52109-49-6Relevant academic research and scientific papers
JNJ-67569762, A 2-Aminotetrahydropyridine-Based Selective BACE1 Inhibitor Targeting the S3 Pocket: From Discovery to Clinical Candidate
Rombouts, Frederik J. R.,Kusakabe, Ken-Ichi,Alexander, Richard,Austin, Nigel,Borghys, Herman,De Cleyn, Michel,Dhuyvetter, Deborah,Gijsen, Harrie J. M.,Hrupka, Brian,Jacobs, Tom,Jerhaoui, Soufyan,Lammens, Lieve,Leclercq, Laurent,Tsubone, Koichi,Ueno, Tatsuhiko,Morimoto, Kenji,Einaru, Shunsuke,Sumiyoshi, Hirokazu,Van Den Bergh, An,Vos, Ann,Surkyn, Michel,Teisman, Ard,Moechars, Diederik
supporting information, p. 14175 - 14191 (2021/10/12)
The discovery of a novel 2-aminotetrahydropyridine class of BACE1 inhibitors is described. Their pKa and lipophilicity were modulated by a pending sulfonyl group, while good permeability and brain penetration were achieved via intramolecular hydrogen bonding. BACE1 selectivity over BACE2 was achieved in the S3 pocket by a novel bicyclic ring system. An optimization addressing reactive metabolite formation, cardiovascular safety, and CNS toxicity is described, leading to the clinical candidate JNJ-67569762 (12), which gave robust dose-dependent BACE1-mediated amyloid β lowering without showing BACE2-dependent hair depigmentation in preclinical models. We show that 12 has a favorable projected human dose and PK and hence presented us with an opportunity to test a highly selective BACE1 inhibitor in humans. However, 12 was found to have a QT effect upon repeat dosing in dogs and its development was halted in favor of other selective leads, which will be reported in the future.
Tetra-(tetraalkylammonium)octamolybdate catalysts for selective oxidation of sulfides to sulfoxides with hydrogen peroxide
Yang, Chuanbo,Jin, Qingping,Zhang, Hua,Liao, Jian,Zhu, Jin,Yu, Bin,Deng, Jingen
experimental part, p. 1401 - 1405 (2010/05/02)
Tetra-(tetraalkylammonium)octamolybdate catalysts are successfully applied in the selective oxidation of various sulfides to sulfoxides with 30% aqueous hydrogen peroxide as oxidant under mild reaction conditions in 94-100% yield and 95-100% selectivity. The octamolybdate catalysts show high catalytic activity in a high ratio of substrate to catalyst (up to 10000:1) and are recyclable, with actively functional groups, including hydroxyl group and CC bonds, tolerated in the oxidation. The Royal Society of Chemistry 2009.
Selective oxidation of sulfides to sulfoxides using a silica immobilised vanadyl alkyl phosphonate catalyst
Al-Hashimi, Mohammed,Fisset, Emilie,Sullivan, Alice C.,Wilson, John R.H.
, p. 8017 - 8019 (2007/10/03)
A range of sulfides can be selectively oxidised to the corresponding sulfoxides in good yields using catalytic quantities of immobilised vanadyl, cobalt or nickel alkyl phosphonates and the reoxidant sodium bromate or vanadyl alkyl phosphonate with tert-b
Selective oxidations of sulfides to sulfoxides using immobilised cerium alkyl phosphonate
Al-Hashimi, Mohammed,Roy, Gopa,Sullivan, Alice C.,Wilson, John R. H.
, p. 4365 - 4368 (2007/10/03)
A range of sulfides can be selectively oxidised to the corresponding sulfoxides in good yields using catalytic quantities of immobilised cerium alkyl phosphonate and either sodium bromate or tert-butyl hydroperoxide as oxidants.
