| 摘要 |
1. A compound having the formula: wherein: X is SO2 or -P(O)-R10; Y is aryl or heteroaryl, with the proviso that X and Z may not be bonded to adjacent atoms of Y; Z is O, NH, CH2 or S; R1 is hydrogen, aryl, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms; R2 is hydrogen, aryl, aralkyl, heteroaryl, heteroaralkyl, cycloalkyl of 3-6 carbon atoms, C4-C8 cycloheteroalkyl, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms; or R1 and R2, together with the atom to which they are attached, may form a ring wherein R1 and R2 represent a divalent moiety of the formula: wherein Q = a carbon-carbon single or double bond, O, S, SO, SO2, -N-R11 or -CONR14; m = 1-3; r = 1 or 2, with the proviso that when Q is a bond, r is equal to 2; R3 is hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, C4-C8 cycloheteroalkyl, aralkyl, or heteroaralkyl; or R1 and R3, together with the atoms to which they are attached, may form a 5 to 8 membered ring wherein R1 and R3 represent divalent moieties of the formulae: wherein Q and m are as defined above; A is aryl or heteroaryl; s is 0-3; u is 1-4; R4 and R5 are each, independently, hydrogen or alkyl of 1-6 carbon atoms, -CN, or -CCH; R6 is hydrogen, aryl, heteroaryl, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, or -C4-C8-cycloheteroalkyl; R8 and R9 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, aryl, aralkyl, heteroaryl, heteroaralkyl, or -C4-C8-cycloheteroalkyl; R10 is alkyl of 1-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, aryl or heteroaryl; R11, is hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, aryl, heteroaryl, -S(O)nR8, -COOR8, -CONR8R9, -SO2NR8R9 or -COR8; R12 and R13 are independently selected from H, -OR8, -NR8R9, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, aryl, heteroaryl, -COOR8; -CONR8R9; or R12 and R13 together form a -C3-C6-cycloalkyl of 3-6 carbon atoms or a -C5-C8-cycloheteroalkyl ring; or R12 and R13, 3 together with the carbon to which they are attached, form a carbonyl group; with the proviso that R10 and R12 or R11 and R112 may form a cycloheteroalkyl ring when they are attached to adjacent atoms; R14 is hydrogen, aryl, heteroaryl, alkyl of 1-6 carbon atoms or cycloalkyl of 3-6 carbon atoms; and n is 0-2; or a pharmaceutically acceptable salt thereof. 2. A compound according to Claim 1 wherein Y is a phenyl ring substituted at the 1- and 4-positions by X and Z, respectively, or a pharmaceutically acceptable salt thereof. 3. A compound according to Claim 1 or Claim 2 wherein X is SO2, or a pharmaceutically acceptable salt thereof. 4. A compound according to any one of Claims 1 to 3 wherein Z is oxygen, or a pharmaceutically acceptable salt thereof. 5. A compound according to any one of Claims 1 to 4 wherein R4 and R5 are hydrogen, or a pharmaceutically acceptable salt thereof. 6. A compound according to any one of Claims 1 to 5 wherein R6 is CH2OH or methyl, or a pharmaceutically acceptable salt thereof. 7. A compound according to any one of Claims 1 to 6 wherein R, and R3, together with the atoms to which they are attached, form a piperazine, piperidine, tetrahydroisoquinoline, morpholine, thiomorpholine, or diazepine ring. 8. A compound according to any one of Claims 1 to 7 wherein R2 is hydrogen. 9. A compound according to Claim 8 wherein R2 is hydrogen such that structure B has the absolute stereochemistry shown below, or a pharmaceutically acceptable salt thereof. 10. A compound according to any one of Claims 1 to 6 wherein R1 is hydrogen, such that this compound has the D-configuration, as shown below: 11. A compound according to Claim 10 wherein R3 is hydrogen, or a pharmaceutically acceptable salt thereof. 12. A compound according to Claim 10 wherein R3 is hydrogen, Y is a phenyl ring substituted at the 1-and 4-positions by X and Z, respectively, X is SO2, and Z is oxygen, or a pharmaceutically acceptable salt thereof. 13. A compound according to Claim 1 which is selected from the group consisting of: 2-[(4-But-2-ynyloxy-benzenesulfonyl)-methyl-amino]-N-hydroxy-3-methyl-butyramide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-methyl-amino]-N-hydroxy-acetamide; N-Hydroxy-2-[(4-methoxy-benzenesulfonyl)-methyl-amino]-3-methyl-butyramide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-pyridin-3-ylmethyl-amino]-N-hydroxy-acetamide hydrochloride; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-acetamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-3-methyl-butyramide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-propionamide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-pyridin-3-ylmethyl-amino]-N-hydroxy-propionamide hydrochloride; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-2-methyl-propionamide; 4-(4-But-2-ynyloxy-benzenesulfonyl)-2,2-dimethyl-thiomorpholine-3-carboxylic acid hydroxyamide; 4-(4-Hept-2-ynyloxy-benzenesulfonyl)-2,2-dimethyl-thiomorpholine-3-carboxylic acid hydroxyamide; 2-(4-But-2-ynyloxy-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid hydroxyamide; 4-Benzoyl-1-(4-But-2-ynyloxy-benzenesulfonyl)-[1,4]diazepane-2-carboxylic acid hydroxyamide; 1-(4-But-2-ynyloxy-benzenesulfonyl)-4-methyl-piperazine-2-carboxylic acid hydroxyamidehydrochloride; 4-[4-(4-Hydroxy-But-2-ynyloxy)-benzenesulfonyl]-2,2-dimethyl-thiomorpholine-3-carboxylic acid hydroxyamide; 4-(4-But-2-ynyloxy-benzenesulfonyl)-3-hydroxycarbamoyl-piperazine-1-carboxylic acid tert-butyl ester; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-2-methyl propionamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-5-guanidino-pentanoic acid hydroxyamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-5-(4-methylbenzenesulfonyl-guanidino)-pentanoic acid hydroxyamide; 3-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-succinamic acid cyclohexyl ester; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-3-cyclohexyl-N-hydroxy propionamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-2-cyclohexyl-N-hydroxy acetamide; 3-tert-Butylsulfanyl-2-(4-but-2-ynyloxy-benzenesulfonylamino)-N-hydroxy propionamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-3-(4-methoxy-benzylsulfanyl)-propionamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N1-hydroxy-succinamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-3-cyclohexyl-N-hydroxy-propionamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-2-cyclohexyl-N-hydroxy-acetamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-4-methyl-pentanoic acid hydroxyamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-4-methylsulfanyl butyramide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-3-phenyl-propionamide; 2-(4-But-2-ynyloxy-benzenesulfonyl)-pyrrolidine-2-carboxylic acid hydroxyamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-3-(1H-indol-3-yl)-propionamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-3-(4-hydroxy-phenyl)-propionamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-3-methyl-butyramide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-4-methyl-pentanoic acid hydroxyamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-6-(2-chloro-benzylamino)-hexanoic acid hydroxyamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-hexanoic acid hydroxyamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-2-phenyl-acetamide; 3-Benzyloxy-2-(4-but-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-propionamide; 2-(4-But-2-ynyloxy-benzenesulfonylamino)-N-hydroxy-acetamide; (2R,3S)-2-({[4-(2-Butynyloxy)phenyl]sulfonyl}amino)-N-hydroxy-3-methylpentanamide; (2R)-2-({[4-(2-Butynyloxy)phenyl]sulfonyl}amino)-N-hydroxy-3,3-dimethylbutanamide; (2S)-2-[(4-But-2-ynyloxy-benzenesulfonyl)-methyl-amino]-N-hydroxy-propionamide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-ethyl-amino]-N-hydroxy-3-methyl-butyramide; 2-[{[4-(2-Butynyloxy)phenyl]sulfonyl}[{[4-(2-Butynyloxy)phenyl]sulfonyl}(2-propynyl)amino]-N-hydroxy-methylbutanamide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-propyl-amino]-N-hydroxy-3-methyl-butyramide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-(3-phenyl-propyl)-amino]-N-hydroxy-3-methyl-butyramide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-cyclopropylmethyl-amino]-N-hydroxy-3-methyl-butyramide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-isobutyl-amino]-N-hydroxy-3-methyl-butyramide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-pyridin-3-ylmethyl-amino]-N-hydroxy-3-methyl-butyramide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-methyl-amino]-2-cyclohexyl-N-hydroxy-acetamide; 2-[(4-But-2-ynyloxy-benzenesulfonyl)-pyridin-3-ylmethyl-amino]-2-cyclohexyl-N-hydroxy-acetamide; 2-{(4-But-2-ynyloxy-benzenesulfonyl)-[4-(2-piperidin-1-yl-ethoxy)-benzyl]amino}-2-cyclohexyl-N-hydroxy-acetamide; 2-{{[4-(2-Butynyloxy)phenyl]sulfonyl}[3-(diethylamino)propyl]amino}-hydroxy-3-methylbutanamide; 2-{{[4-(2-Butynyloxy)phenyl]sulfonyl}[3-(4-morpholinyl)propyl]amino}-N-hydroxy-3-methylbutanamide; 2-{{[4-(2-Butynyloxy)phenyl]sulfonyl}[3-(4-methyl-1-piperazinyl)propyl]-amino}-N-hydroxy-3-methylbutanamide hydrochloride; 2-{{[4-(2-Butynyloxy)phenyl]sulfonyl)[4-(diethylamino)butyl]amino}-hydroxy-3-methylbutanamide; 2-{{[4-(2-Butynyloxy)phenyl]sulfonyl}[4-(4-methyl-1-piperazinyl)butyl]amino N-hydroxy-3-methylbutanamide; 2-[[[4-(2-Butynyloxy)phenyl]sulfonyl][2-(4-morpholinyl)ethyl]amino]-hydroxy-3-methylbutanamide; 2-[{[4-(But-2-ynyloxy)phenyl]sulfonyl}(2-morpholin-4-ylethyl)amino]-N-hydroxyacetamide hydrochloride; 2-{{[4-(2-Butynyloxy)phenyl]sulfonyl}[4-(4-methyl-1-piperazinyl)-2-butynyl]amino}-N-hydroxy-3-methylbutanamide; 2-{[4-(2-Butynyloxy)phenyl]sulfonyl}[4-(diethylamino)-2-butynyl]amino}-N-hydroxy-3-methylbutanamide; 2-{{[4-(2-Butynyloxy)phenyl]sulfonyl}[4-(methylamino)-2-butynyl]amino}-N-hydroxy-3-methylbutanamide; ((2R)-{[4-(2-Butynyloxy)phenyl]sulfonyl}(methyl)amino)[(4-diethylamino)-cyclohexyl]-N-hydroxyethamide; (2R)-{[4-(2-Butynyloxy)phenyl]sulfonyl}amino-N-hydroxy-2-(4-hydroxy-cyclohexyl)ethanamide; (2R
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