US 12,441,756 B2
5′-cyclo-phosphonate modified nucleotides
Zhen Li, San Diego, WI (US); Tao Pei, Middleton, WI (US); and Michael Lawler, Waunakee, WI (US)
Assigned to ARROWHEAD PHARMACEUTICALS, INC., Pasadena, CA (US)
Filed by Arrowhead Pharmaceuticals, Inc., Pasadena, CA (US)
Filed on Jun. 30, 2021, as Appl. No. 17/363,983.
Application 17/363,983 is a continuation of application No. 16/207,870, filed on Dec. 3, 2018, granted, now 11,078,227.
Application 16/207,870 is a continuation of application No. PCT/US2017/036108, filed on Jun. 6, 2017.
Claims priority of provisional application 62/346,304, filed on Jun. 6, 2016.
Prior Publication US 2022/0119439 A1, Apr. 21, 2022
Int. Cl. C07H 19/10 (2006.01); C07H 19/06 (2006.01); C07H 19/16 (2006.01); C07H 19/207 (2006.01); C07H 21/02 (2006.01); C12N 15/113 (2010.01)
CPC C07H 19/10 (2013.01) [C07H 19/06 (2013.01); C07H 19/16 (2013.01); C07H 19/207 (2013.01); C07H 21/02 (2013.01); C12N 15/113 (2013.01); C12N 2310/14 (2013.01); C12N 2310/31 (2013.01); C12N 2310/312 (2013.01); C12N 2310/323 (2013.01); C12N 2310/3231 (2013.01); C12N 2310/3233 (2013.01); C12N 2310/3519 (2013.01)] 16 Claims
 
1. A pharmaceutically acceptable salt of a compound having the structure of Formula I-b:

OG Complex Work Unit Chemistry
wherein D is O or S,
X is a 9-purinyl or 1-pyrimidinyl base;
Y1, Y2, Y3, and Y4 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, or C2-C6 alkynyl;
Z is H, OH, OCH3, O—(CH2)2—OCH3 or halogen;
G1, G2, G3 and G4 are each H;
J is O or S;
K and L are each independently OH, OR16, SR16, or NR16, wherein R16 is selected from H, C1-C10 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, or

OG Complex Work Unit Chemistry
wherein R14 is H or C1-C4 alkyl optionally substituted with one to three substituents independently selected from SH, S—(C1-C4 alkyl), amino, hydroxyl, oxo or —NH—C═(NH)NH2, and R15 is selected from H, or C1-C18 alkyl;
Q is O, S, N(R30), or C(R31)(R32), wherein R30 is H, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, or C2-C6 alkynyl, and R31 and R32 are each, independently, H, halogen, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, or C2-C6 alkynyl; and
A comprises a substituent derived from a phosphate or phosphorothioate moiety of an RNAi agent,
and wherein the pharmaceutically acceptable salt is a sodium salt.