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US 2026/0072036 A1Published application
Bicyclononyne reagents for cell imaging
AssigneeThe General Hospital Corporation
InventorsRalph Weissleder, Jonathan C. Carlson
Life of this patent
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Abstract
The present disclosure provides bicyclononyne based compounds and methods to prepare an antibody conjugate with a fluorophore, as well as the methods of using these conjugates for cellular imaging. In one example, the conjugate may be coupled with a quencher to absorb fluorescence from the fluorophore.
Claims30
A compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is selected from H, C1-3 alkyl, and C1-3 haloalkyl;
- each L1 is independently selected from N(RN), O, C(═O), S(═O)2, C1-6 alkylene, —(OCH2CH2)x—, and —(CH2CH2O)x—;
- n is an integer from 1 to 10;
- each L2 is independently selected from N(RN), O, C(═O), S(═O)2, C1-6 alkylene, —(OCH2CH2)x—, and —(CH2CH2O)x—;
- m is an integer from 1 to 10;
- each L3 is independently selected from N(RN), O, C(═O), S(═O)2, C1-6 alkylene, —(OCH2CH2)x—, and —(CH2CH2O)x—;
- wherein each of said C1-6 alkylene groups within L1, L2, or L3 is optionally substituted with (L4)o-Y3;
- each RN is independently selected from H, C1-3 alkyl, C1-3 haloalkyl, and (L4)o-Y3;
- each L4 is independently selected from N(RN), O, C(═O), S(═O)2, C1-6 alkylene, —(OCH2CH2)x—, and —(CH2CH2O)x—;
- each RN1 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
- p is an integer from 1 to 20;
- o is an integer from 1 to 10;
- each x is independently an integer from 1 to 2,000;
- each Y3 is independently selected from a moiety of formula (i) and a moiety of formula (ii):
- Y1 is selected from NRc1R1A, OR2, and C(═O)R3;
- R1A selected from H, an amine protecting group, and a fluorophore;
- R2 is selected from H, an alcohol protecting group, and a fluorophore;
- R3 is selected from ORa1 and a fluorophore;
- Y2 is selected from C(═O)ORa1, NRc1R1A, OR5;
- and a group reactive with a side chain of an amino acid of a protein;
- Ra1 is selected from H and a carboxylic acid protecting group;
- Rc1 is selected from H, C1-3 alkyl, and C1-3 haloalkyl;
- R4 is selected from H and an amine protecting group;
- and
- R5 is selected from H and an alcohol protecting group.
23 more elements
A protein conjugate of Formula (II):
- or a pharmaceutically acceptable salt thereof, wherein:
- A is a protein;
- y is an integer from 1 to 10;
- R1 is selected from H, C1-3 alkyl, and C1-3 haloalkyl;
- each L1 is independently selected from N(RN), O, C(═O), S(═O)2, C1-6 alkylene, —(OCH2CH2)x—, and —(CH2CH2O)x—;
- n is an integer from 1 to 10;
- each L2 is independently selected from N(RN), O, C(═O), S(═O)2, C1-6 alkylene, —(OCH2CH2)x—, and —(CH2CH2O)x—;
- m is an integer from 1 to 10;
- each L3 is independently selected from N(RN), O, C(═O), S(═O)2, C1-6 alkylene, —(OCH2CH2)x—, and —(CH2CH2O)x—;
- wherein each of said C1-6 alkylene groups within L1, L2, or L3 is optionally substituted with (L4)o-Y3;
- each RN is independently selected from H, C1-3 alkyl, C1-3 haloalkyl, and (L4)o-Y3;
- each L4 is independently selected from N(RN1), O, C(═O), S(═O)2, C1-6 alkylene, —(OCH2CH2)x—, and —(CH2CH2O)x—;
- each RN1 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
- p is an integer from 1 to 20;
- o is an integer from 1 to 10;
- each x is independently an integer from 1 to 2,000;
- each Y3 is independently selected from a moiety of formula (i) and a moiety of formula (ii):
- Y1 is selected from NRc1R1A, OR2, and C(═O)R3;
- R1A, R2, and R3 are each independently selected from a fluorophore;
- Rc1 is selected from H, C1-3 alkyl, and C1-3 haloalkyl;
- each W is selected from:
- (i) O of a side chain of serine, threonine, or tyrosine of the protein A;
- (ii) S of a side chain of cysteine of the protein A;
- (iii) NH of a side chain of lysine of the protein A;
- and
- (iv) C(═O) of a side chain of aspartic acid or glutamic acid of the protein A;
- and
- Y2 is a residue of a group which, prior to conjugation with the protein A, was a group reactive with a side chain of an amino acid of the protein A.
25 more elements
Dependencies are inferred from the claim text.