474070-08-1Relevant articles and documents
Enantiopure Benzofuran-2-carboxamides of 1-Aryltetrahydro-β-carbolines Are Potent Antimalarials In Vitro
Almolhim, Hanan,Bremers, Emily K.,Butler, Joshua H.,Butschek, Grant J.,Carlier, Paul R.,Cassera, Maria B.,Ding, Sha,Merino, Emilio F.,Rizopoulos, Zaira,Slebodnick, Carla,Totrov, Maxim
supporting information, p. 371 - 376 (2022/03/15)
The tetrahydro-β-carboline scaffold has proven fertile ground for the discovery of antimalarial agents (e.g., MMV008138 (1) and cipargamin (2)). Similarity searching of a publicly disclosed collection of antimalarial hits for molecules resembling 1 drew our attention to N2-acyl tetrahydro-β-carboline GNF-Pf-5009 ((±)-3b). Compound purchase, “analog by catalog”, and independent synthesis of hits indicated the benzofuran-2-yl amide portion was required for in vitro efficacy against P. falciparum. Preparation of pure enantiomers demonstrated the pharmacological superiority of (R)-3b. Synthesis and evaluation of D- and F-ring substitution variants and benzofuran isosteres indicated a clear structure-activity relationship. Ultimately (R)-3b was tested in Plasmodium berghei-infected mice; unfavorable physicochemical properties may be responsible for the lack of oral efficacy.
BENZIMIDAZOLES THAT ENHANCE THE ACTIVITY OF OLIGONUCLEOTIDES
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Paragraph 0299; 0303-0305, (2019/11/22)
This disclosure is directed to methods, compounds and compositions for delivering nucleic acids to a cell of interest. In particular, it provides salts that are particularly effective in delivering nucleic acids to cells in the lung for disorders such as cystic fibrosis (CF).
