94-05-3Relevant articles and documents
Efficient, Protecting Group Free Kilogram-Scale Synthesis of the JAK1 Inhibitor GDC-4379
Angelaud, Remy,Burkhard, Johannes,Gosselin, Francis,Lao, David,Marx, Andreas,Ochsenbein, Miriam,Ranjan, Rohit,Stumpf, Andreas,Xu, Di
, p. 2537 - 2550 (2021/11/24)
The development of an improved kilogram-scale synthesis of the JAK1 inhibitorGDC-4379for the treatment of asthma is described. The new process is highlighted by a step-economical construction of a 3-substituted-4-aminopyrazole employing a telescoped oximation and hydrazine condensation of a 1,3-dielectrophile to generate nitrosopyrazole and a novel copper-catalyzed NaBH4reduction of the nitroso group. The endgame process features an amidation of aminopyrazole with acid chloride under Schotten-Baumann conditions to provide access to the penultimate intermediate. A selective N-1 alkylation of the pyrazole moiety was accomplished under phase-transfer conditions, which deliveredGDC-4379with a defined particle-size distribution suitable for micronization after recrystallization and wet milling.
ANDROGEN RECEPTOR ANTAGONISTS
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Paragraph 0534-0536, (2019/08/26)
Compounds that inhibit the androgen receptor, pharmaceutical compositions comprising one or more of the compounds, as well as methods of treating cancer using such compounds are described.
Substituted heteroaryl compounds and compositions and uses thereof
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Paragraph 0745-0748, (2017/12/02)
The invention discloses a substituted ceteroary compound as well as a composition and an application thereof. The compound is a compound shown in a formula (I) or a stereisomer, a tautomer, a nitric oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or prodrug of the compound shown in the formula (I). The invention further discloses a pharmaceutical composition including the compound. The compound and the pharmaceutical composition are capable of adjusting the activity of the AK kinase and can be used for preventing, processing, treating and relieving the JAK-mediated disease or disorder.