US 12,133,855 B2
Lipid-like nanocomplexes and uses thereof
Qiaobing Xu, Lexington, MA (US); and Yamin Li, Somerville, MA (US)
Assigned to Trustees of Tufts College, Medford, MA (US)
Appl. No. 16/966,368
Filed by Trustees of Tufts College, Medford, MA (US)
PCT Filed Feb. 1, 2019, PCT No. PCT/US2019/016362
§ 371(c)(1), (2) Date Jul. 30, 2020,
PCT Pub. No. WO2019/152848, PCT Pub. Date Aug. 8, 2019.
Claims priority of provisional application 62/625,153, filed on Feb. 1, 2018.
Prior Publication US 2020/0368254 A1, Nov. 26, 2020
Int. Cl. A61K 33/04 (2006.01); A61K 9/16 (2006.01); A61K 31/22 (2006.01); A61K 31/575 (2006.01); A61K 47/54 (2017.01); C07C 391/00 (2006.01); A61K 47/69 (2017.01); A61K 48/00 (2006.01)
CPC A61K 31/575 (2013.01) [A61K 9/1658 (2013.01); A61K 31/22 (2013.01)] 16 Claims
 
1. A compound having a structure represented by Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein
A, a hydrophilic head, is selected from:

OG Complex Work Unit Chemistry
wherein:
Ra and Ra′ are each independently selected from H, C1-C20 alkyl, C3-C20 cycloalkyl, C1-C20 heteroalkyl, C1-C20 heterocycloalkyl, C6 monocyclic aryl, and 5-8 monocyclic heteroaryl; and
Z is selected from a C1-C20 bivalent aliphatic radical and a C1-C20 bivalent heteroaliphatic radical;
B is

OG Complex Work Unit Chemistry
wherein
R1 and R2 are each independently at each occurrence a C1-C20 bivalent aliphatic radical;
R3 and R4 are each independently at each occurrence selected from H and C1-C10 alkyl; or, alternatively, R3 and R4, together with the atom to which they are attached, form C3-C10 cycloalkyl;
R5 is independently at each occurrence selected from C1-C24 alkyl, C2-C24 alkenyl, C2-C24 alkynyl, C3-C24 cycloalkyl, C1-C24 heteroalkyl, C1-C24 heterocycloalkyl, aryl, and heteroaryl;
W is independently at each occurrence selected from O, S, and Se;
V is independently at each occurrence selected from a bond, O, S, and Se;
X is independently at each occurrence selected from

OG Complex Work Unit Chemistry
wherein:
L1, L2, L3, and L4 are each independently at each occurrence selected from a bond, O, S, and NRc;
G is independently at each occurrence selected from O, S, and NRd;
Q is independently at each occurrence selected from ORf, SRg, and NRhRi;
r and t are each independently at each occurrence an integer from 1 to 6;
wherein Rc, Rd, Rf, Rg, Rh, and Ri are each independently at each occurrence selected from H, C1-C10 alkyl, C1-C10 heteroalkyl, aryl, and heteroaryl; and
m is 1; and
at least one of W and V is Se.