METHOD FOR PRODUCING BOC-THZ-PHE-D-TRP-LYS(BOC)-THR-NHCHCHNH-DOTA CONJUGATE BEING A PRECURSOR FOR ANTI-TUMOR RADIOPHARMACEUTICS Russian patent published in 2023 - IPC A61K47/66 A61K51/08 

FIELD: peptide chemistry.

SUBSTANCE: invention relates to the field of peptide chemistry and concerns the production of a Boc-Thz-Phe-D-Trp-Lys(Boc)-Thr-NHCH₂CH₂NH-DOTA conjugate having a pentapeptide as a vector, which is an analogue of somatostatin. This conjugate is promising as a targeted carrier of medical radionuclides for use in radionuclide diagnostics and therapy through specific interaction with somatostatin receptors of tumor cells. The technical effect of the invention is high yield up to 46% of Boc-Thz-Phe-D-Trp-Lys(Boc)-Thr-NHCH₂CH₂NH-DOTA conjugate. To achieve it, a method was proposed for obtaining Boc-Thz-Phe-D-Trp-Lys(Boc)-Thr-NHCH₂CH₂NH-DOTA, including alkylation of DO3A(OBu-t)₃ in a mixture of acetonitrile with DMF in the presence of a base such as potash, using ethyl ester of bromoacetic acid to form tetraester of ester (EtO)DOTA(OBu-t)₃ (I), amidation of ethyl ester (I) by the action of excess ethylenediamine, leading to amine NH₂CH₂CH₂NH-DOTA (OBu-t)₃ (II), hydrolysis of tert-butyl groups of amine II in hydrochloric acid solution with the formation of NH₂CH₂CH₂NH-DOTA (DOTA-EDA) (III), condensation of Boc-Thz-Phe-D-Trp-Lys (Boc)-Thr-OH (IV) in the presence of EDC⋅HCl with hydroxysuccinimide in acetonitrile solution leading in situ to an intermediate activated succinimide acid ester IV followed by reaction with amine III leading to the target conjugate Boc-Thz-Phe-D-Trp-Lys(Boc)-Thr-NHCH₂CH₂NH-DOTA(V).

EFFECT: high yield up to 46% of Boc-Thz-Phe-D-Trp-Lys(Boc)-Thr-NHCH₂CH₂NH-DOTA conjugate.

1 cl, 4 ex