916664-23-8Relevant articles and documents
Discovery of Milvexian, a High-Affinity, Orally Bioavailable Inhibitor of Factor XIa in Clinical Studies for Antithrombotic Therapy
Dilger, Andrew K.,Pabbisetty, Kumar B.,Corte, James R.,De Lucca, Indawati,Fang, Tianan,Yang, Wu,Pinto, Donald J. P.,Wang, Yufeng,Zhu, Yeheng,Mathur, Arvind,Li, Jianqing,Hou, Xiaoping,Smith, Daniel,Sun, Dawn,Zhang, Huiping,Krishnananthan, Subramaniam,Wu, Dauh-Rurng,Myers, Joseph E.,Sheriff, Steven,Rossi, Karen A.,Chacko, Silvi,Zheng, Joanna J.,Galella, Michael A.,Ziemba, Theresa,Dierks, Elizabeth A.,Bozarth, Jeffrey M.,Wu, Yiming,Crain, Earl,Wong, Pancras C.,Luettgen, Joseph M.,Wexler, Ruth R.,Ewing, William R.
, (2021/09/28)
Factor XIa (FXIa) is an enzyme in the coagulation cascade thought to amplify thrombin generation but has a limited role in hemostasis. From preclinical models and human genetics, an inhibitor of FXIa has the potential to be an antithrombotic agent with superior efficacy and safety. Reversible and irreversible inhibitors of FXIa have demonstrated excellent antithrombotic efficacy without increased bleeding time in animal models (Weitz, J. I., Chan, N. C. Arterioscler. Thromb. Vasc. Biol. 2019, 39 (1), 7-12). Herein, we report the discovery of a novel series of macrocyclic FXIa inhibitors containing a pyrazole P2′ moiety. Optimization of the series for (pharmacokinetic) PK properties, free fraction, and solubility resulted in the identification of milvexian (BMS-986177/JNJ-70033093, 17, FXIa Ki = 0.11 nM) as a clinical candidate for the prevention and treatment of thromboembolic disorders, suitable for oral administration.
2-[3-(ALKYLSULFONYL)-2H-INDAZOL-2-YL]-3H-IMIDAZO[4,5-B]PYRIDINE DERIVATIVES AND SIMILAR COMPOUNDS AS PESTICIDES
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Paragraph 0746; 0755; 0756, (2019/09/20)
The invention relates to compounds of the formula (Ia) or (Ib), in which Aa, Ab, Ac, Ad, R1, R10 R11, R12, R13, R14, R15, R16, R17, Q, R4, R5, R
Cycloaddition and Cascade Radical Reactions for the Synthesis of Trifluoromethylated Tetrahydrobenzodiazepin-3-ones
Muthengi, Alex,Erickson, Jon,Muriph, Rachel E.,Zhang, Wei
, p. 5927 - 5935 (2019/05/01)
A reaction sequence involving three-component [3 + 2] cycloaddition of azomethine ylides followed by CuI-catalyzed cascade trifluoromethyl radical addition and cyclization is developed for diastereoselective synthesis of fused-tetrahydrobenzodiazepin-3-ones.