US 12,391,685 B2
Inhibitors of RNA-guided nuclease target binding and uses thereof
Amit Choudhary, Boston, MA (US); Basudeb Maji, Cambridge, MA (US); Soumyashree Ashok Gangopadhyay, Boston, MA (US); Miseon Lee, Cambridge, MA (US); and Mengchao Shi, Boston, MA (US)
Assigned to The Broad Institute, Inc., Cambridge, MA (US); and The Brigham and Women's Hospital, Inc., Boston, MA (US)
Appl. No. 17/269,900
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/US2019/047364
§ 371(c)(1), (2) Date Feb. 19, 2021,
PCT Pub. No. WO2020/068304, PCT Pub. Date Apr. 2, 2020.
Claims priority of provisional application 62/831,143, filed on Apr. 8, 2019.
Claims priority of provisional application 62/784,268, filed on Dec. 21, 2018.
Claims priority of provisional application 62/774,012, filed on Nov. 30, 2018.
Claims priority of provisional application 62/765,357, filed on Aug. 20, 2018.
Prior Publication US 2021/0177832 A1, Jun. 17, 2021
Int. Cl. C07D 471/04 (2006.01); A61K 31/4745 (2006.01); A61K 31/7105 (2006.01); A61K 38/46 (2006.01); A61K 47/54 (2017.01); C12N 9/99 (2006.01)
CPC C07D 471/04 (2013.01) [A61K 31/4745 (2013.01); A61K 31/7105 (2013.01); A61K 38/465 (2013.01); A61K 47/54 (2017.08); A61K 47/545 (2017.08); C12N 9/99 (2013.01)] 23 Claims
 
1. A compound having the structure of Formula (I):

OG Complex Work Unit Chemistry
wherein R1 is selected from alkynyl, bicyclic aryl, tricyclic aryl, and polycyclic aryl;
R2 is selected from -L1-X and -L1-R;
R3 is selected from hydrogen, —X, —R, -L2-X, and -L2-R;
R4 is —OH;
Each L1 is independently —CO— or —S(O)2—;
Each L2 is independently selected from —(CH2)n—, —(CH2)n—C(O)O—, —(CH2)n—C(O)—NH—, —C(O)—NH—(CH2)n—, —(CH2)n—NH—C(O)—, —(CH2)n—NH—SO2—, —NH—SO2—(CH2)n—, —(CH2)n—SO2—NH—, —(CH2)n—SO2—, —(CH2)n—SO2—NH—C(O)—, —(CH2)n—RL2—, —RL2—C(O)—O—, —RL2—NH—C(O)—(CH2)n—, —RL2—NH—S(O)2—(CH2)n—, —S—, —S(O)—, and —S(O)2—, wherein each n is independently 0, 1, 2, 3, 4, 5, or 6;
Each X is selected from hydrogen, CN, OH, CF3, COOH, OR, OR, NR2, and halogen;
Each RL2 is selected from C1-C12 linear and/or branched and/or cyclic and/or aromatic bivalent radicals; optionally substituted with one or more groups X and/or with 1-6 heteroatoms selected from O, S, N, P, F, Cl, Br, I, and combinations thereof; and
Each R is selected from C1-12 hydrocarbons, optionally substituted with one or more groups X and/or with 1-10 heteroatoms selected from O, S, N, P, F, Cl, Br, I, and combinations thereof.