Lorthiois, Edwige; Roache, James; Barnes-Seeman, David; Altmann, Eva; Hassiepen, Ulrich; Turner, Gordon; Duvadie, Rohit; Hornak, Viktor; Karki, Rajeshri G.; Schiering, Nikolaus; Weihofen, Wilhelm A.; Perruccio, Francesca; Calhoun, Amy; Fazal, Tanzina; Dedic, Darija; Durand, Corinne; Dussauge, Solene; Fettis, Kamal; Tritsch, Fabien; Dentel, Celine; Druet, Adelaide; Liu, Donglei; Kirman, Louise; Lachal, Julie; Namoto, Kenji; Bevan, Douglas; Mo, Rose; Monnet, Gabriela; Muller, Lionel; Zessis, Richard; Huang, Xueming; Lindsley, Loren; Currie, Treeve; Chiu, Yu-Hsin; Fridrich, Cary; Delgado, Peter; Wang, Shuangxi; Hollis-Symynkywicz, Micah; Berghausen, Joerg; Williams, Eric; Liu, Hong; Liang, Guiqing; Kim, Hyungchul; Hoffmann, Peter; Hein, Andreas; Ramage, Paul; D’Arcy, Allan; Harlfinger, Stefanie; Renatus, Martin; Ruedisser, Simon; Feldman, David; Elliott, Jason; Sedrani, Richard; Maibaum, Juergen; Adams, Christopher M. published the artcile< Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach>, Name: Methyl 1H-indole-7-carboxylate, the main research area is anticoagulant FXIa inhibitors ADME drug design orally bioavailable.
The serine protease factor XI (FXI) is a prominent drug target as it holds promise to deliver efficacious anticoagulation without an enhanced risk of major bleeds. Several efforts have been described targeting the active form of the enzyme, FXIa. Herein, we disclose our efforts to identify potent, selective, and orally bioavailable inhibitors of FXIa. Compound 1, identified from a diverse library of internal serine protease inhibitors, was originally designed as a complement factor D inhibitor and exhibited submicromolar FXIa activity and an encouraging absorption, distribution, metabolism, and excretion (ADME) profile while being devoid of a peptidomimetic architecture. Optimization of interactions in the S1, S1β, and S1′ pockets of FXIa through a combination of structure-based drug design and traditional medicinal chem. led to the discovery of compound 23(I) with subnanomolar potency on FXIa, enhanced selectivity over other coagulation proteases, and a preclin. pharmacokinetics (PK) profile consistent with bid dosing in patients.
Journal of Medicinal Chemistry published new progress about Anticoagulants. 93247-78-0 belongs to class indole-building-block, and the molecular formula is C10H9NO2, Name: Methyl 1H-indole-7-carboxylate.
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles