1206161-97-8 Usage
Description
Different sources of media describe the Description of 1206161-97-8 differently. You can refer to the following data:
1. Filgotinib (GLPG0634) is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively.
2. Filgotinib is a JAK1 inhibitor (IC50 = 10 nM). It is selective for JAK1 over JAK3 (IC50 = 810 nM) but also inhibits JAK2 and tyrosine kinase 2 (Tyk2; IC50s = 28 and 116 nM, respectively), as well as Abl, FLT1, -3, and -4, FMS, Mer, and TBK1 activity by greater than 35% in a panel of 177 tyrosine kinases at 1 μM. Filgotinib inhibits IL-6-induced phosphorylation of STAT1 in CD4+ T cells with an IC50 value of 629 nM in isolated human whole blood. It reduces hind paw macrophage and T cell infiltration and bone erosion in a rat model of collagen-induced arthritis when administered at doses ranging from 0.1 to 30 mg/kg per day for 15 days.
In vitro
In cell lines, GLPG0634 inhibits IL-2- and IL-4-induced JAK1/JAK3/γc signaling and IFN-αB2-induced JAK1/TYK2 type II receptor signaling with IC50 ranged from 150 to 760 nM. GLPG0634 shows higher selectivity for JAK/STAT signaling involving JAK1 than JAK2 kinase in a cellular context. Besides, GLPG0634 also inhibits the differentiation of Th1, Th2, and Th17 cells.
In vivo
Following oral administration, the absolute bioavailability is moderate in rats (45%) and high in mice (～100%). Filgotinib (30 mg/kg daily (Rats); 50 mg/kg twice daily (Mice)) dose-dependently reduces inflammation, cartilage, and bone degradation in the CIA model in rats and mice. Filgotinib (GLPG0634) in DSS-treated mice demonstrates that inhibition of JAK1 is sufficient for achieving strong efficacy in pre-clinical mouse model, correlated to the inhibition of STAT3 phosphorylation in the inflamed colon.
Uses
GLPG-0634 (Filgotinib) is a potent, selective JAK1 inhibitor. Used as an anti-inflammatory agent, it reduces levels of inflammatory cytokines in the bones and tissue of mammals.
Mechanism of action
Filgotinib acts on the JAK-STAT pathway by selectively inhibiting JAK1 phosphorylation and preventing STAT activation, which ultimately results in reduced proinflammatory cytokine signaling.
Side effects
feeling sick (nausea)upper respiratory tract infectionurinary tract infection.dizziness.
Synthesis
The synthesis of?Filgotinib is as follows:With cyclopropanyl chloride in an amidated reaction in a system consisting of N-methylmorpholine and 1,4-dioxane,The amidation reaction time was 4 h,The amidation reaction temperature was 50 ° C,The molar ratio of the intermediate (III), cyclopropanyl chloride, N-methylmorpholine and 1,4-dioxane was 1: 2.8: 2.5:TLC plate to determine the reaction is completed, cooled to room temperature,Adding methylene chloride and water, separating the organic phase with water,Then washed with brine, dried over magnesium sulfate,Evaporated to dryness and the residue was purified over a silica gel column [elution solvent: ethyl acetate / n-hexane (3: 7 v / v)To obtain a solid yellowish solid,That is, Filgotinib, yield 91.2%.
References
Menet et al. (2014), Triazolopyridines as selective JAK1 inhibitors: from hit identification to GLPG0634; Med. Chem., 57 9323
Rompaey et al. (2013), Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases; Immunol., 191 3568
Kavanaugh et al. (2017), Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomized dose-finding study (DARWIN 2); Rheum. Dis., 76 1009
Wang et al. ?(2019), Oncostatin M inhibits differentiation of rat stem Leydig cells in vivo and in vitro; J. Cell. Mol. Med., 23 426
Check Digit Verification of cas no
The CAS Registry Mumber 1206161-97-8 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,0,6,1,6 and 1 respectively; the second part has 2 digits, 9 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 1206161-97:
(9*1)+(8*2)+(7*0)+(6*6)+(5*1)+(4*6)+(3*1)+(2*9)+(1*7)=118
118 % 10 = 8
So 1206161-97-8 is a valid CAS Registry Number.
1206161-97-8Relevant articles and documents
NOVEL PROCESS FOR THE PREPARATION OF FILGOTINIB AND INTERMEDIATES THEREOF
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, (2020/10/20)
The present invention relates to a novel process for the preparation of filgotinib or a pharmaceutically acceptable salt and intermediates thereof which avoid Suzuki coupling reaction. (I)
PROCESSES FOR THE PREPARATION OF FILGOTINIB
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, (2020/03/09)
The present invention relates to processes for the preparation of Filgotinib. The present invention relates to novel processes for the preparation of filgotinib. The present invention also relates to novel intermediates for the preparation of filgotinib.
[1,2,4]triazol[1,5-a]pyridine compound as well as preparation method and medical application thereof
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, (2018/03/24)
The invention relates to a [1,2,4]triazol[1,5-a] pyridine compound as well as a preparation method and medical application thereof. Particularly, the invention relates to the compound shown in a general formula I, the preparation method of the compound, a
