260978-43-6Relevant articles and documents
RHO KINASE INHIBITOR, METHOD FOR PREPARING SAME AND USES THEREOF
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Paragraph 0140, (2021/09/16)
Provided are a Rho kinase inhibitor, a method for preparing same and the uses thereof. The Rho kinase inhibitor designates a compound of Formula I, a stereoisomer thereof or pharmaceutically acceptable salt thereof. The Rho kinase inhibitor promotes endothelial cells and endothelin expression, prostenin expression, and vascular factors NO synthesis and secretion, has a promoting effect on proprostin expression independently of the doses used, shows lower toxicity, while being safer.
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.
Highly Enantioselective Synthesis of 1,2-Amino Alcohol Derivatives via Proline-Catalyzed Mannich Reaction
Pojarliev, Peter,Biller, William T.,Martin, Harry J.,List, Benjamin
, p. 1903 - 1905 (2007/10/03)
Here we report a new catalytic asymmetric synthesis of oxazolidin-2-ones 4 and Cbz-protected 1,2-amino alcohols 5. Our sequence is based on the chemistry of previously unknown 5-acyloxy-oxazolidin-2-ones, which are obtained via proline-catalyzed direct asymmetric three-component Mannich reaction and Baeyer-Villiger oxidation.
