68497-66-5Relevant articles and documents
Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle
He, Shanshan,Li, Kelin,Lin, Billy,Hu, Zongyi,Xiao, Jingbo,Hu, Xin,Wang, Amy Q.,Xu, Xin,Ferrer, Marc,Southall, Noel,Zheng, Wei,Aubé, Jeffrey,Schoenen, Frank J.,Marugan, Juan J.,Liang, T. Jake,Frankowski, Kevin J.
supporting information, p. 6364 - 6383 (2017/08/02)
Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure-activity relationship studies revealed several compounds exhibiting EC50 values below 100 nM. Lead compounds showed inhibition of the HCV pseudoparticle entry, suggesting a different mode of action from existing HCV drugs. Hit 7a and lead 7ii both showed synergistic effects in combination with existing HCV drugs. In vivo pharmacokinetics studies of 7ii showed high liver distribution and long half-life without obvious hepatotoxicity. The lead compounds are promising as preclinical candidates for the treatment of HCV infection and as molecular probes to study HCV pathogenesis.
Super high specific activity tritium labelled receptor ligands - 1. The use of polybromodiphenylacetic acid as a tritiation substrate. Synthesis of a tritium labelled sodium-channel blocker and angiotensin ii antagonist with super high specific activity
Gong, Leyi,Pames, Howard
, p. 31 - 40 (2007/10/03)
We describe herein the synthesis of polybromodiphenylacetic acid (4), a fragment common to the tritiation substrates (8) and (11) of the sodium channel blocker, PD-85639 (1) and the angiotensin II inhibitor EXP-655 (2) respectively. Preparation of (8) and
Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl]-2-oxo-1-pyrrolidineacetamides, including pramiracetam
Butler,Nordin,L'Italien,Zweisler,Poschel,Marriott
, p. 684 - 691 (2007/10/02)
A series of N-[(dialkylamino)alkyl]-2-oxo-1-pyrrolidineacetamides was synthesized. The title compounds reversed electroconvulsive shock (ECS) induced amnesia in mice when administered subsequent to the ECS treatment and were inactive in a general observational test for central nervous system (CNS) activity. Active compounds exhibited an inverted U-shaped dose-response curve. Among the compounds with the broadest dose-response curve, as well as the most potent, were those with the N-[2-[bis(1-methylethyl)amino]ethyl] or 2,6-dimethylpiperidinoethyl residues as amide substituent. The N-(dialkylamino) substituent markedly enhances amnesia-reversal activity, with ethylene providing the optimal chain length. N-[2-[Bis(1-methylethyl)amino]ethyl]-2-oxo-1-pyrrolidineacetamide N(-dialkylamino) substituent was selected for preclinical toxicological evaluation, assigned the investigational number CI-879 and the U.S. adopted name (USAN) pramiracetam. Pramiracetam demonstrated a wide margin of safety in animals and was tolerated in normal human volunteers. It has shown encouraging activity in an open label trial in patients with primary degenerative dementia (PDD or senile dementia of the Alzheimer's type).
