US 11,931,429 B2
Chemiluminescent probes for diagnostics and in vivo imaging
Doron Shabat, Tel-Aviv (IL); Ronit Satchi-Fainaro, Tel Aviv (IL); Nir Hananya, Mitzpe Netofa (IL); Ori Green, Tel Aviv (IL); and Tal Eilon, Tel Aviv (IL)
Assigned to RAMOT AT TEL-AVIV UNIVERSITY LTD., Tel-Aviv (IL)
Filed by RAMOT AT TEL-AVIV UNIVERSITY LTD., Tel-Aviv (IL)
Filed on Oct. 20, 2021, as Appl. No. 17/451,536.
Application 17/451,536 is a division of application No. 16/850,333, filed on Apr. 16, 2020, granted, now 11,179,482.
Application 16/850,333 is a division of application No. 16/072,848, granted, now 10,660,974, issued on May 26, 2020, previously published as PCT/IL2017/050088, filed on Jan. 24, 2017.
Claims priority of provisional application 62/431,618, filed on Dec. 8, 2016.
Claims priority of provisional application 62/287,127, filed on Jan. 26, 2016.
Prior Publication US 2022/0047725 A1, Feb. 17, 2022
Int. Cl. A61K 49/00 (2006.01); C07D 321/00 (2006.01); C07F 5/02 (2006.01); C07F 5/04 (2006.01); C07F 7/18 (2006.01); C07F 9/12 (2006.01); C07F 9/655 (2006.01); C07H 15/203 (2006.01); C07H 15/26 (2006.01); C09B 11/24 (2006.01); C09B 23/01 (2006.01); C09B 23/04 (2006.01); C09B 23/08 (2006.01); C09K 11/06 (2006.01)
CPC A61K 49/0052 (2013.01) [C07D 321/00 (2013.01); C07F 5/025 (2013.01); C07F 5/04 (2013.01); C07F 7/1804 (2013.01); C07F 9/12 (2013.01); C07F 9/65512 (2013.01); C07H 15/203 (2013.01); C07H 15/26 (2013.01); C09B 11/24 (2013.01); C09B 23/0066 (2013.01); C09B 23/04 (2013.01); C09B 23/083 (2013.01); C09K 11/06 (2013.01); C09K 2211/1018 (2013.01)] 10 Claims
 
1. A conjugate of the formula IIIa or IIIb:

OG Complex Work Unit Chemistry
wherein
R1 is selected from the group consisting of a linear or branched (C1-C18)alkyl, and (C3-C7)cycloalkyl;
R2 and R3 each independently is selected from the group consisting of a branched (C3-C18)alkyl and (C3-C7)cycloalkyl, or R2 and R3 together with the carbon atom to which they are attached form a fused, spiro or bridged cyclic or polycyclic ring;
R4 is a caging group;
L is absent or is a linker of the formula L1, L2 or L3, optionally substituted at the aromatic ring with one or more substituents each independently selected from the group consisting of (C1-C18)alkyl and (C3-C7)cycloalkyl, wherein M is absent or is —O— or —NH—, and the asterisk represents the point of attachment to the group Y, provided that M is —O— or —NH— unless R4 is 4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl or —B(OH)2;

OG Complex Work Unit Chemistry
Y is absent or is —O—, provided that Y is —O— unless R4 is 4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl or —B(OH)2, and L is absent;
R7, R8 and R9 each independently is H, or an electron acceptor group selected from the group consisting of halogen, —NO2, —CN, —COOR10, —C(═O)R10 and —SO2R10;
R10 each independently is H or —(C1-C18)alkyl;
X is a linker of the formula —X1—X2—, wherein X1 is selected from the group consisting of (C1-C18)alkylene, (C2-C18)alkenylene, (C2-C18)alkynylene, (C3-C7)cycloalkylene, (C3-C7)cycloalkenylene, (C6-C14)arylene-diyl, (C1-C1s)alkylene-(C6-C14)arylene-diyl, heteroarylenediyl, and (C1-C18)alkylene-heteroarylenediyl, said (C1-C18)alkylene, (C2-C18)alkenylene, (C2-C18)alkynylene, (C3-C7)cycloalkylene, (C3-C7)cycloalkenylene, (C6-C14)arylene-diyl, or heteroarylenediyl being optionally substituted by one or more groups each independently selected from the group consisting of halogen, —COR10, —COOR10, —OCOOR10, —OCON(R10)2, CN, —NO2, SR OR N(R10)2, CON(R10)2, —SO2R10, —SO3H, —S(═O)R10, (C6-C10)aryl, (C1-C4)alkylene-(C6-C10)aryl, heteroaryl, and (C1-C4)alkylene-hetero aryl, and said (C1-C18)alkylene, (C2-C18)alkenylene, or (C2-C18)alkynylene being further optionally interrupted by one or more identical or different heteroatoms selected from the group consisting of S, O and N, and/or at least one group each independently selected from the group consisting of —NH—CO—, —CO—NH—, —N(C1-C8alkyl)-, —N(C6-C10aryl)-, (C6-C10)arylene-diyl, and heteroarylenediyl; and X2 is absent or is —C(O)—; and
Z is a moiety of a fluorophore selected from the group consisting of a fluorescein-based compound, rhodamine-based compound, coumarin-based compound, cyanine dye selected from the group consisting of Cy5, Cy5.5, Cy5.18, Cy7, Cy7.18, and QCy, or boron-dipyrromethene.