US 12,138,321 B2
Half-curcuminoids as amyloid-β PET imaging agents
Chongzhao Ran, Winchester, MA (US); Anna Moore, Stoneham, MA (US); and Jian Yang, Boston, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US)
Filed by The General Hospital Corporation, Boston, MA (US)
Filed on Sep. 22, 2021, as Appl. No. 17/448,463.
Application 17/448,463 is a continuation of application No. 16/314,153, granted, now 11,135,318, previously published as PCT/US2017/039885, filed on Jun. 29, 2017.
Claims priority of provisional application 62/451,433, filed on Jan. 27, 2017.
Claims priority of provisional application 62/356,116, filed on Jun. 29, 2016.
Prior Publication US 2022/0001035 A1, Jan. 6, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 51/04 (2006.01); C07B 59/00 (2006.01); C07C 49/248 (2006.01); C07C 49/252 (2006.01); C07F 5/02 (2006.01); A61P 25/16 (2006.01); A61P 25/28 (2006.01)
CPC A61K 51/0453 (2013.01) [A61K 51/04 (2013.01); A61K 51/0455 (2013.01); C07B 59/002 (2013.01); C07C 49/248 (2013.01); C07C 49/252 (2013.01); C07F 5/02 (2013.01); A61K 2123/00 (2013.01); A61P 25/16 (2018.01); A61P 25/28 (2018.01); C07B 2200/05 (2013.01); C07F 5/022 (2013.01)] 20 Claims
 
1. A compound of Formula Ia:

OG Complex Work Unit Chemistry
a pharmaceutically acceptable salt thereof, or a tautomer thereof, wherein:
R1 is selected from the group consisting of C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl, each of which may be optionally substituted by 1, 2, 3, or 4 independently selected R1A groups;
each R1A is independently selected from the group consisting of halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, OCH2CH2CH2CH2CH2CH2CH2F, NRN1RN2, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 independently selected R6 groups;
R2 is selected from the group consisting of C1-6 alkyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 independently selected R2A groups;
each R2A is independently selected from the group consisting of halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, NRN1RN2, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C1-6 alkyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 independently selected R6 groups;
R3 is selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;
each R6 is independently selected from the group consisting of OH, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, and —(C1-6 alkoxy)-(C1-6 haloalkoxy);
each RN1 is independently selected from the group consisting of H and C1-6 alkyl;
each RN2 is independently selected from the group consisting of C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy; and
m is 1 or 2.