US 10,376,531 B2
Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
Spiros Liras, Brookline, MA (US); Vincent Mascitti, Groton, CT (US); and Benjamin Thuma, Old Lyme, CT (US)
Assigned to Pfizer Inc., New York, NY (US)
Filed by Pfizer Inc., New York, NY (US)
Filed on Jun. 29, 2018, as Appl. No. 16/23,232.
Application 16/023,232 is a continuation of application No. 15/434,508, filed on Feb. 16, 2017, granted, now 10,039,778.
Application 15/434,508 is a continuation of application No. 15/093,178, filed on Apr. 7, 2016, granted, now 9,617,293, issued on Apr. 11, 2017.
Application 15/093,178 is a continuation of application No. 14/714,484, filed on May 18, 2015, granted, now 9,340,553, issued on May 17, 2016.
Claims priority of provisional application 62/139,253, filed on Mar. 27, 2015.
Claims priority of provisional application 62/001,540, filed on May 21, 2014.
Claims priority of provisional application 62/000,211, filed on May 19, 2014.
Prior Publication US 2018/0296585 A1, Oct. 18, 2018
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 493/08 (2006.01); A61K 31/357 (2006.01); A61K 31/706 (2006.01); C07D 309/14 (2006.01); C07H 13/04 (2006.01); C07H 15/26 (2006.01); A61K 31/7008 (2006.01); A61K 31/7056 (2006.01); A61K 38/46 (2006.01); C07H 15/08 (2006.01); C07H 15/12 (2006.01); C07K 5/065 (2006.01); A61K 47/64 (2017.01)
CPC A61K 31/706 (2013.01) [A61K 31/7008 (2013.01); A61K 31/7056 (2013.01); A61K 38/465 (2013.01); A61K 47/64 (2017.08); C07D 309/14 (2013.01); C07D 493/08 (2013.01); C07H 13/04 (2013.01); C07H 15/08 (2013.01); C07H 15/12 (2013.01); C07H 15/26 (2013.01); C07K 5/06078 (2013.01); C12Y 301/00 (2013.01); Y02A 50/463 (2018.01)] 7 Claims
 
1. A compound of Formula (A)

OG Complex Work Unit Drawing
wherein
R1 is —Z—X—Y wherein X is a linker of any of structures L1or L2

OG Complex Work Unit Drawing
each Q is independently absent or is C(O), C(O)—NR4, NR4—C(O),O—C(O)—NR4, NR4—C(O)—O, —CH2—, or —O—, wherein at least two carbon atoms separate the —O— from any other heteroatom group;
each T is independently absent or is alkylene, wherein one or more —CH2— groups of the alkylene, may each independently be replaced with a —O—, wherein the —O— are separated by at least 2 carbon atoms;
Y is an amino acid sequence, a nucleic acid sequence, or an oligomer, and
Z is absent;
each n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40, wherein if n is greater than 1, each T and each Q of each (T-Q-T-Q) is independently selected;
R2 is —N(R3)—C(O)—R3 or —N(R3)—C(O)—OR3; and
each R3 is independently H, —(C1-C5)alkyl, halo-substituted (C1-C5)alkyl, or (C3-C6)cycloalkyl,
each R4 is independently —H, —(C1-C20)alkyl, or (C3-C6)cycloalkyl wherein one to six —CH2— groups of the alkyl or cycloalkyl separated by at least two carbon atoms may be replaced with —O—, —S—, or —N(H)—, and wherein the alkyl and cycloalkyl may be substituted with one to six halo atoms; and
or a pharmaceutically acceptable salt thereof.