55455-94-2Relevant academic research and scientific papers
Astemizole analogues with reduced hERG inhibition as potent antimalarial compounds
Tian, Junjun,Vandermosten, Leen,Peigneur, Steve,Moreels, Lien,Rozenski, Jef,Tytgat, Jan,Herdewijn, Piet,Van den Steen, Philippe E.,De Jonghe, Steven
, p. 6332 - 6344 (2017/10/23)
Astemizole is a H1-antagonist endowed with antimalarial activity, but has hERG liabilities. Systematic structural modifications of astemizole led to the discovery of analogues that display very potent activity as inhibitors of the growth of the Plasmodium parasite, but show a decreased hERG inhibition, when compared to astemizole. These compounds can be used as starting point for the development of a new class of antimalarials.
Biologically Active Compounds through Catalysis: Efficient Synthesis of N-(Heteroarylcarbonyl)-N′-(arylalkyl)piperazines
Kumar, Kamal,Michalik, Dirk,Castro, Ivette Garcia,Tillack, Annegret,Zapf, Alexander,Arlt, Michael,Heinrich, Timo,Boettcher, Henning,Beller, Matthias
, p. 746 - 757 (2007/10/03)
A practical route for the synthesis of new biologically active 5-HT 2A receptor antagonists has been developed. In only three catalytic steps, this class of central nervous system (CNS) active compounds can be synthesized efficiently with high diversity. As the initial step, an anti-Markovnikov addition of amines to styrenes provides an easy route to N-(arylalkyl)piperazines, which constitute the core structure of the active molecules. Here, base-catalyzed hydroamination reactions of styrenes with benzylated piperazine proceeded in high yield even at room temperature. After catalytic debenzylation, the free amines were successfully carbonylated with different aromatic and heteroaromatic halides and carbon monoxide to yield the desired compounds in good to excellent yields. The two key reactions, base-catalyzed hydroamination of styrenes and palladium-catalyzed aminocarbonylation of haloarenes/heterocycles, showed tolerance towards various functional groups, thereby demonstrating the potential to synthesize a wide variety of new derivatives of this promising class of pharmaceuticals.
Synthesis of some substituted quinazolinediones as potential inhibitors of smooth muscle contraction
Akgun,Hollstein,Hurwitz
, p. 735 - 739 (2007/10/02)
3-Substituted 2,4(1H,3H)-quinazolinediones were prepared from the corresponding N-substituted 2-aminobenzamides by treatment with ethyl chloroformate and KOH in ethanol. Also, a series of 3-substituted and 1-methyl-3-substituted 2,4(1H,3H)-quinazolinediones were synthesized by the reaction of 1-methyl-1,4-dihydro- and 1,4-dihydro-2,4-dioxo-3(2H)-quinazolineacetic acid with the corresponding N-substituted piperazines. The 13C NMR spectra and mass spectra of the compounds were measured and signals were assigned. Some of the compounds showed inhibitory action on contractile function of smooth muscle.
