Process for the preparation of mono-protected α,ω-diamino alkanes

Inventors

Menge, Wiro Michael Petrus Bernardus

Assignees

Byondis BV

Abstract

The present invention relates to a process for the synthesis of mono-protected α,ω-diamino alkanes, the use of said process in a process for the synthesis of a linker drug comprising an α,ω-diamino alkane moiety and the use of the process of the present invention in a process for preparing an antibody-drug conjugate comprising an α,ω-diamino alkane moiety.

Core Innovation

The document describes a process for converting a compound of formula (I) into a compound of formula (II) by reacting the formula (I) compound with a compound of formula (IV) in the presence of a coupling reagent. The process further includes treating the compound of formula (II) with a borane reagent, followed by acid hydrolysis to form a compound of formula (III). Variable substituents R and R1, a protective group P, and integer parameters m and n are defined within the stated chemical frameworks.

The document specifies that Z is a therapeutic or diagnostic payload within a linker-drug framework, and it provides Z-containing structures and classes, including maytansinoids, auristatins, duocarmycins, and other payload classes. Y is selected from illustrated embodiments, and additional substituent options are defined for the linker-drug framework using variables such as Rb-Re, Rz/Rz1/Rz2, Rf/Rh, and k/p. The framework therefore supports assembling payload-bearing linker drugs with defined variable substituent sets.

The document also provides a downstream pathway in which the formed linker drug is used to prepare an antibody drug conjugate, including conjugation to antibodies and antigen-binding fragments such as Fab′, F(ab′)2, scFv, sd, minibody, and diabody. Antibody examples include IgG and trastuzumab, and the document lists antigen targets associated with the antibody-drug conjugate use. An additional described downstream sequence includes reacting a linker drug with an activated carbonate to give a drug-linker conjugate, and optionally deprotecting compound (X) to (Xa) as part of forming the next intermediate.

Claims Coverage

The independently claimed subject matter is a two-stage chemical process: first, coupling to convert a compound of formula (I) into a compound of formula (II), and second, borane reagent treatment followed by acid hydrolysis to form a compound of formula (III). The provided claim set indicates one independent claim, clm-00001, with dependent claims refining coupling reagents, borane reagent forms, protective group P selections, the acid type for hydrolysis, and downstream conversion toward antibody-drug conjugates via linker-drug conjugation steps. The inventive features focus on the specific coupling transformation and the subsequent borane-plus-acid-hydrolysis conversion to the next formula compound, within variable substituent and protective-group definitions.

Across the independent claim, the main inventive coverage is the defined sequence of coupling between formula (I) and formula (IV) in the presence of a coupling reagent to obtain formula (II), and converting formula (II) to formula (III) using a borane reagent followed by acid hydrolysis, with R/R1, protective group P, and parameters m and n specified within the chemical definitions. The dependent claims further narrow coupling reagent and borane reagent forms and specify downstream conjugation steps referenced in the document.

Stated Advantages

Documented Applications

No documented applications found