US 12,404,236 B2
Non-peptidic cell-penetrating motifs
Dehua Pei, Columbus, OH (US); George Appiah Kubi, Columbus, OH (US); and Ziqing Qian, Wellesley, MA (US)
Assigned to Ohio State Innovation Foundation, Columbus, OH (US)
Filed by Ohio State Innovation Foundation, Columbus, OH (US)
Filed on Oct. 31, 2023, as Appl. No. 18/498,102.
Application 18/498,102 is a continuation of application No. 17/052,935, granted, now 11,814,341, previously published as PCT/US2019/030915, filed on May 6, 2019.
Claims priority of provisional application 62/666,995, filed on May 4, 2018.
Prior Publication US 2024/0101509 A1, Mar. 28, 2024
Int. Cl. C07C 279/12 (2006.01); A61K 47/54 (2017.01); A61K 47/64 (2017.01); C07K 5/068 (2006.01)
CPC C07C 279/12 (2013.01) [A61K 47/542 (2017.08); A61K 47/64 (2017.08); C07K 5/06086 (2013.01)] 16 Claims
OG exemplary drawing
 
1. A compound having a structure according to Formula I or II

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
or pharmaceutically acceptable salt thereof,
wherein:
A is a non-peptidic multivalent moiety, wherein A is selected from the group consisting of:
(a) a carbocyclyl;
(b) a heterocyclyl;
(c) an aryl;
(d) a heteroaryl; and
(e) a sugar alcohol;
each L is independently a bond, or an alkylene, alkenylene, alkynylene, carbocyclyl, heterocyclyl, or —Rc—X1—Rd—, wherein Rc and Rd are independently selected from alkylene, alkenylene, alkynylene, carbocyclyl, or heterocarbocyclyl, each of which are optionally substituted, and X1 is O, NH, or S;
each M is independently a bond, or an alkylene, alkenylene, alkynylene, carbocyclyl, heterocyclyl, or —Re—X2—Rf—, wherein Re and Rf are independently selected from alkylene, alkenylene, alkynylene, carbocyclyl, or heterocarbocyclyl, each of which are optionally substituted, and X2 is O, NH, or S;
each X is independently a first bonding group that links R1 to A, wherein X is a divalent group;
each Y is a second bonding group that directly or indirectly links A to a guanidine group, wherein the guanidine group refers to the structure:

OG Complex Work Unit Chemistry
each Z is a lone pair;
each R1 is independently a hydrophobic amino acid residue, or analog thereof, having an aromatic side chain;
each R2 is independently absent or a moiety comprising hydrophobic residue;
each R3 is independently a cargo moiety;
each p is independently 1 to 3;
each q is independently 2 to 7; and
each s is independently an integer from 1 to 3.