Hybrid cyclic libraries and screens thereof

A method of treating a hyperproliferative disorder in a patient in need thereof comprising:

• administering a therapeutically effective amount of a compound of Formula I
• or a pharmaceutically acceptable salt or solvate thereof, to the patient, thereby treating the disorder;
• wherein:
• is a single or double bond;
• X1 is O or NR6;
• Y is —C(O)—
• X2 is (CH2)m, O, or NR6;
• Z is
• W is O, CH, CH2, CR4, or CR5;
• L1 and L2 are each independently a direct bond, substituted or unsubstituted —(C1-C6)alkyl-, substituted or unsubstituted —(CH2)nO(C1-C6)alkyl-, substituted or unsubstituted —(CH2)nC(O)—, substituted or unsubstituted —(CH2)nC(O)(C1-C6)alkyl-, substituted or unsubstituted —(CH2)nC(O)O(C1-C6)alkyl-, substituted or unsubstituted —(CH2)nNH(C1-C6)alkyl-, substituted or unsubstituted —(CH2)nC(O)NH(C1-C6)alkyl-, substituted or unsubstituted —(CH2)nS(C1-C6)alkyl-, substituted or unsubstituted —(CH2)nC(O)(CH2)nS(C1-C6)alkyl-, substituted or unsubstituted —(C2-C6)alkenyl-, substituted or unsubstituted —(CH2)nO(C2-C6)alkenyl-, substituted or unsubstituted —(CH2)nC(O)(C2-C6)alkenyl-, substituted or unsubstituted —(CH2)nC(O)O(C2-C6)alkenyl-, substituted or unsubstituted —(CH2)nNH(C1-C6)alkenyl-, substituted or unsubstituted —(CH2)nC(O)NH(C2-C6)alkenyl-, substituted or unsubstituted —(CH2)nS(C2-C6)alkenyl-, substituted or unsubstituted —(CH2)nC(O)(CH2)nS(C2-C6)alkenyl-, substituted or unsubstituted —(C2-C6)alkynyl-, substituted or unsubstituted —(CH2)nO(C2-C6)alkynyl-, substituted or unsubstituted —(CH2)nC(O)(C2-C6)alkynyl-, substituted or unsubstituted —(CH2)nC(O)O(C2-C6)alkynyl-, substituted or unsubstituted —(CH2)nNH(C1-C6)alkynyl-, substituted or unsubstituted —(CH2)nC(O)NH(C2-C6)alkynyl-, substituted or unsubstituted —(CH2)nS(C2-C6)alkynyl-, substituted or unsubstituted —(CH2)nC(O)(CH2)nS(C2-C6)alkynyl-, wherein each alkyl, alkenyl and alkynyl group may be optionally substituted with alkyl, alkoxy, amino, carboxyl, cyano, nitro, or trifluoromethyl;
• each m is independently an integer selected from 0, 1, 2, 3, 4, 5, and 6;
• each n is independently an integer selected from 0, 1, 2, 3, 4, 5, and 6;
• R1 is hydrogen, hydroxyl, or OPG, wherein PG is a protecting group, or
• R1
• wherein
• is a resin;
• R2 is hydrogen, hydroxyl, or alkoxy;
• R3 is hydrogen or alkyl;
• R4 and R5 are each independently hydrogen, hydroxy, alkyl, alkoxy, or OPG, wherein PG is a protecting group;
• R6 is hydrogen or alkyl;
• wherein the Effector Domain has Formula II:
• wherein:
• R7, R9, R11, R13, and R15 are each independently hydrogen or alkyl;
• R8, R10, R12, and R14 are each independently hydrogen, halogen, amino, cyano, nitro, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted perfluoroalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroalkylaryl, (CH2)nCN, (CH2)nCF3, (CH2)nC2F5, (CH2)nOR16, (CH2)nC(O)R16, (CH2)nC(O)OR16, (CH2)nOC(O)R16, (CH2)nNR17R18, (CH2)nC(O)NR17R18, (CH2)nN19RC(O)R16, (CH2)nN19RC(O) OR16, (CH2)nNR19C(O)NR17R18, (CH2)nSR16, (CH2)nS(O)jNR17R18, (CH2)nN19RS(O)jR16, or —(CH2)nNR19S(O)jNR17R18,
• n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;
• j is an integer selected from 0, 1, and 2;
• R16, R17, R18, and R19 are each independently hydrogen, halogen, amino, cyano, nitro, trifluoromethyl, alkyl, alkenyl, alkynyl, cycloalkyl, perfluoroalkyl, alkoxy, alkylamino, alkylthio, aryl, alkylaryl, heteroalkyl, heterocycloalkyl, heteroaryl, or heteroalkylaryl, or
• R16 and R19 are as described above, and R17 and R18, together with the N atom to which they are attached, form a substituted or unsubstituted 5-, 6-, or 7-membered heterocycloalkyl or a substituted or unsubstituted 5-membered heteroaryl,
• wherein each of the above groups listed for R8, R10, R12, and R14 may be optionally independently substituted with 1 to 3 groups selected from halogen, amino, cyano, nitro, trifluoromethyl, alkyl, alkenyl, alkynyl, cycloalkyl, perfluoroalkyl, alkoxy, alkylamino, alkylthio, aryl, alkylaryl, heteroalkyl, heterocycloalkyl, heteroaryl, heteroalkylaryl, (CH2)nCN, (CH2)nCF3, (CH2)nC2F5, (CH2),OR16, (CH2)nC(O)R16, (CH2)nC(O) OR16, (CH2)nOC(O)R16, (CH2)nNR17R18, (CH2)nC(O)NR17R18, (CH2)nN19RC(O)R16, (CH2)nN19RC(O) OR16, (CH2)nNR16C(O)NR17R18, (CH2)nSR16, (CH2)nS(O)jNR17R18, (CH2)nN19RS(O)jR16, and —(CH2)nNR19S(O)jNR17R18.