Sulfamato hydroxamic acid metalloprotease inhibitor

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

• the compound corresponds in structure to formula VIII:
• m is selected from the group consisting of zero, 1, and 2;
• n is selected from the group consisting of zero, 1, and 2;
• p is selected from the group consisting of zero, 1, and 2;
• the sum of m+n+p equals 2;
• one of X, Y, and Z is NR6, and the remaining two of X, Y, and Z are CR8R9 and CR10R11;
• R6 is independently selected from the group consisting of C1–C6-alkanoyl, C6-aryl-C1–C6-alkyl, aroyl, bis(C1–C6-alkoxy-C1–C6-alkyl)-C1–C6-alkyl, C1–C6-haloalkyl, C1–C6-perfluoroalkoxy-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkyl, C3–C6-cycloalkyl, C3–C8-heterocycloalkyl, C3–C8-heterocycloalkylcarbonyl, phenyl, 5- to 6-membered heterocyclo, 5- to 6-membered heteroaryl, C3–C8-cycloalkyl-C1–C6-alkyl, phenyloxy-C1–C6-alkyl, heteroaryloxy-C1–C6-alkyl, heteroaryl-C1–C6-alkoxy-C1–C6-alkyl, heteroarylthio-C1–C6-alkyl, phenylsulfonyl, C1–C6-alkylsulfonyl, 5- to 6-membered heteroarylsulfonyl, carboxy-C1–C6-alkyl, C1–C4-alkoxycarbonyl-C1–C6-alkyl, aminocarbonyl, C1–C6-alkyliminocarbonyl, phenyliminocarbonyl, 5- to 6-membered heterocycloiminocarbonyl, phenylthio-C1–C6-alkyl, C1–C6-alkylthio-C1–C6-alkyl, phenylthio-C3–C6-alkenyl, C1–C4-alkylthio-C3–C6-alkenyl, 5- to 6-membered heteroaryl-C1–C6-alkyl, halo-C1–C6-alkanoyl, hydroxy-C1–C6-alkanoyl, thiol-C1–C6-alkanoyl, C3–C6-alkenyl, C3–C6-alkynyl, C1–C5-alkoxycarbonyl, aryloxycarbonyl, NR8R9—C1–C5-alkylcarbonyl, hydroxy-C1–C5-alkyl, aminocarbonyl, hydroxyaminocarbonyl, aminosulfonyl, amino-C1–C6-alkylsulfonyl, and amino-C1–C6-alkyl, wherein:
• the aminocarbonyl, hydroxyaminocarbonyl, aminosulfonyl, amino-C1–C6-alkylsulfonyl, and amino-C1–C6-alkyl nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of C1–C6-alkyl, aryl-C1–C6-alkyl, C3–C8-cycloalkyl, and C1–C6-alkanoyl;
• as to R8:
• R8 is selected from the group consisting of hydrido, hydroxy, C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, heteroaryl, heteroaryl-C1–C6-alkyl, C2–C6-alkynyl, C2–C6-alkenyl, thiol-C1–C6-alkyl, C1–C6-alkylthio-C1–C6-alkyl cycloalkyl, C1–C6-alkylsulfinyl-C1–C6-alkyl cycloalkyl, C1–C6-alkylsulfonyl-C1–C6-alkyl cycloalkyl, cycloalkyl-C1–C6-alkyl, heterocycloalkyl-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkyl, arylalkoxy-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkoxy-C1–C6-alkyl, hydroxy-C1–C6-alkyl, hydroxycarbonyl-C1–C6-alkyl, hydroxycarbonylaryl-C1–C6-alkyl, aminocarbonyl-C1–C6-alkyl, aryloxy-C1–C6-alkyl, heteroaryloxy-C1–C6-alkyl, arylthio-C1–C6-alkyl, arylsulfonyl-C1–C6-alkyl, arylsulfinyl-C1–C6-alkyl, heteroarylthio-C1–C6-alkyl, heteroarylsulfonyl-C1–C6-alkyl, heteroarylsulfinyl-C1–C6-alkyl, halo-C1–C6-alkyl, alkoxycarbonylamino-C1–C6-alkyl, and amino-C1–C6-alkyl, wherein:
• the amino-C1–C6-alkyl nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of C1–C6-alkyl, aryl-C1–C6-alkyl, cycloalkyl, and C1–C6-alkanoyl, or
• R8 and R9, together with the carbon to which they are bonded, form a carbonyl group, or
• R8 and R9 or R8 and R10, together with the atom(s) to which they are bonded, form a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• as to R9:
• R9 is selected from the group consisting of hydrido, hydroxy, C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, heteroaryl, heteroaryl-C1–C6-alkyl, C2–C6-alkynyl, C2–C6-alkenyl, thiol-C1–C6-alkyl, C1–C6-alkylthio-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfonyl-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfinyl-C1–C6-alkylcycloalkyl, cycloalkyl-C1–C6-alkyl, heterocycloalkyl-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkyl, arylalkoxy-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkoxy-C1–C6-alkyl, hydroxy-C1–C6-alkyl, hydroxycarbonyl-C1–C6-alkyl, hydroxycarbonylaryl-C1–C6-alkyl, aminocarbonyl-C1–C6-alkyl, aryloxy-C1–C6-alkyl, heteroaryloxy-C1–C6-alkyl, arylthio-C1–C6-alkyl, arylsulfonyl-C1–C6-alkyl, arylsulfinyl-C1–C6-alkyl, heteroarylthio-C1–C6-alkyl, heteroarylsulfonyl-C1–C6-alkyl, heteroarylsulfinyl-C1–C6-alkyl, halo-C1–C6-alkyl, alkoxycarbonylamino-C1–C6-alkyl, and amino-C1–C6-alkyl, wherein:
• the amino-C1–C6-alkyl nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of C1–C6-alkyl, aryl-C1–C6-alkyl, cycloalkyl, and C1–C6-alkylcarbonyl, or R9 and R8, together with the carbon to which they are bonded, form:
• a carbonyl group, or
• a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are independently selected from the
• group consisting of nitrogen, oxygen, and sulfur;
• as to R10:
• R10 is selected from the group consisting of hydrido, hydroxy, C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, heteroaryl, heteroaryl-C1–C6-alkyl, C2–C6-alkynyl, C2–C6-alkenyl, thiol-C1–C6-alkyl, C1–C6-alkylthio-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfonyl-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfinyl-C1–C6-alkylcycloalkyl, cycloalkyl-C1–C6-alkyl, heterocycloalkyl-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkyl, arylalkoxy-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkoxy-C1–C6-alkyl, hydroxy-C1–C6-alkyl, hydroxycarbonyl-C1–C6-alkyl, hydroxycarbonylaryl-C1–C6-alkyl, aminocarbonyl-C1–C6-alkyl, aryloxy-C1–C6-alkyl, heteroaryloxy-C1–C6-alkyl, arylthio-C1–C6-alkyl, arylsulfonyl-C1–C6-alkyl, arylsulfinyl-C1–C6-alkyl, heteroarylthio-C1–C6-alkyl, heteroarylsulfonyl-C1–C6-alkyl, heteroarylsulfinyl-C1–C6-alkyl, halo-C1–C6-alkyl, alkoxycarbonylamino-C1–C6-alkyl, and amino-C1–C6-alkyl, wherein:
• the amino-C1–C6-alkyl nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of C1–C6-alkyl, aryl-C1–C6-alkyl, cycloalkyl, and C1–C6-alkylcarbonyl, or
• R10 and R11, together with the carbon to which they are bonded, form a carbonyl group, or
• R10 and R11 or R10 and R8, together with the atom(s) to which they are bonded, form a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• as to R11:
• R11 is selected from the group consisting of hydrido, hydroxy, C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, heteroaryl, heteroaryl-C1–C6-alkyl, C2–C6-alkynyl, C2–C6-alkenyl, thiol-C1–C6-alkyl, C1–C6-alkylthio-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfonyl-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfinyl-C1–C6-alkylcycloalkyl, cycloalkyl-C1–C6-alkyl, heterocycloalkyl-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkyl, arylalkoxy-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkoxy-C1–C6-alkyl, hydroxy-C1–C6-alkyl, hydroxycarbonyl-C1–C6-alkyl, hydroxycarbonylaryl-C1–C6-alkyl, aminocarbonyl-C1–C6-alkyl, aryloxy-C1–C6-alkyl, heteroaryloxy-C1–C6-alkyl, arylthio-C1–C6-alkyl, arylsulfonyl-C1–C6-alkyl, arylsulfinyl-C1–C6-alkyl, heteroarylthio-C1–C6-alkyl, heteroarylsulfonyl-C1–C6-alkyl, heteroarylsulfinyl-C1–C6-alkyl, halo-C1–C6-alkyl, alkoxycarbonylamino-C1–C6-alkyl, and amino-C1–C6-alkyl, wherein:
• the amino-C1–C6-alkyl nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of C1–C6-alkyl, aryl-C1–C6-alkyl, cycloalkyl, and C1–C6-alkylcarbonyl, or R11 and R10, together with the carbon to which they are bonded, form:
• a carbonyl group, or
• a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• only one of R8 and R9 or R10 and R11 may be hydroxy;
• R3a and R3b, together with the nitrogen to which they are bonded, form -GAREY1;
• G is piperidinyl;
• A is selected from the group consisting of:
• (1) —O—,
• (2) —S—,
• (3) —N(Re)—,
• (4) —CO—N(Re)—,
• (5) —N(Re)—CO—,]
• (6) —CO—O—,
• (7) —O—CO—,
• (8) —O—CO—O—,
• (9) —HC═CH—,
• (10) —NH—CO—NH—,
• (11) —C≡C—,
• (12) —NH—CO—O—,
• (13) —O—CO—NH—,
• (14) —N═N—,
• (15) —NH—NH—,
• (16) —CS—N(Re)—,
• (17) —N(Re)—CS—,
• (18) —CH2—,
• (19) —O—[(CH2)1-8]—,
• (20) —[(CH2)1-8]O—,
• (21) —S—CH2—,
• (22) —CH2—S—, and
• (23) a bond;
• R is selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, cycloalkoxyalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, cycloalkylthioalkyl, and heterocycloalkylthioalkyl, wherein:
• the aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C1–C2-alkylene-dioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkylcarbonylamino, and alkoxycarbonyl;
• E is selected from the group consisting of:
• (1) —CO(Rw)—,
• (2) —(Rw)CO—,
• (3) —CONH—,
• (4) —HNCO—,
• (5) —CO—,
• (6) —SO2—Rw—,
• (7) —Rw—SO2—,
• (8) —SO2—,
• (9) —NH—SO2—,
• (10) —SO2—NH—, and
• (11) a bond;
• Y1 is selected from the group consisting of hydrido, alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, alkenyl, heterocycloalkyl, alkoxycarbonyl, and aminoalkyl, wherein:
• the aryl, heteroaryl, or heterocycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of alkylaminocarbonyl, halo, nitro, arylalkyl, aryl, alkoxy, and amino, wherein:
• the amino nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and arylalkyl;
• Re is selected from the group consisting of hydrido, alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, alkyloxycarbonyl, RcRdamino carbonyl, RcRdaminosulfonyl, RcRdaminoalkylcarbonyl, and RcRdaminoalkysulfonyl;
• each Rc and Rd is independently selected from the group consisting of hydrido, alkylcarbonyl, arylalkyl, arylcarbonyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkyl, trifluoromethylalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, thiolalkylcarbonyl, alkenyl, alkynyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein:
• any amino nitrogen of Rc or Rd optionally is substituted with one or two independently selected Ry substituents, or
• any amino nitrogen of Rc or Rd optionally is substituted with two substituents such that the two substituents, together with the amino nitrogen, form:
• a saturated or partially unsaturated heterocyclo optionally substituted with one, two, or three independently selected Rw substituents, or
• a heteroaryl optionally substituted with one, two, or three independently selected Rv substituents;
• each Rv is independently selected from the group consisting of aryl, heteroaryl, heterocyclo, arylcarbonyl, alkylcarbonyl, heteroarylcarbonyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, RyRz-amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkyloxycarbonyl, alkyloxycarbonyloxy, aryloxycarbonyl, arylalkyloxycarbonyl, arylalkyloxycarbonylamino, aryloxycarbonyloxy, carboxy, RyRz-aminocarbonyloxy, RyRz-aminocarbonyl, RyRz-aminoalkylcarbonyl, hydroxyaminocarbonyl, RyRz-aminosulfonyl, RyRz-aminocarbonyl(Ry) amino, trifluoromethylsulfonyl(Ry)amino, heteroarylsulfonyl(Ry)amino, arylsulfonyl(Ry)amino, arylsulfonyl(Ry)aminocarbonyl, alkylsulfonyl(Ry)amino, arylcarbonyl(Ry)aminosulfonyl, and alkylsulfonyl(Ry)aminocarbonyl;
• each Rw is independently selected from the group consisting of hydrido, aryl, heteroaryl, heterocyclo, arylcarbonyl, alkylcarbonyl, hetero arylcarbonyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, RyRz-amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkyloxycarbonyl, alkyloxycarbonyloxy, aryloxycarbonyl, arylalkyloxycarbonyl, arylalkyloxycarbonylamino, aryloxycarbonyloxy, carboxy, RyRz-aminocarbonyloxy, RyRz-aminocarbonyl, RyRz-aminoalkylcarbonyl, hydroxyaminocarbonyl, RyRz-aminosulfonyl, RyRz-aminocarbonyl(Ry) amino, trifluoromethylsulfonyl(Ry)amino, heteroarylsulfonyl-(Ry)amino, arylsulfonyl(Ry)amino, arylsulfonyl(Ry)aminocarbonyl, alkylsulfonyl(Ry)amino, arylcarbonyl(Ry)aminosulfonyl, and alkylsulfonyl(Ry)aminocarbonyl;
• each Ry is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkylcarbonyl, arylcarbonyl, aminoalkylcarbonyl, halo alkylcarbonyl, and hydroxyalkyl, wherein:
• any such group is optionally substituted by one or two independently selected Ru substituents;
• each Rz is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkylcarbonyl, arylcarbonyl, aminoalkylcarbonyl, haloalkylcarbonyl, and hydroxyalkyl, wherein:
• each such group optionally is substituted by one or two independently selected Ru substituents
• each Ru is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkylcarbonyl, arylcarbonyl, aminoalkylcarbonyl, haloalkylcarbonyl, and hydroxyalkyl, wherein:
• the aminoalkyl and aminoalkylcarbonyl are optionally substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, and alkyloxycarbonyl;
• R20 is selected from the group consisting of —O—R21, —NH—O—R22, and —NH—O—R14;
• R21 is selected from the group consisting of hydrido, C1–C6-alkyl, aryl, and aryl-C1–C6-alkyl;
• R22 is a selectively removable protecting group;
• R14 is selected from the group consisting of hydrido and C(W)R15;
• W is selected from the group consisting of O and S;
• and
• 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 optionally is substituted with one or 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-alkylcarbonyl, or
• the amino-C1–C6-alkyl nitrogen optionally is substituted with two substituents such that the two substituents, together with the nitrogen, form a 5- to 8-membered heterocyclo or heteroaryl.

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

• the compound corresponds in structure to formula II:
• R1 and R2, together with the carbon to which they are bonded, form piperidinyl optionally substituted by one, two, or three independently selected Rx substituents;
• each Rx is independently selected from the group consisting of aryl, heteroaryl, heterocyclo, arylcarbonyl, alkylcarbonyl, heteroarylcarbonyl, halogen, cyano, aldehydo, hydroxy, RcRd-amino, RcRd-aminoalkyl, nitro, nitroso, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, alkoxyalkyl, Rc-oxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkyloxycarbonyl, alkyloxycarbonyloxy, aryloxycarbonyl, arylalkyloxycarbonyl, alkyloxycarbonyl-Rc-amino, arylalkyloxycarbonyl-Rc-amino, aryloxycarbonyloxy, carboxy, RcRd-aminocarbonyloxy, RcRd-aminocarbonyl, RcRd-aminoalkylcarbonyl, hydroxy-Rc-aminocarbonyl, RcRd-aminosulfonyl, arylsulfonyl(Rc)amino, RcRd-aminoalkoxy, RcRd-aminocarbonyl(Rc)amino, trifluoromethylsulfonyl(Rc)amino, heteroarylsulfonyl-(Rc)amino, alkylsulfonyl, arylsulfonyl(Rc)amino, arylsulfonyl(Rc)aminocarbonyl, alkylsulfonyl(Rc)amino, arylcarbonyl(Rc)aminosulfonyl, and alkylsulfonyl(Rc)aminocarbonyl;
• each Rc and Rd is independently selected from the group consisting of hydrido, alkylcarbonyl, arylalkyl, arylcarbonyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, thioalkylcarbonyl, alkenyl, alkynyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein:
• any amino nitrogen of Rc or Rd optionally is substituted with one or two independently selected Ry substituents, or
• any amino nitrogen of Rc or Rd optionally is substituted with two substituents such that the two substituents, together with the amino nitrogen, form:
• a saturated or partially unsaturated heterocyclo optionally substituted with one, two, or three independently selected Rw substituents, or
• a heteroaryl optionally substituted with one, two, or three independently selected Rv substituents;
• each Ry is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkylcarbonyl, arylcarbonyl, aminoalkylcarbonyl, haloalkylcarbonyl, and hydroxyalkyl, wherein:
• any such group is optionally substituted by one or two independently selected Ru substituents;
• each Rv is independently selected from the group consisting of aryl, heteroaryl, heterocyclo, arylcarbonyl, alkylcarbonyl, heteroarylcarbonyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, RyRz-amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkyloxycarbonyl, alkyloxycarbonyloxy, aryloxycarbonyl, arylalkyloxycarbonyl, arylalkyloxycarbonylamino, aryloxycarbonyloxy, carboxy, RyRz-aminocarbonyloxy, RyRz-aminocarbonyl, RyRz-aminoalkylcarbonyl, hydroxyaminocarbonyl, RyRz-aminosulfonyl, RyRz-aminocarbonyl(Ry)amino, trifluoromethylsulfonyl(Ry)amino, heteroarylsulfonyl(Ry)amino, arylsulfonyl(Ry)amino, arylsulfonyl(Ry)aminocarbonyl, alkylsulfonyl(Ry)amino, arylcarbonyl(Ry)aminosulfonyl, and alkylsulfonyl(Ry)aminocarbonyl;
• each Rw is independently selected from the group consisting of hydrido, aryl, heteroaryl, heterocyclo, arylcarbonyl, alkylcarbonyl, heteroarylcarbonyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, RyRz-amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkyloxycarbonyl, alkyloxycarbonyloxy, aryloxycarbonyl, arylalkyloxycarbonyl, arylalkyloxycarbonylamino, aryloxycarbonyloxy, carboxy, RyRz-aminocarbonyloxy, RyRz-aminocarbonyl, RyRz-aminoalkylcarbonyl, hydroxyaminocarbonyl, RyRz-aminosulfonyl, RyRz-aminocarbonyl(Ry)amino, trifluoromethylsulfonyl(Ry)amino, heteroarylsulfonyl(Ry)amino, arylsulfonyl(Ry)amino, arylsulfonyl(Ry)aminocarbonyl, alkylsulfonyl(Ry)amino, arylcarbonyl(Ry)aminosulfonyl, and alkylsulfonyl(Ry)aminocarbonyl;
• each Rz is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkylcarbonyl, arylcarbonyl, aminoalkylcarbonyl, haloalkylcarbonyl, and hydroxyalkyl, wherein:
• each such group optionally is substituted by one or two independently selected Ru substituents;
• each Ru is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkylcarbonyl, arylcarbonyl, aminoalkylcarbonyl, haloalkylcarbonyl, and hydroxyalkyl, wherein:
• the aminoalkyl and aminoalkylcarbonyl are optionally substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, and alkyloxycarbonyl;
• Re is selected from the group consisting of hydrido, alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, alkyloxycarbonyl, RcRdaminocarbonyl, RcRdaminosulfonyl, RcRdaminoalkylcarbonyl, and RcRdaminoalkysulfonyl;
• R3a and R3b, together with the nitrogen to which they are bonded, form -GAREY1;
• G is piperidinyl;
• A is selected from the group consisting of:
• (1) —O—,
• (2) —S—,
• (3) —N(Re)—,
• (4) —CO—N(Re)—,
• (5) —N(Re)—CO—,
• (6) —CO—O—,
• (7) —O—CO—,
• (8) —O—CO—O—,
• (9) —HC═CH—,
• (10) —NH—CO—NH—,
• (11) —C≡C—,
• (12) —NH—CO—O—,
• (13) —O—CO—NH—,
• (14) —N═N—,
• (15) —NH—NH—,
• (16) —CS—N(Re)—,
• (17) —N(Re)—CS—,
• (18) —CH2—,
• (19) —O—[(CH2)1-8]—,
• (20) —[(CH2)1-8]O—,
• (21) —S—CH2—,
• (22) —CH2—S—, and
• (23) a bond;
• R is selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, cycloalkoxyalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, cycloalkylthioalkyl, and heterocycloalkylthioalkyl, wherein:
• the aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, C1–C2-alkylene-dioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, intro, hydroxy, hydroxyalkyl, alkylcarbonylamino, and alkoxycarbonyl;
• E is selected from the group consisting of:
• (1) —CO(Rw)—,
• (2) —(Rw)CO —,
• (3) —CONH—,
• (4) —HNCO—,
• (5) —CO—,
• (6) —SO2—Rw—,
• (7) —Rw—SO2—,
• (8) —SO2—,
• (9) —NH—SO2—,
• (10) —SO2—NH—, and
• (11) a bond;
• Y1 is selected from the group consisting of arylalkyl, cycloalkyl, hydroxy, arylalkoxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, alkenyl, heterocycloalkyl, alkoxycarbonyl, and aminoalkyl, wherein:
• the heterocycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of alkylaminocarbonyl, halo, nitro, arylalkyl, aryl, alkoxy, and amino, wherein:
• the amino nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and arylalkyl;
• R20 is selected from the group consisting of —O—R21, —NH—O—R22, and —NH—O—R14;
• R21 is selected group consisting of hydrido, C1–C6-alkyl, aryl, and aryl-C1–C6-alkyl;
• R22 is a selectively removable protecting group;
• R14 is selected from the group consisting of hydrido and C(W)R15;
• W is selected from the group consisting of O and S;
• and
• 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 optionally is substituted with one or 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-alkylcarbonyl, or
• the amino-C1–C6-alkyl nitrogen optionally is substituted with two substituents such that the two substituents, together with the nitrogen, form a 5- to 8-membered heterocyclo or heteroaryl.

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

• the compound corresponds in structure to formula VIII:
• m is selected from the group consisting of zero, 1, and 2;
• n is selected from the group consisting of zero, 1, and 2;
• p is selected from the group consisting of zero, 1, and 2;
• the sum of m+n+p equals 2;
• one of X, Y, and Z is NR6 and the remaining two of X, Y, and Z are CR8R9 and CR10R11;
• R6 is selected from the group consisting of hydrido, C1–C6-alkylcarbonyl, C6-aryl-C1–C6-alkyl, arylcarbonyl, bis(C1–C6-alkoxy-C1–C6-alkyl)-C1–C6-alkyl, C1–C6-alkyl, C1–C6-haloalkyl, C1–C6-perfluoroalkoxy-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkyl, C3–C6-cycloalkyl, C3–C8-heterocycloalkyl, C3–C8-heterocycloalkylcarbonyl, phenyl, 5- to 6-membered heterocyclo, 5- to 6-membered heteroaryl, C3–C8-cycloalkyl-C1–C6-alkyl, phenyloxy-C1–C6-alkyl, heteroaryloxy-C1–C6-alkyl, heteroaryl-C1–C6-alkoxy-C1–C6-alkyl, heteroarylthio-C1–C6-alkyl, phenylsulfonyl, C1–C6-alkylsulfonyl, 5- to 6-membered heteroarylsulfonyl, carboxy-C1–C6-alkyl, C1–C4-alkoxycarbonyl-C1–C6-alkyl, aminocarbonyl, C1–C6-alkyliminocarbonyl, phenyliminocarbonyl, 5- to 6-membered heterocycloiminocarbonyl, phenylthio-C1–C6-alkyl, C1–C6-alkylthio-C1–C6-alkyl, phenylthio-C3–C6-alkenyl, C1–C4-alkylthio-C3–C6-alkenyl, 5- to 6-membered heteroaryl-C1–C6-alkyl, halo-C1–C6-alkylcarbonyl, hydroxy-C1–C6-alkylcarbonyl, thiol-C1–C6-alkylcarbonyl, C3–C6-alkenyl, C3–C6-alkynyl, C1–C5-alkoxycarbonyl, aryloxycarbonyl, NR8R9—C1–C5-alkylcarbonyl, hydroxy-C1–C5-alkyl, aminocarbonyl, hydroxyaminocarbonyl, aminosulfonyl, amino-C1–C6-alkylsulfonyl, and amino-C1–C6-alkyl, wherein:
• the aminocarbonyl, hydroxyaminocarbonyl, aminosulfonyl, amino-C1–C6-alkylsulfonyl, and amino-C1–C6-alkyl nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of C1–C6-alkyl, aryl-C1–C6-alkyl, C3–C8-cycloalkyl, and C1–C6-alkylcarbonyl;
• as to R8:
• R8 is selected from the group consisting of hydrido, hydroxy, C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, heteroaryl, heteroaryl-C1–C6-alkyl, C2–C6-alkynyl, C2–C6-alkenyl, thiol-C1–C6-alkyl, C1–C6-alkylthio-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfonyl-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfinyl-C1–C6-alkylcycloalkyl, cycloalkyl-C1–C6-alkyl, heterocycloalkyl-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkyl, arylalkoxy-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkoxy-C1–C6-alkyl, hydroxy-C1–C6-alkyl, hydroxycarbonyl-C1–C6-alkyl, hydroxycarbonylaryl-C1–C6-alkyl, aminocarbonyl-C1–C6-alkyl, aryloxy-C1–C6-alkyl, heteroaryloxy-C1–C6-alkyl, arylthio-C1–C6-alkyl, arylsulfonyl-C1–C6-alkyl, arylsulfinyl-C1–C6-alkyl, heteroarylthio-C1–C6-alkyl, heteroarylsulfonyl-C1–C6-alkyl, heteroarylsulfinyl-C1–C6-alkyl, halo-C1–C6-alkyl, alkoxycarbonylamino-C1–C6-alkyl, and amino-C1–C6-alkyl, wherein:
• the amino-C1–C6-alkyl nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of C1–C6-alkyl, aryl-C1–C6-alkyl, cycloalkyl, and C1–C6-alkylcarbonyl, or
• R8 and R9, together with the carbon to which they are bonded, form a carbonyl group, or
• R8 and R9 or R8 and R10, together with the atom(s) to which they are bonded, form a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• as to R9:
• R9 is selected from the group consisting of hydrido, hydroxy, C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, heteroaryl, heteroaryl-C1–C6-alkyl, C2–C6-alkynyl, C2–C6-alkenyl, thiol-C1–C6-alkyl, C1–C6-alkylthio-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfonyl-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfinyl-C1–C6-alkylcycloalkyl, cycloalkyl-C1–C6-alkyl, heterocycloalkyl-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkyl, arylalkoxy-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkoxy-C1–C6-alkyl, hydroxy-C1–C6-alkyl, hydroxycarbonyl-C1–C6-alkyl, hydroxycarbonylaryl-C1–C6-alkyl, aminocarbonyl-C1–C6-alkyl, aryloxy-C1–C6-alkyl, heteroaryloxy-C1–C6-alkyl, arylthio-C1–C6-alkyl, arylsulfonyl-C1–C6-alkyl, arylsulfinyl-C1–C6-alkyl, heteroarylthio-C1–C6-alkyl, heteroarylsulfonyl-C1–C6-alkyl, heteroarylsulfinyl-C1–C6-alkyl, halo-C1–C6-alkyl, alkoxycarbonylamino-C1–C6-alkyl, and amino-C1–C6-alkyl, wherein:
• the amino-C1–C6-alkyl nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of C1–C6-alkyl, aryl-C1–C6-alkyl, cycloalkyl, and C1–C6-alkylcarbonyl, or
• R9 and R8, together with the carbon to which they are bonded, form:
• a carbonyl group, or
• a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• as to R10:
• R10 is selected from the group consisting of hydrido, hydroxy, C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, heteroaryl, heteroaryl-C1–C6-alkyl, C2–C6-alkynyl, C2–C6-alkenyl, thiol-C1–C6-alkyl, C1–C6-alkylthio-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfonyl-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfinyl-C1–C6-alkylcycloalkyl, cycloalkyl-C1–C6-alkyl, heterocycloalkyl-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkyl, arylalkoxy-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkoxy-C1–C6-alkyl, hydroxy-C1–C6-alkyl, hydroxycarbonyl-C1–C6-alkyl, hydroxycarbonylaryl-C1–C6-alkyl, aminocarbonyl-C1–C6-alkyl, aryloxy-C1–C6-alkyl, heteroaryloxy-C1–C6-alkyl, arylthio-C1–C6-alkyl, arylsulfonyl-C1–C6-alkyl, arylsulfinyl-C1–C6-alkyl, heteroarylthio-C1–C6-alkyl, heteroarylsulfonyl-C1–C6-alkyl, heteroarylsulfinyl-C1–C6-alkyl, halo-C1–C6-alkyl, alkoxycarbonylamino-C1–C6-alkyl, and amino-C1–C6-alkyl, wherein:
• the amino-C1–C6-alkyl nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of C1–C6-alkyl, aryl-C1–C6-alkyl, cycloalkyl, and C1–C6-alkylcarbonyl, or
• R10 and R11, together with the carbon to which they are bonded, form a carbonyl group, or
• R10 and R11R10 and R8, together with the atom(s) to which they are bonded, form a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• as to R11:
• R11 is selected from the group consisting of hydrido, hydroxy, C1–C6-alkyl, aryl, aryl-C1–C6-alkyl, heteroaryl, heteroaryl-C1–C6-alkyl, C2–C6-alkynyl, C2–C6-alkenyl, thiol-C1–C6-alkyl, C1–C6-alkylthio-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfonyl-C1–C6-alkylcycloalkyl, C1–C6-alkylsulfinyl-C1–C6-alkylcycloalkyl, cycloalkyl-C1–C6-alkyl, heterocycloalkyl-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkyl, arylalkoxy-C1–C6-alkyl, C1–C6-alkoxy-C1–C6-alkoxy-C1–C6-alkyl, hydroxy-C1–C6-alkyl, hydroxycarbonyl-C1–C6-alkyl, hydroxycarbonylaryl-C1–C6-alkyl, aminocarbonyl-C1–C6-alkyl, aryloxy-C1–C6-alkyl, heteroaryloxy-C1–C6-alkyl, arylthio-C1–C6-alkyl, arylsulfonyl-C1–C6-alkyl, arylsulfinyl-C1–C6-alkyl, heteroarylthio-C1–C6-alkyl, heteroarylsulfonyl-C1–C6-alkyl, heteroarylsulfinyl-C1–C6-alkyl, halo-C1–C6-alkyl, alkoxycarbonylamino-C1–C6-alkyl, and amino-C1–C6-alkyl, wherein:
• the amino-C1–C6-alkyl nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of C1–C6-alkyl, aryl-C1–C6-alkyl, cycloalkyl, and C1–C6-alkylcarbonyl, or R11 and R10, together with the carbon to which they are bonded, form:
• a carbonyl group, or
• a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are independently selected from the
• group consisting of nitrogen, oxygen, and sulfur;
• only one of R8 and R9 or R10 and R11 may be hydroxy;
• R3a and R3b, together with the nitrogen to which they are bonded, form -GAREY1;
• G is piperidinyl;
• A is selected from the group consisting of:
• (1) —O—,
• (2) —S—,
• (3) —N(Re)—,
• (4) —CO—N(Re)—,
• (5) —N(Re)—CO—, ]
• (6) —CO—O—,
• (7) —O—CO—,
• (8) —O—CO—O—,
• (9) —HC═CH—,
• (10) —NH—CO—NH—,
• (11) —C≡C—,
• (12) —NH—CO—O—,
• (13) —O—CO—NH—,
• (14) —N═N—,
• (15) —NH—NH—,
• (16) —CS—N(Re)—,
• (17) —N(Re)—CS—,
• (18) —CH2—,
• (19) —O—[(CH2)1-8]—,
• (20) —[(CH2)1-8]O—,
• (21) —S—CH2—,
• (22) —CH2—S—, and
• (23) a bond;
• R is selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, cycloalkoxyalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, cycloalkylthioalkyl, and heterocycloalkylthioalkyl, wherein:
• the aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of halo, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, C1–C2-alkylene-dioxy, hydroxycarbonylalkyl,
• hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkylcarbonylamino, and alkoxycarbonyl;
• E is selected from the group consisting of:
• (1) —CO(Rw)—,
• (2) —(Rw)CO—,
• (3) —CONH—,
• (4) —HNCO—,
• (5) —CO—,
• (6) —SO2—Rw—,
• (7) —Rw—SO2—,
• (8) —SO2—,
• (9) —NH—SO2—,
• (10) —SO2—NH—, and
• (11) a bond;
• Y1 is selected from the group consisting of arylalkyl, cycloalkyl, hydroxy, arylalkoxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, alkenyl, heterocycloalkyl, alkoxycarbonyl, and aminoalkyl, wherein:
• the heterocycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of alkylaminocarbonyl, halo, nitro, arylalkyl, aryl, alkoxy, and amino, wherein:
• the amino nitrogen optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and arylalkyl;
• Re is selected from the group consisting of hydrido, alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, alkyloxycarbonyl, RcRdamino carbonyl, RcRdaminosulfonyl, RcRdaminoalkylcarbonyl, and RcRdaminoalkysulfonyl;
• each Rc and Rd is independently selected from the group consisting of hydrido, alkylcarbonyl, arylalkyl, arylcarbonyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkyl, trifluoromethylalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, thiolalkylcarbonyl, alkenyl, alkynyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein:
• any amino nitrogen of Rc or Rd optionally is substituted with one or two independently selected Ry substituents, or
• any amino nitrogen of Rc or Rd optionally is substituted with two substituents such that the two substituents, together with the amino nitrogen, form:
• a saturated or partially unsaturated heterocyclo optionally substituted with one, two, or three independently selected Rw substituents, or
• a heteroaryl optionally substituted with one, two, or three independently selected Rv substituents;
• each Rv is independently selected from the group consisting of aryl, heteroaryl, heterocyclo, arylcarbonyl, alkylcarbonyl, heteroarylcarbonyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, RyRz-amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkyloxycarbonyl, alkyloxycarbonyloxy, aryloxycarbonyl, arylalkyloxycarbonyl, arylalkyloxycarbonylamino, aryloxycarbonyloxy, carboxy, RyRz-aminocarbonyloxy, RyRz-aminocarbonyl, RyRz-aminoalkylcarbonyl, hydroxyaminocarbonyl, RyRz-aminosulfonyl, RyRz-aminocarbonyl(Ry) amino, trifluoromethylsulfonyl(Ry)amino, heteroarylsulfonyl(Ry)amino, arylsulfonyl(Ry)amino, arylsulfonyl(Ry)aminocarbonyl, alkylsulfonyl(Ry)amino, arylcarbonyl(Ry)aminosulfonyl, and alkylsulfonyl(Ry)aminocarbonyl;
• each Rw is independently selected from the group consisting of hydrido, aryl, heteroaryl, heterocyclo, arylcarbonyl, alkylcarbonyl, hetero arylcarbonyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, RyRz-amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkyloxycarbonyl, alkyloxycarbonyloxy, aryloxycarbonyl, arylalkyloxycarbonyl, arylalkyloxycarbonylamino, aryloxycarbonyloxy, carboxy, RyRz-aminocarbonyloxy, RyRz-aminocarbonyl, RyRz-aminoalkylcarbonyl, hydroxyaminocarbonyl, RyRz-aminosulfonyl, RyRz-aminocarbonyl(Ry) amino, trifluoromethylsulfonyl(Ry)amino, heteroarylsulfonyl-(Ry)amino, arylsulfonyl(Ry)amino, arylsulfonyl(Ry)aminocarbonyl, alkylsulfonyl(Ry)amino, arylcarbonyl(Ry)aminosulfonyl, and alkylsulfonyl(Ry)aminocarbonyl;
• each Ry is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkylcarbonyl, arylcarbonyl, aminoalkylcarbonyl, halo alkylcarbonyl, and hydroxyalkyl, wherein:
• any such group is optionally substituted by one or two independently selected Ru substituents;
• each Rz is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkylcarbonyl, arylcarbonyl, aminoalkylcarbonyl, haloalkylcarbonyl, and hydroxyalkyl, wherein:
• each such group optionally is substituted by one or two independently selected Ru substituents
• each Ru is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkyloxycarbonyl, arylalkyloxycarbonyl, carboxyalkyl, haloalkyl, alkylcarbonyl, arylcarbonyl, aminoalkylcarbonyl, haloalkylcarbonyl, and hydroxyalkyl, wherein:
• the aminoalkyl and aminoalkylcarbonyl are optionally substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, and alkyloxycarbonyl;
• R20 is selected from the group consisting of —O—R21, —NH—O—R22, and —NH—O—R14;
• R21 is selected from the group consisting of hydrido, C1–C6-alkyl, aryl, and aryl-C1–C6-alkyl;
• R22 is a selectively removable protecting group;
• R14 is selected from the group consisting of hydrido and C(W)R15;
• W is selected from the group consisting of O and S;
• and
• 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 optionally is substituted with one or 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-alkylcarbonyl, or
• the amino-C1–C6-alkyl nitrogen optionally is substituted with two substituents such that the two substituents, together with the nitrogen, form a 5- to 8-membered heterocyclo or heteroaryl.