492-41-1Relevant articles and documents
High Regio- and Stereoselective Multi-enzymatic Synthesis of All Phenylpropanolamine Stereoisomers from β-Methylstyrene
Corrado, Maria L.,Knaus, Tanja,Mutti, Francesco G.
, p. 2345 - 2350 (2021/05/17)
We present a one-pot cascade for the synthesis of phenylpropanolamines (PPAs) in high optical purities (er and dr up to >99.5 %) and analytical yields (up to 95 %) by using 1-phenylpropane-1,2-diols as key intermediates. This bioamination entails the combination of an alcohol dehydrogenase (ADH), an ω-transaminase (ωTA) and an alanine dehydrogenase to create a redox-neutral network, which harnesses the exquisite and complementary regio- and stereo-selectivities of the selected ADHs and ωTAs. The requisite 1-phenylpropane-1,2-diol intermediates were obtained from trans- or cis-β-methylstyrene by combining a styrene monooxygenase with epoxide hydrolases. Furthermore, in selected cases, the envisioned cascade enabled to obtain the structural isomer (1S,2R)-1-amino-1-phenylpropan-2-ol in high optical purity (er and dr >99.5 %). This is the first report on an enzymatic method that enables to obtain all of the four possible PPA stereoisomers in great enantio- and diastereo-selectivity.
Selective Nonsteroidal Glucocorticoid Receptor Modulators for the Inhaled Treatment of Pulmonary Diseases
Hemmerling, Martin,Nilsson, Stinabritt,Edman, Karl,Eirefelt, Stefan,Russell, Wayne,Hendrickx, Ramon,Johnsson, Eskil,K?rrman M?rdh, Carina,Berger, Markus,Rehwinkel, Hartmut,Abrahamsson, Anna,Dahmén, Jan,Eriksson, Anders R.,Gabos, Balint,Henriksson, Krister,Hossain, Nafizal,Ivanova, Svetlana,Jansson, Anne-Helene,Jensen, Tina J.,Jerre, Anders,Johansson, Henrik,Klingstedt, Tomas,Lepist?, Matti,Lindsj?, Martin,Mile, Irene,Nikitidis, Grigorios,Steele, John,Tehler, Ulrika,Wissler, Lisa,Hansson, Thomas
, p. 8591 - 8605 (2017/11/03)
A class of potent, nonsteroidal, selective indazole ether-based glucocorticoid receptor modulators (SGRMs) was developed for the inhaled treatment of respiratory diseases. Starting from an orally available compound with demonstrated anti-inflammatory activity in rat, a soft-drug strategy was implemented to ensure rapid elimination of drug candidates to minimize systemic GR activation. The first clinical candidate 1b (AZD5423) displayed a potent inhibition of lung edema in a rat model of allergic airway inflammation following dry powder inhalation combined with a moderate systemic GR-effect, assessed as thymic involution. Further optimization of inhaled drug properties provided a second, equally potent, candidate, 15m (AZD7594), that demonstrated an improved therapeutic ratio over the benchmark inhaled corticosteroid 3 (fluticasone propionate) and prolonged the inhibition of lung edema, indicating potential for once-daily treatment.
Method for preparing norephedrine and norpseudoephedrine
-
Paragraph 0004; 0012; 0013; 0014; 0015, (2017/04/29)
The invention relates to a method for preparing (1R, 2S)-norephedrine, (1R, 2R)-norpseudoephedrine and a midbody thereof. The method comprises the following steps: in the reaction process in the first step, by taking a carrot as a medium, carrying out bio-transforming on 2-oximido-1-phenylacetone and reducing into (R)-2-oximido-1-phenyl propyl alcohol; in the second step, reducing (R)-2-oximido-1-phenyl propyl alcohol into a mixture of (1R, 2S)-norephedrine and (1R, 2R)-norpseudoephedrine; adding a chiral reliquid reagent (R)-O-acetyl mandelic acid and decomposing, thereby acquiring an optical pure (1R, 2S)-norephedrine and (1R, 2R)-norpseudoephedrine monomeric compound.