Liver Injury with Nintedanib: A Pharmacovigilance-Pharmacokinetic Appraisal was written by Raschi, Emanuel;Fusaroli, Michele;Gatti, Milo;Caraceni, Paolo;Poluzzi, Elisabetta;De Ponti, Fabrizio. And the article was included in Pharmaceuticals in 2022.Application In Synthesis of 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide This article mentions the following:
Drug-induced liver injury (DILI) with nintedanib has emerged as an adverse event of special interest in premarketing clin. trials. We characterized DILI with nintedanib in the real world and explored the underlying pharmacol. basis. First, we assessed serious hepatic events reported to the Food and Drug Administration’s Adverse Event Reporting System by combining the disproportionality approach [reporting odds ratio (ROR) with 95% confidence interval (CI)] with individual case assessment. Demog. and clin. features were inspected (seriousness, onset, discontinuation, dechallenge/rechallenge, concomitant drugs) to implement an ad hoc causality assessment scoring system. Second, we appraised physiochem. and pharmacokinetic parameters possibly predictive of DILI occurrence. Significant disproportionality was found for nintedanib as compared to pirfenidone (N = 91; ROR = 4.77; 95% CI = 3.15-7.39). Asian population, low body weight (59 kg), and rapid DILI onset (13.5 days) emerged as clin. features. Hospitalization and discontinuation were found in a significant proportion of cases (32% and 36%, resp.). In 24% of the cases, at least two potentially hepatotoxic drugs (statins, proton pump inhibitors, antibiotics) were recorded. Causality was at least possible in 92.3% of the cases. High lipophilicity and predicted in silico inhibition of liver transporters emerged as potential pharmacokinetic features supporting the biol. plausibility. Although causality cannot be demonstrated, clinicians should consider early monitoring and medication review on a case-by-case basis. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Application In Synthesis of 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide).
7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Application In Synthesis of 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics