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US 2020/0316229 A1Published application
Compounds and compositions useful as radiotracers for imaging of reactive oxidative species
AssigneeWake Forest University Health Sciences
InventorKiran K. Solingapuram Sai
Life of this patent
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Abstract
Provided herein are compounds and compositions useful for imaging, detecting, and/or diagnosing oxidative stress and/or a ROS modulated illness by detection of gamma radiation emitted by the compound, as well as intermediate compounds and methods useful to make the compounds and/or compositions, and methods of use thereof.
Claims20
A compound of Formula (I):
- wherein:
- R1 is a substituted aryl or substituted heteroaryl, which is substituted with —X(CH2)m—R3,
- wherein X is O, S, NH, or CH2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- R3 is:
- (i) an imaging moiety selected from the group consisting of 18F, 76Br, 123I, and 11C;
- (ii) a leaving group selected from the group consisting of a halo (e.g., Cl, F, Br and/or I) and a sulfonate (e.g., triflate, mesylate, tosylate, brosylate and/or nosylate);
- or
- (iii) a chelator moiety (e.g., DOTA, NOTA and DFO) associated with a radioisotope selected from 68Gd, 64Cu, and 89Zr;
- n is 0;
- and
- R2 is H;
- or wherein:
- R1 is halo (e.g., Cl, Br, F, I);
- n is 0, 1, 2, 3, 4, 5, or 6;
- and
- R2 is a substituted aryl or substituted heteroaryl, which is substituted with —X(CH2)m—R3,
- wherein X is O, S, NH or CH2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- R3 is:
- (i) an imaging moiety selected from the group consisting of 18F, 76Br, 123I, and 11C;
- (ii) a leaving group selected from the group consisting of a halo (e.g., Cl, F, Br and/or I) and a sulfonate (e.g., triflate, mesylate, tosylate, brosylate and/or nosylate);
- or
- (iii) a chelator moiety (e.g., DOTA, NOTA and DFO) associated with a radioisotope selected from 68Gd, 64Cu, and 89Zr;
- or a pharmaceutically acceptable salt thereof.
22 more elements
A method of making a compound of Formula (I)(b)(i):
- wherein:
- m is 0 and R3 is CH3;
- or
- m is 1, 2, 3, 4, 5 or 6 and R3 is a leaving group (e.g., a sulfonate (e.g., tosylate, mesylate, brosylate, nosylate, triflate, besylate) or a halo),
- comprising:
- (a) providing a compound of Formula (A):
- wherein PG is a hydroxyl protecting group, and m is as defined above;
- (b) contacting the compound of Formula (A) with a sulfonyl halide (e.g., tosyl chloride) to form a compound of Formula (B):
- wherein PG, m and R3 are as defined above;
- (c) contacting the compound of Formula (B) with Et4NCl and a base (e.g., DBU) to form a compound of Formula (C):
- wherein PG, m and R3 are the same as defined above;
- (d) purifying the compound of Formula (C) to obtain the compound of Formula (C) with a chemical purity of at least 90%;
- and then
- (e) removing the protecting group PG of the compound of Formula (C), to obtain the compound of Formula (I)(b)(i).
11 more elements
A method of producing a radiotracer compound of Formula I:
- wherein:
- R1 is a substituted aryl or substituted heteroaryl, which is substituted with —X(CH2)m—R3,
- wherein X is O, NH, S or CH2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- R3 is an 18F imaging moiety;
- n is 0;
- and
- R2 is H;
- or wherein:
- R1 is halo;
- n is 0, 1, 2, 3, 4, 5, or 6;
- and
- R2 is a substituted aryl or substituted heteroaryl, which is substituted with —X(CH2)m—R3,
- wherein X is O, S, NH or CH2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- and
- R3 is an 18F imaging moiety,
- or a pharmaceutical acceptable salt thereof;
- comprising:
- (a) mixing a precursor compound of Formula (I);
- wherein R1 is a substituted aryl or substituted heteroaryl, which is substituted with —X(CH2)m—R3,
- wherein X is O, NH, S or CH2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- R3 is a leaving group;
- n is 0;
- and
- R2 is H;
- or wherein:
- R1 is halo;
- n is 0, 1, 2, 3, 4, 5, or 6;
- and
- R2 is a substituted aryl or substituted heteroaryl, which is substituted with —X(CH2)m—R3,
- wherein X is O, S, NH or CH2;
- m is 0, 1, 2, 3, 4, 5, or 6;
- R3 is a leaving group selected from a sulfonate (e.g., tosylate) and halo,
- with a solvent and a solution of [18F]F to obtain a reaction mixture;
- (b) heating the reaction mixture obtained in step (a);
- and then
- (c) purifying the reaction mixture, to produce the radiotracer compound.
36 more elements
Dependencies are inferred from the claim text.