US 12,460,244 B2
Inhibitors of RNA-guided nuclease activity and uses thereof
Amit Choudhary, Boston, MA (US); and Kurt Cox, Cambridge, MA (US)
Assigned to The Broad Institute, Inc., Cambridge, MA (US); and The Brigham and Women's Hospital, Inc., Boston, MA (US)
Appl. No. 17/269,995
Filed by THE BROAD INSTITUTE, INC., Cambridge, MA (US); and THE BRIGHAM AND WOMEN'S HOSPITAL, INC., Boston, MA (US)
PCT Filed Aug. 20, 2019, PCT No. PCT/US2019/047362
§ 371(c)(1), (2) Date Feb. 19, 2021,
PCT Pub. No. WO2020/041384, PCT Pub. Date Feb. 27, 2020.
Claims priority of provisional application 62/773,694, filed on Nov. 30, 2018.
Claims priority of provisional application 62/765,352, filed on Aug. 20, 2018.
Prior Publication US 2021/0355522 A1, Nov. 18, 2021
Int. Cl. C12Q 1/44 (2006.01); A61K 31/397 (2006.01); C12N 9/22 (2006.01)
CPC C12Q 1/44 (2013.01) [A61K 31/397 (2013.01); C12N 9/22 (2013.01); G01N 2333/922 (2013.01); G01N 2500/00 (2013.01)] 14 Claims
 
1. A method of inhibiting the nuclease activity of an RNA-guided endonuclease, the comprising contacting an RNA-guided endonuclease-guide complex with a compound of Formula I:

OG Complex Work Unit Chemistry
wherein:
R1 is hydrogen;
R2 is selected from hydrogen,

OG Complex Work Unit Chemistry
 and aryl optionally substituted with one or more R10;
R3 is hydrogen or C1-C3 alkyl;
R4 is hydrogen or C1-C3 alkyl;
R5 is C1-C3 alkyl or C3-C8 cycloalkyl each optionally substituted with one or more R11;
each R10 is independently selected from halogen, C1-C3 alkyl, haloalkyl, and alkoxy;
each R11 is independently selected from halogen, C1-C3 alkyl, haloalkyl, and alkoxy; and
X is C1-C3 alkylalcohol.