2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease

Journal of Medicinal Chemistry
S J HaysJ C Jaen

Abstract

A series of 2-amino-4H-3,1-benzoxazin-4-ones have been synthesized and evaluated as inhibitors of the complement enzyme C1r. C1r is a serine protease at the beginning of the complement cascade, and complement activation by beta-amyloid may represent a major contributing pathway to the neuropathology of Alzheimer's disease. Compounds such as 7-chloro-2-[(2-iodophenyl)-amino]benz[d][1,3]oxazin-4-one (32) and 7-methyl-2-[(2-iodophenyl)amino]benz[d][1,3]oxazin-4-one (37) show improved potency compared to the reference compound FUT-175. Many of these active compounds also possess increased selectivity for C1r compared to trypsin and enhanced hydrolytic stability relative to 2-(2-iodophenyl)-4H-3,1-benzoxazin-4-one (1).

Citations

May 10, 2005·Bioorganic & Medicinal Chemistry Letters·Pei-Wen HsiehYang-Chang Wu
May 17, 2003·European Journal of Medicinal Chemistry·María L López-RodríguezJosé A Ramos
May 17, 2001·Bioorganic & Medicinal Chemistry·U NeumannM Gütschow
Jan 16, 2009·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hans-Georg HäckerMichael Gütschow
Jul 15, 2015·Organic & Biomolecular Chemistry·Sadhan JanaSangit Kumar
Sep 23, 2006·Rapid Communications in Mass Spectrometry : RCM·Loris TonidandelPietro Traldi
Jul 8, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zi-Long TangYin-Chun Jiao
Nov 14, 2017·Chemistry : a European Journal·Kuntal PalChandra M R Volla
Jan 14, 2021·Chembiochem : a European Journal of Chemical Biology·Jian YangSteven H L Verhelst
Jul 19, 2000·Biochimica Et Biophysica Acta·M R EmmerlingK Spiegel
Apr 2, 2009·Journal of Combinatorial Chemistry·Jun CheYulin Lam
Nov 6, 2013·Organic Letters·Ádám SinaiZoltán Novák
Jan 17, 2015·Chemical Reviews·Valentine G NenajdenkoAleksey V Shastin
Apr 16, 2013·The Journal of Organic Chemistry·Zhi-Yuan GeShun-Jun Ji
Feb 6, 2018·Organic Letters·Manthena Chaitanya, Pazhamalai Anbarasan
Dec 12, 2019·The Journal of Organic Chemistry·V P Rama Kishore PuttaChandi C Malakar
Dec 12, 2002·Chemical Reviews·James C PowersKaren Ellis James

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