Page 79 - 《中国药科大学学报》2026年第2期

第 57 卷第 2 期 吴 杰，等：Asundexian 衍生物的设计、合成及活性评价 205

[8] Salomon O, Steinberg DM, Dardik R, et al. Inherited factor XI [14] Wu J, Yue H, Wang XQ, et al. Structure-based design and syn-
deficiency confers no protection against acute myocardial in- thesis of novel FXIa inhibitors targeting the S2' subsite for en-
farction[J]. J Thromb Haemost, 2003, 1(4): 658-661. hanced antithrombotic efficacy[J]. Mol Divers, 2025, 29(5):
[9] Thomas D, Kanefendt F, Schwers S, et al. First evaluation of 4131-4158.
the safety, pharmacokinetics, and pharmacodynamics of BAY [15] Teixeira S, Castanheira EMS, Carvalho MA. Hydrazides as
2433334, a small molecule targeting coagulation factor XIa[J]. J powerful tools in medicinal chemistry: synthesis, reactivity, and
Thromb Haemost, 2021, 19(10): 2407-2416. biological applications[J]. Molecules, 2025, 30(13): 2852.
[10] Piccini JP, Caso V, Connolly SJ, et al. Safety of the oral factor [16] Montazer MN, Asadi M, Moradkhani F, et al. Design, synthe-
XIa inhibitor asundexian compared with apixaban in patients sis, and biological studies of the new cysteine-N-arylacetamide
with atrial fibrillation (PACIFIC-AF): a multicentre, ran- derivatives as a potent urease inhibitor[J]. Naunyn Schmiede-
domised, double-blind, double-dummy, dose-finding phase 2 bergs Arch Pharmacol, 2024, 397(1): 305-315.
study[J]. Lancet, 2022, 399(10333): 1383-1390. [17] Tala SD, Ou TH, Lin YW, et al. Design and synthesis of potent
[11] Rao SV, Kirsch B, Bhatt DL, et al. A multicenter, phase 2, ran- antitumor water-soluble phenyl N-mustard-benzenealkylamide
domized, placebo-controlled, double-blind, parallel-group, conjugates via a bioisostere approach[J]. Eur J Med Chem,
dose-finding trial of the oral factor XIa inhibitor asundexian to 2014, 76: 155-169.
prevent adverse cardiovascular outcomes after acute myocar- [18] Yang SN, Wang YR, Yang YJ, et al. Design, synthesis, and bio-
dial infarction[J]. Circulation, 2022, 146(16): 1196-1206. logical evaluation of 1, 3, 4-thiadiazole derivatives as novel po-
[12] Shoamanesh A, Mundl H, Smith EE, et al. Factor XIa inhibi- tent peptide deformylase inhibitors for combating drug-resistant
tion with asundexian after acute non-cardioembolic ischaemic gram-positive and-negative bacteria[J]. J Med Chem, 2025,
stroke (PACIFIC-Stroke): an international, randomised, double- 68(3): 2942-2962.
blind, placebo-controlled, phase 2b trial[J]. Lancet, 2022, [19] Roehrig S, Ackerstaff J, Núñez EJ, et al. Design and preclinical
400(10357): 997-1007. characterization program toward asundexian (BAY 2433334),
[13] Komiyama M, Iguchi M, Wada H, et al. What is the future posi- an oral factor XIa inhibitor for the prevention and treatment of
tion of factor XIa inhibitors for patients with atrial thromboembolic disorders[J]. J Med Chem, 2023, 66(17):
fibrillation[J]. Eur Cardiol, 2024, 19: e10. 12203-12224.