US 12,332,246 B2
Quinoline based cyanine dye turn-on fluorescent probes and methods of use thereof
David Margulies, Rehovot (IL); Leila Motiei, Rehovot (IL); Pragati Prasad, Rehovot (IL); Tom Granot, Rehovot (IL); and Ohad Suss, Rehovot (IL)
Assigned to YEDA RESEARCH AND DEVELOPMENT CO. LTD., Rehovot (IL)
Filed by YEDA RESEARCH AND DEVELOPMENT CO. LTD., Rehovot (IL)
Filed on Jan. 3, 2021, as Appl. No. 17/140,075.
Application 17/140,075 is a continuation in part of application No. 16/783,524, filed on Feb. 6, 2020, granted, now 11,639,929.
Application 17/140,075 is a continuation in part of application No. PCT/IL2019/050639, filed on Jun. 5, 2019.
Application 16/783,524 is a continuation in part of application No. 15/307,011, previously published as PCT/IL2015/050441, filed on Apr. 28, 2015.
Claims priority of provisional application 61/985,555, filed on Apr. 29, 2014.
Prior Publication US 2021/0156867 A1, May 27, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. G01N 33/58 (2006.01); C07C 227/18 (2006.01); G01N 21/64 (2006.01); G01N 33/50 (2006.01); G01N 33/68 (2006.01)
CPC G01N 33/582 (2013.01) [G01N 21/6428 (2013.01); G01N 21/6458 (2013.01); G01N 33/5008 (2013.01); G01N 33/6803 (2013.01); G01N 2021/6439 (2013.01)] 8 Claims
OG exemplary drawing
 
1. A compound represented by the structure of Formula XXXV:

OG Complex Work Unit Chemistry
wherein
a and t are each independently an integer between 0 and 15;
G1 is selected from the group consisting of: a bond, carbamate, an amide [—C(O)NH or —NHC(O)], amine, C1-C12 alkyl amine, ester, ketone, O, N, S, carbonate, —O-alkyl-NH-carbamoyl phosphate and phosphate;
V1 is selected from the group consisting of: a bond, a triazole, an amide [—C(O)NH or —NHC(O)], —C(O)O—, —OC(O)—, O, NH, N-alkyl, S, —PO4H—, alkyl ether, —NH-alkyl-NH—, —O-alkyl-NH—, and —NH-alkyl-O—
wherein said alkyl is optionally substituted, wherein said alkyl is optionally interrupted by an heteroatom consisting of O, N, P, S, or combination thereof;
X1 is selected from the group consisting of: a bond or C1-C12 alkyl, an amide [—C(O)NH or —NHC(O)], —C(O)O—, —OC(O)—, O, NH, N-alkyl, S, —PO4H—, C1-C12 alkyl ether, C1-C12-alkyl-NH, -alkyl-NHC(O)-alkyl, -alkyl-C(O)NH-alkyl, —NH-alkyl-NH—, —O-alkyl-NH—, and —NH-alkyl-O—
wherein said alkyl is optionally substituted, wherein said alkyl is optionally interrupted by an heteroatom consisting of O, N, P, S, or combination thereof;
L1 is selected from the group consisting of: a bond or C1-C12 alkyl, C(O), an amide [—C(O)NH or —NHC(O)], —C(O)O—, —OC(O)—, O, NH, C1-C12—N-alkyl, S, —PO4H, —PO4H—PO4H—{[(CH2)yO]x}z—PO3H—, wherein y is between 1-5, x is between 1-10 and z is between 1-10, —PO4H—PEG, C1-C12 alkyl ether, C1-C12 alkylamine, C1-C12 alkyl-NH, —C(O)NH-alkyl, —NHC(O)-alkyl, NH-alkyl-NH—, —O-alkyl-NH—, and —NH-alkyl-O—,
wherein said alkyl is optionally substituted, wherein said alkyl is optionally interrupted by an heteroatom consisting of O, N, P, S, or combination thereof;
m, p and q are each independently an integer between 1 and 8;
NTA is selected from the group consisting of: nitrilotriacetic acid, nitrilotriacetic acid complexed with at least one metal ion, and a protected derivative thereof; and
LB is a quinoline-based cyanine dye, or a quinoline-based cyanine dye derivative (QBC);
or a suitable salt thereof.