TY - JOUR
T1 - Diastereoselective synthesis of a novel phosphinic peptide as ACE inhibitor
T2 - Fragment-based design approach
AU - Abdou, Moaz M.
AU - Dong, Dewen
AU - O'Neill, Paul M.
AU - Amigues, Eric
AU - Matziari, Magdalini
N1 - Funding Information:
This work was financially supported by the Key Program Special Fund in XJTLU ( KSF E-52 ).
Publisher Copyright:
© 2022 The Author(s)
PY - 2023/2
Y1 - 2023/2
N2 - In medicinal chemistry for the purpose of lead optimization, hit selection of new isofunctional chemotypes are crucial for the success of identifying novel chemical entities of increased potency. Using fragment-based design approach with the N-selective inhibitor RXP407, a novel phosphinic peptide scaffold that consisted of modified RXP407 fragments was generated. The presented synthetic route is straightforward and produces the desired product Z-RXP407 in moderate yield. The (S,R,S,S)-Z-RXP407 analog has been evaluated for the C- and N-domain constructs of angiotensin-converting enzyme. The potency of this analog has been much lower compared to the parent compound RXP407, providing thus valuable insights regarding further design based on structure–activity relationships.
AB - In medicinal chemistry for the purpose of lead optimization, hit selection of new isofunctional chemotypes are crucial for the success of identifying novel chemical entities of increased potency. Using fragment-based design approach with the N-selective inhibitor RXP407, a novel phosphinic peptide scaffold that consisted of modified RXP407 fragments was generated. The presented synthetic route is straightforward and produces the desired product Z-RXP407 in moderate yield. The (S,R,S,S)-Z-RXP407 analog has been evaluated for the C- and N-domain constructs of angiotensin-converting enzyme. The potency of this analog has been much lower compared to the parent compound RXP407, providing thus valuable insights regarding further design based on structure–activity relationships.
KW - Angiotensin-converting enzyme
KW - Fragment-based design
KW - Phosphinic peptide
KW - RXP407
UR - http://www.scopus.com/inward/record.url?scp=85144571148&partnerID=8YFLogxK
U2 - 10.1016/j.arabjc.2022.104499
DO - 10.1016/j.arabjc.2022.104499
M3 - Article
AN - SCOPUS:85144571148
SN - 1878-5352
VL - 16
JO - Arabian Journal of Chemistry
JF - Arabian Journal of Chemistry
IS - 2
M1 - 104499
ER -