A method for synthesizing degarelix

Abstract

The invention relates to the field of synthesis of medicines and discloses a method for synthesizing degarelix. The method for synthesizing the degarelix comprises the following steps: enabling D-alanine with a protective group coupled with an N end to carry out esterification reaction with amino resin with a protective group coupled with an amino in the presence of a condensation reagent and an activation reagent to obtain peptide resin 1; extending and coupling other protective amino acids one by one by starting from the peptide resin 1 according to a sequence from C end to N end of the amino acid sequence of the degarelix in the presence of the condensation reagent and the activation reagent, to obtain corresponding peptide resins after extending and coupling each time and finally obtain degarelix resin, then carrying out acidolysis to obtain a degarelix crude product, and purifying the degarelix crude product to obtain a degarelix pure product. By virtue of the method for synthesizing the degarelix, a proper synthesizing scheme is selected; the adaptive amino resin and an acidolysis solution are selected; the overall synthesis process is optimized; the purity of the degarelix is obviously improved; the degarelix has a relatively high total yield and is free of pollution to any environment.

Description

A method for synthesizing degarelix technical field The invention relates to the field of pharmaceutical synthesis, in particular to a method for synthesizing degarelix. Background technique Degarelix is ​​a gonadotropin-releasing hormone (GnRH) receptor inhibitor drug developed by Danish Ferring Pharmaceutical Co., Ltd., which reversibly inhibits the pituitary GnRH receptor to reduce the release of gonadotropin and then inhibit the release of testosterone. This product slows the growth and progression of prostate cancer by inhibiting testosterone, which is essential for the continued growth of prostate cancer. Hormone therapy for prostate cancer to lower testosterone levels initially caused a spike in testosterone levels, and this initial stimulation of the hormone receptor temporarily boosted tumor growth rather than inhibiting it, whereas degarelix did not. The U.S. FDA approved Degarelix for marketing in December 2008. It is mainly aimed at patients with advanced pros...

AI Technical Summary

Problems solved by technology

There are many reports about the preparation of degarelix at home and abroad. U.S. Patent No. 5,925,730 adopts the Boc solid-phase synthesis method. The method scale is very small, and the purity is only reported. The product purity is 98%. Simultaneously, the method needs to use hydrofluoric acid (HF ) cracking, which is harmful to people and the environment, is not suitable for large-scale industrial synthesis, and its solid-phase synthesis method cannot maximize the synthesis efficiency and quality of degarelix