2900-27-8Relevant articles and documents
Crystallization method of Boc-amino acid
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Paragraph 0030-0038, (2021/04/17)
The invention belongs to the technical field of medicinal chemistry, and particularly relates to a crystallization method of Boc amino acid. The preparation method comprises the following steps: (1) reacting free amino acid with di-tert-butyl dicarbonate, carrying out post-treatment to obtain a Boc-protected amino acid reaction solution, and carrying out reduced pressure distillation to remove a solvent until the solvent is dry, thereby obtaining a colorless or light yellow transparent oily substance; (2) adding a seed crystal into the obtained oily substance, standing for a period of time at normal temperature, curing the oily substance to be white, and then adding a weak polar solvent for pulping; (3) pulping for a period of time, filtering, washing, and drying under reduced pressure to obtain the product. According to the method, crystallized Boc amino acid cannot be separated out and crystallized by a conventional method, so that the purity of the product is improved, and meanwhile, the product has certain stability and can be stored for a long time without being decomposed.
Discovery of M3Antagonist-PDE4 Inhibitor Dual Pharmacology Molecules for the Treatment of Chronic Obstructive Pulmonary Disease
Armani, Elisabetta,Rizzi, Andrea,Capaldi, Carmelida,De Fanti, Renato,Delcanale, Maurizio,Villetti, Gino,Marchini, Gessica,Pisano, Anna Rita,Pitozzi, Vanessa,Pittelli, Maria Gloria,Trevisani, Marcello,Salvadori, Michela,Cenacchi, Valentina,Puccini, Paola,Amadei, Francesco,Pappani, Alice,Civelli, Maurizio,Patacchini, Riccardo,Baker-Glenn, Charles A.G.,Van De Po?l, Hervé,Blackaby, Wesley P.,Nash, Kevin,Amari, Gabriele
supporting information, p. 9100 - 9119 (2021/07/19)
In this paper, we report the discovery of dual M3 antagonist-PDE4 inhibitor (MAPI) compounds for the inhaled treatment of pulmonary diseases. The identification of dual compounds was enabled by the intuition that the fusion of a PDE4 scaffold derived from our CHF-6001 series with a muscarinic scaffold through a common linking ring could generate compounds active versus both the transmembrane M3 receptor and the intracellular PDE4 enzyme. Two chemical series characterized by two different muscarinic scaffolds were investigated. SAR optimization was aimed at obtaining M3 nanomolar affinity coupled with nanomolar PDE4 inhibition, which translated into anti-bronchospastic efficacy ex vivo (inhibition of rat trachea contraction) and into anti-inflammatory efficacy in vitro (inhibition of TNFα release). Among the best compounds, compound 92a achieved the goal of demonstrating in vivo efficacy and duration of action in both the bronchoconstriction and inflammation assays in rat after intratracheal administration.
One-Pot C-H Arylation/Lactamization Cascade Reaction of Free Benzylamines
Chand-Thakuri, Pratibha,Landge, Vinod G.,Kapoor, Mohit,Young, Michael C.
, p. 6626 - 6644 (2020/07/14)
An efficient method has been developed for the synthesis of seven-membered biaryl lactams involving Pd-catalyzed, native amine-directed, ortho-arylation of benzylamines followed by in situ lactamization. This cascade sequence is enabled by the use of 2-iodobenzoates, which facilitates C-H arylation from the free amine under conditions that typically require an improved directing group approach. This reaction is characterized by a broad substrate scope with good functional group tolerance. The need for an ester versus carboxylic acid-functionalized coupling partner is also explored, as is the potential for synthesizing eight-membered biaryl lactams. Various applications are also investigated, including access to the aza-brassinolide core.
