US 11,746,086 B2
Non-aggregating heptamethine cyanine fluorophores for in vivo imaging
Martin John Schnermann, Rockville, MD (US); Michael Philip Luciano, Frederick, MD (US); and Roger Rauhauser Nani, Frederick, MD (US)
Assigned to The USA, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Filed by The USA, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Filed on Feb. 18, 2021, as Appl. No. 17/179,217.
Application 17/179,217 is a continuation of application No. 16/969,902, granted, now 10,961,193, previously published as PCT/US2019/018153, filed on Feb. 15, 2019.
Claims priority of provisional application 62/631,390, filed on Feb. 15, 2018.
Prior Publication US 2021/0198196 A1, Jul. 1, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 209/10 (2006.01); A61K 49/00 (2006.01); G01N 21/64 (2006.01); G01N 33/533 (2006.01); G01N 33/58 (2006.01); C07D 403/12 (2006.01); C09K 11/06 (2006.01)
CPC C07D 209/10 (2013.01) [A61K 49/006 (2013.01); A61K 49/0032 (2013.01); A61K 49/0058 (2013.01); C07D 403/12 (2013.01); C09K 11/06 (2013.01); G01N 21/6428 (2013.01); G01N 33/533 (2013.01); G01N 33/582 (2013.01); G01N 2021/6439 (2013.01)] 19 Claims
 
1. A conjugate or conjugate precursor, or stereoisomer thereof, according to Formula I:

OG Complex Work Unit Chemistry
wherein m is 3, 4, or 5;
n is 1, 2, or 3;
each p independently is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
R1 is —CR22— where each R2 independently is H, halo, optionally substituted aliphatic, or optionally substituted aryl;
R3 and R4 independently are aliphatic;
R5 to R10 independently are H or aliphatic;
R11 and R12 independently are a sulfonate-containing group;
R13 to R16 independently are aliphatic;
Ra is —(R1)qC(O)Rc where q is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
each Rb independently is C1-C5 aliphatic; and
Rc is a targeting agent-containing group,

OG Complex Work Unit Chemistry
where y is an integer≥1, or —OH, wherein the targeting agent is an antibody, a peptide, a protein, an amino acid, a nucleoside, a nucleotide, a nucleic acid, an oligonucleotide, a carbohydrate, a lipid, a hapten, or a receptor ligand.