Modified proteins and protein binders

A method of binding or modulating DDB1- and CUL4-Associated Factor 1 (DCAF1) in a subject in need thereof, comprising administering a therapeutically effective amount of a compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• is a single bond or a double bond;
• R1 is selected from H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, 5- to 10-membered heteroaryl, —C(O)(C1-8alkyl), —C(O)(C2-8alkenyl), —C(O)(C2-8alkynyl), —C(O)(C1-8haloalkyl), —C(O)(C1-8heteroalkyl), —C(O)(C3-10carbocyclyl), —C(O)(3- to 10-membered heterocyclyl), —C(O)(C6-10aryl), —C(O)(5- to 10-membered heteroaryl), —SO2(C1-8alkyl), —SO2(C2-8alkenyl), —SO2(C2-8alkynyl), —SO2(C1-8haloalkyl), —SO2(C1-8heteroalkyl), —SO2(C3-10carbocyclyl), —SO2(3- to 10-membered heterocyclyl), —SO2(C6-10aryl), and —SO2(5- to 10-membered heteroaryl), wherein each alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents independently selected from halo, hydroxy, oxo, amino, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C1-8alkoxy, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• R2 is selected from C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C3-10carbocyclyl, and 3- to 10-membered heterocyclyl, wherein each alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, carbocyclyl, and heterocyclyl, is independently optionally substituted with one or more substituents independently selected from halo, hydroxy, oxo, amino, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C1-8alkoxy, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• each R3 is independently selected from halo, hydroxy, amino, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C1-8alkoxy, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• and
• n is 0, 1, 2, 3, or 4.

A compound of Formula IIa:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, and C1-8heteroalkyl;
• R2 and R3 are independently selected from H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, and C1-8heteroalkyl;
• each R4 and each R5 are independently selected from H, halo, hydroxy, amino, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C1-8alkoxy, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• n is 0, 1, 2, or 3;
• and
• m is 0, 1, 2, 3, or 4.

A method of binding or modulating DDB1- and CUL4-Associated Factor 1 (DCAF1) in a subject in need thereof, comprising administering a therapeutically effective amount of a compound of Formula II:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, and C1-8heteroalkyl;
• R2 and R3 are independently selected from H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, 5- to 10-membered heteroaryl, —C(O)(C1-8alkyl), —C(O)(C2-8alkenyl), —C(O)(C2-8alkynyl), —C(O)(C1-8haloalkyl), —C(O)(C1-8heteroalkyl), —C(O)(C3-10carbocyclyl), —C(O)(3- to 10-membered heterocyclyl), —C(O)(C6-10aryl), —C(O)(5- to 10-membered heteroaryl), —SO2(C1-8alkyl), —SO(C2-8alkenyl), —SO2(C2-8alkynyl), —SO2(C1-8haloalkyl), —SO2(C1-8heteroalkyl), —SO2(C3-10carbocyclyl), —SO2(3- to 10-membered heterocyclyl), —SO2(C6-10aryl), and —SO2(5- to 10-membered heteroaryl), wherein each alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently optionally substituted with one or more substituents independently selected from halo, hydroxy, oxo, amino, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C1-8alkoxy, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• each R4 is independently selected from halo, hydroxy, amino, cyano, nitro, C1-8alkyl, C2-8lkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C1-8alkoxy, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• and
• n is 0, 1, 2, 3, or 4.

A method of binding or modulating DDB1- and CUL4-Associated Factor 1 (DCAF1) in a subject in need thereof, comprising administering a therapeutically effective amount of a compound of Formula III:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ring A is selected from null, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• X is selected from N and CR7;
• R1 is selected from H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• R2, R3, and R7 are independently selected from H, halo, hydroxy, amino, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C1-8alkoxy, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• R4 and R5 are independently selected from H, halo, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• or
• R4 and R5 are taken together to form oxo;
• each R6 is independently selected from H, halo, hydroxy, amino, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C1-8haloalkyl, C1-8heteroalkyl, C1-8alkoxy, C3-10carbocyclyl, 3- to 10-membered heterocyclyl, C6-10aryl, and 5- to 10-membered heteroaryl;
• and
• n is 0, 1, 2, 3, 4, 5, or 6.