1174321-06-2Relevant articles and documents
Synthesis of BACE1 Inhibitors E2609 / E2071 via Oxime-Olefin Cycloaddition following a Process Risk Mitigation Strategy
Benayoud, Farid,Bracke, Markus,Chanda, Arani,Dimopoulos, Paschalis,Fang, Francis G.,Farthing, Christopher N.,Hall, Adrian,Ishida, Tasuku,Kaneko, Toshihiko,Kayano, Akio,Khan, Afzal,Kim, Dae-Shik,Kita, Yoichi,Lu, Lily,Mitasev, Branko,Motoki, Takafumi,Nagai, Mitsuo,Omori, Masayuki,Schnaderbeck, Matthew,Suzuki, Yuichi,Takaishi, Mamoru,Takeda, Kunitoshi,Wakasugi, Kazunori,Watanabe, Yuzo,Yamamoto, Noboru,Yoshizawa, Kazuhiro,Zhang, Huiming
, (2021/08/24)
Process development of E2609 from the preclinical stage to the clinical stage following a process risk mitigation strategy is described here. Key features include a turbo Grignard reaction monitored by in-situ IR, [3 + 2] cycloaddition in water, chemoselective amide coupling via in-situ protection, and a Reformatsky/decarboxylation approach to install a difluoromethyl group. Toward safe and scalable manufacture of E2071, an analog of E2609, a flow-reaction process for trifluoromethylation of aldehydes is presented here.
C5-C6 OXACYCLIC-FUSED THIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE
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, (2012/10/18)
In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula : (I) and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of ring A, ring B, ring C, R2, R3, R4, m, n, p, and -L1- is as defined herein. The novel compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.
FUSED AMINODIHYDROTHIAZINE DERIVATIVES USEFUL AS BACE INHIBITORS
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, (2012/08/07)
The present invention relates to a fused aminodihydrothiazine derivative of formula (I): wherein X is hydrogen or fluorine; A is CH or N; Y is methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl, methoxy, ethoxy, methoxymethyl or -C≡N; and pharmaceutically acceptable salts thereof; which compound has an Αβ production inhibitory effect or a BACEl inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Αβ and typified by Alzheimer-type dementia.