At baseline, the mean tender joint count was 23.8, the mean swollen joint count was 16.1, and the average disease duration was 7.3 years.
The most common adverse reactions in the Decernotinib group were headache ( 8.7% ), hypercholesterolemia ( 5.2% ), and diarrhea ( 4.5% ).
Serious adverse reactions occurred in similar proportions of patients receiving Decernotinib ( 7.3% ) or placebo ( 5.6% ), but there were more serious infections in the Decernotinib group ( 3.5% ) compared with placebo ( 1.4% ).
Through 24 weeks there were two serious adverse effects that resulted in death; one was cardiac failure in the Decernotinib 100 mg BID group ( previously reported ) and one was pancytopenia in a patient with pneumonia in the Decernotinib 200 mg QD group.
Elevations in transaminase levels and decreases in median neutrophil and lymphocyte counts were observed in the Decernotinib groups and were generally mild.
Decernotinib was associated with small increases in adverse reactions rates, serious infections, and mostly minor laboratory abnormalities. ( Xagena )
comprising the steps of:
ivb) reacting lH-pyrrolo[2,3-b]pyridine (5a) with p-toluenesulfonyl chloride in the presence of an organic solvent to generate l-tosyl-lH-pyrrolo[2,3-b]pyridine (9a)
vb) reacting l-tosyl-lH-pyrrolo[2,3-b]pyridine (9a) in an organic solvent with N-bromosuccinimide to generate 3-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridine (7a)
l-tosyl-lH-pyrrolo[2,3-b]pyridin-3-ylboronic acid (8a) 0H
vii) esterifying l-tosyl-lH-pyrrolo[2,3-b]pyridin-3-ylboronic acid (8a) with pinacolate alcohol in an organic solvent to generate
3 -(4,4,5 ,5 -tetramethyl- 1 ,3 ,2-dioxaborolan-2-yl)- 1 -tosyl- 1 H-pyrrolo[2,3 -bjpyridine (la) :
ixb) reacting the compound of Formula 2a with HC1 to generate the hydrochloride salt of the compound of Formula 2a;
i) reacting the compound of Formula la with the compound of Formula 2a with in the presence of water, an organic solvent, an inorganic base, and a transition metal catalyst to generate a compound of Formula 3a,
|346||M+H393.20||RT 1.60||(DMSO-d6, 300 MHz) 11.95 (bs, 1H), 8.7 (d,|
|1H), 8.25 (m, 2H), 8.12 (d, 1H), 8.02 (d, 1H),|
|7.28 (s, 1H), 7.13 (dd, 1H), 6.38 (bd, 1H), 3.75|
|(m, 2H), 2.06 (m, 1H), 1.83 (m, 1H), 1.46 (s,|
|3H), 0.8 (t, 3H);|
Azaindoles Useful as Inhibitors of Janus Kinases
Azaindoles useful as inhibitors of janus kinases
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