Sulfonyl aryl or heteroaryl hydroxamic acid compounds

A compound or a pharmaceutically-acceptable salt thereof, wherein:

• the compound corresponds in structure to the following formula:
• A is selected from the group consisting of:
• (1) —O—,
• (2) —S—,
• (3) —NRk—,
• (4) —CO—N(Rk)—,
• (5) —N(Rk)—CO—,
• (6) —CO—O—,
• (7) —O—CO—,
• (8) —O—CO—O—,
• (9) —HC═CH—,
• (10) —NH—CO—NH—,
• (11) —C≡C—,
• (12) —N═N—,
• (13) —NH—NH—,
• (14) —CS—N(Rk)—,
• (15) —N(Rk)—CS—,
• (16) —O—CH2—,
• (17) —CH2—O—,
• (18) —S—CH2—,
• (19) —CH2—S—,
• (20) —SO—,
• (21) —SO2—, and
• (22) a bond;
• R is selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, cycloalkoxyalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, cycloalkylthioalkyl, and heterocycloalkylthioalkyl, wherein:
• the aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is optionally substituted with up to two substituents independently selected from the group consisting of alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C1–C2-alkylenedioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and alkoxycarbonyl;
• E is selected from the group consisting of:
• (1) —CORg—,
• (2) —RgCO—,
• (3) —CON(Rk)—,
• (4) —N(Rk)CO—,
• (5) —CO—,
• (6) —SO2Rg—,
• (7) —RgSO2—,
• (8) —SO2—,
• (9) —N(Rk)—SO2—,
• (10) —SO2—N(Rk)—,
• (11) a bond;
• Y is selected from the group consisting of hydrido, alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, nitrile, nitro, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, Raoxyalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocycloalkyl, cycloalkyl, trifluoromethyl, alkoxycarbonyl, and aminoalkyl, wherein:
• the aryl, heteroaryl, arylalkyl, or heterocycloalkyl is optionally substituted with up to two substituents independently selected from the group consisting of alkanoyl, halo, nitro, nitrile, haloalkyl, alkyl, arylalkyl, aryl, alkoxy, perfluoroalkyl, perfluoroalkoxy, and amino, wherein:
• the amino nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of alkyl and arylalkyl;
• Ra is selected from the group consisting of hydrido, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkycarbonyl, RbRcaminoalkanoyl, haloalkanoyl, RbRcaminoalkyl, alkoxyalkyl, haloalkyl, and arylalkyloxy;
• Rg is selected from the group consisting of hydrido, aryl, heteroaryl, heterocyclo, aroyl, alkanoyl, heteroaroyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, RhRi-amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkyloxycarbonyl, alkyloxycarbonyloxy, aryloxycarbonyl, arylalkyloxycarbonyl, arylalkyloxycarbonylamino, aryloxycarbonyloxy, carboxy, RhRi-aminocarbonyloxy, RhRi-aminocarbonyl, RhRi-aminoalkanoyl, hydroxyaminocarbonyl, RhRi-aminosulfonyl, RhRi-aminocarbonyl(Rh)amino, trifluoromethylsulfonyl(Rh)amino, heteroarylsulfonyl(Rh) amino, arylsulfonyl(Rh)amino, arylsulfonyl(Rh)aminocarbonyl, alkylsulfonyl(Rh)amino, arylcarbonyl(Rh)aminosulfonyl, and alkylsulfonyl(Rh)aminocarbonyl;
• each Rh is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, halo alkanoyl, and hydroxyalkyl, wherein:
• any such group is optionally substituted by up to two independently selected Rj substituents;
• Ri is selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, alkoxyalkylalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, halo alkanoyl, and hydroxyalkyl, wherein:
• any such substituent is optionally substituted by up to two independently selected Rj substituents;
• each Rj is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, halo alkanoyl, and hydroxyalkyl, wherein:
• the aminoalkyl and aminoalkanoyl are optionally substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, and alkyloxycarbonyl;
• and
• each Rk is independently selected from the group consisting of hydrido, alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, alkyloxycarbonyl, RcRdamino carbonyl, RcRdaminosulfonyl, RcRdaminoalkanoyl, and RcRdaminoalkysulfonyl;
• R5 and R6 are independently selected from the group consisting of hydrido, hydrocarbyl, hydroxyhydrocarbyl, hydroxy, amino, dihydrocarbylamino, heterocyclo, heterocyclohydrocarbyl, heterocyclooxy, and heterocyclothio;
• R20 is selected from the group consisting of —O—R21, —NR13—O—R22, —NR13—O—R14, and —NR23R24;
• R21 is selected from the group consisting of C1–C6-alkyl, aryl, and aryl-C1–C6-alkyl;
• R22 is a selectively removable protecting group;
• R13 is selected from the group consisting of hydrido, C1–C6-alkyl, and benzyl;
• R14 is selected from the group consisting of hydrido and C(V)R15;
• V is selected from the group consisting of O and S;
• R15 is selected from the group consisting of C1–C6-alkyl, aryl, C1–C6-alkoxy, heteroaryl-C1–C6-alkyl, C3–C8-cycloalkyl-C1–C6-alkyl, aryloxy, aryl-C1–C6-alkoxy, aryl-C1–C6-alkyl, heteroaryl, and amino C1–C6-alkyl, wherein the amino C1–C6-alkyl nitrogen is optionally substituted with:
• up to two substituents independently selected from the group consisting of C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, C3–C8-cycloalkyl-C1–C6-alkyl, aryl-C1–C6-alkoxycarbonyl, C1–C6-alkoxycarbonyl, and C1–C6-alkanoyl, or
• two substituents such that the amino C1–C6-alkyl nitrogen, together with the two substituents, form a 5- to 8-membered heterocyclo or heteroaryl ring;
• as to R23 and R24:
• R23 and R24 are independently selected from the group consisting of hydrido, C1–C6-alkyl, amino C1–C6-alkyl, hydroxy C1–C6-alkyl, aryl, and aryl-C1–C6-alkyl, or
• R23 and R24, together with the nitrogen atom to which they are both bonded, form a 5- to 8-membered ring containing zero or one additional heteroatom that is selected from the group consisting of oxygen, nitrogen, and sulfur;
• each Rb or Rc is independently selected from the group consisting of hydrido, alkanoyl, arylalkyl, aroyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkyl, trifluoromethylalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, arylalkanoyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkanoyl, hydroxyalkanoyl, thioalkanoyl, alkenyl, alkynyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein any amino nitrogen in such substituents is optionally substituted with:
• up to two independently selected non-hydrido Rd substituents, or
• two substituents such that the substituents, together with the amino nitrogen, form:
• a saturated or partially unsaturated heterocyclo group optionally substituted with up to three independently selected non-hydrido Rd substituents, or
• a heteroaryl group optionally substituted with up to three independently selected Rf substituents;
• each Rd or Re is independently selected from the group consisting of hydrido, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkycarbonyl, alkoxycarbonyl, and arylalkyloxycarbonyl;
• and
• each Rf is independently selected from the group consisting of nitro, hydroxy, alkyl, halogen, aryl, alkoxy, cyano, and RdReamino.

A compound or a pharmaceutically-acceptable salt thereof, wherein:

• the compound corresponds in structure to Formula D3:
• as to R5 and R6:
• R5 and R6 are independently selected from the group consisting of hydrido, alkyl, cycloalkyl, acylalkyl, halo, nitro, hydroxy, cyano, alkoxy, haloalkyl, haloalkyloxy, hydroxyalkyl, RbRcaminoalkyl, or
• R5 and R6, together with the atoms to which they are bonded, form an aliphatic or aromatic carbocyclic or heterocyclic ring having 5 to 7 ring members;
• R20 is selected from the group consisting of —O—R21, —NR13—O—R22, —NR13—O—R14, and —NR23R24;
• R21 is selected from the group consisting of C1–C6-alkyl, aryl, and aryl-C1–C6-alkyl;
• R22 is a selectively removable protecting group;
• R13 is selected from the group consisting of hydrido, C1–C6-alkyl, and benzyl;
• R14 is selected from the group consisting of hydrido and C(V)R15;
• V is selected from the group consisting of O and S;
• R15 is selected from the group consisting of C1–C6-alkyl, aryl, C1–C6-alkoxy, heteroaryl-C1–C6-alkyl, C3–C8-cycloalkyl-C1–C6-alkyl, aryloxy, aryl-C1–C6-alkoxy, aryl-C1–C6-alkyl, heteroaryl, and amino C1–C6-alkyl, wherein the amino C1–C6-alkyl nitrogen is optionally substituted with:
• up to two substituents independently selected from the group consisting of C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, C3–C8-cycloalkyl-C1–C6-alkyl, aryl-C1–C6-alkoxycarbonyl, C1–C6-alkoxycarbonyl, and C1–C6-alkanoyl, or
• two substituents such that the amino C1–C6-alkyl nitrogen, together with the two substituents, form a 5- to 8-membered heterocyclo or heteroaryl ring;
• as to R23 and R24:
• R23 and R24 are independently selected from the group consisting of hydrido, C1–C6-alkyl, amino C1–C6-alkyl, hydroxy C1–C6-alkyl, aryl, and aryl-C1–C6-alkyl, or
• R23 and R24, together with the nitrogen atom to which they are both bonded, form a 5- to 8-membered ring containing zero or one additional heteroatom that is selected from the group consisting of oxygen, nitrogen, and sulfur;
• each Rb or Rc is independently selected from the group consisting of hydrido, alkanoyl, arylalkyl, aroyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkyl, trifluoromethylalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, arylalkanoyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkanoyl, hydroxyalkanoyl, thioalkanoyl, alkenyl, alkynyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein any amino nitrogen in such substituents is optionally substituted with:
• up to two independently selected non-hydrido Rd substituents, or
• two substituents such that the substituents, together with the amino nitrogen, form:
• a saturated or partially unsaturated heterocyclo group optionally substituted with up to three independently selected non-hydrido Rd substituents, or
• a heteroaryl group optionally substituted with up to three independently selected Rf substituents;
• each Rd or Re is independently selected from the group consisting of hydrido, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkycarbonyl, alkoxycarbonyl, and arylalkyloxycarbonyl;
• and
• each Rf is independently selected from the group consisting of nitro, hydroxy, alkyl, halogen, aryl, alkoxy, cyano, and RdReamino;
• and
• R4 is a substituent that has a chain length of 3 to about 14 carbon atoms.

A compound or pharmaceutically acceptable salt thereof, wherein:

• the compound corresponds in structure to the following formula:
• as to R5 and R6:
• R5 and R6 are independently selected from the group consisting of hydrido, alkyl, cycloalkyl, acylalkyl, halo, nitro, hydroxy, cyano, alkoxy, haloalkyl, haloalkyloxy, hydroxyalkyl, RbRcaminoalkyl, or
• R5 and R6, together with the atoms to which they are bonded, form an aliphatic or aromatic carbocyclic or heterocyclic ring having 5 to 7 ring members;
• R20 is selected from the group consisting of —O—R21, —NR13—O—R22, —NR13—O—R14, and —NR23R24;
• R21 is selected from the group consisting of C1–C6-alkyl, aryl, and aryl-C1–C6-alkyl;
• R22 is a selectively removable protecting group;
• R13 is selected from the group consisting of hydrido, C1–C6-alkyl, and benzyl;
• R14 is selected from the group consisting of hydrido and C(V)R15;
• V is selected from the group consisting of O and S;
• R15 is selected from the group consisting of C1–C6-alkyl, aryl, C1–C6-alkoxy, heteroaryl-C1–C6-alkyl, C3–C8-cycloalkyl-C1–C6-alkyl, aryloxy, aryl-C1–C6-alkoxy, aryl-C1–C6-alkyl, heteroaryl, and amino C1–C6-alkyl, wherein the amino C1–C6-alkyl nitrogen is optionally substituted with:
• up to two substituents independently selected from the group consisting of C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, C3–C8-cycloalkyl-C1–C6-alkyl, aryl-C1–C6-alkoxycarbonyl, C1–C6-alkoxycarbonyl, and C1–C6-alkanoyl, or
• two substituents such that the amino C1–C6-alkyl nitrogen, together with the two substituents, form a 5- to 8-membered heterocyclo or heteroaryl ring;
• as to R23 and R24:
• R23 and R24 are independently selected from the group consisting of hydrido, C1–C6-alkyl, amino C1–C6-alkyl, hydroxy C1–C6-alkyl, aryl, and aryl-C1–C6-alkyl, or
• R23 and R24, together with the nitrogen atom to which they are both bonded, form a 5- to 8-membered ring containing zero or one additional heteroatom that is selected from the group consisting of oxygen, nitrogen, and sulfur;
• as to R4:
• R4 is selected from the group consisting of phenyl, phenoxy, thiophenoxy, anilino, phenylazo, phenylureido, benzamido, nicotinamido, isonicotinamido, picolinamido, heterocyclo, heterocyclohydrocarbyl, arylheterocyclohydrocarbyl, heteroarylhydrocarbyl, heteroarylheterocyclohydrocarbyl, arylhydrocarbyloxyhydrocarbyl, aryloxyhydrocarbyl, hydrocarboylhydrocarbyl, arylhydrocarboylhydrocarbyl, arylcarbonylhydrocarbyl, arylazoaryl, arylhydrazinoaryl, hydrocarbylthiohydrocarbyl, hydrocarbylthioaryl, arylthiohydrocarbyl, heteroarylthiohydrocarbyl, hydrocarbylthioarylhydrocarbyl, arylhydrocarbylthiohydrocarbyl, arylhydrocarbylthioaryl, arylhydrocarbylamino, heteroarylhydrocarbylamino, and heteroarylthio, wherein:
• any such substituent is optionally substituted by one or more substituents independently selected from the group consisting of hydrocarbyl, hydrocarbyloxy, nitro, cyano, perfluorohydrocarbyl, trifluoromethylhydrocarbyl, hydroxy, mercapto, hydroxycarbonyl, aryloxy, arylthio, arylamino, arylhydrocarbyl, aryl, heteroaryloxy, heteroarylthio, heteroarylamino, heteroarylhydrocarbyl, hydrocarbyloxycarbonylhydrocarbyl, heterocyclooxy, hydroxycarbonylhydrocarbyl, heterocyclothio, heterocycloamino, cyclohydrocarbyloxy, cyclohydrocarbylthio, cyclohydrocarbylamino, heteroarylhydrocarbyloxy, heteroarylhydrocarbylthio, heteroarylhydrocarbylamino, arylhydrocarbyloxy, arylhydrocarbylthio, arylhydrocarbylamino, heterocyclic, heteroaryl, hydroxycarbonylhydrocarbyloxy, alkoxycarbonylalkoxy, hydrocarbyloyl, arylcarbonyl, arylhydrocarbyloyl, hydrocarboyloxy, arylhydrocarboyloxy, hydroxyhydrocarbyl, hydroxyhydrocarbyloxy, hydrocarbylthio, hydrocarbyloxyhydrocarbylthio, hydrocarbyloxycarbonyl, hydroxycarbonylhydrocarbyloxy, hydrocarbyloxycarbonylhydrocarbyl, hydrocarbylhydroxycarbonylhydrocarbylthio, hydrocarbyloxycarbonylhydrocarbyloxy, hydrocarbyloxycarbonylhydrocarbylthio, amino, hydrocarbylcarbonylamino, arylcarbonylamino, cyclohydrocarbylcarbonylamino, heterocyclohydrocarbylcarbonylamino, arylhydrocarbylcarbonylamino, heteroarylcarbonylamino, heteroarylhydrocarbylcarbonylamino, heterocyclohydrocarbyloxy, hydrocarbylsulfonylamino, arylsulfonylamino, arylhydrocarbylsulfonylamino, heteroarylsulfonylamino, heteroarylhydrocarbylsulfonylamino, cyclohydrocarbylsulfonylamino, heterocyclohydrocarbylsulfonylamino, and aminohydrocarbyl, wherein:
• the aminohydrocarbyl nitrogen is substituted:
• with one or two substituent(s) that is/are independently selected from the group consisting of hydrocarbyl, aryl, arylhydrocarbyl, cyclohydrocarbyl, arylhydrocarbyloxycarbonyl, hydrocarbyloxycarbonyl, and hydrocarboyl, or
• two substituents such that the aminohydrocarbyl nitrogen, together with the and two substituents, form a 5- to 8-membered heterocyclic or heteroaryl ring, or
• R4 is selected from the group consisting of cyclohydrocarbyl, single-ringed heterocyclo, phenyl single-ringed heteroaryl, C3–C14 hydrocarbyl, C2–C14 hydrocarbyloxy, phenoxy, thiophenoxy, 4-thiopyridyl, phenylazo, phenylureido, nicotinamido, isonicotinamido, picolinamido, anilino, and benzamido;
• Rb and Rc are independently selected from the group consisting of hydrido, alkanoyl, aralalkyl, aroyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkyl, trifluoromethylalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, aralkanoyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkanoyl, hydroxyalkanoyl, thiolalkanoyl, alkenyl, alkynyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein any amino nitrogen in such substituents is optionally substituted with:
• up to two independently selected non-hydrido Rd substituents, or
• two substituents such that the substituents, together with the amino nitrogen, form:
• a saturated or partially unsaturated heterocyclo group optionally substituted with up to three independently selected non-hydrido Rd substituents, or
• a heteroaryl group optionally substituted with up to three independently selected Rf substituents;
• each Rd or Re is independently selected from the group consisting of hydrido, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkycarbonyl, alkoxycarbonyl, and arylalkyloxycarbonyl;
• and
• each Rf is independently selected from the group consisting of nitro, hydroxy, alkyl, halogen, aryl, alkoxy, cyano, and RdReamino.