OLIGOPEPTIDE LINKER INTERMEDIATE AND METHOD FOR PRODUCTION THEREOF Russian patent published in 2022 - IPC A61K47/64 A61K47/68 A61P35/00 C07K1/02 C07K5/06 C07K5/08 C07K5/10 

FIELD: chemistry.

SUBSTANCE: invention relates to a method for producing an oligopeptide linker intermediate by the formulas (1)-(3), wherein each of AA₁, AA₂, AA₃, and AA₄ is independently selected from a group consisting of the following: -valine- (-Val-), -citrulline- (-Cit-), -alanine- (-Ala-), -lysine- (-Lys-), -phenylalanine- (-Phe-), -glycine- (-Gly-), -leucine- (-Leu-), and -isoleucine- (-Ile-). The method includes: 1) conducting a condensation reaction between the carbonylation reagent, 2-(trimethylsilyl)ethanol, and amino acid AA₁, then amino acid AA₂, or consecutively amino acid AA₁, amino acid AA₂, and amino acid AA₃, or consecutively amino acid AA₁, amino acid AA₂, amino acid AA₃, and amino acid AA₄, resulting in a 2-(trimethylsilyl)ethoxycarbonyl-oligopeptide condensation product; 2) interacting the resulting 2-(trimethylsilyl)ethoxycarbonyl-oligopeptide condensation product and para-aminobenzyl alcohol resulting in a condensation product constituting 2-(trimethylsilyl)ethoxycarbonyl-oligopeptide-para-aminobenzyl alcohol. The carbonylation reagent has a structure of the formula (5), wherein each of R¹ and R² is independently selected from the group of values specified under formula (5). The proposed method is performed in mild reaction conditions and ensures production of a highly pure product. Invention also relates to an application of the above method for producing an antibody-drug conjugate.

EFFECT: creation of an intermediate applicable in producing an antibody-drug conjugate.

(1),

(2),

(3),

wherein R₁ and R₂ are independently selected from a group consisting of:

,.

10 cl, 4 dwg, 1 tbl, 3 ex