US 12,433,961 B2
Near-infrared fluorescent probe specifically targeting tumors as well as synthesis method and use thereof
Huiming Cai, Nanjing (CN)
Assigned to NANJING NUOYUAN MEDICAL INSTRUMENT CO. LTD, Nanjing (CN)
Appl. No. 17/907,973
Filed by NANJING NUOYUAN MEDICAL INSTRUMENT CO. LTD, Nanjing (CN)
PCT Filed May 9, 2022, PCT No. PCT/CN2022/091632
§ 371(c)(1), (2) Date Aug. 30, 2022,
PCT Pub. No. WO2023/165015, PCT Pub. Date Sep. 7, 2023.
Claims priority of application No. 202210191870.6 (CN), filed on Mar. 1, 2022.
Prior Publication US 2025/0009907 A1, Jan. 9, 2025
Int. Cl. A61B 5/00 (2006.01); A61B 8/00 (2006.01); A61B 10/00 (2006.01); A61K 49/00 (2006.01); C07D 401/14 (2006.01); C09K 11/06 (2006.01)
CPC A61K 49/0021 (2013.01) [C07D 401/14 (2013.01); C09K 11/06 (2013.01); C09K 2211/1029 (2013.01); C09K 2211/1044 (2013.01)] 3 Claims
 
1. A method for synthesizing a near-infrared fluorescent probe specifically targeting tumors, wherein the near-infrared fluorescent probe is a compound represented by formula I or a pharmaceutically available salt thereof:

OG Complex Work Unit Chemistry
wherein:
X is a linker molecule selected from PEG4, PEG6, G3 and G6, have the following structures respectively:

OG Complex Work Unit Chemistry
one end of the linker molecule is amino, and the other end of the linker molecule is carboxyl;
Y is a dye molecule having a fluorescence excitation and emission spectrum within a near-infrared (NIR) range, and the compound represented by formula I or pharmaceutically available salt thereof can maintain or enhance the fluorescence of the dye molecule Y;
the method comprises the following steps:
Step a, mixing lapatinib and X in the presence of 2-(7-azabenzotriazole)-N,N,N′,N′-tetramethylurea hexafluorophosphate, an alkaline and a polar solvent;
Step b, dropwise adding the product obtained in Step a into water, extracting and then concentrating, subsequently adding trifluroracetic acid to remove a BOC protective group, and concentrating to obtain a lapatinib-X intermediate compound;
Step c, mixing the lapatinib-X intermediate compound with a dye molecule Y in the presence of 2-(7-azabenzotriazole)-N,N,N′,N′-tetramethylurea hexafluorophosphate, an alkaline and a polar solvent; and
Step d, purifying the product obtained in Step c with a preparative liquid phase to obtain a target compound lapatinib-X-Y, the near-infrared fluorescent probe.