60514-82-1Relevant articles and documents
Gold-Catalyzed Amide/Carbamate-Linked N, O-Acetal Formation with Bulky Amides and Alcohols
Ohsawa, Kosuke,Ochiai, Shota,Kubota, Junya,Doi, Takayuki
, p. 1281 - 1291 (2021/01/14)
A gold-catalyzed N,O-acetal formation was established to construct an amide/carbamate-linked N,O-acetal substructure with bulky alcohols. The acyliminium cation species generated from o-alkynylbenzoic acid ester in the presence of a gold catalyst is highly reactive and underwent nucleophilic attack of various bulky alcohols and phenols at room temperature under neutral conditions, leading to the corresponding N,O-acetals in yields of 34-89% with good functional group tolerance.
Discovery of Novel Inhibitors of LpxC Displaying Potent in Vitro Activity against Gram-Negative Bacteria
Surivet, Jean-Philippe,Panchaud, Philippe,Specklin, Jean-Luc,Diethelm, Stefan,Blumstein, Anne-Catherine,Gauvin, Jean-Christophe,Jacob, Lo?c,Masse, Florence,Mathieu, Ga?lle,Mirre, Azely,Schmitt, Christine,Lange, Roland,Tidten-Luksch, Naomi,Gnerre, Carmela,Seeland, Swen,Herrmann, Charlyse,Seiler, Peter,Enderlin-Paput, Michel,Mac Sweeney, Aengus,Wicki, Micha,Hubschwerlen, Christian,Ritz, Daniel,Rueedi, Georg
supporting information, p. 66 - 87 (2020/01/09)
UDP-3-O-((R)-3-hydroxymyristoyl)-N-glucosamine deacetylase (LpxC) is as an attractive target for the discovery and development of novel antibacterial drugs to address the critical medical need created by multidrug resistant Gram-negative bacteria. By using a scaffold hopping approach on a known family of methylsulfone hydroxamate LpxC inhibitors, several hit series eliciting potent antibacterial activities against Enterobacteriaceae and Pseudomonas aeruginosa were identified. Subsequent hit-to-lead optimization, using cocrystal structures of inhibitors bound to Pseudomonas aeruginosa LpxC as guides, resulted in the discovery of multiple chemical series based on (i) isoindolin-1-ones, (ii) 4,5-dihydro-6H-thieno[2,3-c]pyrrol-6-ones, and (iii) 1,2-dihydro-3H-pyrrolo[1,2-c]imidazole-3-ones. Synthetic methods, antibacterial activities and relative binding affinities, as well as physicochemical properties that allowed compound prioritization are presented. Finally, in vivo properties of lead molecules which belong to the most promising pyrrolo-imidazolone series, such as 18d, are discussed.
Orally bioavailable factor Xa inhibitors containing alpha-substituted gem-dimethyl P4 moieties
Orwat, Michael J.,Qiao, Jennifer X.,He, Kan,Rendina, Alan R.,Luettgen, Joseph M.,Rossi, Karen A.,Xin, Baomin,Knabb, Robert M.,Wexler, Ruth R.,Lam, Patrick Y.S.,Pinto, Donald J.P.
, p. 3341 - 3345 (2014/07/22)
In an effort to identify a potential back-up to apixaban (Eliquis), we explored a series of diversified P4 moieties. Several analogs with substituted gem-dimethyl moieties replacing the terminal lactam of apixaban were identified which demonstrated potent
