6216-62-2Relevant articles and documents
Synthesis and evaluation of chirally defined side chain variants of 7-chloro-4-aminoquinoline to overcome drug resistance in malaria chemotherapy
Dola, Vasantha Rao,Soni, Awakash,Agarwal, Pooja,Ahmad, Hafsa,Raju, Kanumuri Siva Rama,Rashid, Mamunur,Wahajuddin, Muhammad,Srivastava, Kumkum,Haq,Dwivedi,Puri,Katti
, (2017/03/09)
A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methyl-piperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.
Dihydroxyacetone phosphate aldolase catalyzed synthesis of structurally diverse polyhydroxylated pyrrolidine derivatives and evaluation of their glycosidase inhibitory properties
Calveras, Jordi,Egido-Gabas, Meritxell,Gomez, Livia,Casas, Josefina,Parella, Teodor,Joglar, Jesus,Bujons, Jordi,Clapes, Pere
experimental part, p. 7310 - 7328 (2010/03/24)
The chemoenzymatic synthesis of a collection of pyrrolidine-type iminosugars generated by the aldol addition of dihydroxyacetone phosphate (DHAP) to C-α-substituted N-Cbz-2-aminoaldehydes derivatives, catalyzed by DHAP aldolases is reported. L-Fuculose-1-phosphate aldolase (FucA) and L-rhamnulose-1-phosphate aldolase (RhuA) from E. coli were used as biocatalysts to generate configurational diversity on the iminosugars. Alkyl linear substitutions at C-α were well tolerated by FucA catalyst (i.e., 40-70% conversions to aldol adduct), whereas no product was observed with C-α-alkyl branched substitutions, except for dimethyl and benzyl substitutions (20%). RhuA was the most versatile biocatalyst: C-α-alkyl linear groups gave the highest conversions to aldol adducts (60-99%), while the C-α-alkyl branched ones gave moderate to good conversions (50-80%), with the exception of dimethyl and benzyl substituents (20%). FucA was the most stereoselective biocatalyst (90-100% anti (3R,4R) adduct). RhuA was highly stereoselective with (S)-N-Cbz-2-aminoaldehydes (90-100% syn (i.e., 3R,4S) adduct), whereas those with R configuration gave mixtures of antilsyn adducts. For iPr and iBu substituents, RhuA furnished the anti adduct (i.e., FucA stereochemistry) with high stereoselectivity. Molecular models of aldol products with iPr and iBu sub-stituents and as complexes with the RhuA active site suggest that the and adducts could be kinetically preferred, while the syn adducts would be the equilibrium products. The polyhydroxylated pyrrolidines generated were tested as inhibitors against seven glycosidases. Among them, good inhibitors of a-L-fucosidase (IC50 = 1-20 μM), moderate of α-L-rhamnosidase (IC50=7-150 μM), and weak of α-D-mannosidase (IC50 = 80-400 μM) were identified. The apparent inhibition constant values (Ki) were calculated for the most relevant inhibitors and computational docking studies were performed to understand both their binding capacity and the mode of interaction with the glycosidases.
Synthesis of novel amino-acid-derived sulfinamides and their evaluation as ligands for the enantioselective transfer hydrogenation of ketones
Zani, Lorenzo,Eriksson, Lars,Adolfsson, Hans
scheme or table, p. 4655 - 4664 (2009/04/11)
Novel chiral mono-sulfinyl diamines bearing a stereogenic sulfur atom were prepared in moderate to good yields starting from amino acids by means of a reductive amination of the corresponding amino aldehydes. Their potential as ligands for asymmetric catalysis was evaluated in the metal-catalyzed enantioselective transfer hydrogenation of alkyl-aryl ketones. The catalysts were generated in situ from sulfinamides 1a-i and arene complexes of rhodium and ruthenium, and the catalytic reductions led to the formation of chiral alcohols with up to 91% ee. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
