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US 11,447,508 B2Granted
Heteroaromatic silicon-fluoride-acceptors useful for 18F labeling of molecules and biomolecules, and methods of preparing same
AssigneesCalifornia Institute of Technology, The Regents of the University of California
InventorsChristopher Martin Waldmann, Anton A. Toutov, Jennifer Marie Murphy, Robert H. Grubbs
Life of this patent
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Abstract
The present disclosure sets forth novel compounds and compositions including heteroaromatic silicon-fluoride-acceptors, which are useful for PET scanning. The present disclosure further includes novel methods of 18F imaging for PET scanning, the methods comprising the preparation of conjugates and bioconjugates of biological ligands of interest with heteroaromatic silicon-fluoride-acceptors. In certain embodiments the invention is practiced in the form of a kit.
Claims23
A compound of Formula 2:
- wherein in Formula 2,
- F is 19F or 18F;
- A1 is a monocyclic or bicyclic heteroaryl ring optionally substituted with 1-4 Ra groups;
- A2 is a linker;
- A3 is a moiety capable of chemical conjugation or bioconjugation;
- A4 is a moiety comprising a polar auxiliary that optionally contains a charge;
- Ra is, at each independent occurrence, F, Cl, Br, I, CN, NO2, ORc, OC(═O)Rc, OC(═O)ORc, OC(═O)NRcRd, C(═O)Rc, C(═O)NRcRd, C(═O)ORc, NRcRd, NRcC(═O)Rd, NRcC(═O)ORd, NRcC(═O)NRdRe, NRcS(═O)2Rd, NRcS(═O)2NRdRe, SRC, S(═O)Rc, S(═O)2Rc, and S(═O)2NRcRd, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl is optionally substituted by 1, 2, 3, 4, or 5 substituents that are independently F, Cl, Br, I, CN, NO2, ORc, OC(═O)Rc, OC(═O)ORc, OC(═O)NRcRd, C(═O)Rc, C(═O) RcRd, C(═O)ORc, RcRd, RcC(═O)Rd, RcC(═O)ORd, RcC(═O) RdRe, RcS(═O)2Rd, RcS(═O)2 RdRe, SRC, S(═O)Rc, S(═O)2Rc, or S(═O)2 RcRd, or independent Ra groups can optionally be joined to form additional rings;
- Rc, Rd and Re are, at each independent occurrence, H, or optionally substituted C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, and any of Rc, Rd or Re can optionally be joined to form additional rings;
- wherein the Si is bonded to a carbon of A1;
- A1 is not 1,2,3-triazolyl;
- and
- R1 and R2 are each independently an alkyl group.
9 more elements
A compound of Formula 4:
- wherein in Formula 4,
- F is 19F or 18F;
- A1 is a monocyclic or bicyclic heteroaryl ring optionally substituted with 1-4 Ra groups;
- A2 is a linker;
- A3 is a moiety that chemically conjugates or bioconjugates A2 to A5;
- A4 is a moiety comprising a polar auxiliary that optionally contains a charge;
- A5 is a moiety comprising a disease targeting molecule or biomolecule;
- Ra is, at each independent occurrence, F, Cl, Br, I, CN, NO2, ORc, OC(═O)Rc, OC(═O)ORc, OC(═O)NRcRd, C(═O)Rc, C(═O)NRcRd, C(═O)ORc, NRcRd, NRcC(═O)Rd, NRcC(═O)ORd, NRcC(═O)NRdRe, NRcS(═O)2Rd, NRcS(═O)2NRdRe, SRC, S(═O)Rc, S(═O)2Rc, and S(═O)2NRcRd, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl is optionally substituted by 1, 2, 3, 4, or 5 substituents that are F, Cl, Br, I, CN, NO2, ORc, OC(═O)Rc, OC(═O)ORc, OC(═O)NRcRd, C(═O)Rc, C(═O)NRcRd, C(═O)ORc, NRcRd, NRcC(═O)Rd, NRcC(═O)ORd, NRcC(═O)NRdRe, NRcS(═O)2Rd, NRcS(═O)2NRdRe, SRC, S(═O)Rc, S(═O)2Rc, or S(═O)2NRcRd, or independent Ra groups can optionally be joined to form additional rings;
- Rc, Rd and Re are, at each independent occurrence, H, or optionally substituted C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, and any of Rc, Rd or Re can optionally be joined to form additional rings;
- wherein the Si is bonded to a carbon of A1;
- A1 is not 1,2,3-triazolyl;
- and
- R1 and R2 are each independently an alkyl group.
10 more elements
Dependencies are inferred from the claim text.