, mp 174-175 ° C, 1 H NMR (300 MHz, d6-DMSO) d 9.90 (brs; 1 H), 7.88 (AB; 2H; J = 7.5 Hz), 7.84 (AB; 2H; J = 7.5 Hz), 7.71 (d; 2H; J = 8.5 Hz), 7.07 (d; 2H J = 8.5 Hz), 4.20 (t; 2H; J = 7.5, 7.5 Hz), 3.89 (t; 2H; J = 7.5, 7.5 Hz), 2.02 (S; 3H); MS (DCI / NH3) m / 197 (M + H) + and 314 (M + NH4) +. Anal, caled for C17H16N2? 3 (0.25H2O): C, 67.87; H, 5.52; N, 9.31. Found: C, 67.65; H, 5.55; N, 9. 12.

Example 1 5 Nf 2-f (4'-cyano-ri, 1'-biphenyl-4-yl) oxy-1-N-hydroxy-ormamide A solution of Example 14C (78 mg, 0.27 mmol) in THF (2.0 ml) treated with triethylamine (75 μl, 0.54 mmol) and then with formicacetyl anhydride in the form of drops (41 mg, 0.30 mmol) in THF (0.5 ml), stirred for 2 hours at room temperature and separated between ethyl acetate and 1 N aqueous hydrochloric acid. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried (MgSO4) and concentrated. Purification by chromatography on silica gel with 0.2% > Acetic acid / ethyl acetate and subsequent recrystallization of the cold methanol gave 14.7 mg (1.9%) of the title compound.

Mp 142-145 ° C; 1 H NMR (300 MHz, d6-DMSO) d 10.17 and 9.74 (br s; 1 H), 8.34 and 7.98 (br s; 1 H), 7.88 (AB; 2H; J = 7.5 Hz), 7.84 (AB; 2H; J = 7.5 Hz), 7.73 (d; 2H; J = 8.5 Hz), 7.07 (d; 2H); J = 8.5 Hz), 4.14-4.26 (m; 2H); 3.77-3.88 (m; 2H); MS (DCI / NH3) m / e 300 (M + NH4) +. Anal, caled for C 16 H 14 N 2 O 3 (0.125H 2 O): C, 67.54; H, 5.05; N, 9.84. Found: C, 67.59; H, 5.32; N, 9.53.

Example 16 N-f 1 -r4-r (2E-phenylethenyl) phenoxymethyl-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazoledinyl) ethyp-N-hydroxyformamide Example 1 6A 3- (3,4,4-trimethyl-2, 5-dioxoimidazolidin-1-yl) -2-methoxymethyloxy-prop-1-ene A mixture of 1,5,5 trimethylhydantoin (7.0 g, 49.2 mmol ), powdered potassium carbonate (8.16 g, 59 mmol) and 2-methoxymethyloxy-allyl chloride (7.65 g, 56 mmol) in dry DMF (100 mL) was heated at 1000 ° C with stirring for 1. 5 h. The reaction mixture was cooled, filtered and the filtrate was concentrated, then partitioned between ethyl acetate and water. The organic extract was washed twice with water, brine, dried and concentrated, then purified via chromatography on silica gel, levigating with 50% ethyl acetate: hexane to give 10.58 g (89%) of the title compound. MS (DCI / NH3) m / e 243 (M + H) + and 260 (M + NH4) +.

Example 16B 1-bromo-3- (3,4,4-trimethyl-2, 5-dioxoimidazolidin-1-yl) propan-2-one A solution at 0 ° C of Example 1 6A (1 0.58 g, 43.7 mmol) in acetone (200 ml) was treated sequentially with a potassium carbonate solution (0.58 g), 4.2 mmol) in water (60 ml) and N-bromo succinimide (8.56 g, 48 mmol) and the resulting mixture was stirred with the ice bath in place. About 2 additional portions of 1.5 g of N-bromo succinimide were added after 1 and 2 h, respectively. The ice bath was then removed, and the reaction was allowed to stir for an additional 10 minutes, then concentrated and extracted twice with ethyl acetate. The combined extracts were washed with NaHS03 0.5M aq, 1 M NaHC03, water, salt, dried and concentrated. The residue was purified by chromatography on silica gel, levigating with 50% ethyl acetate: hexane to give 7.39 g (61%) of the title compound. MS (DCI / N H3) m / e 277/279 (M + H) + and 294/296 (M + N H4) +.

Example 16C 1- (4'-Bromophenyloxy) -3- (3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl) -2-propanone To a suspension of 4-bromophenol (3.99 g, 23.0 mmol) and cesium carbonate (7.45 g, 22.9 mmol) in DMF (150 ml) was added a solution of 1 6B bromoketone (3 g, 1-1.5 mmol) in DMF (5 ml), in the form of drops over 30 minutes. The suspension was maintained at room temperature for 16 h, diluted with ethyl acetate (500 ml) and the organics were washed with water, brine and dried over magnesium sulfate and concentrated in vacuo. Flash chromatography (hexane / ethyl acetate 1: 1) gave 2.55 g of 16C as a white solid.

Example 16D To a hot (100 ° C) solution of 16C (0.5 g, 1.35 mmol) and tributyl (phenylethynyl) tin (0.64 g, 1.62 mmol, Aldrich) in toluene (25 ml) was added a catalytic amount of Pd (PPh3) )4. The reaction was brought to reflux and held for 7 h. The resulting black solution was diluted with ethyl acetate (125 ml) and the organics were washed with 1M NaOH, brine, dried over magnesium sulfate and concentrated in vacuo. Flash chromatography (gradient levigation; hexane / ethyl acetate 4: 1 to 1: 1) gave 0.24 g of the desired compound after trituration with diethyl ether.

Example 16E N-f1-f4-f (2E-phenylethylene) phenoxmethyl-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazoledinyl) ethy-N-hydroxyformamide The title compound it was prepared in the same way as example 2D, E, F, substituting 16D for 2C. 1 H NMR (300 MHz, d 6 -DMSO) d 9.90 (s, 0.5 H), 9.58 (s, 0.5 H), 8.31 (s, 0.5 H), 7.9 (s, 0.5 H), 7.57-7.54 (m, 6 H) ), 7.38-7.33 (m, 2H), 7.26-7.08 (m, 6H), 6.94-6.90 (m, 2H), 4.80-4.60 (m, 0.5H), 4.55-4.40 (m, 0.5H), 4.16 -4.04 (m, 4H), 3.76-3.73 (m, 2H), 3.61-3.57 (2, 2H), 2.79 (s, 6H), 1.28 (s, 12H). MS (ESI) m / e M-H (436), M + H (438).

Anal, caled for C24H27N3? 5 »1.0H2O: C, 63.28; H, 6.41; N, 9.22. Found: C, 63.06; H, 5.97; N, 8.94.

Example 17 N-f1-rr4- (2-furanyl) phenoxymethyl-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyne-N-hydroxyformamide Prepared in the same manner as example 16 , substituting 2- (tributylstannyl) furan for tributyl (phenylethynyl) tin in Example 16D. 1H NMR (300 MHz, d6-DMSO) d 9.86 (s, 0.5H), 9.53 (s, 0.5H), 8.30 (s, 0.5H), 7.91 (s, 0.5 H9, 7.67-7.61 (m, 6H) , 6.96-6.94 (m, 4H), 6.79-6.74 (d, 2H, J = 3.4 Hz), 6.55-6.54 (m, 2H), 4.80-4.60 (m, 0.5H), 4.45-4.30 (m, 0.5 H), 4.17-3.98 (m, 6H), 3.76-3.70 (m, 2H), 3.62-3.56 (m, 2H), 2.79 (s, 6H9, 1.28 (s, 12H), MS (ESI) m / e M + H (402), MH (400), M + NH 4 (419) Anal, caled for C 2 O H 23 N 306: C, 59.84; H, 5.77; N, 10.46, Found: C, 59.83; H, 5.90; N, 10.12.

Example 18 N-f1-rr (4'-butoxiri.1'-bifenill-4-yl) oxymethin-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethylen-N-hydroxyformamide Example 18A 1- (4'-butyloxy-ri, 1'-biphenin-4-yl) oxy) -3- (3,4,4-trimethyl-2,5-dioxoamidazolidin-1-yl) - 2-propanone To a hot (75 ° C) solution of Example 16C (0.1 g, 0.27 mmol) and 4-butoxyphenylboronic acid (0.08 g, 0.41 mmol) in DME (2 ml) was added a 1M Na 2 CO 3 solution (0.4 ml). ), followed by a catalytic amount of PdCI2 (dppf). The reaction was maintained at 100 ° C for 2 h, diluted with ethyl acetate (25 ml), washed with saturated ammonium chloride, water, brine, dried over magnesium sulfate and concentrated in vacuo. Flash chromatography (20% ethyl acetate in methylene chloride) gave 0.105 g of 5 as a white solid.

Example 18B N-ri-rr (4'-butoxy-1,1-biphen-4-yl) oxpmethyl-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) etin-N-hydroxyl ormamide prepared in the same manner as examples 2D, E, F, substituting 18A for 2C. 1H NMR (300 MHz, d6-DMSO) d 9.87 (s, 0.5H), 9.55 (s, 0.5H), 8.31 (s, 0.5H), 7.91 (s, 0.5H), 7.55-7.50 (m, 8H ), 6.98-6.95 (m, 8H), 4.80-4.60 (m, 0.5H), 4.50-4.35 (m, 0.5H), 4.16-4.06 (m, 4H), 4.01-3.96 (t, 4H, J = 7.0, 5.9 Hz), 3.76-3.70 (m, 2H), 3.62-3.59 (m, 2H), 2.80 (s, 6H), 1.72-1.65 (m, 4H), 1.48-1.40 (m, 4H), 1.29 (s, 12H), 0.96-0.91 (t, 6H, J = 7.1, 7.5 Hz). MS (ESI) m / e M + H (484), M + NH 4 (506). Anal, caled for C26H33N3O6: C, 64.57; H, 6.87; N, 8.68. Found: C, 64.70; H, 7.04; N, 8.50.

Example 19 N-ri-fr (4'-fluorof1 .1, -bifen1-4-yl) oxylmethyl-2- (3.4.4-triflumethyl-2,5-dioxo-1-imidazo lid in diethyl-N-hydroxyl) ormamide Example 1 9A 3- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) -propan-f1, 21-oxirane The title compound was prepared following the procedures described by examples 5A and 5C, but using alcohol to the iliac instead of 3-buten-1 -ol.

Example 19B N-ri -rr (4'-fluorori .1'-bifenin-4-inoxpmetill-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazo I id iniDetill-N-hidroxif ormamida Prepared in accordance to the reaction sequence described in Examples 5D to 5H, substituting 19A for 5C in Example 5D, and 4- (4'-fluorophenyl) -phenol for 4'-hydroxy-4-biphenylcarbonitrile in Example 5F. H NMR (300 MHz, d6-DMSO) d 9.86 (S, 0.5H), 9.54 (S, 0.5H), 8.31 (S, 0.5H), 7.91 (S, 0.5 H), 7.67-7.57 (M, 6H ), 7.27-7.22 (M, 3H), 7.01 -6.97 (M, 3H), 4.96-4.70 (M, 0.5H), 4.50-4.40 (M, 0.5H), 4.1 8-4.08 (M, 3H), 3.77-3.73 (M, 2H), 2.79 (S, 6H), 1.28 (S, 12H), MS (ESI) m / e 430 (M + H), 428 (MH), Anal, caled for C22H24N3O5F » 0.5H2O: C, 60.26; H, 5.74; N, 9.58, Found: C, 60.48; H, 5.66; N, 8.72.

EXAMPLE 20 N-Ri-R (3,4,4-trimethyl-2, 5-dioxo-1-midazolidinyl) methyH-2-rf4'- (trifluoromethyl I) f 1,1 '-biphenyl-1,4-inoxyl] ethyl ester N-hydroxyformamide Was prepared according to the reaction sequence described in Examples 5D through 5H, substituting 19A for 5C in Example 5D and substituting 4- (4'-trifluoromethyl) phenol for 4'-hydroxycarbonitrile. 4-biphenyl in example 5F. 1H NMR (300 MHz, d6-DMSO) d 9.80 (S, 0.5H), 9.58 (S, 0.5H), 8.32 (S, 0.5H), 7.92 (S, 0.5H), 7.87-7.84 (D, 4H , J = 8.1 Hz), 7.79-7.76 (D, 4H, J = 8.8 Hz), 7.72-7.69 (d, 4H, J = 8.4 Hz), 7.06-7.02 (m, 4H), 4.80-4.60 (m, 0.5H), 4.45-4.40 (m, 0.5H), 4.20-4.12 (m, 4H), 3.78-3.74 (m, 2H), 3.63-3.62 (m, 2H), 2.08 (s, 6H), 1.30 ( s, 12H). MS (ESI) m / e M-H (478), M + H (480). Anal, caled for C23H2 N3O5F3- »0.5H2O: C, 56.55; H, 5.15; N, 8.60. Found: C, 56.52; H, 5.07; N, 8.43.

Example 21 N-f1-rr (4'-methoxy, 1'-biphenyl-4-yl) oxylmethyl-2- (3,4,4-trimethyl-2,5-d-oxo-1-imidazolidinyl) etip-Nh The ormamide droxif was prepared according to the reaction sequence described in Examples 5D to 5H, substituting 19A for 5C in Example 5D and substituting 4- (4'-methoxyphenyl) phenol for 4'-hydroxy-4-biphenyl carbonitrile. in example 5F. 1H NMR (300 MHz, d6-DMSO) d 9.89 (s, 0.5H), 9.57 (s, 0.5H), 8.31 (s, 0.5H), 7.91 (s, 0.5H), 7.56-7.53 (d, 8H , J = 8.8 Hz), 7.01-6.94 (m, 8H), 4.80-4.60 (m, 0.5H), 4.44-4.35 (m, 0.5H), 4.17-3.95 (m, 4H), 3.74-3.71 (m , 2H), 3.63-3.58 (m, 2H), 2.79 (s, 6H), 1.28 (s, 12H). MS (ESI) m / e M + H (442).

Anal. Caled for: C23H26N3O6 »0.25H2O: C, 62.08; H, 6.00; N, 9.44. Found: C, 62.25; H, 6.30; N, 8.94.

Example 22 N-ri-rr (4'-methiiri.1'-biphenin-4-yl) oxpmethyl-2- (3,4,4-trimethyl-2,5-dioxo-1-midazolidinyl) etip- N-hydroxyformamide Was prepared according to the reaction sequence described in Examples 5D to 5H, substituting 19A for 5C in Example 5D, and substituting 4- (4'-methylphenyl) phenol for 4'- carbonitrile. hydroxy-4-biphenyl in Example 5F. H NMR (300 MHZ, d6-DMSO) d 9.89 (s, 0.5H), 9.57 (s, 0.5H), 8.31 (s, 0.5H), 7.92 (s, 0.5H), 7.59-7.56 (d, 4H) , J = 8.8 Hz), 7.52-7.49 (d, 4H, J = 8.1 Hz), 7.24-7.22 (d, 4H, J = 7.7 Hz), 7.00-6.97 (m, 4H), 4.80-4.60 (m, 0.5H), 4.40-4.35 (m, 0.5H), 4.40-4.1 (m, 4H), 3.80-3.55 (m, 2H), 3.60-3.50 (m, 2H), 2.79 (s, 6H), 2.32 ( s, 6H), 1.28 (s, 12H). MS (ESI) m / e 424 (M-H), 426 (M + H). Anal. Caled for: C23H27N3? 5-0.25H2O: C, 64.24; H, 6.44-1 N, 9.77. Found: C, 64.30; H, 6.55; N, 9.36.

Example 23 N-f1-rrí4'-butoxif1.1'-bifen¡p-4-iPoxpmetiH-2- (4,4-dimeti-2,5-dioxo-1-imidazolidiniPetin-N-hydroxyformamide) EXAMPLE 23A 1-Bromo-3- (4,4-dimethyl-2,5-dioxoimidazolidin-1-yl) propan-2-one The title compound was prepared following the procedure described in Examples 16A and 16B, except that 5.5 dimethylhydantoin is substituted by 1,5,5 trimethylhydantoin in Example 16A.

Example 23B N-ri-rr (4'-butoxyp.1'-biphenip-4-iPoxi-1-methyl-2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinium-Petin-N-hydroxyl ormamide) Prepared according to the procedures of the example 16C and 16E, replacing example 23A and 16B and 4- (4'-butyloxyphenyl) phenol with 4-bromophenol in example 16C, 1H NMR (300 MHz, d6-DMSO) d 9.86 (s, 0.5H), 9.55 ( S, 0.5H), 8.36 (s, 0.5H), 8.34 (s, 0.5H), 8.32 (s, 0.5H), 7.94 (s, 0.5H), 7.55-7.51 (m, 8H), 6.99-6.96 (m, SH), 4.85-4.80 (m, 0.5H), 4.40-4.36 (m, 0.5H), 4.20-4.06 (mm, 2H), 4.01-3.97 (m, 4H), 3.78-3.71 (m, 2H), 3.60-3.51 (m, 2H), 1.73-1.66 (m, 6H), 1.48-1.38 (m, 4H), 1.25 (s, 12H), 0.96-0.86 (m, 6H), MS (ESI) m / e MH (468) Anal Caled for: C25H3o 3? 6: C, 63.95; H, 6.65; N, 8.94 Found: C, 63.89; H, 6.91; N, 8.63.

Example 24 N-ri-r (4,4-Dimeti-2,5-dioxo-1-amidazolidiniPmetin-2-f (4'-ethoxy-1'-biphenin-4-iPoxylethyl-N-hydroxyformamide) Prepared according to the procedures of Example 23B, except that 4- (4'-ethoxyphenyl) phenol is replaced by 4- (4'-butyloxyphenyl) phenol. 1H NMR (300 MHz, d6-DMSO) d 9.84 (s, 0.5H), 9.52 (s, 0.5H), 8.37 (s, 2H), 8. 32 (s, 2H), 7.92 (s, 0.5H), 7.55-7.52 (m, 8H), 6.98-6.95 (d, 4H, J = 8.8 Hz), 4. 90-4.80 (m, 0.5H), 4.45-4.30 (m, 0.5H), 4.19-3.98 (m, 8H), 3.74-3.67 (m, 2H), 3.59-3.53 (M, 2H), 1.36-1.25 (m, 18H). MS (ESI) m / e M-H (440), M + H (442). Anal. Caled for: C23H27N3O6 «0.5H2O: C, 61.32; H, 6.26, N, 9.32.

Found: C, 61.12; H, 6.35; N, 9.32.

Example 25 N-ri-ff4- (1,3-benzodolox-5-yl) phenoxyphene-2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinium-Petin-N-hydroxyformamide) Prepared according to the procedures of example 23B, except that 4- (3 ', 4'-methylenedioxyphenyl) -phenol is replaced by 4- (4'-butyloxyphenyl) phenyl H NMR (300 MHz, d6-DMSO) d 9.84 (s, 0.5 H), 9.52 (s, 0.5H), 8.37-8.31 (m, 3H), 7.91 (s, 0.5H), 7.55-7.52 (d, 4H, J = 8.5 Hz), 7.19 (s.2H), 7.09 -7.06 (m, 2H), 6.97-6.93 (d, 6H, J = 10.2 Hz), 6.03 (s, 4H), 4.70-4.60 (m, 0.5H), 4.45-4.30 (m, 0.5H), 4.16 -3.96 (s, 6H), 3.73-3.57 (m, 5H), 1.27 (s, 12H), MS (ESI) m / e M + H (442), MH (440), Anal Caled for: C22H23N3O7- »0.50H2O: C, 58.66; H, 5.37; N, 9.32, Found: C, 58.70; H, 5.80; N, 8.79.

Example 26 N-f1-ff (4'-Butoxif1,1'-bifeniH-4-yl) oxylmethyl-2- (3-methy-2,5-d-oxo-1-midazolidinyl) et.pN-hydroxyformamide Example 26A 1 -bromo-3- (3-methyl -2,5-dioxoimidazo-idin-1-iPpropan-2-one) The title compound was prepared following the procedure described in Examples 16A and 16B, except that 1-methylhydantoin was replaced by 1 , 5,5 trimethylhydantoin in Example 16A.

Example 26B N-f1-rr (4'-Butoxip.1'-bifenill-4-iPoxylmetin-2- (3-methy-2,5-dioxo-1-imidazole id ini l) etin-N-hydroxyform amide Prepared according to the procedures of example 16C and 16E, substituting example 26A for 16B and 4- (4'-butyloxyphenyl) phenoxy for 4-bromophenol in example 16C.1H NMR (300 MHz, d6-DMSO) d 9.97 (s) , 0.5H), 9.60 (s, 0.5H), 8.34 (s, 0.5H), 7.97 (s, 0.5H), 7.55-7.50 (m, 8H), 6.99-6.91 (m, 8SH), 4.86-4.82 (m, 0.5H), 4.33-4.31 (m, 0.5H), 4.18-4.12 (m, 2H), 3.99-3.94 (m, 4H), 2.85 (s, 6H), 1.82-1-68 (m, 4H), 1.50-1.38 (m, 6H), 0.96-0.91 (m, 6H), MS (ESI) m / e MH (454), Anal Caled for: C24H29N3O6 «0.25C4H50: C, 63.51; H, 6.44; N, 8.88, Found: C, 63.59; H, 6.46; N, 8.68.

Example 27 N-f1-rr4- (3-tieniPfenoxylmetill-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazole id iniPetin-N-hydroxyform amide Prepared according to the procedures of Example 16C and 16E , substituting 4- (4 '- (3-thienyl) phenyl) phenol for 4-bromophenol in Example 16C, 1H NMR (300 MHz, d6-DMSO) d 9.90 (s, 0.5H), 9.57 (s, 0.5H ) 8.31 (s, 0.5H), 7.91 (s, 0.5H), 7.75-7.74 (m, 2 H), 7.67-7.60 (m, 6H), 7.52-7.49 (m, 2H), 6.96-6.92 ( m, 4H), 4.80-4.6 (m, 0.5H), 4.50-4.4 (m, 0.5H), 4.19-3.98 (m, 6H), 3.81-3.70 (m, 2H), 3.61-3.56 (in, 2H) ), 2.79 (s, 6H), 1.29 (s, 12H), Anal.Called for: C2oH23N3? 5S: C, 57.54; H, 5.55; N, 10.06.Found: C, 57.72; H, 5.84; N, 9.76 .

EXAMPLE 28 N-f1-rr (1,1'-biphenin-4-yl) oxymethyl-2- (3,4,4-trimethyl-2,5-dioxo-1-m id azo I id in i I ) et i nN -hydroxif orma mida Prepared according to the procedures of example 16C and 16E, replacing 4-phenyl-phenol with 4-bromophenol in Example 16C. 1 H NMR (300 MHz, d 6 -DMSO) d 9.90 (S, 0.5H), 9.57 (S, 0.5H), 8.30 (S, 0.5H), 7.92 (S, 0.5H), 7.62-7.60 (D, 8H , J = 8.1 Hz), 7.45-7.40 (t, 4H, J = 5.8, 7.8 Hz), 7.33-7.28 (t, 2H, 3 = 7.1, 6.9 Hz), 7.02-6.97 (m, 4H), 4.80- 4.60 (m, 0.5H), 4.45-4.40 (m, 0.5H), 4.18-4.01 (m, 4H), 3.77-3.70 (m, 2H), 3.63-3.6 (m, 2H), 2.80 (s, 6H) ), 1.28 (s, 12H). MS (ESI) m / e M-H (410), M + H (412). Anal. Caled for: C22H25N3O5- »0.2SH2O: C, 63.25; H, 6.17; N, 10.10. Found: C, 63.94; H, 6.41; N, 9.60.

Example 29 N-f1-rr (3'-chloro-4'-fluorof1.1'-biphenyl-4-iPoxpmetin-2- (3,4,4-trimethyl-2,5-dioxo-1-amidazolidinyl) etin-Nh The droxiformamida was prepared according to the procedures of Example 16C and 16E, substituting 4- (4'-fluoro-3'-chlorophenyl) phenol for 4-bromophenol in Example 16C, 1H NMR (300 MHz, d6). -DMSO) d 9.90 (s, 0.5H), 9.57 (s, 0.5H), 8.31 (s, 0.5H), 7.92 (s, 0.5H), 7.84-7.82 (m, 2H), 7.65-7.61 (m , 6H), 7.49-7.43 (t, 2H, J = 9.2.8.8 Hz), 7.02-6.96 (m, 4H), 4.80-4.60 (m, 0.5H), 4.43-4.40 (m, 0.5H), 4.21 -4.06 (M, 4H), 3.82-3.70 (m, 2H), 3.62-3.59 (m, 2H), 2.79 (s, 6H), 1.28 (s, 12H), MS (ESI) m / e MH (462) ), M + H (464), Anal Caled for: C22H23N3? 5CIF-0.25H2O: C, 56.41; H, 5.05; N, 8.97. Found: C, 56.78, H, 5.24, N, 8.55.

EXAMPLE 30 N-Ri-rf (2'-methyl-1,1'-biphenylyl-4-iPoxi-methyl-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazo lid iniPetiH-N-hydroxyform amide Prepared from according to the procedures of example 16C and 16E, substituting 4- (3'-methyl-phenyl) phenol for 4-bromophenol in example 16C, 1H NMR (300 MHz, d6-DMSO) d 9.90 (s, 0.5H), 9.57 (s, 0.5H), 8.32 (s, 0.5H), 7.93 (s, 0.5H), 7.28-7.14 (m, 12H), 6.99-6.64 (m, 4H), 4.90-4.80 (m, 0.5H) ), 4.42-4.40 (m, 0.5H), 4.22-4.04 (m, 6H), 3.82-3.74 (m, 2H), 3.62-3.58 (m.2H), 2.80 (s, 6H), 2.20 (s, 6H), 1.29 (s, 12H), MS (ESI) m / e M + H (426), MH (424).

Anal. Caled for: C23H27N3? 5 »0.25H2O: C, 64.24; H, 6.44; N, 9.77. Found: C, 64.50; H, 6.69; N, 9.31.

Example 31 N-f1-ff (4'-cyanoiri.1'-bifenin-4-ii) oxylmetin-2- (2.5-dioxo-1 imidazolidiniPeti l-N-hydroxiformamide Example 31A 3- (4- (4'-carbonitrilophenyl) phenoxp-1-bromopropan-2-one The title compound was prepared according to the procedure described in Examples 16A and 16B, but replacing 4- (4'-cyanophenyl) -phenol for 1, 5,5-trimethylhydantoin in Example 16A.

Example 31B N-ri-rr (4'-cyanolf1.1'-biphenin-4-yl) oxylmethyl-2- (2,5-dioxo-1-imidzo I id i ni!) Eti HNh id roxiformam ida Se prepared according to the procedures of Example 16C and 16E, substituting Example 31A for 16B and hydantoin for 4-bromophenol in Example 16C. 1 H NMR (300 MHz, DMSO-d 6) d 3.6-3.8 (m, 2 H), 3.92 (d, 2 H, J = 8.4 Hz), 4.10-4.25 (m, 2 H), 4.3-4.4 (m, 0.5 H) , 4.8-4.9 (m, 0.5H), 7.0-7.1 (m, 2H), 7.74 (d, 2H, J = 9.0 Hz), 7.84 (d, 2H, J = 8.4 Hz), 7.89 (d, 2H, J = 8.4 Hz), 7.98 (s, 0.5H), 8.1-8.2 (M, IH), 8.35 (s, 0.5H), 9.57 (br s, 0.5H), 9.53 (br s, 0.5H). MS (ESI +) 395 (M + H).

Anal. Caled for C20H18N4O5 »0.2H2O» 0.4EtOAc: C, 59.88; H, 5.03; N, 12.93. Found: C, 59.80; H, 4.81; N, 12.74.

Example 32 N-f1-rr (4'-cyanoif1.1'-biphenylyl-4-iPoxi1metn-2- (1,1-dioxido-3-oxo-1,2-benzisothiazol-2- (3H) -iPet i HNh id roxiformam id a Was prepared according to the procedures of example 16C and 16E, replacing example 31A by 16B and saccharin by 4-bromophenol in example 16C.IH NMR (300 MHz, DMSO-d6) d 3.9-4.2 (m , 2H), 4.2-4.3 (m.2H), 4.45-4.55 (m, 0.5H), 5.0-5.1 (m, 0.5H), 7.0-7.1 (m, 2H), 7.74 (d, 2H. 8.4 Hz), 7.85 (d, 2H, J = 8.7 Hz), 7.88 (d, 2H, J = 8.4 Hz), 8.0-8.2 (m, 3.5H), 8.3-8.4 (m, 1.5H), 9.78 ( s, 0.5H), 10.14 (s, 0.5H), MS (ESI-) 476 (MH), Anal Caled for C24H19N3O6S «1.1H2O: C, 57.97; H, 4.30; N, 8.45 Found: C, 58.01; H, 3.96; N, 8.16.

Example 33 N-f1-f (4,4-dimeti-2,5-dioxo-1-imidazole id inyl) metip-2-ff4'- (trifluoromethoxpfl, 1'-bifen i 11-4-iHoxiletill-Nh id roxiformam id a Was prepared according to the procedures of Example 23B, except that 4- (4'-trifluoromethoxy phenyl) -phenol was replaced by 4- (4'-butyloxyphenyl) -phenol. 1 H NMR (300 MHz, DMSO-d 6) d 1.27 (s, 6H). 3.5-3.8 (m, 2H), 4-0-4.3 (m, 2H), 4.4- 4.5 (m, 0.5H), 4.8-4.9 (m, 0.5H), 7.0-7.2 (m, 2H), 7.42 (d, 2H, J = 7.8 Hz), 7.64 (d, 2H, J = 8.4 Hz), 7.75 (d, 2H, J = 8.7 Hz), 7.93 (s, 0.5H), 8.33 (s, 0.5H) , 8.35 (s, 0.5H), 8.40 (s, 0.5H), 9.56 (s, 0.5H), 9.87 (s, 0.5H). MS (ESI +) 482 (M + H). Anal. Caled for C22N2iN3? 6F3: C, 54.88; H, 4.60; N, 8.72. Found: C, 55.22; H, 4.87; N, 8.36.

Example 34 N-f 1-f f 4 - (4-phenyl-1-piperidinyl) phenoxylmethyl-2- (3, 4,4-tri-methyl-2, 5-di oxo-1-imidazo idiniPetill-N-hydroxyformamide It was prepared according to the procedures of example 16C and 16E, substituting 4-phenyl-N-phenyl piperidine (prepared as in Warner-Lambert patent WO 97/19068), by 4-bromophenol in example 16C. 1 H NMR (300 MHz, DMSO-d 6) d 1.27 (s, 3 H), 1.28 (s, 3 H), 1.7-1.9 (m, 4 H), 2.55-2.75 (m, 3 H), 2.78 (s, 1.5 H) , 2.79 (s, 1.5H), 3.5-3.8 (m, 4H), 3.9-4.1 (m, 2H), 4.3-4.4 0.5H), 4.7-4.8 (m, 0.5H), 6.81 (d, 2H, J = 8.7Hz), 6.93 (d, 2H, J = 9.0 Hz), 7.15-7.25 (m, 1H), 7.25-7.35 (m, 4H), 7.89 (s, 0.5H), 8.30 (s, 0.5H) ), 9.54 (s, 0.5H), 9.86 (5, 0.5H). MS (ESI +) 495 (M + H). Anal. Caled for C27H34N4O5: C, 65.56; H, 6.92; N, 11.32. Found: C, 65.35; H, 7.24; N, 10.93.

EXAMPLE 35 N-Ri-R (4.4-dimethyl-2,5-dioxo-1-imidazolidiniPmetin-2-ff4 '- (trifluoromethylP1.1'- b if en i p-4-iHoxilet i HNh id roxiformam ida Prepared from according to the procedures of example 23B, except that 4- (4'-trifluoromethylphenyl) phenol is replaced by 4- [4'-butyloxyphenyl) phenol.1H NMR (300 MHz, DMSO-d6) d 1.28 (s, 6H), 3.5-3.8 (m, 2H), 4.1-4.3 (m. 2H), 4.4-4.5 (m, 0.5H), 4.8-4.9 (m, 0.5H), 7.0-7.2 (m, 2H), 7.72 (d.2H, J = 8.4 Hz), 7.78 (d, 2H, J = 8.4 Hz), 7.86 (d, 2H, 3 = 8.4 Hz), 7.93 (s, 0.5H), 8. 33 (s, 0.5H), 8.35 (s, 0.5H), 8.40 (s, 0.5H), 9.56 (s, 0.5H), 9.87 (s 0.5H). MS (ESI +) 466 (M + H). Anal. Caled for C22H22H3O5Fz »0.6 \ - \ 2O: C, 55.49; H, 4.91; N, 8.82.

Found: C, 55.55; H, 4.66; N, 8.77.

Example 36 N-ri-ff (3'-cyanori, 1, -biphenin-4-y-oxo-1-methyl-2-rmethir (4-methylphenylsulphonine-N-hydroxyformamide) was prepared according to the procedures of Example 16C and 16E , replacing Example 31A by 16B and N-methyl- (p-tolyl) sulfonamide by 4-bromophenol in Example 16C.1H NMR (300 MHz, DMSO-d6) d 2.41 (s, 3H), 2.70 (s, 1.5 H), 2.73 (s, 1.5H), 3.05-3.35 (m, 2H), 4.0-4.2 (m, 2H), 4.3-4.4 (m, 0.5H), 4.8-4.9 (m, 0.5H), 7.06 (d, 2H, J = 8.7 Hz), 7.46 (d, 2H, J = 8.1 Hz), 7.65-7.8 (m, 4H), 7.85 (d, 2H, J = 8.7 Hz), 7.89 (d, 2H, J = 8.7 Hz), 8.04 (s, 0.5H), 8.40 (s, 0.5H), 9.71 (s, 0.5H), 10.0 (s, 0.5H), MS (ESI +) 480 (M + H). Caled for C25H25N305S: C, 62.61; H, 5.25; N, 8.76, Found: C, 62.52; H, 5.27; N, 7.98.

Example 37 N-f1-rr (4'-cyanori, 1'-biphenin-4-yl) oxymethylene-2-f4.4-dimethy-2,5-dioxo-3- (3-pyridinylmethyl-1-imid-azolidinipetiH -N-hydroxyform amide Example 37A 3- (3-pyridinylmethyl)) - 2,5-dioxo-4,4-dimethyl imidazole The title compound was prepared following the procedures described in examples 68A, 68B and 69B, except that 3-picolyl chloride is replaced by methyl iodide in example 68B.

Example 37B N-ri-ff (4'-cyanof1,1'-biphen-p-4-yl) oxy-methyl-2-f4,4-dimethyl-2,5-dioxo-3- (3-pyridinylmethyl-1-imidazo-idinilletin- N-hydroxyformamide The title compound was prepared according to the procedures of Example 16C and 16E, replacing Example 31A with 16B and 37A with 4-bromophenol in Example 16C, 1H NMR (300 MHz, DMSO-d6) d 1.25 ( s, 6H), 3.6- 3.7 (m, 1 H), 3.8-3.9 (m, 1 H), 4.1-4.3 (m, 2H), 4.4-4.5 (m, 0.5H), 4.56 (s, 2H) , 4.85-4.95 (m, 0.5H), 7.0-7.1 (m, 2H), 7.35 (dd, IH, J = 8.1.4.8 Hz), 7.7-7.8 (m, 3H), 7.86 (d, 2H, J = 8.4 Hz), 7.90 (d, 2H, J = 8.4 Hz), 7.96 (s, 0.5H), 8.34 (s, 0.5H), 8.45-8.50 (narrow m, IH), 8.60 (s, IH), 9.64 (s, 0.5H), 9.97 (s, 0.5H), MS (ESI (+)) 514 (M + H).

Anal. Caled for C28H27N5O- »1.7H2O: C, 61.80; H, 5.63; N, 12.87. Found: C, 61.77; H, 5.08; N, 12.48.

Example 38 N-f2-y (4'-cyanoyl-1,1'-biphenyl-4-yl) oxp-1-methylpropip-N-hydroxyformamide The title compound was prepared according to the procedures of Example 16C and 16E, substituting 3-bromo-2-butanone for 16B and 4- (4'-cyanophenyl) phenol for 4-bromophenol in Example 16C. 1 H NMR (300 MHz, DMSO-d 6) d 1.1-1.3 (m, 6 H), 3.8-4.0 (m, 1 H), 4.3-4.7 (m, 1 H), 7.0-7.1 (m, 2 H), 7.6-7.7 (m, 2H), 7.8-7.9 (m, 4H), 8.02 (s, 0.5H), 8. 28 (s, 0.25 H), 8.33 (s, 0.25 H), 9.43 (s, 0.25 H), 9.60 (s, 0.25 H), 9.85 (s, 0.25H), 9.95 (s, 0.25 H). MS (ESI +) 311 (M + H). Anal. Caled for C18H18N2O3 »0.2H2O: C, 68.86; H, 5.91; N, 8.g2. Found: C, 68.73; H, 5.7g; N, 8.58.

EXAMPLE 3g N-f1-rf (3'-cyanof1.1'-biphenyl-4-yl) oxy-methyl-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinium-Petm-N-hydroxyformamide) Example 3gA 3'-cyano-4-hydroxy biphenyl A 250 ml flask was charged with 2.21 g (2.7 mmol) [1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium (II) • CH2Cl2 and 6.26 g (2.73 mmol) of 3-iodobenzonitrile, 6.0 g (3.g5 mmol) of 4-methoxyphenylboronic acid and 12.45 g (8.20 mmol) of cesium fluoride was added as solids, followed by the addition of 1 80 ml of 1,2-dimethoxyethane. The flask was rinsed with N2 and the suspension was heated to reflux, which was maintained for 3 hours. The cooled reaction mixture was filtered through a pad of 300 g of flash silica gel and the pad was washed with 1 l of ethyl acetate. The ethyl acetate was concentrated and the residue was purified by flash chromatography, levigating with 1 0% hexanes / g?% ethyl acetate to give 3.3 g of the desired product (58% yield). This material was dissolved in 50 ml of anhydrous CH 2 Cl 2 and the solution was cooled in a dry ice-acetone bath and a solution of boron tribromide (40 ml, 4 mmol) was added dropwise under an inert atmosphere. The reaction solution was then stirred at room temperature overnight. The reaction solution was cooled in an ice bath and 5 ml of H20 were added dropwise, followed by the addition of 20 ml of 1 N HCl. The mixture was stirred for 1 hour and the resulting suspension was filtered, and the filtrate was transferred to a separatory funnel and the organic layer was separated and set aside. The filtered solid was washed with H2O and ethyl acetate and filtered and the filtrate was transferred to the separatory funnel, and the organic layer was combined with the previous organic layer, dried over Na2SO4, filtered and the filtrate was concentrated to 3.05 g of a white solid (99% yield).

Example 39B N-ri -rr (3'-cyanori .1'-bifenin-4-iPoxi1met.p-2- (3.4.4-trimethyl-2.5-dioxo-1-im idazo I id i nil) eti HNh id roxiformam ida Prepared according to the procedures of example 16C and 16E, replacing 3'-cyano-4-hydroxy biphenyl by 4-bromophenol in the example 16C. 1 H NMR (DMSO-d 6) d 9.86 (s, 1 / 2H), 9.48-g.63 (c, 1 / 2H), 8.33 (s, 1 / 2H), 8.09 (s, 1H), 7.97 (d, 1H, J = 4.5 Hz), 7.93 (s, 1 / 2H), 7.75 (d, 1H, J = 4.5 Hz), 7. 70 (d, 2H, J = 6.0 Hz), 7.63 (t, 1H, J = 4.5 Hz), 7.00-7.07 (c, 2H), 4.83-4.90 (c, 1 / 2H), 4.60-4.67 (c, 1 / 2H) ESI (+): 409 (M-27), 437 (M + H), 454 (M + NH 4), 459 (M + Na) Anal. Caled for: C23H24N4O5.0.25C4H8O2: C, 62.87; H, 5.71; N, 12.21. Found: C, 62.68; H, 5.55; N, 12.27.

Example 40 N-ri-rrf4 '- (methylthio) ri.1, -bifenill-4-iPoxi1metin-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazole id iniPetill-N-hydroxyl ormamide Prepared according to to the procedures of example 16C and 16E, substituting 4'-thiomethyl-4-hydroxy biphenyl for 4-bromophenol in the example 16C. 1H NMR (DMSO-d6) d 9.48-9.96 (BS, 1H), 8.34 (S, 1 / 2H), 7.94 (S, 1 / 2H), 7.54-7.63 (C, 4H), 7.29-7.34 (C, 2H), 6.97-7.03 (C, 2H), 4.82-4.92 (C, 1 / 2H), 4.39-4.47 (C, 1 / 2H), 4.07-4.25 (C, 2H), 3.73-3.85 (C, 1H) ), 3.59-3.68 (C, 1H), 2.80 (S, 1.5H), 2.79 (S, 1.5H) MS (ESI (-)) 456 ((MH)) 913 ((2M-H) Theory: 458,175 Found : 458.1747 Anal Caled for: C23H27N305S C, 60.37; H, 5.95; N, 9.ig; S, 7.01; Found: C, 60.2g; H, 5.82; N. g.08; S, 6.g8.

Example 41 Nf 1-f4-ff4- (trifluoromethylP-phenoxyphenoxymethyl H-2- (3,4,4-tri-methyl-2,5-dioxo-1-imidazolidinylPetill-N-hydroxyformamide) Prepared according to the procedures of Example 16C and 16E, substituting 4- (4'-trifluoromethylphenoxy) phenol for 4-bromophenol in Example 16C.IH NMR (DMSO-d6) d 9.46-g.g7 (C, IH), 8.33 (S, 1 / 2H), 7.94 (S, 1 / 2H), 7.71 (S, 1H), 7.69 (S, 1H), 7.04-7.14 (C, 4H), 6.g7-7.03 (C, 2H), 4.81-4.91 (C, 1 / 2H), 4.39-4.47 (C, 1 / 2H), 4.14-4.22 (C, 1H), 4.04-4.13 (C, 1H), 2.81 (S, 1.5H), 2.80 (S, 1.5H), 1.30 ( S, 1.5H) MS (ESI (-) 494 (MH), 530 (M + CI), 989 (2M-H), 1011 (2M + Na2H) Theory: 496.169, Found: 496.1696 Anal Caled for: C23H24F3N3O6 Theory : C, 55.75; H, 4.88; N, 8.48; F, 11.50, Found: C, 55.68; H, 4.92; N, 8.40; F, 11.24.

Example 42 N-ri-rrf4 '- (trifluoromethoxypri, 1'-biphenin-4-haloxymethyl-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethiH-2-N-hydroxyform amide prepared according to the procedures of Example 16C and 16E, substituting 4'-trifluoromethoxy-4-hydroxy biphenyl for 4-bromophenol in Example 16C, 1HNMR, 400Mz (DMSD-d6): d 9.46-9.84 (c, 1H); 8.26 (s, 1 / 2H) .7.87 (s, 1 / 2H), 7.67 (s, 1H), 7.65 (s, 1H), 7.57 (s, 1H), 7.55 (s, 1H), 7.34 (s, 1H), 7.32 (s, 1H), 6.94-6.97 (c, 2H), 4.78-4.82 (c, 1 / 2H), 4.34-4.38 (c, 1 / 2H), 4.02-4.17 (c, 2H); 3.67-3.77 (c, 1H), 3.53-3.60 (c, 1H), 2.73 (s, 1.5H), 2.72 (s, 1.5H), 1.22 (s, 3H), 1.21 (s, 3H), MS ( ESI (-)): 494 (MH), 530 (M + CI), 989 (2M-H), 1011 (2M + Na-2H) Theory: 496.16g5 Found: 496.1680 Anal Caled, for C23H24F3N3O6 Theory: C , 55.75; H, 4.88; N, 8.48; F, 11.50, Found: C, 55.69; H, 4.94; N, 8.23; F, 11.71.

Example 43 N-f1-rrf4 '- (methylsulfoniPf1.1'-biphenin-4-ioxy-1-methyl-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinium-Petip-N-hydroxyformamide) Prepared according to the procedures of the example 48A, 48B and 48C, substituting 16B for 23A for 4-bromophenol in example 48A, 1HNMR, 400MHz (DMSO-d6): d 9.47-9.98 (c, 1 H), 8.35 (s, 1 / 2H), 7.92- 8.00 (c, 4.5H), 7.77 (s, 1H), 7.75 (s, 1H), 7.07-7.10 (c.2H), 4.85-4.94 (c, 1 / 2H), 4.42-4.50 (1 / 2H); 4.13-4.30 (c, 9H); 3.76-3.86 (c, 1 H); 3.63-3.69 (c, 1 H), 3.39 (s, 3H); 2.83 (s, 1.5H); 2.82 (s, 1.5 H), 1.32 (s, 3H), 1.31 (s, 3H), MS [ESI (-)]: 488 (MH), 977 (2M-H), gg9 (2M + Na-2H) [ESI (+) ]: 490 (M + H), 507 (M + NH4), 512 (M + Na) Anal, caled, for C23H28.5N3O7.75S: Theory: C, 54.91, H, 5.71; N, 8.35; S, 6.37 Found: C.54.85; H, 5.76; N, 8.00; S, 6.31.

EXAMPLE 44 Np-rrr3 '- (Cyanomethyl) -4'-methoxyiri.1'-bifenH-4-yloxy-1-methyl-2- (3,4,4-trimetho- 2,5-d-oxo-1-imidazolidinyl) ethyl -N-hydroxyformamide It was prepared according to the procedures of example 16C and 16E, substituting 4- (3'-cyanomethyl-4'-methoxyphenyl) phenol for 4-bromophenol in example 16C. 1 H NMR (300 MHz, DMSO-d 6) d; 1,275, 1,290 (6H), 2,788, 2,800 (3H), 3. 566-3,641 (m, 1H), 3,708-3,821 (m, 1H), 4,047-4,214 (m, 2H), 4.39g- 4,416 (m, 0.5H), 4,846 (m, 0.5H), 6.g73- 7.013 (2H), 7.110-7.140 (1H), 7. 543-7.608 (m, 4H), 7.291 (s, 0.5H), 8.319 (s, 0.5H), 9.576 (s, 0.5H), 9. g04 (s, 0.5H). MS (ESI) m / e 481 (M + H) +, 498 (M + NH 4) +, 479 (M-H). "Anal, caled for C 25 H 28 N 4 O 6" 0.5 MeOH: C, 61.68; H, 6.08; N, 11.28.

Found: C, 62.07; H, 6.21; N, 10.91.

EXAMPLE 45 N-Ri-rrr3 '- (CyanomethylPF1.1'-biphenin-4-inoxpmetin-3- (4,4-dimethyl-2, 5-dioxo-1-imidazolidinPprop.mN-hydroxyformamide The title compound is prepared according to the procedures of Example 5, except that methylation step was avoided in example 5B and 4- (3'-cyanomethylphenyl) phenol was replaced by 4'-hydroxy-4-biphenylcarbonitrile in example 5F. (300 MHz, DMSO-d6) d, 1.27 (s, 6H), 1.70-2.00 (m, 2H), 3.37-3.47 (m, 2H), 3.96-4.08 (s + m, SH), 7.00-7.03 ( d, 2H, 8.4Hz), 7.28-7.31 (d, 1H, 8.7Hz), 7.426-7.477 (t, 1H, 7.5Hz), 7.56-7.61 (m, 4H), 7.915 (s, 0.73H), 8.28 -8.34 (1.27H), 9.55 (S, 0.75H), 9.96 (s, 0.25H), MS (ESI) m / e 451 (M + H) +, 468 (M + NH4) +, 449 (MH) Anal, caled for C25H28N4O6- »MeOH: C, 62.22; H, 6.26; N, 11.61, Found: C, 62.25; H, 5.95; N, 11.57.

EXAMPLE 46 N-RI-Rr (4, -butoxy-1'-biphenyl-4-iPsulfoninmetin-2- (4,4-dimethyl-2,5-dioxo-1-imidazolidine-Petill-N-hydroxyl ormamide Example 46A 1- (4-bromophenylthio) -3- (4,4-dimethyl-2,5-dioxoimidazolidin-1-iP-2-propanone A solution of 4-bromothiophenol (2.15 g, 11.4 mmol) in DMF (50 ml) at room temperature was treated with cesium carbonate (5.57 g, 17.1 mmol) for 20 minutes, treated in a simple portion with example 23A ( 2.5 g, 9.5 mmol), was stirred for 1 hour at room temperature and diluted with water, extracted with ethyl acetate, the combined extracts were washed with water and brine, dried (Na 2 SO), concentrated and purified in vacuo. silica gel with 20 to 35 to 50% ethyl acetate / hexane to provide 3.17 g (90%) of the title compound as a white solid. MS (APCl) m / e 371, 373 (M + H) +, 388, 390 (M + NH 4) +, 369, 371 (M-H), 405, 407 (M + CI). " Example 46B 1-f (4'-Butoxip, 1'-bipheniH-4-iPthio1-3- (4,4-dimethyl-2,5-dioxoimidazolidin-1-iP-2-propanone) A solution of Example 46A (700 mg, 1.89 mmol) in DME (20 ml) at room temperature was treated with 4-n-butoxybenzeneboronic acid (54g mg, 2.83 mmol), tatrakis- (triphenylphosphine) -palladium (218 mg, 0.18g mmol) and 1M sodium carbonate (3.54 ml, 3.54 mmol), the reaction vessel was sealed and heated ag? C for 6 hours, diluted with ethyl acetate, washed with saturated ammonium chloride solution sequentially, water and brine, dried (Na2SO4). , concentrated and purified on silica gel with 30 to 50% ethyl acetate / dichloromethane to give 650 mg (78%) of the title compound as a yellow solid MS (APCl) m / e 441 (M + H) +, 458 (M + NH 4) +, 439 (MH), 475 (M + CI) '.

Example 46C N-ri-rr (4'-butoxy, 1'-biphenyl-4-iPthio-1-methyl-2- (4.4-dimethyl-2,5-d-oxo-1-imidazolidin and Petip-N-hydroxy-ormamide The title compound is prepared from 46B, following the procedures described in example 2D, 2E, 2F, 1H NMR (300 MHz, DMSO-d6) d, 0.919-0.967 (t, 3H, J = 7.2Hz9, 1225-1.237 (s + s, 6H), 1389-1.512 (m, 2H), 1666-1.760 (m, 2H), 3.110-3.192 (m, 2H), 3.528-3.735 (m, 2H), 3.g87-4.030 (t, 2H) , J = 6.3 Hz), 4,030 (m, 0.5H), 4,750 (m, 0.5H), 6,991-7,020 (d, 2H, J = 9 Hz), 7,383-7,417 (dd, 2H, J = 1.8, 8.4 Hz), 7.561-7.601 (4H), 1.5 H), 9.56 (s, 7.767 (s, 0.5H), 8.299 (s, 1H), 8.337 (s, 0.5H), 9.457 (br s, 0.5H), 9.695 (br s, 0.5H) MS (ESI) m / e 484 (MH) 'High resolution MS (FAB) Cale.M / z for m + 485.1984, observed m / z 485.1980.

Example 46D N-ri-rr (4'-butoxyri.1'-bifenill-4-iPsulfonillmetill-2- (4.4-dimeti-2.5-dioxo-1- imidazo I id iniPet¡HNh¡droxif ormamide A solution of Example 46C ( 127 mg, 0.262 mmol) in methanol (2 ml), and pH 7 buffer (1 ml) at 0 ° C was treated with oxone (402 mg, 0.655 mmol) for 30 minutes, then at room temperature for 1 hour, neutralized with saturated sodium bicarbonate, extracted with dichloromethane, the combined extracts were washed with brine, dried (Na2SO4) and concentrated.The crude mixture was purified on silica gel with 50% ethyl acetate / hexane then 10% methanol dichloromethane to give 82 mg (60%) of the title compound as a white solid.1H NMR (300 MHz, DMSO-d6) d; 0.g2-0.g7 (t, 3H, 7.5Hz), 1.20, 1.22 (s + s, 6H), 1.42-1.52 (m, 2H), 1.68-1.77 (m, 2H), 3.41-3.72 (m , 3.5H), 4.02-4.06 (t, 2H, 6.6Hz), 4.52 (m, 0.5H), 4.8g (m, 0.5H), 7.05-7.08 (d, 2H, 8.4Hz), 7.70-7.74 ( 2H), 7.gi (s, 3.5H), 8.10 (s, 0.5H), 8.32-8.35 (d, 1H, g.6Hz), 9.48 (s, 0.5H), 9.62 (s, 0.5H). MS (ESI) m / e 518 (M + H) +, 535 (M + NH4) +, 516 (MH) ", 552 (M + Cl) \ Anal, caled for C25H28N4O6" 0.25H2O: C, 57.51; H , 6.08; N, 8.04, Found: C, 57.78; H, 6.18; N, 7.84.

Example 47 N-ri-rr (4'-cyanop, 1'-biphenin-4-iPoxpmetin-3- (4,4-dimethyl-2,5-dioxo-1-imidazolidin I) propyl-N-hydroxyl ormamide Example 47A 1-bromo-4- (3,4 l4-trimethyl-2,5-dioxoimidazolidin-1-iPbutan-2-one) To a suspension of Cu Br 2 (1.91 g, 8.5 mmol) and lithium bromide (1. 48 g, 17 mmol) in THF (10 ml) was added a solution of 1.06 g (5.3 mmol) of 1 - ((1 ', 2' oxi ran i I) prop i I-4, 4-di methyl -2, 5-di oxo imidazo I id i na (prepared from Example 5A following the procedure of Example 5C) in 15 mL of THF. The reaction mixture was stirred for 2 h at room temperature, then it was separated between ethyl acetate and ph7 buffer. The organic extract was washed with brine, dried and concentrated. The residue was filtered through a plug of silica by levigating with ethyl acetate, and the filtrate was concentrated to give a white solid, which was dissolved in acetone (25 ml), cooled to 0 ° C, then treated with 2.5 ml of Jones 8M reagent and stirred at room temperature for 3 h. The reaction was quenched with 2 ml of isopropanol, then separated between ethyl acetate and water. The organic extract was washed with brine, dried and concentrated. The residue was filtered through a plug of silica by levigating with ethyl acetate, and the filtrate was concentrated to give the title compound.

Example 47B Np -rr (4'-cyanop, 1, -bifenin-4-iPoxpmetiH-3- (4.4-dimethyl-2,5-dioxo-1-im idazo I id in il) prop i ll-Nh id roxiformam ida The title compound was prepared according to the procedures of Example 16C and 16E, except substituting 47A for 16B and 4'-hydroxy-4-biphenylcarbonitrile for 4-bromophenol in Example 16C, Pf 202-204oC 1H NMR (300 MHz, DMSO-d6) d; 1.272 (6H), 1.70-2.00 (m, 2H), 3.38-3.46 (t, 2H, J = 6 Hz), 3.02-4.18 (m, 2.5H), 4.46-4.57 (m, 0.5H), 7.03-7.06 (d, 2H, J = 8.7 Hz), 7.605-7.724 (d, 2H, J = 8.7 Hz), 7.82-7.g2 (m, 6.5H), 8.26-8.35 (1.5H) ), g.75 (s), 9.96 (s) (1H) MS (ESI) m / e 437 (M + H) +, 454 (M + NH4) +, 45 (MH) \ Anal, caled for C25H28N4O6 » 0.25H2O: C, 62.64; H, 5.60; N, 12.70. Found: C, 62.55; H, 5.47; N, 12.65.

Example 48 N-r4-rrr4 '- (methylsulfoniPf1,1-biphenin-4-inoxpmetiH-2- (4.4-dimethyl-2.5-d-oxo-1-imidazo lid iniPetill-N-hydroxyl ormamide Example 48A 1- (4 '- (t'methyl) ri, 1'-b-phenyl-4-yl) oxy) -3- (4,4-dimethyl-2,5-dioxoimidazolidin-1- il) -2-propanone A solution of 4'-hydroxy-4-biphenylmethylsulfide (1.18 g, 5.47 mmol) in DMF (25 ml) at room temperature was treated with cesium carbonate (2.2 g, 6.84 mmol) for 20 minutes, it was treated in a simple portion with 23A (1.2 g, 4.56 mmol), stirred for 2 hours at room temperature and diluted with water, extracted with ethyl acetate, the combined extracts were washed with water and brine, dried ( Na2SO), concentrated and purified on silica gel with 50 to 80% ethyl acetate / hexane to provide 1.0 g (55%) of the title compound as a white solid. MS (APCl) m / e 30g (M + H) +, 416 (M + NH 4) +, 3g 7 (M-H) ", 433 (M + CI)".

Example 48B Np -rrr4 '- (thiomethyl) f 1 .1' -bifenill-4-iHoxylmetin-2- (4,4-dimethyl-2,5-dioxo-1-imidazolidiniPetip-N-hydroxyl ormamide) The title compound was prepared from 48A following the procedures described in example 2D, 2E, 2F.MS (ESI) m / e 44 (M + H) +, 461 (M + NH 4) +, 466 (M + Na) +, 422 (MH) Example 48C N-ri -rrr4 '- (methylsulfoniPri. 1' -bifeniH-4-illoxi1metin-2- (4.4-dimethyl-2,5-dioxo-1-imidazo I idin i Petill-N-hydroxyl ormamide A solution of example 48B ( 440 mg, 0.8g3 mmol) in methanol (100 ml) and water (50 ml) at 0 ° C was treated with oxone (1.27 g, 2.06 mmol) and sodium bicarbonate (1.74 mg, 2.06 mmol) during 1 hour, then at room temperature for 1.5 hours, diluted with water, extracted with dichloromethane, the combined extracts were washed with brine, dried (Na 2 SO) and concentrated.The crude mixture was purified on silica gel with 80% ethyl acetate / hexane, then 10% methanol / dichloromethane, then recrystallized from dichloromethane / hexane to provide 375 mg (70%) of the title compound as an off-white solid.1H NMR (300 MHz, DMSO -d6) d; 1 .26-1 .27 (s + s, 6H), 3.24 (s, 3H), 3.53-3.80 (m, 2H), 4.08-4.24 (m, 2H), 4.37-4.48 (m, 0.5H), 4.80-4.92 (m, 0.5H), 7.04-7.08 (dd, 2H, J = 3, 8.4 Hz), 7.72-7.75 (d, 2H, J = 8.7 Hz), 7.89-8.00 (4.5 H), 8.33- 8.40 (1 .5H), 9.56 (s, 0.5H), 9.88 (s, 0.5H). MS (ESI) m / e 476 (M + H) +, 493 (M + NH 4) +, 474 (M-H) ", 510 (M + CI) \ Anal, caled for C22H25N3O7" 0.25H2O: Example 49 N-ri-ff (3'-cyanori, 1'-biphenin-4-iPoxi-1-methyl-2- (2,5-dioxo-1-pyrrol idin i Petill-N-hydroxyformamide) Example 49A 1- (4'-cyano-f1,1'-biphenyl-1,4-yl) oxp-3- (2,5-dioxopyrrolidin-1-iP-2-propanone) The title compound was prepared as in Example 3C , except that potassium succinimide (0.10 g, 0.05 mmol) was used in place of potassium phthalimide Purification by trituration with ethyl acetate gave 0.10 g (68%) of the title compound as a white solid MS (APCl) m / e (M + CI) +.

Example 49B () -r 1- (4'-c and a non-M, 1 '-bif eni H-4-yl) oxy) -3- (2, 5-di oxo pyrro I idin- 1-il) -prop-2-hydroxylamine The title compound was prepared from 49B using the procedure described in Example 2D and 2E.

Example 4gC N-ri-fr (3'-cyanop, 1'-biphenyll-4-iPoxi-methyl-2- (2,5-dioxo-1-pyrroldiniPetiH-N-hydroxyformamide) The title compound was prepared from 4gB using the procedure described in the Example.

Mp 128 ° C 1 H NMR (300 MHz, DMSO-d 6) d 10.01 (s, 0.5H), .9.63 (s, 0.5H), 8.34 (s, 0. 5H), 7.98 (s, 0.5H), 7.00-7.82 (m, 4H), 7.73 (d, 2H, J = 8.8 Hz), 7.06-6.80 (m, 2H), 4.g? -4.78 (m, 0.5H), 4.37-4.24 (m, 0.5H), 4.22-4.04 (m, 2H), 3.74- 3.60 (m, 2H), 2.65-2.61 (m, 4H). MS (ESI) m / e 394 (M + H) +, 411 (M + NH 4) +, 392 (M-1) +. Anal, caled for C21H19N3O5 »H2O: C, 61.30; H, 5.14; N, 10.21.

Found: C, 61.20; H, 5.03; N, 10.03.

Example 50 N-ri-rr (4'-cyanori.1'-biphenin-4-yl) oxymethyl-2- (4,4-dimethyl-2,6-dioxo-1-pyrperid ini Petilj- N-hydroxy-ormamide The title compound was prepared as in Example 49, except that potassium-3,3-dimethylglutarimide (0.16 g, 1.1 mmol) was used in place of potassium succinimide, Mp 121 ° C, 1 H NMR (300 MHz, d6-DMSO) d 9.88-g.78 (s, 0.5H), 9.60-9.52 (s, 0.5H), 8.31 (s, 0.5H), 7.95 (s, 0.5H), 7.00-7.82 (m , 4H), 7.73 (d, 2H, J = 8.0 Hz), 7.02 (d, 2H, J = 8.8 Hz), 4.88-4.77 (s, 1H), 4.30-3.78 (m, 4H), 2.56 (s, 4H), 0.08 (s, 6H), MS (ESI) m / e 436 (M + H) +, 458 (M + NH4) +, 434 (MH) +.

Examples 51 and 52 N-riS-rí (4'-cyanop.1'-biphenin-4-yl) oxpmethyl-2- (2,5-dioxo-1-pyrrolidinePetin-N-hydroxyformamide N-ri R-rr (4'-cyanori, 1 '-bifenill-4-iPoxi1metin-2- (2, 5-dioxo-1-pyrrolidiniPetil1- Nh id roxiformam id a Example 51 A and 52A A solution of Example 49B (0.2 g, 0.55 mmol), D-mannose diacethonide (0.13 g, 0.50 mmol) and acetic acid (0.03 ml, 0.50 mmoi) in CHCl3 (5 ml) was heated to reflux for 1 6h, it was cooled and separated between CH2Cl2 and saturated aqueous sodium bicarbonate. The organic layer was washed sequentially with water and brine, dried (MgSO4) and concentrated. Purification by HPLC provided the two enantiomers 51A (31%) and 52A (16%).

Example 51 B A solution of 51 A in MeOH (1 ml) and HCl (conc) (0.5 ml) was stirred at room temperature for 1 5 min, treated with saturated aqueous sodium bicarbonate, and separated between ethyl acetate and Water. The organic layer was dried (MgSO4) and concentrated to provide 0.014 g (79%) of the corresponding hydroxylamine, which was then formulated as in Example 2F.

Example 52B The title compound was prepared according to Example 51 B, but using Example 52A instead of Example 51 A.

Example 53 N-ri-rr (4'-cyanori.1'-bipheniH-4-iPoxylmethin-2- (3-ethyl-3-methyl-2,5-dioxo-1-pyrroldylinopetip-N-hydroxyformamide) The title compound was prepared as in Example 40, except that potassium-3-methyl-3-ethyl succinimide (0.22 g, 1.53 mmol) was used in place of potassium succinimide, 1 H NMR (300 MHz, d6-DMSO) d O.gg-g. 94 (br, 0.5H), 9.64-g.58 (br, 0.5H), 8.31 (d, 0.5H, J = 1.8 Hz), 7.03 (d, 0.5H, J = 2.0 Hz), 7.87 (q, 4H, J = 4.1 Hz), 7.74 (d, 2H, J = 8.g Hz), 7.04 (dd, 2H, J = 8.8, 2.6 Hz), 4.03-4.81 (m, 0.5H), 4.44-4.33 ( m, 0.5H), 4.24-4.05 (m, 2H), 3.85-3.71 (m, 1H), 3.62-3.53 (m, 1H), 2.60-2.38 (m, 2H), 1.64-1.46 (m, 2H) , 1.18 (d, 3H, J = 4.4 Hz), 0.85-0.75 (m, 3H) MS (ESI) m / e 436 (M + H) +, 434 (MH) +, 458 (M + Na) + 453 (M + NH4) + Anal, caled for C24H25 305: C, 66.10; H, 5.78; N, g.6 Found: C, 66.07; H, 5.58; N, 0.37.

Example 54 N-r4-r4- [F (4-Chlorophenoxy) -phenipslfonillmetintetrahydro-2H-pyran-4-n-N-hydroxyformamide Example 54A The title compound was prepared as in Example 2D, but using 5,6-dihydro-2H-pyran-2-one (4.3 g, 43 mmol) instead of 1- (4- (4'- carbonitrilophenyl) phenoxy) -3-thiophenoxypropan-2-one and O-benzyl hydroxylamine in place of hydroxylamine to provide the corresponding oxime. Purification on silica gel with 1% > methanol / dichloromethane gave 8.5 g (06%)) of the title compound as a clear liquid. MS (ESI) 207 (M + H) + Example 54B N-í4- [4-rr (4-chlorophenoxy) phenesulfonylmethyltetrahydro-2H-pyran-4-yl-N-benzyloxy amine To a solution of phenoxyphenyl-4-chloro-4'-methylsulfone (0.76 g, 2.7 mmol) (preparation described in J. Med. Chem. 20, 427-433, 1986) at -78 ° C was added n-BuLi (1.1 ml, 2.7 mol). After stirring at -78 ° C for 15 minutes, BF3 »OEt2 was added, followed by Example 54A. After 1 h, the reaction mixture was separated between water and ethyl acetate, dried (MgSO) and concentrated. Recrystallization from ethyl acetate gave 0.41 g (35%) of the desired compound as a white solid. MS (ESI) m / e 488 (M + H) +, 51 0 (M + Na) +.

Example 54C N-r4-y4-rr (4-chlorophenoxy) phenylsulfonipmethyltetrahydro-2H-pyran-4-iH-N-benzyloxyformamide A solution of 54B (0.05 g, 0.10 mmol) in CH2Cl2 (2 ml) was treated with formic anhydride p-methoxyphenyl, was stirred at room temperature for 16 h, treated with H 2 O, and separated between ethyl acetate and brine. The organic layer was dried (MgSO4) and concentrated. Purification on silica gel with 10% ethyl acetate / dichloromethane gave 0.01 7 g (32%) of the desired compound as a white solid.

Example 54D N-F4-r4-rr (4-chlorophenoxy) phenylHsulfoniHmethiHtetrahydro-2H-pyran-4-ip-N-hydroxyformamide A solution of 54C (0.017 g, 0.033 mmol) and black Pd (0.006 g) in dioxane (2 ml ) and acetic acid (2 ml) was stirred under H 2 for 20 min, treated with NaHCO 3, separated between ethyl acetate and water. The organic layer was dried (MgSO4) and concentrated. Purification on silica gel with 2% MeOH / dichloromethane gave 0.002 g (14%) of the desired compound. 1 H NMR (dd-DMSO) d 0.50-9.45 (br, 1H), 8.19 (s, 1H), 7.90-7.86 (m, 2H), 7.53-7.50 (m, 2H), 7.22-7.18 (m, 4H) , 3.70-3.58 (m, 4H), 3.55-3.44 (m, 2H), 2.22-2.07 (m, 2H), 2.07-1.91 (m, 2H). MS (ESI) 424 (M-H) +, 426 (M + H) +, 488 (M + Na) +.

EXAMPLE 55 N-ri-rr (4'-cyanori, 1'-biphenyl-4-iPoxi-1-methyl-2-y [(2-methoxycarbonylphenyl) -thioletip-Nh idroxyformamide The title compound was prepared following the procedure of Example 2B, C, D, E, F, but using methyl thiosalicylate (600 mg, 2.39 mmol) in place of thiophenol in Example 2B: Two rotamers mixture: 1 H NMR (300 MHz, d 6 -DMSO) d 10.11 ( s, 1H), 0.73 (s, 1H), 8.41 (s, 1H), 7.05 (s, 1H), 7.90-7.05 (m, 4H), 4.75 (m, 1H), 4.2804.24 (m, 4H0, 4.18 (m, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 3.31-3.18 (m, 4H), MS (ESI) m / e 463 (M + 1) +.

Anal, caled for C25H22N2? 5S: C, 64.2; H, 4.7g; N, 6.06. Found: C, 64.6g; H, 4.63; N, 5.92.

Example 56 N-ri-rr (4'-cyanop, 1'-biphenyl-4-iPoxyl-methyl-5-r (4-methyl-2-oxo-2H-1-benzopyran-6-iPoxi) pe ntill-Nh id roxiformam id to Example 56A 6- (4-m eti I-2-QXO-2- H-1-benzo pyran-6-yl) oxy-1-hex-1-en or The title compound was prepared following the procedure of Example 5A, but using 6-hydroxy-4-methylcoumarin (500 mg, 2.84 mmol) instead of 5,5-dimethylhydantoin and 5-hexen-1-ol in place of 3-buten-1-ol.

Purification on silica gel with 20% ethyl acetate / hexanes gave 560 mg (76%) of the title compound. 1H NMR (300 MHz, d6-DMSO) d 7.34 (dd, 1H), 7.24-7.20 (m, 2H), 6.40 (d, 1H), 5.00-5.77 (m, 1H), 5.04 (dq, 1H), 4.08 (dq, 1H), 4.06 (t, 2H), 2.43 (d, 3H), 2.10 (q, 2H), 1.75 (dt, 2H), 1.53 (dt, 2H).

Example 56B N-ri-rr (4'-cyanori.1'-bifeniH-4-iPoxi1metn-5-r (4-methyl-2-oxo-2H-1-benzopyran-6-iPoxi-pe ntill- Nh id roxiformam id a The title compound was prepared following the procedures of examples 5C, 1B, 2C, 2D, 2E and 2F, but using 56A (500 mg, 1.04 mmol) instead of 5B in Example 56B. on silica gel with 50% ethyl acetate / hexanes gave 400 mg (75%) of the title compound, Mixture of two rotamers, 1 H NMR (300 MHz, d6-DMSO) d 0.80 (s, 1H), 9. 51 (s, 1H), 8.42 (s, 1H), 8.03 (s, 1H), 7.86 (m, 8H), 7.73-7.70 (m, 4H), 7. 34 (d, 2H), 7.24-7.21 (M, 4H), 7.08-7.04 (m, 4H), 6.40 (s, 2H), 4.60 (s, 1H), 4.18-3.99 (m, 9H), 2.43 (s, 6H), 1.86-1.54 (m, 12H), MS (ES1) m / e 513 (M + 1) +. Anal, caled for C3oH28N2? 6: C, 70.30; H, 5.51; N, 5.47. Found: C, 70. 52, H.5.85; N, 5.20.

Example 57 N-ri-rr (4'-cyanop.1'-biphenyl-4-yl) oxymethyl-4-y (4-methyl-2-oxo-2H-1-benzo pyran-6-i I) oxil buti HNh id roxiformam da The title compound was prepared following the procedure of Example 56, but using 4-penten-1-ol in place of 5-hexen-1-ol in Example 56A. Mix of two rotamers: 1 H NMR (300 MHz, d 6 -DMSO) d 0.04 (s, 1 H), 0.55 (s, 1 H 0, 8.44 (s, 1 H), 8.06 (s, 1 H), 7.86 (m, 8 H), 7.73-7.70 (m, 4H), 7.35 (d, 2H), 7.26-7.22 (m, 4H), 7.08-7 / 05 (m, 4H), 6.40 (s, 2H), 4.65 (m, 1H), 4.17-4.04 (m, OH), 2.44 (s, 6H), 1.77 (m, 8H), MS (ESI) m / e 400 (M + 1) +. Anal, caled for C29H26N2O6 »0.75H2O: C, 68.03; H, 5.41; N, 5.47, Found: C, 68.21; H, 5.25; N, 5.28.

EXAMPLE 58 Np - [[(4'-cyanori, 1'-biphenin-4-y-oxo-1-methyl-4-r (4-metii-2-oxo-2H-1-benzo-pi-7-y) I) oxy] butyl ll-Nh id roxiformam id a The title compound was prepared following the procedure of Example 56, but using 7-hydroxy-4-methylcoumarin (500 mg, 2.8 mmol) in place of 6-hydroxy-4-methylcoumarin and 4-penten-1-ol in place of 5-hexen-1-ol in Example 56A. Mixture of two rotamers: 'H NMR (300 MHZ, d6-DMSO) d 9.g5 (s, 1H), g.55 (s, 1H), g.44 (s, 1H), 8.05 (s, 1H) , 7.00-7.82 (m, 8H), 7.73-7.67 (m, 6H), 7.08-7.04 (m, 4H), 7.01-6.95 (m, 4H), 6.21 (s, 2H), 4.64 (m, 1H) , 4.20-4.01 (m, 9H), 2.40 (s, 6H), 1.80-1.74 (m, 8H); MS (ESI) m / e 499 (M + 1) +. Anal, caled for C29H26N206: C, 69.87, H, 5.26; N, 5.691. Found: C, 69.51; H, 5.33; N, 5.40.

Example 50 N-ri-rf (4'-cyanoi-1'-b-phenyl-4-p-oxime-5-r (4-methy-2-oxo-2H-1-benzo p! n-7-Poxyl pent i HN-hydroxyformatum a The title compound was prepared following the procedure of example 56, but using 7-hydroxy-4-methylcoumarin (500 mg, 2.8 mmol) instead of 6-hydroxy -4-methylcoumarin in Example 56 A. Mix of two rotamers: 1H NMR (300 MHZ, d6-DMSO) d 9.89 (s, 1H0, 0.50 (s, 1H), 8.42 (s, 1H), 8.03 (s, 1H ), 7.00-7.82 (m, 8H), 7.73-7.66 (m, 6H), 7.08-7.03 (m, 4H), 6.98-6.94 (m, 2H), 6.21 (s, 2H), 4.60 (m, IH) ), 4.15-3.98 (m, 9H), 2.40 (s, 6H), 1.84-1.40 (m, 12H), MS (ESI) m / e 513 (M + 1) +. Anal, caled for C30H28N2O6: C, 70.30; H, 5.51; N, 5.47. Found: C, 70.35; H, 5.52; N, 5.17.

Example 60 N-ri-rr (4'-cyanori, 1'-biphenyl-4-yl) oxylmethyl-2- (5,5-dimethyl-2,4-dioxo-3-oxazolidinyl) ethy-N-hydroxyformamide The compound of the title was prepared as in Example 49, except that 5,5-dimethyloxazolidinine-2,4-dione (300 mg, 0.8 mmol) was used in place of succinimide. Mixture of two rotamers: 'H NMR (300 MHZ, d6-DMSO) d 10.08 (s, 1H), 9.70 (s, 1H), 8.35 (s, 1H), 7.98 (s, 1H), 7.90-7.83 (m , 8H), 7.74 (d, 4H), 7.06 (d, 4H), 4.00 (M, 1H), 4.47 (m, 1H), 4.24-4.16 (m, 4H), 3.85 (d, 1H), 3.80 ( d, 1H), 3.69-3.65 (m, 1H), 3.64-3.61 (m, 1H), 1.49 (s, 6H), 1.48 (s, 6H); MS (ESI) m / e 441 (M + 18) +.

Example 61 N-ri-rr (4'-cyanori.1'-biphenin-4-yl) sulfoninmetn-2- (3,4,4-trimeti-2,5-dioxo-1-imidazolidiniPetiH-N-hydroxyl ormamide Example 61A 1-r (4'-cyanof1,1'-biphenin-4-yl) thio1-3- (3,4,4-trimethyl-2,5-dioxoimidazolidin-1-iP-2-propanone A solution of 4'- thiol-4-biphenylcarbonitrile (150 mg, 0.71 mmol) in 6 ml of DMF at -5 ° C was treated with potassium carbonate (80 mg, 0.645 mmol) and 1-bromo-3- (3,4,4-trimethyl) -2,5-d -oxo-1-imidazolidin-1-ii) -2-propanone (179 mg, 0.645 mmol), was stirred 1 h at -5 ° C, quenched with saturated NH 4 Cl, extracted with ethyl acetate was washed with brine, dried over Na 2 SO 4, filtered and concentrated to a solid Purification on silica gel with 1: 1 ethyl acetate / hexanes gave 200 mg (75%) of the title compound. 300 MHZ, d6-DMSO) d 7.04-7.87 (m, 4H), 7.72 (d, 2H), 7.43 (d, 2H), 4.55 (s, 2H), 4.27 (s, 2H), 2.80 (s, 3H ), 1.32 (s, 6H).

Example 61B N-ri-rr (4, -cyano1,1'-biphenyl-4-yl) thiolmethyl-2- (3,4,4-trimethy-2,5-dioxo-1-imidazolidinium-Petill-N-hydroxyformamide) of the title was prepared from 61A following the procedures of Example 2D, 2E and 2F.RTM .. Two rotamers mixture:? NMR (300 MHZ, d6-DMSO) d 0.76 (s, 1H), 9.51 (s, 1H), 8.29 (s, 1H), 7.93-7.87 (, 8H), 7.75-7.72 (m, 5H), 7.50-7.44 (m, 4H), 4.60 (m, 1H), 4.10 (m, 1H), 3.80-3.60 ( m, 4H), 3.25-3.15 (m, 4H), 2.77 (s, 6H), 1.25 (s, 12H).

Example 61C N- [1-rr (4'-cyanof1.1'-biphenin-4-iPsulfoniHmet.p-2- (3,4,4-trimeti-2,5-dioxo-1-imidazolidiniPetill-N- Hydroxyformamide A solution of 61B (81 mg, 0.18 mmol) in 4: 1 THF / H 2 O at 0 ° C was treated with OXONE (140 mg) and NaHCO 3 (33 mg), stirred at 0 ° C for 30 min, then 23 ° C for 1 h, quenched with H20, extracted with ethyl acetate, washed with brine, dried over Na2SO4, filtered and concentrated to a white solid, purification on silica gel with 2% methanol / dichloromethane provided 43 mg (40%) of the title compound: Mixture of two rotamers:? NMR (300 MHZ, d6-DMSO) d 9.71 (s, 1H), 9.54 (s, 1H), 8.00 (s, 1H), 8.07- 7.96 (m, 16H), 7.74 (s, 1H), 4.90 (m, 1H), 4.54 (M, 1H), 3.74-3.60 (M, 4H), 3.55-3.44 (m, 4H), 2.74 (s, 3H), 2.74 (s, 3H), 1.24-1.72 (m, 12H), MS (ESI) m / e 485 (M + 1) +, Anal, caled for C23H2 N4O6S: C, 57.01; H, 4.99; N , 11.56, Found: C, 56.86; H, 5.21; N, 11.28.

EXAMPLE 62 Np-yr (4'-cyanop, 1'-biphenin-4-yloxymethyl] -2- (3-methyl-2,5-dioxo-1-imidazolidinium-Petip-N-hydroxyformamide) The title compound was prepared as in Example 49, except that 1-methylhydantoin was used in place of succinimide Mixture of two rotamers: 'H NMR (300 MHZ, d6-DMSO) d 9.g7 (s, 1H), 9.61 (s, 1H), 8.35 ( s, 1H), 7.98 (s, 1H), 7.90-7.83 (m, 8H), 7.73 (d, 4H), 7.03 (d, 2H), 7.01 (d, 2H), 4.88-4.84 (m, 1H) , 4.39-4.35 (m, 1H), 4.22-4.08 (m, 4H), 3.07 (s, 2H), 3.94 (s, 2H), 3.75-3.57 (m, 4H), 2.86 (s, 3H), 2.85 (s, 3H); MS (ESI) m / e 408 (M + 1) +. Anal, caled for C21H20N4O5: C, 61.76; H, 4.04; N, 13.72. Found: C, 61. 47; H, 5.00; N, 13.30.

Example 63 N- [1-rr (4'-cyanop.1'-b-phenyl-4-yl) sulfoninmetl1-2- (4.4-dimeti-2.5-dioxo-1- im id azo I id ini I) eti HNh id roxiformam ida The title compound was prepared following the procedure of Example 61, but using 1-bromo-3- (4,4-dimethyl-2,5-dioxo-1-imidazolidin-1-yl) - 2-propanone in place of 1-bromo-3- (3,4,4-trimethyl-2,5-d-oxo-1-imidazoIidin-1-yl) -2-propanone in Example 61A. Mixture of two rotamers: 1 H NMR (300 MHZ, d6-DMSO) d 9.66 (s, 1 H), 9.51 (s, 1 H), 8.38 (s, 1 H), 8.34 (s, 1 H), 8.10 (s, 1 H) , 8.07-7.96 (s, 16H), 7.74 (s, 1H), 4.94-4.86 (M, 1H), 4.58-4.50 (m, 1H), 3.80-3.37 (m, 8H), 1.23-1.20 (m, 12H); MS (ESI) m / e 488 (M + 18) +. Anal, caled for C22H22N4O6S: C, 56.16; H, 4.71; N, 11.91. Found: C, 56.12; H, 5.00, N, 11.50.

Example 64 () -N-ri-f (4l-chloro-ri, 1'-biphenyl-4-yl) oxy-methyl-2- (3,4,4-trimethyl-2,5-d-oxo-1-imidazole) id iníDetip-N-hydroxif ormamide Example 64A 1 - [4"-chloro-1 ', 1" -bifenyl-4'-yl) oxp-3- (3,4,4-trimethyl-2,5-dioxoimidazolidin-1 - P-propan-2-one A solution of Example 16B (0.81 g, 2.93 mmol), 4-chloro-4'-hydroxybiphenium (0.50 g, 2.44 mmol) and potassium carbonate (0.35 g, 2.57 mmol) in dry DMF (50 mL) was stirred at room temperature. The mixture was separated between ethyl acetate and water and the aqueous layer was filtered and extracted with ethyl acetate (1 x), the combined organic extracts were diluted with an equal volume of hexanes and washed sequentially with water. (3x) and brine (2x), dried (Na2SO4) and concentrated to give 0.89 g of a pooled waxy solid, which was purified on silica gel with 40% ethyl acetate / dichloromethane to give 0.46 g (47%) ) of the title compound as a colorless solid, Mp 165-166 ° C; MS (DCI / NH 3) m / e 370 (M + NH 4) +.

Example 64B () -N-ri -rr (4'-chloro-ri. 1 '-bifenin-4-yl) oxyl-methyl-2- (3,4,4-trimethyl-2,5-d-oxo-1 - imidazolidiniPetip-N-hydroxyformamide The ketone of Example 64B was converted sequentially to the corresponding oximes, hydroxylamine and the final compound as described in Examples 2D, 2E and 2F.The title compound was purified on silica gel with 2.5% methanol / dichloromethane to provide the title compound as a colorless solid, which was recrystallized from ethyl acetate / hexanes Pf 124-125 00C; MS (DCI / NH3) m / e 446 (M + H) + and 463 (M + NH4) +. 1 H NMR (300 MHz), CDCl 3) d 0.90 (s; 0.5H), 9.58 (s; 0.5H), 8.32 (s; 0.5H), 7.02 (s, 0.5H), 7.65 (d; 2H; J = Hz), 7.61 (d; 2H; J = 9 Hz), 7.47 (d; 2H; J = g Hz), 6.gg (d; 1H; J = g Hz), 6.g7 (d; 1H; J = g Hz), 4.86 (m, 0.5H), 4.42 (m; 0.5H), 4.08-4.23 (m; 2H), 3.82-3.70 (m; 1H), 3.55-3.65 (m; 1H), 2.80 (s; 1.5H), 2.78 (s; 1.5 H), 1.30 (s; 3H), 1.28 (s; 3H); Anal, caled for C22H24N3O5Ci: C, 50.26; H, 5.42; N, 0.42. Found: C, 50.54; H, 5.61; N, 0.13.

Example 65 (+) - N-f1-fr (3'-cyanomethyl-p.1'-biphenin-4-yl) oxpmetin-2- (3,5,5-trimethyl-2,4-dioxo-1) -imidazol idin il) propyl1-N-hydroxyform amide Example 65A 1- (3 - [(3'-Cyanomethyl-1, 1-binfen-4-yl) oxp-propan-2-on-1-yl) -3,4,4-trimethyl-2 , 5-dioxoimidazolidine The title compound was prepared as in Example 5F, but using 40'-hydroxy-3-biphenylcarbonitrilomethane (0.95 g, 2.80 mmol) in place of 40'-hydroxy-4-biphenylcarbonitrile. Purification on silica gel with 100% ethyl acetate gave 0.78 g of the title compound. MS (DCI / NH3) m / e 437 (M + NH4) +.

Example 65B (+) - N-ri-rr (3'-cyanomethyl-1,1,1'-biphenin-4-poxpmetin-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazole id inyl) propyl -Nh id roxiformam ida Example 65A (0.78 g, 1.87 mmol) was processed sequentially according to the procedures in Example 2D, 2E, and 2F without purification of the intermediates Purification on silica gel with 100%> acetate ethyl ester gave 500 mg (1.08 mmol) of the title compound.1H NMR (300 MHz, DMSO) 0.00 (s: 0.5H), 0.58 (s: 0.5H), 8.36 (s, 0.5H), 7.02 (s: 0.5H), d 7.60 (m; 4H), 7.46 (t; 1H J = 8 Hz), 7.30 (d; 1H; J = 8 Hz), 7.02 (d; 2H; J = 8 Hz), 4.50 (m; 0.5H), 4.18 (m; 0.5H), 4.12 (s; 2H), 4.10 (m; 2H), 3.45 (m; 2H), 2.80 (s; 3H), 1.02 (m; 1H), 1.80 (m; m; 1H), 1.30 (s: 6H) MS (DCI / NH3) m / e 482 (M + NH4) + Anal, caled for C25H28N4O5: c, 64.66; H, 6.03; N, 12.07.

Example 66 (+) - N-ri-rr (4'-cyano-ri, 1'-biphenip-4-p-oxylmethyl-2-psopropyl-O-tet-N-hydroxyformamide) Example 66A (+) - 1-f (4'-cyano-1, 1'-biphenin-4-i) oxy-3-isopropylthio-2-propanol A solution of isopropylthiol (0.48 g, 6.4 mmol) in THF (20 ml) was treated with K2CO3 (0.5 g, 3.6 mmol). After 30 minutes, 3 - [(4'-cyano- [1,1'-biphenyl] -4-i) oxy] - (1,2) oxirane (0.8 g, 3.10 mmol) was added in a single portion. The resulting solution was stirred at 70 ° C for 3 hours, quenched by adding an excess aqueous sodium bicarbonate solution and separated between ethyl acetate and brine. The organic layer was dried (Na2SO4), the product was purified on silica gel with 50% ethyl acetate / hexanes to provide 0.0 g (2.75 mmol, 86%) of the title compound. MS (DCI / NH3) m / e 345 (M + NH4) + and 362 () M + NH4 + NH3) +.

Example 66B (+) - N- [1-rr (4'-cyano-ri, 1'-b-phenyl-4-y) oxy-methyl-2-isopropylthioetiH-N-hydroxyformamide. Example 66A was processed according to the procedures in Example 2C, 2D, 2E and 2F, providing the title compound as a light orange foam. 1 H NMR (300 MHz, DMSO) 0.00 (s: 0.5H), 0.60 (s: 0.5H), 8.42 (s: 0.5H), 8.04 (S.0.5H), d 7.85 (m; 4H), 7.75 ( d; 2H J =? Hz), 7.05 (d; 2H; J = 9 Hz), 4.63 (m; 1H), 4.17 (m; 3H), 3.0 (m; 1H), 2.70 (m; 1H), 1.22 (dd; 6H; J = 7.50 Hz); MS (DCI / NH3) m / e 388 (M + NH4) +. Anal, caled for C2oH22N2O3S: C, 64.86; H, 5.04; N, 7.57. Found: Example 67 (+) - N-ri - [[(3'-cyanomethyl-p, 1'-biphenyl-1-4-poxpmetill-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidiniPetin-N- hydroxyl ormamide Example 67A (+) - 1- [4- (3'-Cyanomethylphenpfenoxyl-3- (3,4,4-trimethyl-2,5-dioxo-1-imidazo lid inyl) -2-propanol The title compound was prepared as in Example 4A, but using 4'-hydroxy-3-biphenylcarbonitrilomethane (170 mg, 0.64 mmol) and 3,5,5-trimethylhydantoin (37 mg, 0.06 mmol) in place of 4'-hydroxy-4-biphenylcarbonitrile and 5,5-dimethylhydantoin: Purification on silica gel with 100% ethyl acetate gave 130 g of the title compound, MS (DCI / NHs) m / e 415 (M + NH 4) +.

Example 67B (+) - N-ri-rr (3'-cyanomethyl- [1,1, -biphenyl-4-i) oxolmetin-2- (3,4,4-trimethyl-2,5-dioxo- 1 - imidazole id in.l) etin-Nh id roxiformam ida Example 67A was processed according to the procedures in Examples 2C, 2D, 2E and 2F to provide the title compound. 1 H NMR (300 MHz, DMSO) 0.86 (s: 0.5H), 0.58 (s: 0.5H), 8.34 (s: 0.5H), 7.92 (s: 0.5H), d 7.60 (m; 4H), 7.46 (t; 1H J = 8 Hz), 7.30 (d; 1H; J = 8 Hz), 7.02 (d; 2H; J = 8 Hz), 4.85 (m; 0.5H), 4.42 (m; 0.5H), 4.10 (m; 2H), 4.12 (s; 2H), 3.68 (m; 1H), 3.62 (m; 1H), 2.80 (s; 3H), 1.30 (s: 6H). MS (DCI / NH3) m / e 468 (M + NH4) +. Anal, caled for C24H26N4Os: c, 62.85; H, 5.84; N, 11.85. Found Example 68 (+) - N-ri-rr (4'-cyano-p, 1'-biphenin-4-iPoxi-methyl-2- (3-ethyl-4,4-dimethyl-2,5-dioxo-1-imidazo I id inl) ethn-hid roxiformam ida Example 68A 4,4-Di-met il-2, 5-dioxo-N- (4-m-ethoxy-benzyl) imidazole id a solution of 4,4-dimethyl-2,5-dioxoimidazolidine (17.0 g, 133 mmol) , 4-methoxybenzyl chloride (30.0 g, 102 mmol) and potassium carbonate (27.5 g, 200 mmol) in dry DMF (600 mL) was heated at 8O00C under nitrogen for 3 h. The volume was reduced under high vacuum to about 174 of the original volume and the resulting solution was separated between ethyl acetate and water. The aqueous layer was washed and extracted with ethyl acetate (2x). The combined organic extracts were washed sequentially with water (2x) and brine (2x), dried (Na2SO) and concentrated under vacuum to provide 32.07 g of a solid. The pure title compound was obtained by recrystallization from ethyl acetate and hexanes to provide 24.5 g (74% >) of a colorless solid. Pf 1 09-1 1 1 ° C; MS (DCI / N H3) m / e 249 (M + H) + and 266 (M + NH4) +.

Example 68B 3-ethyl-1- (4'-methoxybenzyl) -2,5-dioxo-4,4-dimethylimidazolidine A solution of 4,4-dimethyl-2, 5-dioxo-N- (4-methoxybenzyl) imidazolidine ( 3.5 g, 14.1 mmol) in THF (100 ml) was treated with sodium hydride (0.5 g, 21.2 mmol), stirred for 10 min, treated with iodoethane (3.3 g, 21.2 mmol), it was stirred at 50 ° C for 3 hours, then treated with HCl solution (10%) and separated between ethyl acetate and brine. The organic layer was dried and concentrated to provide 3.8 g (1 3.8 mmol, T8%) of the title compound as a white solid. MS (DCI / NH3) m / e 204 (M + N H4).

Example 68C 3-eti 1-2, 5-dioxo-4, 4-d imeti! imidazole id ina A solution of 3-ethyl-1- (4'-methoxybenzyl) -2,5-dioxo-4,4-dimethylimidazolidine (3.86 g, 14.0 mmol) in methoxybenzene (100 ml) was treated with aluminum trichloride (5.5 g, 42 mmol) was stirred at 75 ° C for 30 minutes, then the reaction was emptied into HCl solution (10%) and partitioned between ethyl acetate and brine. The organic layer was dried and concentrated. Purification by recrystallization with ethyl acetate gave 2.1 g (1 3.5 mmol, 86%) of the title compound as a white solid. MS (DCI / NH3) m / e 1 74 (M + N H4) +.

Example 68D 1 -r (4'-cyano-M, 1'-bif eniH-4-i) oxy-1-3- (3-ethyl-5,5-di methi I-2,4-d -oxo-1-imidazolidiniP-2 -propanone A solution of 3-ethyl-2,5-dioxo-4,4-dimethyl-idedazolidine (0.7 g, 4.5 mmol) in DMF (100 ml) was treated with potassium carbonate (0.6 g, 4.5 mmol) and 1 - [ (4'-cyano- [1,1'-biphenyl] -4i) oxy] -3-bromo-2-propinone (1.0 g, 3.0 mmol) was stirred at 25 ° C for 20 hours, then the reaction it was emptied into aqueous HCl solution (10%) and separated between ethyl acetate and brine The organic layer was dried and concentrated, purification on silica gel with 50% ethyl acetate gave 0.8 g (1.07 mmol). , 66%) of the title compound as a white solid MS (DCI / NH3) m / e 424 (M + NH4) +.

Example 68E (+) - N-ri-rr (4'-cyano-p, 1'-biphenin-4-iPoxpmetill-2- (3-ethyl-4,4-dimethyl-2,5-dioxo-1 -imidazole id iniPetill-N-hydroxyl ormamide Example 68B (0.72 g, 1.77 mmol) was processed sequentially according to the procedures in Example 2D, 2E and 2F without purification of the intermediates.Silica gel purification with 60% ethyl acetate / hexanes provided 158 mg (0.35 mol) of the title compound.1H NMR (300 MHz, DMSO) 9.85 (s: 0.5H), 9.54 (s: 0.5H), 8.32 (s: 0.5H), 7.94 (s: 0.5H), d 7.86 (m; 4H), 7.72 (d; 2H J =? Hz), 7.08 (d; 2H; J =? Hz), 4.85 (m; 0.5H), 4.42 ((m 0.5H), 4.18 (m, 2H), 3.78 (m, 1H), 3.62 (m, 1H), 1.32 (s: 6H), 1.12 (m; 3H), MS (DCI / NH3) m / e 468 (M + NH4) + Anal, caled for C2 H26N405: C, 64.00; H, 5.78; N, 12.44.

Example 60 (+) - N-ri-rr (4'-cyano-f1.1'-biphenip-4-yl) oxylmetin-2- (3-benzyl-4,4-dimethyl-2,5-dioxo-1) -imidazolidinyl) ethyl 1-N-hydroxyl ormamide Example 6TA 3-ben ci! -1-Ib '-methoxy ben cy! -2,5-dioxo-4,4-di methyl imidazo lidna The title compound was prepared as in Example 68B, but using benzyl iodine (3.0 g, 18 mmol) in place of iodoethane. Purification on silica gel with 50% ethyl acetate gave 4.0 g of the title compound.

MS (DCI / NH3) m / e 356 (M + N H4) +.

Example 6QB 3-benzyl 1-2, 5-dioxo-4,4-d imethyl imidazo I idine A solution of 3-benzyl-1- (4'-methoxybenzyl) -2,5-dioxo-4,4-dimethylimidazolidine ( 3.0 g, 11.54 mmol) in acetonitrile (100 ml) was treated with a solution of cerium ammonium nitrate (31 g, 57.7 mmol) in 65 ml of water, stirred at 25 ° C for 15 minutes, the reaction was then diluted with ethyl acetate and partitioned between ethyl acetate and brine. The organic layer was dried and concentrated. Purification by recrystallization with ethyl acetate / hexane gave 1.58 g (7.25 mmol, 63%) of the title compound as a white solid. MS (DCI / NH3) m / e 236 (M + N H4) +.

Example 69C 1 - [(4'-cyano-ri. 1 '-bifenii1-4-i) oxy1-3- (3-etii-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) -2-propanone The The title compound was prepared as in Example 68D, but using 3-benzyl-2, 5-dioxo-4,4-dimethylimidazolidine (0.5 g, 2.28 mmol) instead of using 3-ethyl-2, 5-dioxo-4 , 4-dimethylimidazolidine. Purification on silica gel with 30% ethyl acetate / chloroform gave 634 mg of the title compound. MS (DCI / NH3) m / e485 (M + N H4) +.

Example 6QD (+) - N- [1 - [[(4'-cyano-ri, 1'-bifeniH-4-iPoxylmethyl-2- (3-ethyl-4,4-dimethyl-2,5-dioxo-1-imidazolidiniPetip- N-Hydroxyformamide Example 6TC (0.62 g, 1.33 mmol) was processed sequentially according to the procedures in Example 2D, 2E and 2F without purification of the intermediates.Silification on silica gel with 70% ethyl acetate / hexanes provided 230 mg (0.45 mmol) of the title compound.1H NMR (300 MHz, DMSO) 0.05 (s: 0.5H), 0.64 (s: 0.5H), 8.35 (s: 0.5H), 7.04 (s; 0.5H) , d 7.86 (m; 4H), 7.75 (d; 2H J =? Hz), 7.30 (d; 2H; J =? Hz), 7.25 (m; 3H), 7.06 (m; 2H), 4.00 (m; 0.5H), 4.52 (s; 2H), 4.50 (m; 0.5H), 4.18 (m; 2H), 3.82 (m; 1H), 3.62 (m; 1H), 1.22 (s: 6H). NH3) m / e 530 (M + NH4) +.

Example 70 (+) - N-ri-rr (4'-cyano-p.1'-biphenin-4-i) oxpmetn-2- (3.5.5-trimethyl-2,4-d-oxo-1. Imidazole idin i Petill-Nh id roxiformam ida Example 70A 1-α (4'-cyano-1,11-biphenin-4-phenyl-3- (3,5,5-trimethyl-2,4-d-oxo-1-imidazolidinyl) -2-propanol A solution of 5,5-dimethylhydantoin (2.0 g, 15.6 mmol) in DMF (20 ml) was treated with sodium tert -butoxide (1.5 g, 15.6 mmol), stirred for minutes, treated with iodomethane (2.2 g, 15.6 mmol), stirred at 40 ° C for 3 hours. The resulting solution was treated with sodium tert-butoxide (1.5 g, 15.6 mmol) followed by 3 - [(4'-cyano- [1,1'-biphenyl] -4-i) oxy] - (1,2) oxirane (1.15 g, 4.58 mmol), was stirred at 100 ° C for 20 minutes, treated with HCl solution (10%) and separated between ethyl acetate and brine. The organic layer was dried and concentrated to provide 1.35 g (75%) of the title compound as a white solid. MS (DCI / N H3) m / e 41 1 (M + N H4) +.

Example 70B 1-r (4'-cyano- [1,1'-biphenin-4-i) oxyl-3- (3,5,5-trimethyl-2,4-dioxo-1-imidazolidinopy-2-propanone Example 70A (1 .35 g, 3.4 mmol) was processed according to the procedures in Example 2 C. Purification on silica gel with 30% ethyl acetate gave 1.2 g (3.1 mmol, 00%) of the title compound. DCI / NH3) m / e 400 (M + NH4) +.

Example 70C (+) - Np - [r (4'-cyano-ri, 1'-biphenin-4-y) oxymethyl-2- (3,5,5-trimetyl-2,4-dioxo-1 - imidazolidiniPetill-N-hydroxiformamide Example A-2648T0.0-B (1.2 g, 3.07 mmoi) was processed sequentially according to the procedures in Example 2D, 2E and 2F without purification of the intermediates. silica gel with 30% ethyl acetate / hexanes gave 380 mg (2.20 mmol) of the title compound.1 H NMR (300 MHz, DMSO) 0.00 (s: 0.5H), 0.68 (s: 0.5H), 8.38 ( s: 0.5H), 7.08 (s: 0.5H), d 7.88 (m; 4H), 7.72 (d; 2H J =? Hz), 7.08 (d; 2H; J =? Hz), 4.92 (m; 0.5 H), 4.42 (m; 0.5H), 4.2Ó (m; 2H), 3.50 (m; 2H), 2.88 (s; 3H), 1. 32 (s: 6H). MS (DCI / NH3) m / e 454 (M + NH4) +. Anal, caled for C23H24N4O5: c, 63.30; H, 5.55; N, 12.60. Found EXAMPLE 71 N-Ri-y (4'-methoxy-1,1'-bif en-n-4-yl) sulphonylmethyl-N-hydroxyl ormamide Example 71A 4'-methoxy-4-thiomethyl biphenyl A solution of 4-bromothioanisole (6.15 g, 20.4 mmol) in DMF (60 ml) was treated sequentially with palladium (II) acetate (0.34 g, 1.5 mmol) and tri- o-tolylphosphine (0.04 g, 3.0 mmol) then 4-methoxyphenylboronic acid (5.06 g, 32.3 mmol) and cesium carbonate (10.2 g, 58.8 mmol). The mixture was stirred at 75 ° C for 8 hours, then room temperature for 15 hours. The resulting suspension was separated between water and ether / hexane, 2: 1. The organic layer was dried with Mg2SO4 and concentrated to provide crude product as a yellow solid. Recrystallization from ether at -20 ° C afforded 2.61 g (30%) of the title compound. MS (ESI +) m / e 231 (M + H).

Example 71B 4- (4'-methoxyphenyl) -P-phenyl methyl sulfone A solution of Example 71A (2.61 g, 11.3 mmol) in chloroform (100 ml) was treated with m-chloroperbenzoic acid (6.52 g, 22.7 mmol), stirred at 0 ° C for 3 hours and then warmed to 10 ° C over 1 hour.The mixture was separated between aqueous solution of dilute sodium bicarbonate and chloroform, dried (Mg2SO4), and concentrated to provide crude product as a White solid.Recrystallized from dichloromethane and ether to give 1.80 g (64%) of the title compound: MS (ES I +) m / e 263 (M + H) and 280 (M + NH 4).

Example 71 C NM -! 7 (4'-methoxy H 11 '-b-phenyl-4-yl) sulfoninmethyl] ethyl] -N-benzyloxy amine A suspension of Example 71 B (0.26 g, 1.0 mmol) in THF (40 mL) was cooled to -78 ° C under argon atmosphere treated with n BuLi (0.40 mL of a 2.5 M solution in hexane, 1.0 mmol) and stirred for 3 hours. The resulting suspension was treated with BF3 »Et20 (0.127 mL, 1.0 mmol) then the O-benzyl oxime of acetaldehyde (0.1 5 g, 1.0 mmol) J. Med. Chem. 1,007, vol. 40, number 1 3, pages 1 055-1 068 (Stewart, et al). [J. Med. Chem. 1 007, vol. 40, 1055-1068 (Stewart, et al)] in THF (10 ml). Stirred 1 hour at -78 ° C, then 1 hour at room temperature. The mixture was separated between ether and phosphate buffer pH 7. The organic extracts were washed with brine, dried (Mg2SO4), and concentrated to give the crude product as a white powder, which was purified on silica gel with dichloromethane. methanol to provide 0.15 g (36%) of the title compound. MS (ESI +) m / e 412 (M + H).

Example 71 D N- [1 -rr (4'-methoxy [1,1 '-bifeniH-4-iPsulfoninmetinetin-N-benzyloxyiformamide A solution of Example 71 c (0. 1 g, 0.27 mmol) in THF (50 ml) was cooled to 0 ° C under argon atmosphere, treated with formicacetic anhydride (0.24 g, 2.7 mmol), stirred for 5 minutes at 0 ° C, then at room temperature for 16 hours, separated between HCl 1 N and ethyl acetate The organic extracts were washed with saline, dried (MgSO4), and concentrated to give crude oil product, which was purified on silica gel with dichloromethane / methanol to give 14 mg (0600 mg). %)) of the title compound. MS (ES I +) m / e 440 (M + H) and 457 (M + NH 4).

Example 71 E N-ri -f (4'-methoxyiri, 1'-bif in n-4-yl) sulfonylmethyl-ethyl] -N-hydroxyformamide A solution of Example 71 D (14 mg, 0.26 mmol) in THF (20 ml) was treated with 10% > carbon palladium (35 mg, catlytic amount) and hydrogen gas at atmospheric pressure and stirred at RT for 1 8 hours. The suspension was filtered through Celite pad and concentrated to give crude product as a white solid, which was purified by trituration in ethyl acetate to give 66 mg (73%) of the title compound.

EXAMPLE 72 Np - [[(4'-Chloro [1,1 '-bifeni n-4-iPsulfonyl] methyethyl-1-N-hydroxyformamide) The title compound was synthesized according to the procedures described in Example 71, except using 4-chlorophenylboronic acid in place of 4-methoxyphenylboronic acid in Example 71 A. Purification of the crude final product by recrystallization from ethyl acetate gave 36 mg of the title compound, MP 178-180 ° C, 1H NMR (DMSO-d6). ) 3 1.16 (d, 1.5H, J = 6.6 Hz), 1.22 (d; 1.5 H, J = 6.6 Hz), 3.50 (dd, 1H, J = 4.8, 14.7 Hz), 3.57-3.73 (m, 1H) , 4.28-4.41 (m, 0.5H), 4.61-4.77 (m, 0.5H), 7.50 (d, 2H, J = 8.4 Hz), 7.81 (d, 2H, J = 8.4 Hz), 7.01 (s, 0.5 H), 7.02-8.00 (m, 4H), 8.07 (s, 0.5H), 0.45 (s, 0.5H), 0.86 (s, 0.5H), MS (ESI +) m / e 354 (M + H), 376 (M + Na); Anal.Called for C16H16N04SCI C, 54.31; H, 4.55; N, 3.05. Found: C, 54.46; H, 4.43; N, 3.85.

Example 73 N-RI-L-R4- (1,3-benzodioxol-5-iPphenylsulfoninmetinene-N-hydroxyformamide) The title compound was synthesized according to the procedures described in Example 71, except for 3,4- to 3-amino acid. methylenedioxybenzeneboronic acid instead of 4-methoxyphenylboronic acid in the Example 71A Mp 200-201oC; 1H NMR (DMSO-d6) d 1.16 (d, 1.5H, J = 6.6 Hz), 1.22 (d, 1.5H, J = 6.6 Hz), 3. 44-3.70 (m, 2H), 4.28-4.40 (m, 0.5H), 4.61-4.76 (m, 0.5H), 6.11 (s, 2H), 7. 06 (d, 1H, J = 7.8 Hz), 7.20 (d, 1H, J = 8.4 Hz), 7.39 (s, 1H9, 7.86-7.94 (m, 4. 5H), 8.08 (s, 0.5H), T.48 (s, 0.5H), 0.00 (s, 0.5H); MS (ESI +) 364 (M + H), 381 (M + NH 4); Anal. Cacld for: C1 7H 17N06S C, 56.1 0; H, 4.71; N, 3.85. Found: C, 55.97; H, 4.62; N, 3.81.

Example 74 N-f 1 - [[[4- (4-chlorophenoxypfeniHsulfoipmetipetip-N-hydroxyformamide Example 74A 4-C orphenoxyphenyl methyl sulfone A solution of 4-chlorophenol (5.54 g, 43 mmol) in DMSO (75 ml) was treated sequentially with potassium t-butoxide (5.15 g, 46 mmol) then with a solution of 4-fluorophenyl methyl sulfone (5.00 g, 29 mmol) in DMSO (25 ml), was heated at 1 20 ° C for 2 hours, cooled to room temperature, then separated between dichloromethane and 1 N sodium hydroxide, dried (Mg2SO4), and concentrated to give crude product as a white solid. Recrystallization from ethyl acetate and hexane provided 5.44 g (66%) of the title compound. MS (ESI +) m / e 300 (M + NH 4).

Example 74B Nf 1 - [[[4- (4-Chlorophenoxyphenyl] sulfoniHmethyl-1-ethyl-N-hydroxy-amide The title compound was prepared from Example 74A according to the procedures described in Example 71 C-71 E. The purification of the final compound Crude by recrystallization from ethyl acetate gave 388 mg of the title compound, mp 144-145 ° C; 1H NMR (DMSO-d6) d 1.15 (d, 1.5H, J = 6.6 Hz), 1.21 (d, 1.5H, J = 6.6 Hz), 3. 30-3.68 (m, 2H), 4.25-4.37 (m, 0.5H), 4.60-4.70 (m, 0.5H), 7.16-7.23 (m, 4H), 7.53 (d, 2H, J = 8.9 Hz), 7.83-7.g2 (m, 2.5H), 8.06 (s, 0.5H), 0.45 (s, 0. 5H), g.87 (s, 0.5H); MS (ESI +) 370 (M + H), 387 (M + NH 4); Anal, caled for: C16H16NO5SCI C, 51. g6; H, 4.36; N. 378. Found: C, 52.22; H, 4.37; N, 3.80.

Example 75 N-M-ff (4 '-metoxif 1,1' -bif in iH-4-yl) sulfoniHmetippropip-N-hydroxyl ormamide Example 75A 1- (4'-methoxy-1, 1'-biphen-4-yl) sulfonyl-2-butanol A solution of Example 71B (0.70 g, 2.67 mmol) in THF (200 ml) cooled to -78 ° C under argon was treated with nBuLi (1.17 ml of 2.5 M solution in hexane, 2.03 mmol), stirred 4 hours at -78 ° C, then treated with propionaldehyde (0.40 ml, 5.34 mmol) as drops. The reaction mixture was allowed to warm to room temperature over 1.5 h, was quenched with saturated aqueous NH4CI solution (50 ml), separated between ether and water, dried (Mg2SO4), and concentrated to give 0.00 g of product crude, which was purified on silica gel with dichloromethane / methanol to provide 0.78 g (01%) of the title compound. MS (ESI +) m / e 321 (M + H), 338 (M + NH 4).

Example 75B 1- (4'-methoxy-1,1 '-biphenin-4-iPsulfonip-1-butene A solution of Example 75A (0.45 g, 1.40 mmol) in dichloromethane (40 ml) cooled to 0 ° C was treated sequentially with triethylamine (0.20 ml, 2.1 mmol) and methanesulfonyl chloride (0.12 ml, 1.55 mmol) in the form of drops, stirred at room temperature for 3 hours, then treated with 1,8-diazabicyclo [ 5.4.0] undec-7-ene (0.21 ml, 1.40 mmol), refluxed for 2 hours, cooled to RT, and separated between dilute sodium bicarbonate solution and dichloromethane.The organic extract was washed with 1N HCl, then with brine, dried (Mg2SO4) and concentrated to give crude white solid product.Recrystallization from ether at -20 ° C gave 0.34 g (80%) of the title compound .MS (ESI +) m / e 303 (M + H), 320 (M + NH 4).

Example 75C Nf 1 -ff (4'-methoxyiri, 1 '-bifeniH-4-iPsulfonipmetHHropip-N-hydroxyamine A solution of Example 75B (0.34 g, 1.12 mmol) in THF (40 ml) was treated with hydroxylamine hydrochloride (0.30 g, 5.62 mmol) and potassium carbonate (0.78 g, 5.62 mmol), refluxed for 5 hours, cooled to room temperature, separated between ether and water, dried (Mg2SO4) and concentrated to give crude product as a clear, colorless oil Recrystallization from ethyl acetate and ether yielded 0.25 g (67%) of the title compound, MS (ESI +) m / e 336 (M + H).

EXAMPLE 75D N- (1-rf (4'-methoxy-1,1'-biphenyl-4-yl) sulfonyl-1-methyl-propyl-N-hydroxyformamide A solution of Example 75C (0.24 g, 0.72 mmol) in THF (30 ml) cooled at 0 ° C it was treated with formic acetic anhydride (64 mg, 0.72 mmol), stirred for 2 hours, separated between water and dichloromethane, dried (Mg2SO4), and concentrated to give 0.25 g of the crude product, which it was recrystallized from ethyl acetate to provide 106 mg (41%) of the title compound: Pf 1T9-200 ° C; 1H NMR (DMSO-d6) 30.60-0.80 (m, 3H), 1.40-1.60 (m, 2H) , 3.41-3.60 (m, 2H), 3.82 (s, 3H0, 3.06-4.07 (m, 0.5H), 4.43-4.54 (m, 0.5H), 7.08 (d, 2H, J =? 0 Hz), 7.71-7.78 (m, 2H), 7.87-7.06 (m, 4.5H), 8.17 (s, 0.5H), 0.4g (s, 0.5H), g.84 (s, 0.5H), MS (ESI + 364 (M + H), 381 (M + NH4) Anal, caled for: C18H21N05S: C, 50.48; H, 5.82; N, 3.85 Found: C, 50.67; H, 5.77; N, 3.80.

Example 76 N-f1-Ri.1-dimethyl-2-r (4 '- (trifluoromethylPP, 1, -biphenyl-4-allylsulfonylletyl-N-h-hydroxylformamide) Example 76A 4- (4'-trifluoromethylphenol P-phenyl methyl sulfone) The title compound was prepared according to the procedure given in Example 73A by substituting 4-triufluoromethyl-phenylboronic acid for 3,4-methylenedioxybenzeneboronic acid Purification by recrystallization from ethyl acetate. ethyl and ether gave 3.70 g (72%) of the title compound, MS (ESI +) m / e 318 (M + NH4).

Example 76B 1- (4'-trif luoromethyl) 1.1 '-bifeni-l-4-yl) sulfonin-2-methyl-2-pro-panol The title compound was prepared according to the procedure described in Example 75A substituting Example 76A by Example 71B and replacing acetone with propionaldehyde. Purification of the crude product by recrystallization from ethyl acetate, ether and pentane afforded 1.40 g (73%) of the title compound. MS (ESI +) m / e 376 (m + NH 4).

Example 76C N-f1-Ri.1-dimethyl-2-r (4 '- (trifluoromethylPri.1, -bifenyl-4-insulfonylpetiH-N-hydroxyformamide) The title compound was prepared from Example 76B of According to the procedures described in Examples 75B, 75C and 75D, purification of the final product by recrystallization from ethyl acetate and ether gave 17 mg of the title compound, MP 167-16T ° C, 1 H NMR (DMSO-d 6). 3 1.52 (s, 6H), 3.71 (s, 2H), 7.83-8.03 (m, 8.5H), 8.17 (s, 0.5H), 0.43 (s, 0.5H), 10.0 (s, 0.5H); (ESI +) 402 (M + H), 410 (M + NH 4), 424 (M + Na); Anal, caled for: C18H18N04F3S C, 53.86; H, 4.52; N, 3.48. Found: C, 53.58; H, 4.48; N, 3.10.

EXAMPLE 77 N-Ri-R (PhenylmethoxPmetill-2-rr4 '- (trifluoromethyl) p, 1'-biphenyl-4-ylsulfonylletiH- Nh idroxyformamide The title compound was synthesized according to the procedures described in Examples 75A -75D, except that Example 76A was replaced by Example 71B, and substituting benzyloxyacetaldehyde for propionaldehyde in Example 75 A. Purification of the final crude product by recrystallization from ethyl acetate gave 0.53 g of the title compound, Mp 172 ° C; 1H NMR (DMSO-d6) 3 3.37-3.61 (m, 3H), 3.61-3.72 (m, 1H), 4.28-4.50 (m, 2.5H), 4.81-4.03 (m, 0.5H), 7.20-7.35 ( m, 5H), 7.85-8.06 (m, 8.5H) 8.18 (s, 0.5H), 0.57 (s, 0.5H), T.T6 (s, 0.5H), MS (ESI +) 404 (M + H) , 511 (M + NH4); Anal, caled for: C24H22NO5F3S C, 58.41; H, 4.4T; N, 2.83.

Found: C, 58.43; H, 4.54; N, 2.77.

Example 78 N-ri- (hydroxymethyl) -2-rr (4 '- (trifluoromethylP [1,1'-biphenin-4-illsulfoninetip-N-hydroxyformamide A solution of Example 78 (35 mg, 0.07 mmol) in THF (3 ml) and methanol (5 ml) was treated with palladium on carbon, 10%> (30 mg, 0.03 mmol) and hydrogen gas at atmospheric pressure, stirred at room temperature for 16 hours, filtered through Celite, and concentrated to give a crude product Purification by recrystallization from ethyl acetate, ether and hexane gave 20 mg (70%) of the title compound, Mp 159-161 ° C, 1 H NMR (DMSO-d 6) 3 3.25-3.68 (m , 4H), 3.08-4.10 (m, 0.5H), 4.54-4.66 (m, 0.5H), 4.97-5.09 (m, 1H9, 7.81-8.07 (m, 8.5H), 8.14 (s, 0.5H), 9.44 (s, 0. 5H), 0.85 (s, 0.5H); MS (ESI +) 404 (M + H), 421 (M + NH 4), 426 (M + Na); Anal, caled for: C17H16NO5F3S C, 50.61; H, 3.00; N, 3.47. Found: C, 50.57; H, 3.03; N, 3.37.

Example 70 N-1-r (4,4-dimeti-2,5-d-oxo-1-imidazole idin) methyH-2-fí (4 '- (trifluoromethyl) M- 1' -bifen i n- 4-intioletill-Nh id roxiformam ida EXAMPLE 70A 1-r (4'-trifluoromethiip.1'-biphenyl-4-Pthio1-3- (4,4-dimethyl-2,5-dioxoimidazolidin-1-yl) -2-propanone The mixture of Example 46A ( 608 mg, 1.88 mmol), tetrakis (217 mg, 0. 19 mmol), 4-trifluorophenylboronic acid (714 mg, 3.76 mmol) and NaOH (1M, 3.76 ml, 3.76 mmol) in DME (20 ml) was refluxed under Ar for 4 h.

The mixture was evaporated to a small volume and separated between CH2CI2 / brine. The CH2Cl2 layer was collected, dried (Na2SO2), filtered and evaporated to dryness. Purification of the final crude product on silica gel with 20% -40% ethyl acetate / CH2Cl2, gave 0.820 g of the title compound. (MS (DCI / NH3) m / e 4545 (M + NH4) +, 437 (M + H) +.

Example 70B N-ri- (4,4-Dimeti-2,5-dioxo-1-imidazolidiniPmetip-2-ff4 '- (trifluoromethyl) p.1'-biphenin-4-illthioletin-N-hydroxyformamide The title compound is obtained following the procedures in Examples 2D-F (even), but substituting Example 7gA (0.82 g, 1.88 mol) for Example 2 C. Purification of the final crude product on silica gel with 5% methanol / dichloromethane, gave 434 mg of the title compound.1H NMR (300 MHz, d6-DMSO) d 9.75 and 9.52 (br s, 1H), 8.37 and 8.33 (s, 1H), 8.31 and 7.77 (s, 1H), 7.90 (d; 2H , J = 8.4 Hz), 7.81 (d, 2H, J = 8.4 Hz), 7.71 (m, 2H), 7.47 (m, 2H), 4.60 and 4.00 (m, 1H), 3.52-3.77 (m, 2H) , 3.08-3.46 (m, 2H), 1.28 and 1.25 and 1.23 (s, 6H) MS (DCI / NH3) m / e 400 (M + NH4) +, 482 (M + H) +. Anal, caled for C22H22F3N3? 4S "0.5 CH3OH: C, 54.31; H, 4.86; N, 8.44, Found: C, 54.43; H, 4.82; N, 8.08.

Example 80 NMr (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) met.p-2-IT4 '- (trifluoromethyl) -Pri, 1'-bifin-4-illsulfoninetin-N-hydroxyform amide Example 70 was converted to Example 80 following the procedure described in Example 46D. mp 180-182 ° C; 1 H NMR (300 MHz, d6-DMSO) d 0.66 and 0.51 (br s, 1 H), 8.30 and 8.35 (s, 1 H), 8.10 and 7.73 (s, 1H), 7.70-8.02 (m, 6H) , 7.80 (d, 2H, J = 8.4 Hz), 4.01 and 4.55 (m, 1H), 3.45-3.80 (m, 4H), 1.24 and 1.23 and 1.21 (s, 6H). MS (DCI / NH3) m / e 531 (M + NH4) +, 514 (M + H) +. Anal, caled for C22H22F3N3? 6S- »0.75 H20: C, 50.14; H, 4.49; N, 7.97. Found: C, 50.27; H, 4.49; N, 7.97.

EXAMPLE 81 N-Ri-F (2,5-Dioxo-1-imidazolidinium-Pillill-2-rr4 '- (Trifluoromethoxy) p, 1'-biphenin-4-yloxyethyl] -N-h id roxiformam id a Example 81A 1-bromo-3- (2,5-dioxoimidazolidin-1-yl) propan-2-one The title compound was prepared following the procedures in Examples 16A and 16B, but substituting hydantoin for 1,5,5-trimethylhydantoin.

EXAMPLE 81B N-Ri-f (2,5-dioxo-1-imidazolidinyl) methylene-2-rr4 '- (trifluoromethoxy) f1,1'-biphenin-4-ipoxpetill-Nh id roxiformam ida The title compound was prepared following the sequence described in Examples 16C and 16E, but substituting 81A for 16B and 4- (4'-trifluoromethoxy-phenyl) -phenol for 4-bromophenol. 1 H NMR (DMSO-d 6) d g.92 (S, 0.5H). 0.60 (BS, 0.5H), 8.31 (S, 0.5u), 8.16 (S, o.5H), 8.14 (S. 0.5H), 7.02 (S, 0.5H), 7.76-7.72 (M, 4H), 7.6.4-7.62 (D, 4H, J = 8.4 Hz), 7.42 - 7.40 (D, 4H.3 = 8.6 Hz), 7.02-6.08 (M, 4H), 4.84-4.82 (M, 0.5H), 4.38-4.35 (M, 0.5H) 1 4.10-4.04 (MM, 4H) . Anal. Caled for: C20H18N3O6F3: C, 52.08; H, 4.00; N, 0.13. Found: C, 53.01; H, 4.03; N, 0.13.

EXAMPLE 82 Np-rrr4 '- (Trifluoromethyl) p.1'-biphenip-4-α-sulfoninmethyl-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinium-Petip-N-hydroxyformamide) The title compound was prepared following the procedures described in Example 46A, 46B, 46C and 46D, except that the Example 16B by 23A in Example 46A and 4-trifluoromethylbenzeneboronic acid by 4-butyloxybenzeneboronic acid in the Example 46B. 1 H NMR (dd-DMSO) g.70 (S, 0.5H), 0.54 (s, 0.5H), 8.10 (5, 0.5H), 8.05-7.07 (m, 6H), 7.80 (d, 2H, J = 7.8 Hz), 7.75 (s, 0.5H), 4.07-4.86 (m, 0.5H), 4. 60-4.48 (M, 0.5H), 3.80-3.44 (m, 4H), 2.75 (s, 3H), 1.24 (s, 3H), 1.22 (s, 3H). MS (ESI) 528 (M + H), 545 (M + NH 4), 526 (M-H). Anal. Caled for: C23H24N306SF3 C, 52.36; H, 4.58; N, 7.06. Found: C, 52.05; H, 4.70; N, 7.63.

Example 83 N-ri-rr (4'-butiiri.1'-biphenin-4-yl) oxylmetin-2- (3-methyl-2,5-dioxo-1-imidazolidiniPetiH-N-hydroxyl ormamide The title compound was prepared following the procedures described in Example 16C and 16E, except that Example 26A was replaced by 16B and 4- (4'-butylphenyl) phenol by 4-bromophenol.1H NMR (dd-DMSO) 1O.OO-T. 04 (hr, 0.5H), 0.64-0.58 (hr, 0.5H), 8.34 (s, 0.5H), 7.08 (s, 0.5H), 7.58 (d, 2H, J = 8.8 Hz), 7.52 (d, 2H, J = 8.6 Hz), 7.24 (d, 2H, J = 8.5 Hz), 7.00-6.02 (m, 2H), 4.02-4.70 (m, 0.5H), 4.41-4.30 (m, 0.5H), 4.20 -4.03 (m, 2H), 3.05 (d, 2H, 3 = 7.8 Hz), 3.75-3.57 (m, 2H), 2.86 (s, 1.5H), 2.85 (s 1.5H), 2.60 (t, 2H) , J = 7.4 Hz), 1.63-1.51 (rn, 2H), 1.39-1.25 (m, 2H), 0.01 (t, 3H, J = 7.4 Hz), MS (ESI) 440 (M + H), 457 ( M + NH4), 438 (MH), Anal Caled for: C24H29N3O5 »0.15H2O C, 64.02; H, 6.60; N, 0.46. Found: C, 64.760 H.6.62; N, 0.20.

Example 84 N-Ri-1 (3-methyl-2,6-dioxo-1-imidazolidinyl) metin-2-rr4 '- (trifluoromethoxy) ri, 1'-biphenyl-hypoxylethyl-N-hydroxyformamide The compound of the title was prepared following the procedures described in Example 16C and 16E, except that Example 26A was replaced by 16B and 4- (4'-trifluoromethoxy) phenol by 4-bromophenol. 1H NMR (d6-DMSO) 10.02-9.92 (br 0.5H), 9.64-g.58 (br, 0.5H), 8.35 (s, 0.5H), 7.08 (s, 0.5H), 7.74 (d, 2H) , J = 8.0 Hz), 7.64 (d, 2H, J = 8.8 Hz), 7.41 (d, 2H, J = 8.1 Hz), 7.03-6.07 Im. 2H), 4.01-4.82 (m, 0.5H), 4.41-4.31 (m, 0.5H), 4.21-4.07 (m, 2H), 3.06 (d, 2H, J = 7.7 Hz), 3.72-3.57 (m, 2H), 2.86 (s, 1.5H), 2.85 (s, 1.5H). MS (ESI) 468 (M + H), 485 (M + NH 4), 466 (M-H).

Anal, caled for: C21 H2oN306F3 C, 53.06; H, 4.31; N, 8.00 Found: C, 53.85; H, 4.40; N, 8.85.

Example 85 N-r4-r4-r (4'-chlorop, 1'-biphenip-4-yl) sulfonyl-1-methytetrahydro-2H-pyran-4-yl-N-hydroxyformamide Example 85A N-r4-r4-r (4'-chlorof1.1 '-bifenyl-4-yl) sulfonipmethyltetrahydro-2H-pyran-4-iH-N-benzyloxyamine The title compound was prepared following the procedure described in Example 54A, except that 4'-chloro-4-O-methyl-sulfone-biphenyl was used in place of phenoxyphenyl-4-chloro-4'-methylsulfone.

Example 85B N-r4-r4-r (4'-chloro-1'-biphenin-4-iPsulfonylmethetrahydro-2H-pyran-4-in-N-hydroxyamine A solution of 85A (0.436 g, 0.02 mmol) was treated with (CF3C02) 3B (4.6 ml, 1M solution in THF, 4.6 mmol), then stirred overnight at room temperature The solution was concentrated, separated between ethyl acetate and aqueous Na2CO3 and the organic extracts were dried ( MgSO4), concentrated, then purified via column chromatography to give the title compound in 51% yield.

Example 85C N-r4-r4-r (4'-chloro, 1'-b-phenyl-4-yl) sulfonylmethetrahydro-2H-pyran-4-yl-N-hydroxyformamide Example 85B was converted to the compound of the title using the formylation procedure of Example 2F. 1H NMR (d6-DMSO) 0.52-0.48 (br, 1H), 8.23 (s, 1H), 7.07 (s, 4H), 7.81 (d, 2H, J = 8.4 Hz), 7.50 (d, 2H; J = 8.5 Hz), 3.72 (s, 2H), 3.69-3.46 (m, 4H), 2.35-1.94 (m, 4H). MS (ESI) 410 (M + H), 427 (M + NH 4), 432 (M + Na), 408 (M-H).

Example 86 N-RI-Fff4- (4-chlorophenoxpfeninsulfonylmethip-2- (4,4-dimethyl-2,5-dioxo-1-imidazolidiniPetip-N-hydroxyformamide) The title compound was prepared following the procedures described in the examples 46A, 46C and 46D, except that 4- (4'-chlorophenoxy-phenophenol was used in place of 4-bromothiophenol.) 1 H NMR (dd-DMSO) 9.67 (S, 0.5H), 9.50 (s, 0.5H), 8.36 (d , 1H, J = 13.2 Hz), 8.10 (s, 0.5H), 7.00 (dd, 2H, J = 8.8, 3.0 Hz), 7.68 (s, 0.5H), 7.53 (d, 2H, J = 8.8 Hz) , 7.20 (d, 4H, J = 8.8 Hz), 4.80-4.77 (m, 0.5H), 4.52-4.40 (m, 0.5H), 3.68-3.38 (m, 4H), 1.25-1.21 (m, 6H) MS (ESI) 406 (M + H), 513 (M + NH 4), 404 (MH), Anal Caled for: C 21 H 22 N 3 O 7 SCI C, 50.85; H, 4.47; N, 8.47 Found: C, 50.53; H, 4.58; N, 8.25.

Example 87 N-p-rrr4- (4-chlorophenoxyphenHsulfoniHmet.p-2- (3.4, 4-trimethyl-l, 2,5-dioxo-1-imidazole, d, n-1) etN-N-hydroxyformamide The title compound was prepared following the procedures described in Examples 46A, 46C and 46D, except that 16B was used instead of 23A and 4- (4'-chlorophenoxy) thiophenol instead of 4-bromothiophenol. 1H NMR (d6-DMSO) 9.78-9.71 (m, 0.5H), 0.58-0.40 (m 0.5H), 8.09 (s, 0.5H), 7.80 (dd, 2H, J = 5.8, 2.0 Hz), 7.68 (s, 0.5H), 7.53 (d, 2H, J = 0.2 Hz), 7.20 (d, 4H, J = 8.8 Hz), 4.88-4.78 (m, 0.5H), 4.50-4.38 (m, 0.5H) , 3.72-3.40 (m, 4H), 2.76 (s, 1.5H), 2.76 (s, 1.5H), 1.26-1.22 (m, 6H). MS (ESI) 510 (M + H), 527 (M + NH 4) 508 (M-H). Anal. Caled for: C22H24N3? 7SCI C, 51.81; H, 4.74; N, 8.23. Found: C, 51.61; H, 4.00; N, 7.06.

Example 88 N-ri-rr (4-butiiri.1'-bifenill-4-yl) sulfonipmetill-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazole idin Petill-N-hydroxy ormamide The title compound was prepared following the procedures described in Example 46A, 46B, 46C and 46D, except that Example 16B was replaced by 23A in Example 46A and 4-n-butylbenzeneboronic acid by 4-butyloxybenzeneboronic acid in Example 46B. 1H NMR (dd-DMSO) 0.70 (s, 0.5, H), 0.54 (s, 0.5H), 8.10 (S.0.5H), 7.04 (d, 4H, J = 1.0 Hz), 7.73 (s 0.5H) ), 7.60 (dd, 2H, J = 8.1, 2.0 Hz), 7.35 (d.2H, 8.4HZ), 4.06-4.86 (m, 0.5H), 4.60-4.48 (m, 0.5H), 3.77- 3.42 (m, 4H), 2.75 (s 3H), 2.64 (t, 2H, J = 7.4 Hz), 1.64-1.54 (m, 2H), 1.40-1.27 (m 2H), 1.24 (s, 3H) 1.22 (s, 3H), 0.91 (t, 3H, J = 7.5 Hz).

MS (ESI) 516 (M + H), 533 (M + NH 4), 538 (M + CI) .514 (M-H). Anal. Caled for: C26H33N306S C, 60.56; H, 6.45-, N, 8.14. Found: C. 60. 32; H, 6.44; N, 8.09.

Example 89 Np-rr (4'-butiiri, 1'-biphenyl-4-iPoxi1metin-2- (4.4-dimethyl-2,5-dioxo-1-imidazo I id iniPetin-N-hydroxyl ormamide The title compound was prepared according to the procedures of Example 23B, except that 4- (4'-butylphenyl) -phenol was replaced in place of 4- (4'-ethoxyphenyl) -phenol.1H NMR (DMSO-d6) d 0.03 (t, 3H , J = 8 Hz), 1.28 (s, 6H), 1.30-1.30 (m, 2H), 1.50-1.65 (m, 2H), 2.60 (t, 2H, J = 7 Hz), 3.51-3.64 (m, 1H), 3.67-3.80 (m, 1H), 4.03-4.24 (m, 2H), 4.35-4.48 (m, 0.5H), 4.78-4.92 (m, 0.5H), 6.99 (dd, 2H, J = 3 , 9 HZ), 7.25 (d, 2H, J = 9 Hz), 7.53 (d, 2H, J = 9 Hz), 7.58 (d, 2H, J = 9 Hz), 7.94 (s, 0.5H), 8.34 (d, 1H, J = 6 Hz), 8.30 (s, 0.5H), 9.55 (s, 0.5H), 0.87 (s, 0.5H), MS (ESI-) 452 (MH), Anal Caled for: C25H31N3O5 C, 66.20; H, 6.88; N, 9.26 Found: C, 65.99; H, 6.71; N, 9.19.

Example 90 N-ri-rrr3 '- (cyanomethylPri.1'-biphenin-4-ylp-methan-2- (4,4-dimethyl-2,5-dioxo-1 imidazolidiniPetill-N-hydroxyl ormamide Compound of the title was prepared according to the procedures of Example 23B, except that 4- (3'-cyanomethylphenyl) -phenol was replaced in place of 4- (4'-ethoxyphenyl) -phenol.1H NMR (DMSO-d6) d 2.80 (s, 6H), 3.52-3.83 (m, 2H), 4.10 (s, 2H), 4.12-4.1-5 (m, 2H), 4.38 (4.46, mH, J = 0.5 Hz), 4.80-4.00 (m , 0.5H), 7.03 (dd, 2H, J = 3,? Hz), 7.30 (d, 1H, J = 10 Hz), 7.48 (t, 1H.J = 10 Hz), 7.57-7.66 (m, 4H ), 7.03 (s, 0.5H), 8.34 (d, 1H, J = 6 Hz), 8.30 (s, 0.5H), 0.55 (s, 0.5H), 0.88 (s, 0.5H), MS (ESI- ) 435 (MH) Anal Caled for: C23H24N4O5-0.25CH3CO2C2H5 C, 62.87; H, 5.71; N, 12.21, Found: C, 62.85; H, 5.00; N, 12.16.

Example 01 N-RI-R4- (2-tethenyl) phenoxmethyl-2-p- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinium-PethiH-N-hydroxyformamide) The title compound was prepared following the procedures of Examples 16C and 16E, except that 4-84 '- (2-thienyl) phenyl) phenol was replaced by 4-bromophenol in Example 16C. 1 H NMR (DMSO-d 6) d 1.20 (s 6H). 2.80 (s, 3H), 3.54-3.66 (m, 1H), 3.60-3.84 (m, 1H), 4.04-4.22 (m, 2H), 4.33-4.47 (m 0.5H), 4.77-4.00 (m, 0.5H), 6.06 (dd, 2H, J = 3,? Hz), 7.08-7.13 (.m, 1H), 7.38 (d, 1H, J = 3 Hz), 7.46 (d, 1H, J = 4 Hz ), 7.50 (d, 2H, J = 0 Hz), 7.02 (s, 0.5H), 8.31 (s, 0.5H), T.54 (s, 0.5H), 0.86 (s, 0.5H). MS (ESI-) 416 (M-H).

Anal. Caled for: C2OH23N3O5S-0.25H2O C. 56.92; H, 5.61; N, 9.95. Found: C, 56.65; H, 5.48; N, 9.77.

Example 92 Np-rr (3-nitrori.1'-biphenyl-4-iPoxylmethyl-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidiniPetip-N-hydroxyform amide) The title compound was prepared following the procedures of Examples 16C and 16E, except that 4-phenyl-2-nitrophenol was replaced by 4-bromophenol in Example 160. 1H NMR (DMSO-d6) d 1.28 (s, 6H), 2.80 (s, 3H), 3.54- 3.65 (m, 1H), 3.70-3.88 (m, 1H), 4.22-4.39 (m, 2H), 4.40-4.50 () m, 0.5H), 4.80-4.01 (m, 0.5H), 7.34-7.41 ( m, 2H), 7.43-7.52 (m, 2H), 7.71 (d, 2H, J = 8 Hz), 7.87 (s, 0.5H), 8.0 (d, 1H, J =? Hz), 8.16 (dd, 1H, J = 3.6 Hz), 8.20 (s, 0.5H), 0.55 (s, 0.5H), 9.80 (s, 0.5H) MS (ESI-) 455 (MH) Anal, caled for: C22H24N407 C, 57.88; H, 5.29; N, 12.27, Found: C, 57.62; H, 5.44; N, 11.95.

EXAMPLE 93 N-p-rr (4'-methipip.1'-biphenin-4-yl) oxylmethin-2-rr3- (methylsulfonylPaminolfeninetill-N-hydroxyl ormamide) Example 93A 3- (Methylsulfonyl) amino-1-bromo-benzene The m-bromine aniline was dissolved in 40 ml of pyridine and cooled to 0 ° C, followed by the addition of MsCl in the form of drops via syringe. After 10 minutes, the solution was warmed to room temperature and stirred for 4 h. Upon concentration in vacuo, the residue was separated between 350 ml of H 2 O and 500 ml of CH 2 Cl 2 in a separating funnel. The organics were separated and washed with 100 ml of 3N HCl, 200 ml of saturated NaHCO3 and dried over MgSO4. Upon filtration and concentration in vacuo, an off-white solid was obtained. This product was recrystallized from CH2Cl2 / hexanes to give 6.7 g (90% >) of T3A as white needles.

Example T3B 3- (methylsulfoniPamino-1 - (prop-2-eniP-benzene) Using a sealed glass vessel, the sulfonamide T3A (3.0 g, 12.1 mmol) was suspended in 10 ml of toluene, followed by the addition of the allylbutyl reactant tin and was bubbled with argon for 5 min. To the previous suspension were added 280 mg (2 mol%) of Pd (PPh3) 4 and the vessel was sealed and heated at 120 ° C for 17 h. a homogeneous solution, which turned dark brown after 30 min.After cooling, the catalyst was filtered, washed with CH2Cl2 / MeOH.The concentration of the filtrate followed by purification on silica gel, levigating with 1.0% ethyl acetate. ethyl / hexanes, and then 20% ethyl acetate / hexanes, gave T3B, 0.00 g (38%) as a colorless oil, which solidified upon letting it remain.

EXAMPLE 93C N-ri-rr (4'-met.IM.1'-b¡fen¡p-4-iPoxpmetip-2-rr3- (methylsulfoniPaminolfeniHetip-N-hydroxyformamide) The title compound was prepared from Example 93B, When epoxidizing first as described in example 5C, then opening the epoxide with 4'-hydroxy-4-biphenylcarbonitrile as in example 5F, then follow the sequence of reactions described in examples 2C to 2F. 1H NMR (DMSO-d6 ) d 2.32 (s, 3H), 2.88 (d, 2H, J = 6 Hz), 2.96 (s, 1H), 2.98 (s, 3H), 4.03-4.11 (m, 1H), 4.15-4.27 (m, 1.5H), 4.72-4.82 (bs, 0.5H), 6.07-7.10 (m, 4H), 7.05 (s, 1H), 7.20-7.30 (m, 3H), 7.50 (d, 2H, J =? Hz ), 7.57 (d, 2H, J = 9 HZ), 7.73 (s, 0.5H), 8.25 (s, 0.5H), 0.18 (s, 0.5H), 10.01 (s, 0.5H). ) 453 (MH) Anal Caled for: C24H26N205S C, 63.41; H, 5.76; N, 6.16 Found: C, 63.16; H, 6.12; N, 5.76.

EXAMPLE 04 N-p-rrr3- (diethylamine) carboniphenyl] metip-2-r (4'-methylM.1'-bifeniH-4-yl) oxyjet I ll-N-h Id roxiformam ida Example T4A 3-bromo-1- (N, N-diethylcarboxamide) -benzene Diethylamine (10.0 ml, 07 mmol) was dissolved in 60 ml of dry ethyl ether and cooled to 0 ° C. Benzoyl chloride (3.67 ml, 28 mmol) was dissolved in 10 ml of dry ethyl ether and slowly added dropwise via syringe to the above solution. A white paste was developed on the addition and stirring was continued for 10 min at 0 ° C, then it was heated at room temperature for 1 h. The mixture was poured into a separatory funnel containing 500 ml of ethyl ether and 75 ml of 10% NaOH. The organics were separated and washed a second time with 75 ml of 10% NaOH, followed by 75 ml of 10% HCl, then 200 ml of water. A final wash with 100 ml of brine followed by drying over MgSO4, filtration and then concentration in vacuo afforded 94A as a colorless liquid, 5.9 g (83%), which was used without further purification.

Example 94B N-ri - [rr3- (d.ethylamino) carboninphenyl] metip-2 - [(4'-methylip, 1'-biphenin-4-Poxylethyl-Nh idroxyformamide) The title compound was prepared following the procedure described in Examples 93B and 93C, except that 94A was replaced by 93A. 1 H NMR (DMSO-d6) d 0.08-1.20 (bd, 6H), 2.32 (s 3H), 2.03 (d, 2H, J = 6 Hz), 3.1 1 - 3.48 (bd, 4H), 4.0 -4.1 3 (m, 1 H), 4.1 6-4.30 (m, 1 .5H). 4.74-4.86 (bs, 0.5H), 6.08 (d, 2H, J = 0 Hz), 7.13-7.40 (m, 6H), 7.50 (d, 2H, J = 8 Hz), 7.56 (d.2H, J = 9 Hz), 7.73 (s, 0.5H), 8.23 (s, 0.5H), 0.63 (s, 0.5H), 10.02 (s, 0.5H). MS (ESI +) 461 (M + H). Anal. Caled for: C28H32N204-1 .5H20 C, 68.07; H, 7.23; N, 5.74. Found: C, 68.06; H, 7.00; N, 5.42.

Example 85 Np-rr (4'-cyanori, 1'-biphenyl-4-iPoxpmetin-2-f (4, -cyano [1,1'-biphenin-4-iPoxiletip-N-hydroxyformamide] The title compound was prepared using the procedures of Examples 5F, 5G and 5H, except that Example 3B was used in place of 5E, 1H NMR (DMSO-d6) d 4.18-4.36 (m, 4H), 4.43-4.57 (bs, 0.5H), 4.07- 5.03 (bs, 0.5H), 7.10 (d, 4H, J =? Hz), 7.77 (d, 4H, J = 9 Hz), 7.81-7.95 (M, 8H), 8.13 (s, 0.5H), 8.42 (s, 0.5H), 0.75 (s, 0.5H), 10.15 (s, 0.5H), MS (DCI / NH3) M + H (400), M + 18 (507), Anal Caled for: C3OH23N3O4- »0.25H2O C, 72.03; H, 4.70; N, 8.50 Found: C, 72.80; H, 4.74; N, 8.26.

Example 96 NM-rr (4'-cyanoM.1'-biphenip-4-yl) oxpmetip-2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide The title compound was prepared according to the procedures of Example 23B, except that 4- (4'-cyanophenyl) -phenol was replaced in place of 4- (4'-ethoxyphenyl) -phenol. 1H NMR (DMSO-d6) d 1.27 (s, 6H), 3.50-3.66 (m, 1H), 3.67-3.82 (m, 1H), 4.08-4.28 (m, 2H), 4.38-4.50 (m, 0.5H ), 4.80-4.93 (m, 0.5H), 7.06 (dd, 2H, 3 = 3.9 HZ), 7.73 (d, 2H, J = 9 Hz), 7.82-7.93 (m, 4H), 7.94 (s) , 0.5H), 8.35 (d.1H, J = 6Hz), 8.40 (5, 0.5H), 0.56 (s, 0.5H), 0.87 (s, 0.5H). MS (ESI-) 421 (M-H).

Anal. Caled for: C22H22N4O5-0.25H20 C, 61.80; H. 5.3 1; N. 13.12. Found: C, 61.82; H.5.34; N, 12.82.

Example 07 Npr (4.4-dimethyl-2,5-dioxo-1-imidazolidin-N-methyl-2-ff4 '- (2-ethoxyethoxy) T 1,1'-bif in i p-4-iHoxMet i 11- N- Hydroxyformate The title compost was prepared according to the procedures of Example 23B, except that 4- (4 '- (2-methoxyethoxy) -phenyl) -phenol was replaced in place of 4- (4'-ethoxyphenyl) - phenol.1H NMR (DMSO-d6) d 1.26 (s, 6H), 3.33 (s, 3H), 3.50-3.64 (m, 1H), 3.66-3.60 (m, 2H), 3.70-3.81 (m, 1H) , 4.03-4.22 (m, 4H), 4.35-4.48 (m 0.5H), 4.78-4.00 (M, 0.5H), 6.08 (dd, 4H, J = 3.9 Hz), 7.55 (dd, 4H. J = 3.6 Hz), 7.91 (s, 0.5H), 8.33 (d, 1H, J = 7 Hz), 8.40 (s, 0.5H), 9.55 (s, 0.5H), 9.86 (s 0.5H) ,) MS (ESI-) 470 (M-1) Anal Caled for: C24H29N3O7 C, 61.13; H, 6.19; N. 8.91 Found: C, 60. 86; H, 6.41; N, 8.65.

EXAMPLE 98 Nf 1 -T (4,4-di-methyl-2, 5-di oxo-1-imidazo I idyl) metip-2 - [(4'-propoxy [1, 1'-bif in i ll-4-i I) oxy1et ill- N-hydroxyformamide The title compound was prepared according to the procedures of Example 23B, except that 4- (4'-propyloxyphenyl) -phenol was substituted instead of 4. - (4'-ethoxyphenyl) -phenol.

Cale, for C24H29N306: C, 63.28; H, 6.42; N, 0.22. Found: C, 63.25; H, 6.48; N, 0.20. Spec. mass (ESI): +456 (m + 1), +473 (m + 18), -454 (m-1), -400 (m + 35) 1 H NMR (DMSO-d6): 0.90 (3H, t, J = 6 Hz), 1.17 (2.4H, s), 1.20 (3.6H, s), 1.65 (2H, sextuple, J = 6 Hz), 3.46-3.55 (1H, m), 3.59-3.74 (1H , m), 3.86 (2H, t, J = 6 Hz), 3.96- 4.06 (1H, m), 4.06-4.14 (1H, m), 4.08-4.38 (0.6H, m), 4.72-4.81 (0.4H , m), 6.88 (4H, d, J = 4.8 Hz), 7.42, (2H, d, J = 4.8 Hz), 7.44 (2H, d, J = 4.8 Hz), 7.83 (0.4H, s), 8.24 (1H, s), 8.28 (0.6H, s), 0.43 (0.6H, s), 0.74 (0.4H, s). 13C NMR (DMSO-d6): 10.4, 22.0, 24.4, 24.5, 36.0, 36.4, 52.1, 56.1, 57.8, 57.0, 64.7, 65.0, 60.0, 114.8, 115.0, 127.2, 132.0, 132.8, 132.0, 155.0, 155.2, 157.0, 157. 1, 157.0, 158.2, 163.1, 177.2, 177.3.

Example 99 N-f1 -f (4,4-dimeti-2,5-dioxo-1-ylazidazol din) metin-2-f (4'-pentyloxy f 1,1'-bifeni p-4 -il) oxy-ethyl-N-hydroxyl ormamide The compound of the compound was prepared according to the procedures of Example 23B, except that 4- (4'-pentyl! oxyphenyl) -phenol was substituted, instead of 4- (4'-). ethoxy phenyl) -phenol. 1 H NMR (300 MHz, DMSO-d 6) d 0.00 (t, 3 H, 3 = 6.0 Hz), 1.27 (s, 6 H), 1.3-1.5 (m, 4 H), 1.7-1.8 (m, 2 H), 3.5- 3.8 (m 2H), 3.08 (t, 2H, 1 = 6.9 Hz), 4.0-4.2 (m, 2H), 4.35-4.45 (m, 0.5H), 4.8-4.9 (m, 0.5H), 6.0- 7.0 (m, 4H), 7.5- 7.6 (m.4H), 7.02 (s, 0.5H), 8.3-8.4 (m, 1.5H), 0.53 (s, 0.5H), 0.84 (s, 0.5H). MS (ESI) 484 (M + H), 501 (M + NH 4).

Anal, caled for C26H33N306: C, 64.57; H, 6.87; N, 8.68. Found: C, 64.27; H, 6.85; N, 8.60. Example 100 N-ri-frf3 '- (cyanomethyl) ri, 1'-biphenin-4-yl-1-sulfoninmethyl-3- (4.4-dimeti-2), 5- dioxo-1-imidazolidinium propyl HN-hydroxyform amide The title compound was made according to the procedures of example 61, but using example 23A instead of example 16B and 4'-thiol-3-cyanomethyl biphenyl instead of 4'-thiol-4-biphenylcarbonitrile in Example 61A. 1H NMR (300 MHz, d6-DMSO) d 9.98 (br, 0.5H), 9.63 (br 0.5H), 8.31 (s, 0.5H), 8.23 (s, 0.5H), 8.12 (s, 0.5 H), 7.99-7.92 (m, 4H), 7.82 (s, 0.5H), 7.74 (m, 2H), 7.57 (t, 1H), 7.46 (d, 1H), 4.52 (m, 0.5H), 4.14 (s, 2H), 4.00 (m, 0.5H), 3.69-3.57 (m, 2H), 342- 3.28 (m.2H), 1.02-1.88 (m, 1H), 1.78-1.64 (m, 1H), 1.21 (s, 6H); MS (ESI) m / e 409 (M + 1) +. Anal, caled for C2 H26N4O6S: c, 57.82; H, 5.26; N, 11.24. Found: C, 57.56; H, 5.41; N, 10.89.

Example 101 Np- [rr4 '- (trifluoromethoxy) ri.1'-bifeniH-4-insulfonillmetip-2- (3,4,4-trimeti- 2, 5-d-oxo-1-imidazolidinyl) ethyl] -N-hydroxyl ormamide The title compound was prepared following the procedures of Example 46, except that Example 16B was replaced by 23A in Example 46A and 4-trifluoromethoxybenzeneboronic acid by 4-butoxybenzeneboronic acid in Example 46B. 1H NMR (300 MHz, d6-DMSO) d 9.72 (br, 0.5H), 9.56 (br, 0.5H), 8.10 (s, 0. 5H), 7.00 (m, 4H), 7.04-7.88 (m, 2H), 7.74 (s, 0.5H), 7.53 (d, 2H), 4.01 (m, 0.5H), 4.54 (m, 0.5H), 3.75-3.44 (m, 4H), 2.75 (s, 3H), 1.24-1.22 (m, 6H); MS (ESI) m / e 544 (M + 1) +. Anal, caled for C23H24F3N3? 7S: C, 50.83; H, 4.45; N, 7.73. Found: C, 51.17; H, 4.77; N, 7.29.

Example 102 Np-ff (4, -cianop, 1'-biphenylyl-4-iPsulfoninmetill-2- (3-methyl-2,5-dioxo-1-imidazolidiniPetiH-N-hydroxyform amide The title compound was made according to The procedures of Example 61, but using Example 26A instead of Example 16B in Example 61A, 1H NMR (300 MHz, d6-DMSO) d 9.83 (s, 0.5H), 0.58 (s, 0.5H), 8.00 ( s, 0.5H), 8.04-8.00 (m, 8H), 7.80 (s, 0.5H), 4.94-4.85 (m, 0.5H), 4.52-4.43 (m, 0.5H), 3.01-3.88 (m, 2H) ), 3.78-3.44 (m, 4H), 2.80 (s, 1.5H), 2.70 (s, 1.5H), MS (ESI) m / e 457 (M + 1) +. Anal, caled for C21H20F4N4O6S: C, 55.26; H, 4.42; N, 12.27, Found: C, 54.99; H, 4.38; N, 12.07.

Example 103 N-ri-rrr3 '- (cyanomethyl) ri, 1'-biphenip-4-msulfonipmetm-2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) etin-N- hydroxyformamide The title compound was prepared following the procedures of Example 46, except that Example 16B was replaced by 23A in Example 46A and 3-cyanomethylbenzeneboronic acid by 4-butoxybenzeneboronic acid in Example 46B. The title compound was made in the usual manner from the a-bromo ketone and 4-bromothiophenol. ? NMR (300 MHz, 4-DMSO) d 0.71 (5.0.5H), 0.56 (5.0.5H), 8. 1 0 (s, 0.5H), 8.03- 7.94 (m, 4H), 7.75 (m, 2.5H ), 7.57 (t, 2H), 7.46 (d, 2H), 4.06-4.88 (m, 0.5H), 4.50-4.49 (m, 0.5H), 4.14 (s, 9H), 3.69-3.48 (m, 4H) ), 2.75 (s, 3H), 1.24 (s, 3H), 1.22 (s, 3H); MS (ESI) n See 409 (M + 1) +. Anal, caled for 024H26N4O6S: C, 57.82; H, 5.26; N, 1 1 .24. Found: C, 57.73; H, 5.36; N, 10.95.

EXAMPLE 104 Np -rf (4'-cyanori. 1 '-bifenin-4-iPoxinmetin-2- (1,6-dihydro-3-methyl-6-oxo-1-pyridaziniPetill-N-hydroxyformamide) The title compound was prepared following the procedures of Example 3C and 3D, except that the potassium salt of 6-methyl-3 (2H) -pydazinone (generated in situ with potassium carbonate) was replaced by potassium phthalimide in Example 3C.1H NMR (300 MHz, CD3OD) d 8.31 (s, 0.5H), 7.01 (s 0.5H), 7.76 (s, 4H), 7.67.64 (d, 2H), 7.38 (dd, 1 H), 7.08 (d.2H) ), 6.04 (dd, 1 H), 5.20-5.1 1 (m, 0.5H), 4.64-4.52 (m, 2H), 4.42-4.32 (m, 2H), 4.27-4.19 (m 0.5H), 9- .35 (s, 1.5H), 1.34 (s, 1.5H), MS (ESI) m / e 405 (M + 1) +, Anal, caled for C22H20N4O4: C, 65.34, H, 4.08, N. 13.85. Found: C, 64.85 H, 5.36; N, 13.44.

Example 105 (+) - N-ri-rr (4'-cyanori, 1'-biphenip-4-yl) sulfoniHmetin-2- (4,4-dimethyl-2,5-dioxo-1-imidazolidiniPetiPN-hydroxyformamide) The compound of the title was made according to the procedures of example 61, but using example 47A instead of example 16B in example 61A.1H NMR (300 MHz, d6-DMSO) d 0.08 (s 0.5H), 0.62 (s) 0.5H). 8.31 (s, 0.5H), 8.22 (5, 0.5H), 8.12 (s, 0.5H), 8.05-7.06 (m, 8H), 7.82 (s.0.5H) .4.5-5- 4.46 (m, 0.5H), 4.07- 3.07 (m, 0.5H), 3.70-3.56 (m, 2H), 3.32-3.24 (m, 2H), 1.02-1.88 (m, 0.5H), 1.76-1.64 ( m, 0.5H), 1.21-1.18 (m, 6H), MS (ESI) m / e 485 (M + 1) +.

Example 106 (+) - N-Ri-rrr4- (4-fluorophenoxy) phenylsulfonipmetin-2- (4,4-dimethyl-2,5-dioxo-1-midazolidinyl) ethy-N-hydroxyformamide The title compound was made according to the procedures of Example 61, but using Example 26A instead of Example 16B and 4- (4'-fluorohenoxp-benzene thiol in 4'-thiol-4-biphenylcarbonitrile in Example 61A. 1H NMR (300 MHz, d6-DMSO) d 9.66 (s, 0.5H), 0.50 (s, 0.5H), 8.30 (s, 0.5H), 8.35 (s, 0.5H), 8.10 (s, 0.5H) , 7.88 (dd, 2H), 7.68 (s, 0.5H), 7.36-7.30 (m, 2H), 7.26-7.20 (m, 2H), 7.15 (d, 2H), 4.88-4.80 (m, 0.5H) , 4.51-4.41 (m, 0.5H), 3.70-3.30 (m, 4H), 1.24-1.22 (m, 6H); MS (ESI) m / e 480 (M + H) +. Anal, caled for C21H22FN307S: C, 52.60; H, 4.62; N, 8.76. Found: C, 52.70; H, 4.57; N, 8.68.

Example 107 N-f1-rf4- (4-pyridinium pfenoxpmetiH-2- (3,4,4-trimethi-2,5-dioxo-1-imidazolidin) -Petin-N-hydroxyformamide The title compound was prepared following the procedures of Examples 16C and 16E, except that 4- (4-pyridinyl) -phenol was replaced in place of 4-bromophenol in Example 16C Pf: 217-218 ° C 1H NMR (DMSO-d6): d.53-0.07 ( c, 1H), 8.55-8.60 (c, 2H), 8.32 (s, 1 / 2H), 7.02 (s, 1 / 2H), 7.77 (s, 1H), 7.75 (s, 1H), 7.65 (s, 1H), 7.64 (s, 1H), 7.01-7.08 (c, 2H), 4.82-4.80 (c, 1 / 2H), 4.30-4.46 (c, 1 / 2H), 4.18-4.25 (c, 1H), 4.08-4.17 (c, 1H), 3.71-3.83 (c, 1H9, 3.57-3.66 (c, 1H), 2.78 (s, 1.5H), 2.77 (s, 1.5H), 1.27 (s, 3H), 1.26 (s, 3H) MS (ESI (+)) 413 (M + H), 435 (M + Na), 847 (2M + Na) Anal, caled for: C21H24N4O5-0.5H2O C, 5T.84; H, 5.08; N, 13.29.

Found: C, 60.18; H, 6.05; N, 13.10.

EXAMPLE 108 (S) -N-Ri-R (4,4-dimethyl-2,5-dioxo-1-yl-idazolidinyl) metill-2-ff4'- (trifluoromethoxpfl, 1'-bif eni p-4-yl] oxy ] et i HNh id roxiformam ida Example 108A (R) 1 - (4- (4 '- (trifluoromethoxypheniPfenoxp-3-benzyloxy-2-propanol) A solution of 4- (4'-trifluoromethoxyphenyl) -phenol (1854 g, 7.3 mmol) and (S) -2- (benzyloxymethyl) -oxirane (1.0 g, 6.1 mmol) in DMF (15 mL) was treated with potassium carbonate (1,007 g, 7.3 mmol), then stirred at 80 ° C overnight. The reaction mixture was allowed to cool to room temperature, was poured into water (100 ml) and extracted twice with ethyl acetate (200 m.times.2) The combined organics were washed with saturated aqueous NH4CI, water, brine, dried (Na2SO4) and concentrated The purification via flash silica chromatography by levigating with 20 to 25% ethyl acetate: hexane gave 2.03 g (80% yield) of 108A as a white solid.

Example 108B A solution of example 1 08A (1505 g, 3.6 mmol), di-Boc hydroxylamine (1,007 g, 4.3 mmol), triphenyl phosphine (1.23 g, 4.7 mmol) in THF (15 ml) treated with diethylazodicarboxylate (0.735 ml, 4.7 mmol) at room temperature, stirred for 1 h, then concentrated. The crude was purified by column chromatography, levigating 100% ethyl acetate: hexane to give 1.16 g (50%) of 1 08B.

Example 1 08C A solution of example 1 08B (248 mg, 0.4 mmol) in THF (3 ml) was hydrogenated (H 2 -globe) overnight in the presence of 23 mg of 10% pd in carbon. The reaction mixture was filtered, concentrated and purified via silica gel column chromatography, levigating with 25% ethyl acetate: hexane to give 180 mg (85%) of the title compound.

Example 108D A solution of example 1 08C (228 mg, 0.42 mmol), 5,5-dimethyl hydantoin (94 mg, 0.73 mmol) and triphenyl phosphine (1 65 mg, 0.63 mmol) in THF (4 ml) was treated with diethylazodicarboxylate (0.1 ml, 0.63 mmol) added in the form of drops via syringe. The resulting light yellow solution was stirred at room temperature for 45 min, concentrated and purified via silica gel column chromatography, levigating with 25% ethyl acetate: hexane to give 1 03 mg (71%) of 08D.

Example 108E (S) -NM-r (4,4-dimethy-2,5-d-oxo-1-yl-idazolidin-Pmethyl-2-rr4'- (trifluoromethoxy) ri, 1'-biphenyl-4-inoxyletin -N-Hydroxyamine A sample of example 108D (11.0 mg, 0.20 mmol) in methylene chloride (3 ml) was treated with TFA (1.5 ml), added dropwise via syringe The reaction was stirred at room temperature for 40 min, then it was concentrated and the residue was partitioned between ethyl acetate and aqueous NaHCO3 The organic extract was washed with brine, dried (Na2SO4) and concentrated to give 1 1 3 mg (86% o) of 108E as a white solid.

Example 108F (S) -NMr (4,4-dithmet-2,5-dioxo-1-imidazolidinyl) methyH-2-rr4'- (trifluoromethoxypropyl, 1'-bif eni ll-4-i lloxil eti 11- N -hydroxyp orme mida The title compound was prepared from 108E following the procedure of Example 2F.MS (ESI) m / e 482 (M + H) +.

Example 100 (R) -N-ri-r (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) metill-2-r4'- (trifluoromethoxy) M, -b-phenyl-4 -Ipoxy-1-ethyl-1-N-hydroxyformamide The title compound was prepared following the procedures of Example 108, except that (R) -2- (benzyloxymethyl) -oxirane was used in place of (S) -2- (benzyloxymethyl) - oxirane. 1H NMR (300 MHz, d6-DMSO) d 0.86 (s, 0.5H), 0.55 (s, 0.5H), 8.30 (s, 0.5H), 8.35 (s, 0.5H), 8.33 (s, 0.5H) , 7.03 (s, 0.5H), 7.76-7.73 (m, 2H), 7.64 (d, 2H), 7.42 (d, 2H), 7.02 (dd, 2H), 4.01-4.80 (m, 0.5H), 4.47 -4.38 (m, 0.5H), 4.23-4.06 (m, 2H), 3.70-3.50 (m, 2H), 1.27 (s, 1.5H), 1.26 (s, 1.5H); MS (ESI) m / e 482 (M + 1) +.

EXAMPLE 110 Nr-rrr4 '- (trifluoromethoxy)) p-1'-biphenyl-4-ylmethyl-3- (4,4-dimethyl-2,5-dioxo-1-imdiazolidinyl) propyn-hydroxyformamide The title compound was prepared according to the procedures of Example 5, except that the methylation step in Example 5B was avoided and substituting 4- (4'-trifluoromethoxyphenyl) phenol for 4'-hydroxy-4-biphenylcarbonitrile in the example 5F. Pf: 197.1-197.9 ° C. * H NMR (300 MHz, d6-DMSO) d 1.27 (s, 6H), 1.70-2.00 (m, 2H), 3.35-3.46 (2H), 3.97-4.16 (m, 2.75H), 4.51 (br s, 0.25 H), 7.00-7.03 (d, 2H, J = 9 Hz), 7.30-7.42 (d, 2H), J =? Hz), 7.60-7.63 (d, 2H, J =? Hz), 7.72-7.75 (d, 2H, J =? Hz), 7.30-7.42 (d, 2H, J =? Hz), 7.60-7.63 (d , 2H, J =? Hz), 7.72-7.75 (d, 2H, J = 9 Hz), 8.25-8.35 (2H), 0.55 (s, 0.75H), 0.05 (br s, 0.25 H), MS (ESI) ) m / e 406 (M + H) +, 518 (m + Na) +, 4T4 (mH) -, 530 (m + CI) -. Anal, caled for C23H24F3N3? 6: C, 55.75; H, 4.88; N, 8.48. Found: C, 55.72; H, 5.07; N, 8.50.

EXAMPLE 111 N- [1- [4 - [(4-pi Ridinylthio) phenoxy] -1-methyl-2- (4,4-di methyl-2, 5-dioxo-1-imidazole id! Ni!) Eti HN- hydroxyl ormamide The title compound was prepared following the procedures of Example 23B, except that it was replaced (prepared by the addition of 4-hydroxythiophenol to 4-chloropyridine) by 4- (4'-butyloxyphenyl) -phenol. 1H NMR (300 MHz, d6-DMSO) d 1258-1.272 (s + s, 6H), 3.402-3.703 (m, 2H), 4.082-4.248 (m, 2H), 4.437 (m, 0.5H), 3.861 ( m, 0.5H), 5.750 (s, 1H), 6.927-6.948 (dd, 2H), J = 1.5, 4.8 Hz), 7.063-7.102 (dd, 2H, J = 3, 8.7 Hz), 7.520-7.557 ( d, 2H, J = 8.4 Hz), 7.030 (s, 0.5H), 8.323-8.343 (dd, 2H, J = 1.2, 4.8 Hz), 8.301 (s, 0.5H), 0.555 (s, 0.5H), 0.866 (s, 0.5H).

MS (ESI) m / e 431 (M + H) +, 453 (m + Na) +, 429 (m-H) -, 465 (m + CI) - EXAMPLE 112 N-1-rrf (4-chlorophenoxy) phen illsulfonipmethen-3- (4,4-d-imethyl-2,5-dioxo-1-imidazolidinopropine-N-hydroxyformamide) The title compound was prepared in accordance to the procedures of Example 61, except that 4- (4'-chlorophenoxy) benzene thiol was replaced by 4'-thiol-4-biphenylcarbonitrile and Example 47A by Example 16B in Example 61A.1H NMR (d6-DMSO) 9.94 (s, 0.5H), 0.58 (s, 0.5H), 8.23 (d, 0.5H, J =? 5 Hz), 8.11 (s, 0.5H), 8.05 (d, 0.5H, J = 0.2 Hz) , 7.80-7.83 (m, 2H), 7.76 (s, 0.5H), 7.54-7.50 (m, 2H), 7.22-7.16 (m, 4H), 4.52-4.41 (m, 0.5H), 4.10-3.02 (m, m, 0.5H), 3.66-3.37 (m, 2H), 3.31-3.24 (m, 3H), 1.06-1.84 (m, 1H), 1.74-1.62 (m, 1H), 1.28-1.21 (m, 6H) MS (ESI) m / e 508 (MH), 510 (m + H), 532 (M + Na).

Example 113 N-ri-rr (4'-cyanofl.1.1"-biphenin-4-iPoxylmetill-2- (1,6-dihydro-6-oxo-1-pyridaziniPetill-N-hydroxyform amide The compound of The title was prepared following the procedures of Example 104, except using pyridazinone instead of 6-methyl-3 (2H) -pyridazinone.1H NMR (d6-DMSO)? (s, 0.5H), 0.64 (s, 0.5 H), 8.28 (s, 0.5H), 7.06-7.83 (m, 5.5H), 7.75-7.71 (m, 2. OH), 7.47-7.41 (m, 1H), 7.07-6.05 (m, 3H), 5.11-5.00 (m, 0.5H), 4.62-4.12 (m, 4.5H).

MS (ESI) m / e 391 (M + H), 413 (M + Na), 389 (M-H). Anal, caled for 021H18F4N4O: C, 63.15; H, 4.79; N, 14.02. Found: C, 63. 33; H, 4.66; N, 13.68.

EXAMPLE 114 N-Ri-rrf4 '- (aminosulfoniPp, 1'-biphenyl) -4-inoxylmetin2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinylPetill-N-hydroxyformamide The title compound was prepared following the procedures of Examples 16C and 16E, except that 4- (4'-sulfonamidaphenyl) -phenol was replaced by 4-bromophenol, Mp 203-205 ° C 1H NMR (DMSO-d6): d 0.88 (bs, 1 / 2H), 0.54 (bs, 1 / 2H), 8.32 (s, 1 / 2H), 7.56-8.01 (c, 5 1 / 2H), 7.34 (s, 1H), 7.00-7.14 (c, 4H) , 4.78-4.07 (c, 1 / 2H), 4.34-4.50 (c, 1 / 2H), 4.06-4.27 (c, 2H), 3.69-3.85 (c, 1H), 3.57-3.68 (c, 1H), 2.78 (s, 3H), 1.17-1.28 (c, 6H) .13C NMR (DMSO-d6): d 176.5, 176.2, 163.1, 158.1, 154.2, 154.1, 128.3, 128.2, 128.0, 127.0, 126.8, 126.2, 115.2 , 64.8, 60.7, 36.7, 36.4, 24.2, 21.4 MS (ESI (+)) 401 (M + H), 508 (M + NH4), 513 (M + Na) Example 115 N-Ri-rrr4 '- (trifluoromethoxy) ri.1'-bifenyl-4-insulfonylmetn-2- (4,4-dimethyl-2,5-dioxo-1-imidazo I idin) l) ethyN-hydroxyformamide The title compound was prepared following the procedures of Example 46, except that 4-trifluoromethoxybenzeneboronic acid was replaced by 4-butyloxybenzeneboronic acid in Example 46B. Mp 195-197 ° C 1 H NMR (DMSO-d 6) d 9.62 (bs, 1H 9, 8.29-8.43 (c, 1H), 8.10 (s, 1 / 2H), 7.05-8.05 (c, 4H), 7.02 (d , 1H, J = 3 Hz), 7.88 (d, 1H, J = 3 Hz), 7.74 (s, 1 / 2H), 7.54 (s, 1H), 7.40 (s, 1H), 4.87-4.00 (c, 1 / 2H), 4.50-4.63 (c, 1 / 2H), 3. 43-3.80 (c, 4H), 1.22 (s, 6H). 13C NMR (DMSO-d6): d 177.2, 1771.1, 162.3, 157.1, 155.0, 154.8, 148.7, 144. 0, 143.0, 138.0, 137.8, 137.5, 120.2, 128.6, 128.4, 127.0, 127.7, 121.5, 118.4, 57.8, 53.3, 53.0, 51.3, 47.5, 38.8, 38.1, 24.31, 24.30. MS (ESI (+)) 530 (M + H), 547 (M + NH 4), 552 (M + Na), 1076 (2M + NH 4), 1081 (2M + Na) HRMS: CALC: 530,120 Found: 530.1193 Anal, caled for C22H22F3N307S C, 49.90; H, 4.19; N, 7.94. Found: C, 49.58; H, 4.10; N, 7.75; F, 11.04; S, 5.96.

Example 116 N-p-f4-r (4-pyridine and loxpfen-sulfonopyrin-N-hydroxy ormamide) Example 116A 4-f4- (methylsulfonyl) phenoxypyridine A mixture of 4-methylsulfonylphenol (2.93 g, 17 mmol) and 4-chloropyridine hydrochloride (2.93 g, 19.5 mmol) was heated to 150 ° C, resulting in a gradual melting, which was stirred at 150 ° C for 4h, then separated between ethyl acetate and 1N NaOH. The organic extract was dried over MgSO4 and concentrated to 1.3 g of a yellow solid. The solid was recrystallized from ethyl acetate-ether, to give 0.81 g of the title compound as a white solid.

Example 116B N- [1- [4 - [(4-pyridinyl-p-phenylsulfonyl-1-ethyl-1-N-hydroxyformamide) The title compound was prepared following the procedures of Example 75, except that Example 116A was replaced by 71B and acetaldehyde by propionaldehyde. 180-181 ° C 1 H NMR (DMSO-d 6): 9.71 (bs, 1H), 8.54 (d, 2H, J = 3 Hz), 8.05 (s, 1 / 2H), 7. 07 (d, 2H, J = 6 Hz), 7.84 (s, 1 / 2H), 7.40 (d, 2H, J = 6 Hz), 7.03-7.13 (c, 2H), 4.63-4.73 (c, 1 / 2H), 4.28-4.39 (c, 1 / 2H), 3.59-3.78 (c, 1H), 3.48 (dd, 1H, J = 3.10.5 Hz), 1.20 (dd, 3H, J = 4.5, 10.5 Hz). 13C NMR (DMSO-d6): d 162.62, 162.61, 161.33, 158.33, 158.31, 156.74, 151. 77, 135.40, 135.13, 130.74, 130.45, 120.56, 120.34, 113.27, 56.50, 49. 59, 45.02, 19.05, 17.71 MS (ESI (+)) 337 (M + H), 359 (M + Na), 391 (M + Na + MeOH), 695 (2M + Na) Anal, caled for C15H16N2O5S.0.5H2O C.52.16; H, 4.06; N, 8.11: S. 9.28. Found: C, 52.32; H, 4.78; N, 7.98; S, 9.45.

Example 117 Nf 1-yl (4-cyanophenoxy) phenylsulfonylmethyl-2- (4,4-d, methyl-2, 5-dioxo-1-imidazolidinium-Petill-N-hydroxyformamide) The title compound was prepared according to the procedures of the example 61, except that 4- (4'-cyanophenoxy) benzene thiol was replaced by 4-thiol-4-biphenylcarbonitrile and Example 23A by Example 16B, in Example 61A.1H NMR (300 MHz, d6-DMSO) d 9.70 (s, 0.5H), 9.50 (s, 0.5H), 8.39 (s, 0.5H), 8.34 (s, 0.5H), 8.10 (s, 0.5H), 7.08-7.01 (m, 4H), 7.68 (s, s, 0.5H), 7.37-7.27 (m, 4H), 4.88-4.77 (m, 0.5H), 4.52-4.41 (m, 0.5H), 3.78-3.30 (m, 4H), 1.24-1.22 (m, 6H); MS (ESI) m / e 487 (M + 1) +. Anal, caled for C22H22N4O7S: C, 54.31; H, 4.56 Found: C, 54.17; H, 4.70.

Example 118 N-f1-ff4-fr4- (trifluoromethoxy) phenoxy1-phenylsulfonylmethane-3- (4,4-dimethyl-2,5-dioxo-1-imidazolidinopropyl-N-hydroxyformamide) The compound of The title was prepared according to the procedures of Example 61, except that 4- (4'-trifluoromethoxyphenoxybenzene thiol was replaced by 4'-thiol-4-biphenylcarbonitrile and Example 47A by Example 16B, in Example 61A.1H NMR ( d6-DMSO) 0.06 (s, 0.5H), 0.60 (s, 0.5H), 8.32 (s, 0.5H), 8.23 (s, 0.5H), 8.11 (s, 0.5H), 7.03-7.86 (m, 2H), 7.75 (s, 0.5H), 7.48 (d, 0.5H, J = 8.8 Hz), 7.25 (dd, 4H, J = 22.8, 8.8 Hz), 4.53-4.42 (m, 0.5H), 4.04- 3.93 (m, 0.5H), 3.65-3.46 (m, 2H), 3.34-3.22 (m, 2H), 2.02-1.62 (m, 2H), 1.26 (s, 3H), 1.23 (s, 3H). (ESI) 560 (M + H), 577 (M + NH 4), 582 (M + Na), 558 (MH).

Anal, caled for C23H2 N308SF3 C, 49.37; H, 4.32; N, 7.51. Found: C, 49.46; H, 4.23; N, 7.47.

Example 119 N-1-ff4-y4- (trifluoromethoxpfenoxpfenipsulfoniHmetip-2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyp-N-hydroxyformamide The title compound was prepared according to the procedures of Example 61, except that 4- (4'-trifluoromethoxyphenoxy) benzene thiol was replaced by 4'-thiol-4-biphenylcarbonitrile in Example 61 A. H NMR (de-DMSO) 9.51 (s, 0.5H) , 0.70 (s, 0.5H), 8.00 (s, 0.5H), 7.01 (dd, 2H, J = 8.0, 3.1 Hz), 7.68 (s, 0.5H), 7.47 (d, 2H, J = 0.2 Hz) , 7.31-7.21 (m, 4H), 4.00-4.78 (m, 0.5H), 4.51-4.40 (m, 0.5H), 3.74-3.40 (m, 4H), 2.76 (d, 3H, J = 1.7 Hz) , 1.27-1.22 (m, 6H), MS (ESI) 558 (MH), 560 (M + H), 577 (M + NH4), 582 (M + Na), Anal, caled for C23H24N308SF3 C, 49.37; , 4.32; N, 7.51, Found: C, 49.41; H, 4.29; N, 7.36.

Claims (15)

1 . A compound of formula (I): or a pharmaceutically acceptable salt or prodrug thereof, wherein A is hydrogen; n is zero; R-] and R3 are independently selected from the group consisting of (1) hydrogen and (2) alkyl of one to six carbon atoms; R2 and R are independently selected from the group consisting of (1) hydrogen; (2) alkyl of one to six carbon atoms; (3) alkenyl of one to six carbon atoms; (4) alkynyl of one to six carbon atoms; (5) alkoxyalkyl; (6) alkoxycarbonylalkyl, wherein the alkylene and alkyl groups are independently from one to six carbon atoms; (7) halogalkyl of one to six carbon atoms; (8) hydroxyalkyl, wherein the alkylene group is from one to six carbon atoms; (9) - (alkylene) -S (O) p-alkyl, wherein the alkylene is from one to six carbon atoms, and the alkyl is from one to six carbon atoms; (10) fenium; (1 1) phenylaoxyalkyl, wherein the alkylene and alkyl groups are independently from one to six carbon atoms; (12) phenylalkyl, wherein the alkylene group is from one to six carbon atoms; (13) phenoxyalkyl, wherein the alkylene group is from one to six carbon atoms; (14) - (alkylene) -N (R5) S02-phenyl, wherein the alkylene is from one to six carbon atoms, and wherein R5 is selected from the group consisting of (a) hydrogen and (b) one to six carbon atoms; (1 5) (heterocycle) oxyalkyl, wherein the alkylene group is from one to six carbon atoms; (16) - (alkylene) -S (0) p-heterocycle, wherein the alkylene group is from one to six carbon atoms; (17) - (alkylene) -heterocycle, wherein the alkylene group is from one to six carbon atoms; and (18) - (alkylene) -NR6R7, wherein the alkylene group is from one to six carbon atoms, wherein for (15) - (17), the heterocycle is selected from the group consisting of (a) pyridyl , (b) pyrazinyl, (c) pyridazinyl, (d) furyl, (e) thienyl, (f) soxazolyl, (g) oxazolyl, (h) thiazolyl and (i) isothiazolyl, and wherein for (10) - (17), phenyl, phenyl parts of phenylalkoxyalkyl, phenylalkyl, - (alkylene) -N (R5) SO-phenyl, phenoxyalkyl, and - (alkylene) -S (O) p-phenyl, and the heterocycle, heterocyclic portions of (heterocycle) oxyalkyl, - (alkylene) -heterocycle and - (alkylene) -S (0) p-heterocycle are optionally substituted with one, two or three substituents independently selected from the group consisting of (a) alkyl of one to six carbon atoms; (b) alkoxy of one to six carbon atoms; (c) alkoxyalkyl, wherein the alkyl group and the alkylene group are independently from one to six carbon atoms; (d) halo; (e) haloalkyl of one to six carbon atoms; (f) hydroxy; (g) hydroxyalkyl of one to six carbon atoms; (h) - (alkylene) -heterocycle, (i) - (alkylene) -phenyl, (j) -N (R5) SO2-alkyl, (k) phenyl, wherein the phenyl is optionally substituted with 1, 2, 3 , 4 or 5 substituents independently selected from the group consisting of (i) cyano, (ii) nitro, and (iii) halo, (I) -C (O) OR 5; and (m) -C (O) NRxRy, wherein Rx and Ry are independently selected from the group consisting of (i) alkyl of one to six carbon atoms, (ii) phenyl and (iii) phenylalkyl, wherein para ( ii) and (iii), the phenyl and the phenyl portion of phenylalkyl are optionally substituted with substituents independently selected from the group consisting of halo and alkoxy of one to six carbon atoms, and wherein for (1 8), R? 6 and R17 are independently selected from the group consisting of (a) hydrogen; (b) alkyl of one to six carbon atoms; (c) cycloalkyl of three to eight carbon atoms; (d) cycloalkylalkyl, wherein the cycloalkyl group is from three to eight carbon atoms, and the alkylene group is from one to ten carbon atoms; (e) alkanoium of one to ten carbon atoms; (f) phenyl and (g) phenylalkyl, wherein the alkylene group is from three to ten carbon atoms, wherein for (f) and (g), the phenyl and phenyl portion of phenylalkyl are optionally substituted with one or two substituents independently selected from the group consisting of (i) alkyl of one to six carbon atoms; (ii) akoxy of one to six carbon atoms; (iii) perfluoroalkyl of one to six carbon atoms; (iv) halo; (v) haloalkion of one to six carbon atoms and (vi) alkanoyl of one to six carbon atoms; or R6 and R7, taken together with the nitrogen atom to which they are attached, define a group selected from the group consisting of (1) morpholinyl; (2) thiomorpholinyl; (3) thiomorpholinyl sulfone; (4) pyrrolidinyl; (5) piperazinyl; (6) piperidinyl; (7) succinimidyl; (8) maleimidyl; (9) glutarimidyl; (10) phthalimidyl; (11) naphthalimidyl; (16) wherein for (1) - (23), the groups defined by R6 and R7, together with the nitrogen atom to which they are attached, are optionally substituted with one or two substituents independently selected from the group consisting of (a) halo, (b) alkyl, (c) alkoxy, (d) phenoxy, (e) phenylalkyl and (f) benzyloxy; or

R1 and R2, taken together with the carbon atom to which they are attached form a ring selected from the group consisting of (1) spiroalkyl of three to eight carbon atoms and (2) tetrahydropyranyl; or R3 and R4, taken together with the carbon atom to which they are attached, form a spiroalkyl group of three to eight carbon atoms; or RT and R3 taken together with the carbon atoms to which they are attached are a carbocyclic ring of 5, 6 or 7 members; X is selected from the group consisting of (1) -O-; (2) -N R5SO2 -, * (3) -S (O) p-; and (4) -C (O) -; where each group is drawn with its end to the left, being the end that joins the alkylene group and its end on the right hand, being the end to which it joins An; Ap is phenyl, which is optionally substituted with one or two substituents independently selected from the group consisting of (a) alkyl of one to six carbon atoms; (b) perfluoroalkyl of one to six carbon atoms; (c) halo; (d) haloalkyl of one to six carbon atoms; (e) alkoxy of one to six carbon atoms; (f) hydroxy; (g) hydroxyalkyl of one to six carbon atoms; (h) alkoxyalkyl, wherein the alkyl and alkyiene groups are independently from one to six carbon atoms; e (i) nitro; Y is selected from the group consisting of (1) a covalent bond, (2) -O-, (3) alkylene of two to four carbon atoms, (4) piperidinyl, (5) alkylene of two carbon atoms, ( 6) alkynylene of two carbon atoms, (7) -S (O) p- and (8) -C (O) -; and Ar2 is an aryl group selected from the group consisting of (1) phenyl; (2) pyridyl; (3) pyrazinyl; (4) pyridazinyl; (5) fuplo; (6) thienyl; (7) isoxazolyl; (8) oxazolyl; (9) thiazolyl e (10) isothiazolyl, wherein the aryl group is optionally substituted with one, two or three substituents independently selected from the group consisting of (a) alkyl of one to six carbon atoms; (b) alkoxy of one to six carbon atoms; (c) alkoxy of one to six carbon atoms substituted with alkoxy of one to six carbon atoms; (d) -alkyl-CO2R5; (e) -alkyl-NRxRy; (f) alkoxyalkyl, wherein the alkyl group is from one to six carbon atoms, and the alkylene group is from one to six carbon atoms; (g) cyano; (h) cyanoalkyl of one to six carbon atoms; (i) halo; (j) haloalkyl of one to six carbon atoms; (k) hydroxy; (I) hydroxyalkyl of one to six carbon atoms; (m) hydroxyalkyl, wherein the alkyl group is from one to six carbon atoms; (n) thioalkoxy of one to six carbon atoms; (o) thioalkoxyalkyl, wherein the alkyl group is from one to six carbon atoms, and the alkylene group is from one to six carbon atoms; (p) phenylalkoxy, wherein the alkylene group is from one to six carbon atoms; (q) phenoxy; (r) phenoxyalkyl, wherein the alkylene group is from one to six carbon atoms; (s) (heterocycle) oxy; (t) (heterocycle) oxyalkyl, wherein the alkylene group is from one to six carbon atoms; (u) perfluoroalkyl of one to six carbon atoms; (v) perfluoroalkoxy, wherein the perfluoroalkyl part is from one to six carbon atoms; (w) sulfonylalkyl, wherein the alkyl part is from one to six carbon atoms; (x) sulfonylalkyl, wherein the alkyl part is from one to six carbon atoms;

And (y) | - Or where X is selected from -CH2-, -CH2O- and -O-, and Y is selected from -C (O) - and - (C (R ") 2) V-, where R" is hydrogen or alkyl from one to four carbons, and v is 1 -3; (z) -N (R5) S02R5 ', wherein R5 is as previously defined and R5. is selected from the group consisting of (i) hydrogen and (i) alkyl of one to six carbon atoms; and (aa) -S02N (R5) (R5 <). where for (s) and (t), the heterocycle part of (heterocycle) oxy and (heterocycle) oxyalkyl are selected from the group consisting of (i) pyridyl; (ii) pyrazinyl; (iii) pyridazinyl; (iv) furyl; (v) thienyl; (vi) isoxazolyl; (vii) oxazolyl; (vii) thiazolyl and (ix) isothiazolyl, and wherein for (s) and (t), the heterocycle part of (heterocycle) oxy and (heterocycle) oxyalkyl are optionally substituted with one or two substituents independently selected from the group consisting of (i) alkyl of one to six carbon atoms; (ii) alkoxy of one to six carbon atoms; (iii) perfluoroalkyl of one to six carbon atoms; (iv) halo; (v) cyano; (vi) cyanoalkyl; (vii) haloalkyl of one to six carbon atoms, and (vii) alkanoyl of one to six carbon atoms, and wherein for (q) and (r), the phenyl part of phenoxy and phenoxyalkyl are optionally substituted with one or two substituents independently selected from the group consisting of (i) alkyl of one to six carbon atoms; (ii) alkoxy of one to six carbon atoms; (Ii) perfluoroalkyl of one to six carbon atoms; (iv) halo; (v) cyano; (vi) cyanoalkyl; (vi) haloalkyl of one to six carbon atoms and (viii) alkanoyl of one to six carbon atoms. 2. A compound according to claim 1, wherein A is hydrogen; Ri, R3 and R4 are independently selected from hydrogen or alkyl of one to six carbon atoms; X is selected from the group consisting of (D -O-, (2) -S (0) p-, and (3) -NR5S02-, and ART is phenyl, which is optionally substituted 3. A compound according to to claim 2, wherein R2 is alkyl of one to six carbon atoms

4. A compound according to claim 3 selected from the group consisting of (±) -N- [1 - [[[3 '- ( cyanomethyl) - [1,1'-biphenyl] -4-yl] oxy] methyl] pentyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'- biphenyl] -4-yl) oxy] methyl] -3-methylbutyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl] ) oxy] methyl] -2-methylbutyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] pentyl ] -N-hydroxyformamide; (+) - N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methylene] ethyl] -N-h idroxyformamide; (±) -N- [2 - [(4'-cyano [1,1'-biphenyl] -4-yl) oxy] -1-methylpropyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-methoxy [1,1] -biphenyl] -4-yl) sulfonyl] methyl] ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-chloro [1,1'-biphenyl] -4-yl) sulfonyl] methyl] ethyl] -N-hydroxyformamide; (±) -N- [1 - [[[4- (1,3-benzodioxol-5-yl) phenyl] sulfonyl] methyl] ethyl] -N-hydroxyformamide; (±) -N- [1 - [[[4- (4-chlorophenoxy) phenyl] sulfonyl] methyl] ethyl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-methoxy] [1,1'-b-phenyl] -4-yl) sulfonyl] methyl] propyl] -N-hydroxyformamide; (±) -N- [1- [1,1-Dimethyl-2 - [(4'-trifluoromethyl) [1,1'-biphenyl] -4-yl] sulfonyl] ethyl] -N-hydroxyformamide; and N- [1- [4 - [(4-pyridinyloxy) phenyl] sulfonyl]] ethyl] -N-hydroxyformamide.

5. A compound according to claim 2, wherein R2 is hydrogen.

6. A compound according to claim 5, which is N- [2 - [(4'-cyano- [1, 1'-bif eni I] -4-i I) oxy jet] -N-hydroxyl orma Measure

7. A compound according to claim 2, wherein R2 is selected from the group consisting of (1) phenyl, wherein the phenyl group is substituted or unsubstituted; (2) phenoxyalkyo, wherein the alkylene group is from one to six carbon atoms, and wherein the phenyl group is substituted or unsubstituted; (3) - (alkylene) -S (O) p-phenyl, wherein the alkylene group is from one to six carbon atoms, p is zero, and the phenyl group is substituted or unsubstituted; (4) - (alkylene) -S (0) p-alkyl; (5) hydroxyalkyl, wherein the alkylene group is from one to six carbon atoms; (6) - (alkylene) -N (R5) S? 2-phenyl, wherein the alkylene is from one to six carbon atoms, the phenyl group is substituted or unsubstituted; and R5 is selected from the group consisting of (a) hydrogen and (b) alkyl of one to six carbon atoms; (7) phenylalkoxyalkyl, wherein the alkylene and alkyl groups are independently from one to six carbon atoms and the phenyl group is substituted or unsubstituted; (8) - (alkylene) -heterocycle, wherein the heterocycle is substituted or unsubstituted; (9) (heterocycle) oxyalkyl, wherein the alkylene group is from one to six carbon atoms and the heterocycle is substituted or unsubstituted, and (10) - (alkylene) -phenyl, wherein the phenyl group is substituted or unsubstituted.

8. A compound according to claim 7, selected from the group consisting of (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] - 2-phenoxyethyl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-cyano-1 [1,1'-biphenyl] -yl) oxy] methyl-2- (phenylthio) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenl] -4-yl) oxy] methyl] -2- (4-methylphenyl) ethyl] -N-hydroxyformamide; (±) -N- [2 - [(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] -1- (4-fluorophenyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4-fluorophenyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(3'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- [methyl [(4-methylphenyl) sulfonyl] amino] ethyl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -yl) oxy] methyl] -2 - [[(2-methoxycarbonyl) f enyl] thio] ethyl] -Nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -5 - [(4-methyl-2-oxo-2H-1- benzopi ran-6-i I) oxy] pent il] -Nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -4 - [(4-methyl-2-oxo-2H-1- benzo pira n-6-i I) oxy] butyl] -Nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -4 - [(4-methyl-2-oxo-2H-1- be nzo pira n-7-i I) oxy] butyl] -Nh'drox¡f orma mida; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -5 - [(4-methyl-2-oxo-2H-1- benzopi ran-7-I) oxy] penti l] -Nh id roxiformam da;

(±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2-isopropylthioethyl] -N-hydroxyformamide; (+) - N- [1 - [(phenylmethoxy) methyl] -2 - [[4 '- (trifluoromethyl) [1,1'-biphenyl] -4-yl] su If on il] et il] -Nh id roxiformam ida; (±) -N- [1- (hydroxymethyl) -2 - [[(4 '- (trifluoromethyl) [1,1'-biphenyl] -4-yl] sulfonyl] ethyl] -N-hydroxyformamide; (±) - N- [1 - [[(4'-meth] l [1,1'-biphenyl] -4-ii) oxy] methyl] -2 - [[3- (methylsulfonyl) -am]] in il] et il] -Nh id roxiformam ida; (±) -N- [1 - [[[3-8-diethylamino) carbonyl] phenyl] methyl] -2 - [(4'-methyl [1,1'-biphenyl] -4- il) oxy] et il] -Nh id roxiformam ida; N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2 - [(4'-cyano [1,1'-biphenyl] -4-i I) oxy] ethyl] -N-hydroxy-ormamide; N- [1 - [[(4'-cyano [1,1'-biphenyl) -4-yl) oxy] methyl] -2- (1,6-dihydro-3-methyl-6-oxo-1-pi) ridazin il) ethyl] -Nh id roxiformam ida; and N- [1 - [[(4'-cyano [1,1"-biphenyl] -4-yl) oxyl] methyl] -2- (1,6-dihydro-6-oxo-1-pi ridazin il) ethyl] -Nh id roxiformam ida 9. A compound according to claim 2, wherein R2 is - (alkylene) -NR6R7

10. A compound according to claim 9, wherein -NR6R7 is

11. A compound according to claim 10, selected from the group consisting of (+) - N- [1 - [[(4'-butoxy [1,1'-biphenyl] -4-yl) oxy] methyl] -2- ( 4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [(4'-ethoxy [1,1'-b] phenyl] -4 -yl) oxy] etl] -N-hydroxyformamide; (±) -N- [1 - [[4- (1,3-benzodioxol-5-yl) phenoxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifluoromethoxy) [1,1'-bifeni] - 4-yl] oxy] ethyl] -Nh id roxiformam ida; (±) -N- [1 - [(4,4-Dimethyl-2,5-dioxo-1-imidazolidinyl) met!] -2 - [[4 '- (trifluoromethyl) [1,1'-biphenyl] 4-yl] oxy] ethyl] -N-hydroxyformamide; (+) - N- [1 - [[[3 '- (Cyanomethyl) [1,1'-biphenyl] -4-yl] oxy] methyl] -3- (4,4-dimethyl-2,5-dioxo -1-imidazolidinyl) propyl]] - N-hydroxyformamide; (±) -N- [1 - [[(4'-Butoxy [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo- 1 -imidazolidinyl) ethyl] -N-hydroxyl ormamide; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -3- (4,4-dimethyl-2,5-dioxo-1 -imidazolidinyl) propyl] -N-hydroxyformamide; (+) - N- [1 - [[[4 '- (methylsulfonyl) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo -1-imidazolidinyl) ethyl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1 -imidazolidinyl) ethyl] -N-hydroxyformamide; (+) - N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trif I uoromethyl) [1,1'-biphenyl] -4-yl] thio] ethyl] -N-hyd roxiformam ida; (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (t rif I uo rom eti l) [1, 1 '-bif en il] -4-yl] sulf onyl] eti l] -Nh id roxiformam ida, (±) -N- [1 - [[[4- (4-chlorophenoxy) phenyl] sulfonyl] methyl] -2 - (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyform amide, (±) -N- [1 - [[(4'-butyl [1,1'-biphenyl]] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[[3, - (Cyanomethyl) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-imidazolidinyl) ) ethyl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1 -imidazolidinyl) ethyl] -N-hydroxyform amide; (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4 '- (2-methoxyethoxy) [1,1'-biphenyl] -4-yl] oxy] ethyl] -N-hydroxyformamide; (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [(4'-propoxy [1,1'-bif in]] - 4-yl) oxy] and il] -Nh id roxiformam ida; N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [(4'-pentyloxy [1,1'-b ife nor l] -4- i I) oxy] ethyl] -N-hydroxyformamide; (±) -N- [1 - [[[3 '- (Cyanomethyl) [1,1'-biphenyl] -4-yl] sulfonyl] methyl] -3- (4,4-dimethyl-2,5-dioxo -1-imidazole id inyl) propyl] -N-hydroxy ormamide; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo - 1-imidazole id inyl) ethyl] -N-hydroxyformamide; (+) - N- [1 - [[[4- (4-fluorophenoxy) phenyl] sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-im-dazolyl) ethyl) ethyl ] -N-hydroxyformam ida; (S) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-ylamdazolidinyl) methyl] -2 - [[4'- (trifluoromethoxy) [1,1 '-bif en il] -4-yl] oxy] ethyl] -N-hydroxyf ormamide; (R) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trif) uoromethoxy) [1 , 1 '-bif in yl] -4-yl] oxy] ethyl] -N-hydroxy-ormamide; N- [1 - [[[4 '- (tr'fluoromethoxy)] [1,1'-biphenyl] -4-yl] oxy] methyl] -3- (4,4-dimethyl-2,5-dioxo) -1-imidazolidinyl) propyl] -N-hydroxyformamide; N- [1- [4 - [(4-pyridinylthio) f-enoxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxy-ormamide; N- [1 - [[[(chlorofenoxy) phenyl] sulfonyl] methyl] -3- (4,4-di methyl-2, 5-dioxo-1 -im id azo I id in il) pro pil] -N -hydroxyformamide; N- [1 - [[[4 '- (trifluoromethoxy) [1,1'-biphenyl] -4-yl] sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ) ethyl] -N-hydroxyform amide; N- [1 - [[[(4-cyanophenoxy) f eni IJsulfonyl I] methyl] -2- (4,4-di methyl-2,5-di oxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; and N- [1 - [[4 - [[4- (trifluoromethoxy) phenoxy] phenyl] sulfonyl] methyl] -3- (4,4-dimethyl-2,5-d-oxo-1 -im- d azo I id ¡ni I) propi lNh id roxiformam da.

12. A compound according to claim 9 selected from the group consisting of (±) -N- [1 - [[(4'-cyano- [1,1'-b-phenyl] -4-yl) oxy] methylene] -2- (2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl) ethyl] -Nh'droxif ormamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2, 5-dioxoimidazolidin-1-yl) etl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -3- (3,4,4-trimethyl-2) , 5-dioxo im a dd Izo di n I-1 -i I) propi l] -Nh id roxiformam ida; (±) -N- [1- [4 - [(2-E-phenylethyl) phenoxy] methyl] -2- (3,4,4-tr'met-I-2,5-dioxo-1-imidazolidinyl) ethyl] -Nh id roxiformam ida; (±) -N- [1 - [[4- (2-furanyl) phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-Butoxy [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo -1-im id azol din il) et il] -Nh id roxiformam ida; (+) - N- [1 - [[(4'-Fluoro [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo -1-im id azo I id i nil) eti l] -Nh id roxiformam ida; (±) -N- [1 - [(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifiuoromethyl) [1, 1'-biphenol] ] -4-i I] oxy] ethyl] -Nh id roxiformam ida; (±) -N- [1 - [[(4'-methoxy [1,1'-biphenyl] -yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1 -imidazole id inyl) ethyl] -N-hydroxy ormamide; (±) -N- [1 - [[(4'-methyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo -1-im id azo I id ini l) ethyl] -N-hydroxy ormamide; (±) -N- [1 - [[(4'-Butoxy [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3-methyl-2,5-dioxo-1-imidazolidinyl) ) ethyl] -N-hydroxy ormamide; (±) -N- [1 - [[4- (3-thienyl) phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[([1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ) ethyl] -N-hydroxy ormamide; (+) - N- [1 - [[(3'-chloro-4'-fluoro [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl- 2,5-dioxo-1-imidazolidinii) ethyl] -N-hydroxyformamide; (+) - N- [1 - [[(2'-methyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo -1-imidazole id inyl) ethyl] -N-hydroxyformam ida; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxy ormamide; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (1,1-dioxido-3-oxo-1,2) -benzisothiazol-2 (3 H) -yl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[4- (4-phenyl-1-piperidinyl) phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- [4,4-dimethyl-2,5-dioxo-3 - (3-pyridinylmethyl) -1-imidazole id ini l] ethyl] -N-hydroxyl ormamide; (+) - N- [1 - [[(3'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo -1-im id azol id inil) eti l] -Nh id roxiformam ida; (±) -N- [1 - [[[4 '- (methylthio) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (3,4,4-trimethyl-2,5 -dioxo-1-imidazolidinyl) ethyl] -N-hydroxyl ormamide; (±) -N- [1- [4 - [[4- (trifluoromethyl) phenoxy] phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] - N-hydroxy ormamide; (±) -N- [1 - [[[4 '- (trifluoromethoxy) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (3,4,4-trimeti-2, 5 -d-oxo-1-imidazole id inyl) ethyl] -2-N-hydroxyformamide; (±) -N- [1 - [[[4 '- (methylsulfonyl) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (3,4,4-trimeti-2) , 5-dioxo-1-imidazolidinyl) ethyl] -Nh idroxif ormamide; (±) -N- [1 - [[[3 '- (Cyanomethyl) -4'-methoxy [1,1'-biphenyl] -4-yl] oxy] meth] -2- (3, 4,4-trimethyl-2,5-dioxo-1-imidazole id inyl) ethyl] -Nh idroxif ormamide; (+) - N- [1 - [[(3'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (2,5-dioxo-1-pyrrolidinyl) ethyl] - N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,6-dioxo-1 -pi pendí nil) et i I] - N-hydroxyformamide; N- [1 S - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (2,5-dioxo-1-pyrrolidinyl) ethyl] -Nh id roxiformam ida; N- [1R - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (2,5-dioxo-1-pyrrolidinyl) etl] - Nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3-ethyl-3-methyl-2,5-dioxo -1-pi rro I idinil) ethyl] -Nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (5,5-dimethyl-2,4-dioxo-3 -oxazolidinyl) ethyl] -N-hydroxyform amide; (±) -N- [1 [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (3,4,4-trimethyl-2,5-dioxo- 1-imidazolidinyl) ethyl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3-methyl-2,5-dioxo-1-imidazole id inil) ethyl] -Nh idroxif ormamide; (+) - N- [1 - [[(4'-chloro- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5- dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[3'-Cyanomethyl- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,5,5-trimethyl-2,4-dioxo -1-imidazolidinyl) propyl] -N-hydroxyformamide; (+) - N- [1 - [[(3'-Cyanomethyl- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5- d oxo- 1 -im idazole id i nil) et il] -Nh id roxiformam ida; (+) - N- [1 - [[(4'-cyano- [1,1'-b-phenyl] -4-yl) oxy] meth] -2- (3-ethyl-4.4 -d-methyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyform amide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3-benzyl-4,4-dimethyl- 2,5-dioxo-1-imidazolidinyl) ethyl] -Nh idroxif ormamide; (+) - N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-i) oxy] methyl] -2- (3,5,5-trimethyl-2,4- dioxo-1-imidazole idin il) ethyl] -Nh idroxif ormamide; (±) -N- [1 - [(2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4 '- (trifluoromethoxy) [1,1'-biphen-yl] -4-yl] oxy] ethyl] -Nh id roxiformam id a, (±) -N- [1 - [[[4 '- (trifluoromethyl) [1,1'-biphenyl] -4-yl] sulfonyl] methyl] -2- (3, 4,4-trimethyl-2, 5-dioxo-1-imidazolidinyl) ethyl] -Nh idroxif ormamide; (±) -N- [1 - [[(4'-Butyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3-methyl-2,5-dioxo-1-imidazolidinyl) ) ethyl] -N-hydroxyformamide; (+) - N- [1 - [(3-methyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifluoromethoxy) [1,1'-biphenyl] -4-yl ] oxy] ethyl] -N-hydroxyformamide; (±) -N- [1 - [[[4- (4-chlorophenoxy) pheny] sulfonyl] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-im id azo I id i nil) eti l] -Nh id roxiformam ida; (±) -N- [1 - [[(4-Butyl [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (3,4,4-trimethyl-2,5-dioxo- 1-imidazole idinyl) ethyl] -N-hydroxyl ormamide; (±) -N- [1- [4- (2-thienyl) phenoxy] methyl] -2- [1- (3,4,4-trimethyl-2,5-dioxo-1-imidazole id inyl) ethyl] -N-hydroxy ormamide; (±) -N- [1 - [[(3-nitro [1,1, -biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimetii-2,5-dioxo- 1-imidazolidinyl) ethyl] -Nh idroxif orm amide; (±) -N- [1 - [[[4 '- (trifluoromethoxy) [1,1'-biphenyl] -4-yl] sulfonyl] methyl] -2- (3,4,4-trimeti-2, 5 -d-oxo-1-imidazole id inyl) etl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (3-methyl-2,5-dioxo-1-imidazole Id inil) ethyl] -Nh id roxiformam da; (+) - N- [1 - [[[3 '- (cyanomethyl] [1,1'-biphenl] -4-yl] sulfonyl] meth] -2- (3, 4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[4- (4-pyridinyl) phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-ylazolidinyl) ethyl] -N- hydroxyformamide; N- [1 - [[[4 '- (aminosulfonyl) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1 -imidazolidinyl) ethyl] -N-hydroxyformamide; and N- [1 - [[4 - [[4- (trifluoromethoxy) phenoxy] phenyl] sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) etii] -N- hydroxyl ormamide.

13. A compound according to claim 1, wherein R2 and R2, taken together with the carbon atom to which they are attached, form a ring selected from (1) spiroalkyl of three to eight carbon atoms and (2) tetrahydropyranyl.

14. A compound according to claim 13, selected from the group consisting of N- [4- [4 - [[(4-chlorophenoxy) phenyl] suifonyl] methyl] tetrahydro-2H-pyran-4-yl] -N -hydroxyformamide and N- [4- [4 - [(4'-chloro [1,1'-biphenyl] -4-yl) sulfonyl] methyl] tetrahydro-2H-pyran-4-yl] -N-hydroxyformamide.

15. A compound selected from the group consisting of (+) - N- [1 - [[(4'-cyano- [1,1'-biphenl] -4-yl) oxy] methyl] -2- phenoxyethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (phenyl) ethyl] -N-h id roxiformam id a; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (2,3-dihydro-1,3-dioxo- 1H-isoindol-2-yl) and 11] -N-hydroxy-ormamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5- d ioxo imidazo lid i n-1 -il) et il] -nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -3- (3,4,4-trimethyl-2,5- dioxo im id azo lidi n- 1-il) prop il] -Nh id roxiformam ida; (+) - N- [1 - [[[3 '- (Cyanomethyl) - [1,1'-biphenyl] -4-yl] oxy] methyl] pentyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-ii) oxy] methyl] -3-methylbutyl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-Cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2-methylbutyl] -N-h idroxyformamide; (±) -N- [1 - [[(4'-cyano- [1, 1'-biphenyl] -4-yl) oxy] methyl] pentyl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-Cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4-methylphenyl) ethyl] -N -hydroxyformamide; (±) -N- [2 - [(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] -1- (4-fluorophenyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4-fluorophenyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1, 1'-bifeni I] -4-I) oxy] meti Ijeti IJ-N-h id roxiformam id a; (±) -N- [2 - [(4'-cyano- [1,1'-bif enyl] -4- yl) oxy] ethyl] -N-h idroxyformamide; (±) -N- [1- [4 - [(2E-phenylethenyl) phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazole dinyl) ethyl] - N-hydroxyformamide; (+) - N- [1 - [[4- (furanyl) phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl] -N-hydroxyformamide Da; (±) -N- [1 - [[(4'-butoxy [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2, 5-dioxo-1-im id azo I id ini I) eti l] -Nh id roxiformam da; (+) - N- [1 - [[(4'-fluoro [1,1'-biphenyl] -4 -l) oxy] methyl] -2- (3,4,4-trimethyl-2,5-d-oxo-1-imidazolidinyl) etl] -N-hydroxyformamide; ) -N- [1 - [(3,4,4-Tr'methyl-2,5-d-oxo-1-amidazolidinyl) methyl] -2 - [[4'- (trifluoromethyl) [ 1,1 '-bif in yl] -4-yl] oxy] ethyl] -N-hydroxy-ormamide; (±) -N - [[1 - [[(4'-methoxy [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5- dioxo-1-imidazolidinyl) ethyl] -Nh idroxif ormamide; (±) -N- [1 - [[(4'-methyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo -1-im id azol idin il) ethyl] -Nh id roxiformam ida; (+) - N- [1 - [[(4'-Butoxy [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1 -imidazol idin il) ethyl] -Nh idroxif ormamide; (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyI] -2 - [(4'-ethoxy [1,1'-biphenyl]] -4-ii) oxy] ethyl] -N-hydroxy ormamide; (±) -N- [1 - [[4- (1,3-benzodioxol-5-yl) f-enoxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-im id azo I id i nil) eti l] -Nh id roxiformam id a; (+) - N- [1 - [[(4'-Butoxy [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3-methyl-2,5-dioxo-1-im) id azolid i nil) et il] -Nh id roxiformam ida; (±) -N- [1 - [[4- (3-thienyl) phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolindinyl) etl] -N -hydroxyformamide; (+) - N- [1 - [[([1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ) ethyl] -N-hydroxyform amide; (±) -N- [1 - [[(3'-chloro-4'-fluoro [1,1'-biphenyl] -4-ipoxy] methyl] -2- (3,4,4-trimethyl-2, 5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(2'-methyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2 - (3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxy-ormamide; (+) - N- [1 - [[(4'-cyanol [1,1'- biphenyl] -4-yl) oxy] methyl] -2- (2,5-dioxo-1-im id azol id ini I) eti l] -Nh id roxiformam ida; (±) -N- [1 - [[ (4'-cyanol [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (1,1-dioxido-3-oxo-1,2-benzisotro-azo 1-2 (3 H) -i 1) eti I] - N-hydroxyformamide; +) - N - [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'-trifluoromethoxy) [1,1'-biphenyl] -4-yl ] oxy] ethyl] -N-hydroxyformamide; ±) -N- [1 - [[4- (4-phenyl-1-piperidinyl) phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-midazolidinyl) ethyl] - N-hydroxyformamide; +) - N - [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'-trifluoromethyl] [1,1, -biphenyl] -4-yl ] oxy] etl] -N-hydroxy ormamide; ±) -N- [1 - [[(3'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- [methyl [(4-methylphenyl) sulfonyl] amino] ethyl] - N-hydroxyformamide; ±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- [4,4-dimethyl-2,5-dioxo-3- (3-pyridinylmethyl) -1-imidazolidinyl] ethyl] -Nh idroxif ormamide; ±) -N- [2 - [(4'-cyano [1,1'-biphen-yl] -4-yl) oxy] -1-methy1propyl] -N-h id roxiformam ida; ±) -N- [1 - [[(3'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo- 1-midazolidinyl) ethyl] -N-hydroxyformamide; +) - N- [1 - [[[4 '- (methylthio) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (3,4,4-trimetii-2,5- dioxo-imidazolidinyl) etl] -N-hydroxyformamide; ±) -N- [1- [4 - [[4- (trifluoromethyl) phenoxy] phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo--imidazolidinyl) ethyl] -Nh idroxif ormamide; ±) -N- [1 - [[[4 '- (trifluoromethoxy) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (3,4,4-trimethyl-J, 5 -di oxo-1-imidazo I id inyl) ethyl] -2-N-hydroxyformamide; ±) -N- [1 - [[[4 '- (methylsulfonyl) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (3,4,4-trimet-2,5) -lioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; +) - N- [1 - [[[3 '- (Cyanomethyl) -4'-methoxy [1,1'-biphenyl] -4-yl] oxy] meth] -2- (3,4,4 -rimeti-2,5-dioxo-1-imidazolidinyl) ethyl] -Nh idroxif ormamide; (±) -N- [1 - [[[3 '- (Cyanomethyl) [1,1'-biphenyl] -4-yl] oxy] methyl] -3- (4,4-dimethyl-2,5-dioxo -1-imidazolidinyl) propyl]] - N-hydroxyformamide; (±) -N- [1 - [[(4'-Butoxy [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo- 1 -imidazolidinyl) etl] -N-hydroxyl ormamide; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -3- (4,4-dimethyl-2,5-dioxo-1 -imidazole id inyl) propyl] -Nh idroxif ormamide; (±) -N- [1 - [[[4 '- (methylsulfonyl) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo -1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(3'-cyano [1,1'-b-phenyl] -4-yl) oxy] methyl] -2- (2,5-dioxo-1-pyrrolidinyl) ethyl ] -N-hydroxy ormamide; (±) -N- [1 - [[(4'-cyano [1,1'-bifenii] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,6-dioxo-1 -piperidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1S - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (2,5-dioxo-1-pyrroidinyl) ethyl] - N-hydroxyformamide; (±) -N- [1R - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (2,5-dioxo-1-pyrrolidinyl) ethyl] - N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3-ethyl-3-methyl-2,5-dioxo -1-pyrrolidinyl) ethyl] -N-hydroxyform amide; N- [4- [4 - [[(4-chlorophenoxy) phenyl] sulfonyl] methyl] tetrahydro-2 H -pyran-4-yl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2 - [[(2-methoxycarbonyl) -f eni l] t io] eti l] -Nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -5 - [(4-methyl-2-oxo-2H-1- benzopyran-6-yl) oxy] pentyl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -4 - [(4-methyl-2-oxo-2H-1- benzo piran-6-i I) oxy] butyl] -Nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -4 - [(4-methyl-2-oxo-2H-1- benzopyran-7-i I) oxy] buti I] - Nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxl] methyl] -5 - [(4-methyl-2-oxo-2H-1- benzopyran-7-i I) oxy] pent i I] - Nh id roxiformam ida, (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (5,5-dimethyl-2,4-dioxo-3-oxazole idin l) ethyl] -Nh idroxif orma mida; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (3,4,4-trimeti-2,5 -dioxo-1-imidazol idin il) ethyl] -Nh idroxif ormam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3-methyl-2,5-d -oxo-1) -imid azo I idi ni l) eti l] -Nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo - 1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-chloro- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5- dioxo-1-midazolidinyl) ethyl] -N-hydroxyformamide; (+) - N- [1 - [[(3'-cyanomethyl- [1,1'-biphenyl] -4-i) oxy] methyl] -2- (3,5,5-trimethyl-2,4- dioxo-1-imidazolidinyl) propyl] -N-hydroxyformamide; (+) - N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-i) oxy] methyl] -2-isopropylthioethyl] -N-hydroxyformamide; (±) -N- [1 - [[(3'-cyanomethyl- [1,1'-biphenyl] -4-i) oxy] methyl] -2- (3,4,4-trimethyl-2,5- dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy-methyl] -2- (3-ethyl-4,4-dimethyl-2,5- dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3-benzyl-4,4-di methyl) 2,5-dioxo-1-imidazole id i nyl) ethyl] -Nh id roxiformam id a; (±) -N- [1 - [[(4'-cyano- [1,1'-biphenyl] -4-i) oxy] methyl] -2- (3,5,5-trimethyl-2,4- dioxo-1-midazolidinyl) ethyl] -N-hydroxyformamide; (+) - N- [1 - [[4'-methoxy [1,1'-biphenyl] -4-yl) sulfonyl] methyl] ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-chloro [1,1'-biphenyl] -4-yl) sulfonyl] methyl] ethyl] -N-hydroxyformamide; (±) -N- [1 - [[[4- (1,3-benzodioxol-5-yl) phenyl] sulfonyl] methyl] ethyl] -N-hydroxyformamide; (±) -N- [1 - [[[4- (4-chlorophenoxy) phenyl] sulfonyl] methyl] ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-methoxy [1,1'-biphenyl] -4-yl) sulfonyl] methyl] propyl] -N-hydroxyformamide; (+) - N- [1- [1,1-dimethyl-2 - [(4 '- (trifluoromethyl) [1,1'-biphenyl] -4-yl] sulfonyl] ethyl] -N-hydroxyformamide; ) -N- [1 - [(phenylmethoxy) methy1] -2 - [[4 '- (trifluoromethyl) [1,1'-biphenyl] -4-yl] sulfonyl] ethyl] -N-hydroxyformamide; (±) -N- [1- (hydroxymethyl) -2 - [[(4 '- (trifluoromethyl) [1,1'-biphenyl] -4-yl] sulfonyl] ethyl] -N-hydroxyformamide; (±) - N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifluoromethyl) [1,1'-biphenyl] -4-yl ] thio] ethyl] -Nh idroxif ormamide; (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifluoromethyl ) [1,1'-bif en yl] -4-yl] sulfonyl] etl] -Nh'droxif ormamide; (+) - N- [1 - [(2,5-dioxo-1-imidazolidinyl) methyl) ] -2 - [[4 '- (trifluoromethoxy) [1,1'-biphenyl] -4-yl] oxy] ethyl] -N-hydroxyformamide; (+) - N- [1 - [[[4 '- (trifluoromethyl) [1,1'-biphenyl] -4-yl] sulfonyl] methyl] -2- (3,4,4-trimethyl-2, 5 -di oxo-1 -imidazol idin il) ethyl] -Nh idroxif ormamide; (±) -N- [N- [1 - [[(4'-butyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3-methyl-2,5-dioxo- 1-im id azo I id i nil) eti l] -Nh id roxiformam ida; (±) -N- [1 - [(3-methyl-2,5-dioxo-1-imidazole idyl) methyl] -2 - [[4'- (trifluoromethoxy) [1,1'-b-phenyl] ] -4-yl] oxy] ethyl] -N-hydroxyformamide; N- [4- [4 - [(4'-chloro [1,1'-biphenyl] -4-yl) sulfonyl] methyl] tetrahydro-2 H -pyran-4-yl] -N-hydroxyformamide; (±) -N- [1 - [[[4- (4-chlorophenoxy) phenyl] sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N- hydroxyl ormamide; (+) - N- [1 - [[4- (4-chlorophenoxy) phenyl] sulfonyl] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-im id azo I idin i I) eti l] -Nh id roxiformam ida; (±) -N- [1 - [[(4-Butyl [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (3,4,4-trimethyl-2,5-dioxo- 1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[(4'-Butyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo-1 -imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 [[[3 '- (Cyanomethyl) [1,1'-biphenyl] -4-yl] oxy]] methyl] -2- (4,4-dimethyl-2,5-dioxo - 1-imidazole id inyl) ethyl] -N-hydroxyform amide; (±) -N- [1- [4- (2-thienyl) phenoxy] methyl] -2- [1- (3,4,4-trimethyl-2,5-dioxo-1-imidazoyldinyl) ethyl] -N -hydroxiform amide; (+) - N- [1 - [[(3-nitro [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo- 1-imidazolidinyl) ethyl] -N-hydroxyl ormamide; (±) -N- [1 - [[(4'-methyl [1,1'-biphenyl] -4-yl) oxy] methyl] -2 - [[3- (methylsulfonyl) -am and] phenyl] ethyl] -Nh id roxiformam ida; (±) -N- [1 - [[[3- (diethylamino) carbonyl] phenyl] methyl] -2 - [(4'-methyl [1,1'-biphenyl] -4-yl) oxy] ethyl] - Nh id roxíf orma mida; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2 - [(4'-cyano [1,1'-biphenyl]] -4- I) oxy] eti I] - Nh id roxiformam ida; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) oxy] methyl] -2- (4,4-dimethyl-2,5-dioxo -1-imidazo-idinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinii) methyl] -2 - [[4 '- (2-methoxyethoxy) [1, 1'-bif in il] -4-yl] oxy] ethyl] -Nh id roxiformam da, (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-amidazolidinyl) methyl] ] -2 - [(4'-propoxy [1,1'-biphenyl] -4-yl) oxy] ethyl] -Nh idroxif ormamide; (±) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [(4'-pentyloxy [1,1'-bif eni l] -4 -il) oxy] et il] -Nh id roxiformam ida; (±) -N- [1 - [[[3 '- (cyanomethyl] [1,1'-biphenii] -4-yl] sulfonyl] methyl] -3- (4,4-dimethyl-2,5 -dixo-1-imidazole id inyl) propyl] -Nh idroxif ormamide; (±) -N- [1 - [[[4 '- (trifluoromethoxy) [1,1'-biphenyl] -4-yl] sulfonyl] methyl] -2- (3,4,4-trimeti-2,5 -dioxo-1-imidazolidinyl) ethyl] -Nh idroxif ormamide; (+) - N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (3-methyl-2,5-dioxo-1-im id azi i di nil) eti I] - Nh id roxiformam ida; (±) -N- [1 - [[[3 '- (Cyanomethyl) [1,1'-biphenyl] -4-yl] sulfonyl] methyl] -2- (3,4,4-trimethyl-2,5 -dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 [[(4'-cyano [1,1"-biphenyl] -4-yl) oxyl] methyl] -2- (1,6-dihydro-3-methyl-6-) oxo- 1 -pi ridazi nil) etiI] -Nh id roxiformam id a; (±) -N- [1 - [[(4'-cyano [1,1'-biphenyl] -4-yl) sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; (±) -N- [1 - [[[4- (4-fluorophenoxy) phenyl] sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -Nh idroxif ormamide; (+) - N- [1 - [[4- (4-pyridinyl) phenoxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1-midazole id inyl) ethyl] - Nh hydroxyp ormamide, (S) -N- [1 - [(4,4-dimethyl-2,5-d-oxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifluoromethoxy)] 1,1'-biphenyl] -4-yl] oxy] ethyl] -N-hydroxyformamide; (R) -N- [1 - [(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) methyl] -2 - [[4'- (trifluoromethoxy) [1,1'-biphenyl] -4 -yl] oxy] ethyl] -N-hydroxyformamide; N- [1 - [[[4 '- (trifluoromethoxy) [1,1'-biphenyl] -4-yl] oxy] methyl] -3- (4,4-dimethyl-2,5-dioxo- 1 -imidazolidiniI) propyl] -Nh id roxiformam ida; N- [1- [4 - [(4-pyridinylthio) phenoxy] methyl] -2- (4,4-di methyl-2,5-dioxo-1-i midazolidinyl) ethyl] -N-hydroxyformamide; N- [1 - [[[(4-chlorophenoxy) phenyl] sulfonyl] methyl] -3- (4,4-dimethyl-2,5-d-oxo-1-imidazole id i nyl) propyl] -Nh idroxif ormamide; N- [1 - [[(4'-cyano [1,1"-biphenyl] -4-yl) oxyl] methyl] -2- (1,6-dihydro-6-oxo-1-pi ridazin il ) ethyl] -Nh id roxiformam ida; N- [1 - [[[4 '- (aminosulfonyl) [1,1'-biphenyl] -4-yl] oxy] methyl] -2- (3,4,4-trimethyl-2,5-dioxo-1 -imidazoiidinyl) ethyl] -Nh idroxif orm amide; N- [1 - [[[4 '- (trifluoromethoxy) [1,1'-bifenii] -4-yl] sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazole id inil) etiI] -Nh idroxif ormamide; N- [1- [4 - [(4-pyridinyloxy) phenyl] sulfonyl] ethyl] -N-hydroxy-ormamide; N- [1 - [[(4-cyanophenoxy) phenyl] sulfonyl] methyl] -2- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) ethyl] -N-hydroxyformamide; N- [1 - [[4 - [[4- (trifluoromethoxy) phenoxy] phenyl] sulfonyl] methyl] -3- (4,4-dimethyl-2,5-dioxo-1-imidazolidinyl) propyl] -N-hydroxyformamide; and N- [1 - [[4 - [[4- (trifluoromethoxy) phenoxy] phenyl] sulfonyl] methyl] -2- (4,4-dimethyl-2,5-di oxo-1-yl idazol idinyl) et il ] -Nh id roxiformam ida. 1 6. A compound according to claim 1 which is (S) -N- [1 - [(4,4-dimethyl-2, 5-dioxo-1-imidazolidinyl) methyl] -2 - [[ 4 '- (trifluoromethoxy) [1,1'-bifenyl] -4-yl] oxy] ethyl] -Nh id roxiformam ida. 17. A method for inhibiting matrix metalloproteinases in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a compound of claim 1. 18. A composition for inhibiting matrix metalloproteinases comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 1.