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1. A compound having the structure of Formula I-R or I-S or a pharmaceutically acceptable isolated optical isomer, enantiomer, racemate, salt, hydrate or solvate thereof:wherein
A is pyrimidine optionally substituted with one or more of R4; B is aryl, aralkyl, heterocyclyl, or heterocyclylalkyl; C is aryl, aralkyl, heterocyclyl or heterocyclylalkyl; Y1 and Y2 are both null, or one of Y1 or Y2 is —NH— or —O— and the other Y1 or Y2 is null; Z is —C(O)— or —S(O)2—; each R1 is independently H or C1-4 alkyl; R2 is —OH, —O—R8, —N(R1)—SO2—R7, —NR41R42, —N(R1)—(CRaRb)m—COOR8, —N(R1)—(CRaRb)m—CO—N(R1)(R40), —N(R1)—(CRaRb)m—N(R1)C(O)O(R8), —N(R1)—(CRaRb)m—N(R1)(R40), —N(R1)—(CRaRb)m—CO—N(R1)-heterocyclyl, or —N(R1)—(CRaRb)m-heterocyclyl, which heterocyclyl may be optionally (singly or multiply) substituted with R7; each R3 and R4 is independently H, halo, alkyl, alkyl substituted (singly or multiply) with R31, alkoxy, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, aryl, heterocyclyl, —OH, —OR7, —CN, —NO2, —NR1R7, —C(O)R7, —C(O)NR1R7, —NR1C(O)R7, —SR7, —S(O)R7, —S(O)2R7, —OS(O)2R7, —S(O)2NR1R7, —NR1S(O)2R7, —(CRaRb)mNR1R7, —(CRaRb)mO(CRaRb)mR7, —(CRaRb)mNR1(CRaRb)mR7 or —(CRaRb)mNR1(CRaRb)mCOOR8; or any two R3 or R4 groups on the same carbon atom taken together form oxo; each R31 is independently H, halo, hydroxyl, —NR41R42, or alkoxy; each R40 is independently H, R7, alkyl which may be optionally (singly or multiply) substituted with R7, or R40 and R1 taken together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl which may be optionally (singly or multiply) substituted with R7; each R41 and R42 is independently R40, —(CHR40)n—C(O)O—R40, —(CHR40)n—C(O)—R40, —(CH2)n—N(R1)(R7), aryl or heteroaryl any of which aryl or heteroaryl may be optionally (singly or multiply) substituted with R7; or any two R41 and R42 taken together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl which may be optionally (singly or multiply) substituted with R7; W1 is null or -L1-(CRaRb)m-L1-R6; each L1 is independently, from the proximal to distal end of the structure of Formula I-R or I-S, null, —C(O)O—, —S(O2)—, —S(O)—, —S—, —N(R1)—C(O)—N(R1)—, —N(R1)—C(O)—O—, —C(O)— or —S(O2)—NR1—; each Ra and Rb is independently H, halo, alkyl, alkoxy, aryl, aralkyl, heterocyclyl, heterocyclylalkyl (any of which alkyl, alkoxy, aryl, aralkyl, heterocyclyl or heterocyclylalkyl may be optionally (singly or multiply) substituted with R7), —(CHR40)mC(O)OR40, —(CHR40)mOR40, —(CHR40)mSR40, —(CHR40)mNR41R42, —(CHR40)mC(O)NR41R42, —(CHR40)mC(O)N(R1)(CHR40)m—NR41R42, —(CHR40)mC(O)—N(R1)(CHR40)mC(O)NR41R42, —(CHR40)mC(O)N(R1)—(CHR40)mC(O)OR40, or —(CHR40)m—S—S—R40; or any two Ra and Rb taken together with the carbon atom(s) to which they are attached form a cycloalkyl or heterocyclyl optionally substituted (singly or multiply) with R7; or R1 and any one of Ra or Rb taken together with the atom(s) to which they are attached form heterocyclyl optionally substituted (singly or multiply) with R7; R5 is R7, —(CRaRb)m-L2-(CRaRb)m—R7, or -(-L3-(CRaRb)r-)s-L3-R7, wherein the carbon atoms of any two adjacent —(CRaRb)m or —(CRaRb)r groups may be taken together to form a double bond (—(C(Ra)═(C(Ra)—) or triple bond (—C≡C—); R6 is H, alkyl, aryl, heteroaryl, heterocyclyl, heterocycloalkyl, any of which may be optionally substituted (singly or multiply) with R7 or —(CRaRb)m-L2-(CRaRb)m—R7; each R7 is independently R10; a ring moiety selected from cycloalkyl, aryl, aralkyl, heterocyclyl or heterocyclylalkyl, where such ring moiety is optionally singly or multiply substituted with R10; or when a carbon atom bears two R7 groups such two R7 groups are taken together to form oxo or thioxo, or are taken together to form a ring moiety selected from cycloalkyl, aryl, heterocyclyl or heterocyclyl, wherein such ring moiety is optionally singly or multiply substituted with R10; each R10 is independently H, halo, alkyl, haloalkyl, perhaloalkyl, —(CRaRb)mOH, —(CRaRb)mOR8, —(CRaRb)mCN, —(CRaRb)mNH(C═NH)NH2, —(CRaRb)mNR1R8, —(CRaRb)mO(CRaRb)mR8, —(CRaRb)mNR1(CRaRb)mR8, —(CRaRb)mC(O)R8, —(CRaRb)mC(O)OR8, —(CRaRb)mC(O)NR1R8, —(CRaRb)mNR1(CRaRb)mC(O)OR8, —(CRaRb)mNR1C(O)R8, —(CRaRb)mC(O)NR1S(O)2R8, —(CRaRb)mSR8, —(CRaRb)mS(O)R8, —(CRaRb)mS(O)2R8, —(CRaRb)mS(O)2NR1R8 or —(CRaRb)mNR1S(O)2R8; each R8 is independently H, alkyl, aryl, —(CRaRb)m-L2-(CRaRb)m—R1 or -(-L3-(CRaRb)r)s-L3-R1; L2 is independently, from the proximal to distal end of the structure of Formula I-R or I-S, null, —O—, —OC(O)—, —NR1—, —C(O)NR1—, —N(R1)—C(O)—, —S(O2)—, —S(O)—, —S—, —C(O)— or —S(O2)—N(R1)—; each L3 is independently null, —O—, or —N(R1)— each m is independently 0, 1, 2, 3, 4, 5 or 6; each n is independently 0 or 1 or 2; p is 0, 1, 2 or 3; q is 0, 1, 2 or 3; each r is independently 2, 3, or 4; and each s is independently 1, 2, 3, or 4. |
