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Synthesis of a Complex and Highly Potent PCSK9 Inhibitor.
Kuethe, Jeffrey T; Lee, Joshua; Thaisrivongs, David; Yasuda, Nobuyoshi; Pollack, Scott R; Leone, Joseph; DaSilva, Jimmy; Biba, Mirlinda; Tsay, Fuh-Rong; Regalado, Erik L; Qi, Ji; Li, Hongming; Poggetto, Guilherme Dal; Cohen, Ryan.
Afiliação
  • Kuethe JT; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Lee J; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Thaisrivongs D; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Yasuda N; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Pollack SR; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Leone J; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • DaSilva J; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Biba M; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Tsay FR; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Regalado EL; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Qi J; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Li H; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Poggetto GD; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Cohen R; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Org Lett ; 25(27): 5001-5005, 2023 07 14.
Article em En | MEDLINE | ID: mdl-37382389
ABSTRACT
The solution-based gram-scale synthesis of complex and highly potent proprotein convertase subtilisin-like/kexin type 9 (PCSK9) inhibitor 1 is presented. Construction of Northern fragment 2, followed by stepwise installation of Eastern 3, Southern 4, and Western 5 fragments, provided macrocyclic precursor 19. This intermediate was cross-linked via an intramolecular azide-alkyne click reaction, which preceded macrolactamization to afford the core framework of compound 1. Finally, coupling with poly(ethylene glycol) side-chain-based 6 gave the PCSK9 inhibitor 1.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pró-Proteína Convertase 9 Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pró-Proteína Convertase 9 Idioma: En Ano de publicação: 2023 Tipo de documento: Article