	US 12,409,171 B2
	Pharmaceutically active pyrazolo-pyridone modulators of DCN1/2-mediated cullin neddylation
Hoshin Kim, Lexington, KY (US); Rodney Kiplin Guy, Lexington, KY (US); Jared T. Hammill, Lexington, KY (US); Daniel Charles Scott, Marion, KY (US); Brenda Arlene Schulman, Martinsried (DE); and Bhuvanesh Singh, Old Westbury, NY (US)
Assigned to University of Kentucky Research Foundation, Lexington, KY (US); Memorial Sloan-Kettering Cancer Center, New York, NY (US); and St. Jude Children's Research Hospital, Inc., Memphis, TN (US)
Appl. No. 17/618,952
Filed by UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, Lexington, KY (US); MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US); and St. Jude Children's Research Hospital, Inc., Memphis, TN (US)
PCT Filed Jun. 22, 2020, PCT No. PCT/US2020/038998 § 371(c)(1), (2) Date Dec. 14, 2021, PCT Pub. No. WO2020/257790, PCT Pub. Date Dec. 24, 2020.
Claims priority of provisional application 62/864,331, filed on Jun. 20, 2019.
Prior Publication US 2022/0280488 A1, Sep. 8, 2022
Int. Cl. A61K 31/437 (2006.01)

CPC A61K 31/437 (2013.01)

20 Claims

1. A DCN1/2-mediated cullin neddylation modulator according to Formula I:

wherein;

R₁is alkyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, haloaryl, alkyl ester, alkyl carboxylic acid, alkyl amide, or cyanomethyl;

R₂is alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, haloaryl, or cyanomethyl;

R₃is selected from —NHC(═O)—R₆, —NHC(═O)—NH—R₆, —NHSO₂—R₆, —C(═O)—NH—R₆, or —CH₂C(═O)—R₆;

R₄is selected from alkyl, acyl, aryl, or heteroaryl;

R₅is selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, carboxylic acid, nitrile, or —(CH₂)_n—X—R₇,

R₆is selected from alkyl, alkenyl, acyl, aryl, or heteroaryl;

R₇is selected from H, alkyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycle, heterocycloalkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, alkyl ester, alkyl carboxylic acid, alkyl amide, cyanomethyl, or —Y—Z—Y—R₈;

R₅is H or biotin;

X is selected from O, NH, S, or Linker;

each Y is independently selected from CH₂, NH, O, or S;

Z is —(OCH₂CH₂)_n—, alkyl linker, or aminoalkyl linker;

Linker is selected from —(OCH₂CH₂)_n—(PEG), alkyl linker, or aminoalkyl linker; and

each n is independently an integer from 0 to 20.