Discovery of hydroxy pyrimidine Factor IXa inhibitors. Issue 15 (1st August 2020)

• Record Type: Journal Article
• Authors: Jayne, Charles L.; Andreani, Teresa; Chan, Tin-Yau; Chelliah, Mariappan V.; Clasby, Martin C.; Dwyer, Michael; Eagen, Keith A.; Fried, Steve; Greenlee, William J.; Guo, Zhuyan; Hawes, Brian; Hruza, Alan; Ingram, Richard; Keertikar, Kartik M.; Neelamkavil, Santhosh; Reichert, Paul; Xia, Yan; Chackalamannil, Samuel
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 15(2020)
• Publication Date: 2020-08-01
• Subjects: BIKIOSQYMWPNJO-RMRSYLNJSA-N -- YNTOWEYGMDJVIV-UHFFFAOYSA-N -- YCERDQYNHAVFPL-UHFFFAOYSA-N -- UHGFPMUGEQINGV-UHFFFAOYSA-N -- WPANETAWYGDRLL-UHFFFAOYSA-N -- HTYARUULLOPGKD-UHFFFAOYSA-N -- VWDSNVUXQDDXBN-UHFFFAOYSA-N -- YYXYBWIDIWTCGS-UHFFFAOYSA-N -- RRCZRUXYTNNVBQ-LJGSYFOKSA-N -- BFWYZZPDZZGSLJ-UHFFFAOYSA-N -- ICXSUHAVDAEXSZ-UHFFFAOYSA-N -- KHLISQCRWOJMHJ-UHFFFAOYSA-N -- DRGUQIQEUWFBDE-UHFFFAOYSA-N -- QIKYZXDTTPVVAC-UHFFFAOYSA-N -- HHKUTNPBFUUYPS-UHFFFAOYSA-N -- NJXPYZHXZZCTNI-UHFFFAOYSA-N -- RGJCJWXNNDARPQ-UHFFFAOYSA-N -- DRRYZHHKWSHHFT-UHFFFAOYSA-N -- ZJYIRVSPPOOPCL-UHFFFAOYSA-N; Factor IXa inhibition -- Factor IXa -- Pyrimidine -- Thrombosis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127279
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The synthesis and structure activity relationship development of a pyrimidine series of heterocyclic Factor IXa inhibitors is described. Increased selectivity over Factor Xa inhibition was achieved through SAR expansion of the P1 element. Select compounds were evaluated in vivo to assess their plasma levels in rat.