22261-94-5Relevant articles and documents
Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection
He, Shanshan,Xiao, Jingbo,Dulcey, Andrés E.,Lin, Billy,Rolt, Adam,Hu, Zongyi,Hu, Xin,Wang, Amy Q.,Xu, Xin,Southall, Noel,Ferrer, Marc,Zheng, Wei,Liang, T. Jake,Marugan, Juan J.
supporting information, p. 841 - 853 (2016/02/23)
Recently, we reported that chlorcyclizine (CCZ, Rac-2), an over-the-counter antihistamine piperazine drug, possesses in vitro and in vivo activity against hepatitis C virus. Here, we describe structure-activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC50 values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improved in vivo pharmacokinetic properties. The optimized molecules can serve as lead preclinical candidates for the treatment of hepatitis C virus infection and as probes to study hepatitis C virus pathogenesis and host-virus interaction.
Synthesis and investigations of double-pharmacophore ligands for treatment of chronic and neuropathic pain
Vardanyan, Ruben,Vijay, Gokhale,Nichol, Gary S.,Liu, Lu,Kumarasinghe, Isuru,Davis, Peg,Vanderah, Todd,Porreca, Frank,Lai, Josephine,Hruby, Victor J.
experimental part, p. 5044 - 5053 (2009/12/04)
Acids 9a-f as possible bivalent ligands designed as a structural combination of opioid μ-agonist (Fentanyl) and NSAID (Indomethacin) activities and produced compounds which were tested as analgesics. The obtained series of compounds exhibits low affinity and activity both at opioid receptors and as cyclooxygenase (COX) inhibitors. One explanation of the weak opioid activity could be stereochemical peculiarities of these bivalent compounds which differ significantly from the fentanyl skeleton. The absence of significant COX inhibitory properties could be explained by the required substitution of an acyl fragment in the indomethacin structure for 4-piperidyl.
Reductive alkylation of aromatic amines with enol ethers
Reddy, T. Jagadeeswar,Leclair, Michael,Proulx, Melanie
, p. 583 - 586 (2007/10/03)
Reductive alkylation of aromatic amines with 2-methoxypropene using 1.0 equivalent of HOAc and NaBH(OAc)3 in 1,2-dichloroethane (DCE) at room temperature furnished N-isopropyl amines in 50-98% yields. This method was successfully extended to trimethylsilyl enol ethers. The mild reaction conditions provide a new alternative procedure for the reductive amination of electron deficient aromatic amines.