PSMA-targeted NIR dyes and their uses
The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for a method for synthesizing a compound of the formula:
1. A method for synthesizing a compound of the formula:
wherein n is 0, 1, 2, 3, or 4;
further wherein R 3 , R 4 , and R 5 are independently selected from the group consisting of H + , Na + , K + , and NH 4 + ; R 6 , R 7 , R 8 , and R 9 are independently selected from the group consisting of H + , Na + , K + , and NH 4 + ; and R 10 H + ;
comprising the steps of:
(a) reacting a compound of formula I:
with a compound of formula:
in the presence of a polar organic solvent, 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate and N,N-Diisopropylethylamine under argon and
(b) reacting the resulting compound with sodium carbonate and a dye compound of the formula
2. The method of claim 1 , wherein the polar organic solvent is selected from the group consisting of dimethyl sulfoxide, dimethylformamide, and water.
3. A method for synthesizing an isotopic form of a compound of the formula:
wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of H 2 , H 3 , C 13 and C 14 ;
further wherein n is 0, 1, 2, 3, or 4;
further wherein R 3 , R 4 , and R 5 are independently selected from the group consisting of H + , Na + , K + , and NH 4 + ; R 6 , R 7 , R 8 , and R 9 are independently selected from the group consisting of H + , Na + ,K + , and NH 4 + ;and R 10 H + ;
comprising the steps of:
(a) reacting an isotopic form of a compound of formula:
wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of H 2 , H 3 , C 13 and C 14 ,
with an isotopic form of a compound of formula:
wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of H 2 , H 3 , C 13 and C 14 ,
in the presence of a polar organic solvent, 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate and N,N-Diisopropylethylamine under argon to provide an isotopic form of a compound that comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of H 2 , H 3 , C 13 and C 14 ,
(b) reacting the isotopic form of the compound obtained in step (a) with sodium carbonate and an isotopic form of a dye compound of the formula:
wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of H 2 , H 3 , C 13 and C 14 .
4. A method for synthesizing a compound of the formula:
wherein n is 0, 1, 2, 3, or 4
(a) reacting a compound of formula
with a compound of formula:
in the presence of a polar organic solvent, 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate and N,N -Diisopropylethylamine under argon
(b) reacting the resulting compound thereof with sodium carbonate and a dye compound of the formula: