ABT-494 intermediate CAS NO.1428243-24-6

ABT-494intermediate

1,3-Pyrrolidinedicarboxylicacid,4-ethyl-,1-(phenylmethyl)ester,(3R,4S)-;(3R,4S)-4-ethyl-1,3-Pyrrolidinedicarboxylicacid1-(phenylmethyl)ester;UpadacitiChemicalbooknibImpurity1;(3R,4S)-1-((benzyloxy)carbonyl)-4-ethylpyrrolidine-3-carboxylate;ClofazimineImpurity11;UpadacitinibImpurity42

1428243-24-6

C15H19NO4分

277.32

820-324-3

443.9±45.0 °C(Predicted)

1.216±0.06 g/cm3(Predicted)

(pKa)4.48±0.40(Predicted)

At week 12, the proportion of ACR20 responses was higher with ABT-494 (62%, 68%, 80%, 64%, and 76% for the 3, 6, 12, 18, and 24 mg doses, respectively) than with placebo (46%) (using nonresponder imputation) (P < 0.05 for the 6, 12, and 24 mg doses). There was a significant dose-response relationship among all ABT-494 doses (P < 0.001). The proportions of patients achieving ACR50 and ACR70 responses were significantly higher for all ABT-494 doses (except the 12 mg dose for the ACR70 response) than for placebo, as were changes in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). Rapid improvement was demonstrated by significant differences in ACR20 response rates and changes in the DAS28-CRP for all doses compared with placebo at week 2 (the first postbaseline visit). The incidence of adverse events was similar across groups; most were mild, and infections were the most frequent. One serious infection (community-acquired pneumonia) occurred with ABT-494 at 12 mg. There were dose-dependent increases in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, but the LDL cholesterol:HDL cholesterol ratios were unchanged through week 12. Mean hemoglobin levels remained stable at lower doses, but decreases were observed at higher doses.