US 2025/0170282 A1Published application

Compositions, methods, and systems for the synthesis and use of imaging agents

AssigneeLantheus Medical Imaging, Inc.

InventorsHeike S. Radeke, Richard R. Cesati, Ajay Purohit, Thomas D. Harris, Simon P. Robinson, Ming Yu, David S. Casebier, Carol Hui Hu, Matthias Broekema, David C. Onthank

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Abstract

The present invention relates to systems, compositions, and methods for the synthesis and use of imaging agents, or precursors thereof. An imaging agent precursor may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in 18F. In some cases, an imaging agent may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs. In some embodiments, methods and compositions for assessing perfusion and innervation mismatch in a portion of a subject are provided.

Claims23

Dependent claims

A compound of the formula:

R0—Ar-L-R1
wherein
Ar is substituted or unsubstituted, monocyclic or bicyclic aryl or substituted or unsubstituted, monocyclic or bicyclic heteroaryl;
L is a bond;
substituted or unsubstituted, cyclic or acyclic alkylene;
substituted or unsubstituted, cyclic or acyclic alkenylene;
substituted or unsubstituted, cyclic or acyclic alkynylene;
or substituted or unsubstituted, cyclic or acyclic heteroaliphatic;
R1 is a substituted or unsubstituted nitrogen-containing moiety;
and
R0 is halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORA1, —N(RA2)2, —SRA1, —C(═O)RA1, —C(═O)ORA1, —C(═O)SRA1, —C(═O)N(RA2)2, —OC(═O)RA1, —OC(═O)ORA1, —OC(═O)SRA1, —OC(═O)N(RA2)2, —NRA2C(═O)RA2, —NRA2C(═O)ORA1, —NRA2C(═O)SRA1, —NRA2C(═)N(RA2, —SC(═O)RA1, —SC(═O)ORA1, —SC(═O)SRA1, —SC(═O)N(RA2)2, —C(═NRA2)RA1, —C(═NRA2)ORA1, —C(═NRA2)SRA1, —C(═NRA2)N(RA2)2, —OC(═NRA2)RA1, —OC(═NRA2)ORA1, —OC(═NRA2)SRA1, —OC(═NRA2)N(RA2)2, —NRA2C(═NRA2)RA2, —NRA2C(═NRA2)ORA1, —NRA2C(═NRA2)SRA1, —NRA2C(═NRA2)N(RA2)2, —SC(═NRA2)RA1, —SC(═NRA2)ORA1, —SC(═NRA2)SRA1, —SC(═NRA2)N(RA2)2, —C(═S)RA1, —C(═S)ORA1, —C(═S)SRA1, —C(═S)N(RA2)2, —OC(═S)RA1, —OC(═S)ORA1, —OC(═S)SRA1, —OC(═S)N(RA2)2, —NRA2C(═S)RA2, —NRA2C(═S)ORA1, —NRA2C(═S)SRA1, —NRA2C(═S)N(RA2)2, —SC(═S)RA1, —SC(═S)ORA1, —SC(═S)SRA1, —SC(═S)N(RA2)2, —S(═O)RA1, —SO2RA1, —NRA2SO2RA1, —SO2N(RA2)2, —CN, —SCN, or —NO2
each occurrence of RA1 is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
and each occurrence of RA2 is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an amino protecting group, or two RA2 groups are joined to form an optionally substituted heterocyclic ring;
and
R0 or R1 is substituted with an imaging moiety selected from the group consisting of 18F, 76Br, 124I, and 131I, or is associated with an imaging moiety selected from the group consisting of 64Cu, 89Zr, 99mTc, and 111In through a chelator, or is an imaging moiety selected from the group consisting of 18F, 76Br, 124I, and 131I;
or a salt thereof;
provided the compound is not of the formula:

14 more elements

A compound of the formula:

R0—Ar-L-R1
wherein
Ar is substituted or unsubstituted, monocyclic or bicyclic aryl or substituted or unsubstituted, monocyclic or bicyclic heteroaryl;
L is a bond;
substituted or unsubstituted, cyclic or acyclic alkylene;
substituted or unsubstituted, cyclic or acyclic alkenylene;
substituted or unsubstituted, cyclic or acyclic alkynylene;
or substituted or unsubstituted, cyclic or acyclic heteroaliphatic;
R1 is a substituted or unsubstituted nitrogen-containing moiety;
and
R0 is halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORA1, —N(RA2)2, —SRA1, —C(═O)RA1, —C(═O)ORA1, —C(═O)SRA1, —C(═O)N(RA2)2, —OC(═O)RA1, —OC(═O)ORA1, —OC(═O)SRA1, —OC(═O)N(RA2)2, —NRA2C(═O)RA2, —NRA2C(═O)ORA1, —NRA2C(═O)SRA1, —NRA2C(═O)N(RA2, —SC(═O)RA1, —SC(═O)ORA1, —SC(═O)SRA1, —SC(═O)N(RA2)2, —C(═NRA2)RA1, —C(═NRA2)ORA1, —C(═NRA2)SRA1, —C(═NRA2)N(RA2)2, —OC(═NRA2)RA1, —OC(═NRA2)ORA1, —OC(═NRA2)SRA1, —OC(═NRA2)N(RA2)2, —NRA2C(═NRA2)RA2, —NRA2C(═NRA2)ORA1, —NRA2C(═NRA2)SRA1, —NRA2C(═NRA2)N(RA2)2, —SC(═NRA2)RA1, —SC(═NRA2)ORA1, —SC(═NRA2)SRA1, —SC(═NRA2)N(RA2)2, —C(═S)RA1, —C(═S)ORA1, —C(═S)SRA1, —C(═S)N(RA2)2, —OC(═S)RA1, —OC(═S)ORA1, —OC(═S)SRA1, —OC(═S)N(RA2)2, —NRA2C(═S)RA2, —NRA2C(═S)ORA1, —NRA2C(═S)SRA1, —NRA2C(═S)N(RA2)2, —SC(═S)RA1, —SC(═S)ORA1, —SC(═S)SRA1, —SC(═S)N(RA2)2, —S(═O)RA1, —SO2RA1, —NRA2SO2RA1, —SO2N(RA2)2, —CN, —SCN, or —NO2;
each occurrence of RA1 is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
and each occurrence of RA2 is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an amino protecting group, or two RA2 groups are joined to form an optionally substituted heterocyclic ring;
and
R0 or R1 is substituted with an imaging moiety selected from the group consisting of 18F, 76Br, and 124I, or is associated with an imaging moiety selected from the group consisting of 64Cu, 89Zr, 99mTc, and 111In through a chelator, or is an imaging moiety selected from the group consisting of 18F, 76Br, and 124I;
or a salt thereof;
provided that when Ar is phenyl, when L is —CH2—, when R1 is
and when R0 is an imaging moiety selected from the group consisting of 18F, 76Br, and 124I, then Ar is substituted;
and
further provided the compound is not of the formula:

17 more elements

A compound of the formula:

R0—Ar-L-R1
wherein
Ar is substituted or unsubstituted, monocyclic or bicyclic aryl or substituted or unsubstituted, monocyclic or bicyclic heteroaryl;
L is a bond;
substituted or unsubstituted, cyclic or acyclic alkylene;
substituted or unsubstituted, cyclic or acyclic alkenylene;
substituted or unsubstituted, cyclic or acyclic alkynylene;
or substituted or unsubstituted, cyclic or acyclic heteroaliphatic;
R1 is a substituted or unsubstituted nitrogen-containing moiety;
and
R0 is halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORA1, —N(RA2)2, —SRA1, —C(═O)RA1, —C(═O)ORA1, —C(═O)SRA1, —C(═O)N(RA2)2, —OC(═O)RA1, —OC(═O)ORA1, —OC(═O)SRA1, —OC(═O)N(RA2)2, —NRA2C(═O)RA2, —NRA2C(═O)ORA1, —NRA2C(═O)SRA1, —NRA2C(═O)N(RA2, —SC(═O)RA1, —SC(═O)ORA1, —SC(═O)SRA1, —SC(═O)N(RA2)2, —C(═NRA2)RA1, —C(═NRA2)ORA1, —C(═NRA2)SRA1, —C(═NRA2)N(RA2)2, —OC(═NRA2)RA1, —OC(═NRA2)ORA1, —OC(═NRA2)SRA1, —OC(═NRA2)N(RA2)2, —NRA2C(═NRA2)RA2, —NRA2C(═NRA2)ORA1, —NRA2C(═NRA2)SRA1, —NRA2C(═NRA2)N(RA2)2, —SC(═NRA2)RA1, —SC(═NRA2)ORA1, —SC(═NRA2)SRA1, —SC(═NRA2)N(RA2)2, —C(═S)RA1, —C(═S)ORA1, —C(═S)SRA1, —C(═S)N(RA2)2, —OC(═S)RA1, —OC(═S)ORA1, —OC(═S)SRA1, —OC(═S)N(RA2)2, —NRA2C(═S)RA2, —NRA2C(═S)ORA1, —NRA2C(═S)SRA1, —NRA2C(═S)N(RA2)2, —SC(═S)RA1, —SC(═S)ORA1, —SC(═S)SRA1, —SC(═S)N(RA2)2, —S(═O)RA1, —SO2RA1, —NRA2SO2RA1, —SO2N(RA2)2, —CN, —SCN, or —NO2;
each occurrence of RA1 is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
and each occurrence of RA2 is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an amino protecting group, or two RA2 groups are joined to form an optionally substituted heterocyclic ring;
and
R0 or R1 is substituted with an imaging moiety selected from the group consisting of 18F, 76Br, and 124I, or is associated with an imaging moiety selected from the group consisting of 64Cu, 89Zr, 99mTc, and 111In through a chelator, or is an imaging moiety selected from the group consisting of 18F, 76Br, and 124I;
or a salt thereof;,
provided that when Ar is phenyl, R0 is not 18F;
further provided that when Ar is phenyl, when L is —CH2—, when R1 is
and when R0 is an imaging moiety selected from the group consisting of 76Br and 124I, then Ar is substituted;
and
further provided the compound is not of the formula:

18 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/029,057Filed 17 Jan 2025
Priority: 9 Sep 2011
Published: 29 May 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification24 codes

A61K 51/0459
Having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins: having six-membered rings with two nitrogen atoms as the only ring hetero…
A61P 9/06
Drugs for disorders of the cardiovascular system: antiarrhythmics
A61K 51/04
Characterised by the carrier , i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus: organic compounds
A61K 51/0453
Having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins: having five-membered rings with two or more ring hetero atoms, at least one…

Family

Application61/533,133Us provisional application · filed 9 Sep 2011
Application61/656,489Us provisional application · filed 6 Jun 2012
Application61/656,492Us provisional application · filed 6 Jun 2012
Application14/343,627Continuation · filed 30 Jun 2014
Application15/364,678Continuation · filed 30 Nov 2016
Application16/828,119Continuation · filed 24 Mar 2020
Application17/724,713Continuation · filed 20 Apr 2022
Application19/029,057Continuation
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From the US filing history. Foreign family members aren’t listed.