US 12,065,458 B2
Trialkyne linking agents and methods of use
Zhen Li, Westfield, NJ (US); Erich Altenhofer, Madison, WI (US); Jeffrey Carlson, Madison, WI (US); Matthew Fowler-Watters, Madison, WI (US); and Bo Chen, Madison, WI (US)
Assigned to Arrowhead Pharmaceuticals, Inc., Pasadena, CA (US)
Appl. No. 16/970,130
Filed by Arrowhead Pharmaceuticals, Inc., Pasadena, CA (US)
PCT Filed Feb. 15, 2019, PCT No. PCT/US2019/018232
§ 371(c)(1), (2) Date Aug. 14, 2020,
PCT Pub. No. WO2019/161213, PCT Pub. Date Aug. 22, 2019.
Claims priority of provisional application 62/790,300, filed on Jan. 9, 2019.
Claims priority of provisional application 62/633,763, filed on Apr. 27, 2018.
Claims priority of provisional application 62/646,739, filed on Mar. 22, 2018.
Claims priority of provisional application 62/631,683, filed on Feb. 17, 2018.
Prior Publication US 2022/0402947 A1, Dec. 22, 2022
Int. Cl. C07F 9/06 (2006.01); A61K 47/54 (2017.01); C07C 205/59 (2006.01); C07C 235/34 (2006.01); C07D 403/14 (2006.01); C12N 15/113 (2010.01)
CPC C07F 9/06 (2013.01) [A61K 47/545 (2017.08); C07C 205/59 (2013.01); C07C 235/34 (2013.01); C07D 403/14 (2013.01); C12N 15/113 (2013.01); C12N 2310/14 (2013.01); C12N 2310/351 (2013.01)] 19 Claims
 
1. A compound of Formula III,

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein,
L1, L2, and L3 are each linkers of the formula:

OG Complex Work Unit Chemistry
L4 is selected from the group consisting of:

OG Complex Work Unit Chemistry
wherein custom character indicates the point of attachment;
R4 is H or optionally substituted alkyl;
X is O or S; and
RNA comprises or consists of an RNAi agent.