4498-68-4Relevant articles and documents
Nucleophilic carbenes and pseudo-cross-conjugated mesomeric betaines of indazole starting from analogues of the alkaloid-betaine nigellicine
Schmidt, Andreas,Merkel, Lars,Eisfeld, Wolfgang
, p. 2124 - 2130 (2005)
The alkaloid Nigellicine possesses the indazolium-3-carboxylate ring system as electronically relevant partial structure which represents a member of the class of pseudo-cross-conjugated mesomeric betaines. Indazolium-3-carboxylate, prepared starting from indazole-3-carboxylic acid by an esterification- methylation-saponification sequence, can be converted into the isoconjugated phenyl- and 4-(nitrophenyl)-amidates and the thiocarboxylate as additional examples of pseudo-cross-conjugated systems. In accordance with results of ab initio calculations decarboxylation of indazolium-3-carboxylate with formation of the nucleophilic carbene indazol3-ylidene begins at approximately 40°C as evidenced by temperature-dependent NMR spectroscopy. The carbene can be trapped with protons as indazolium salts, and carbon dioxide which reconstitutes the pseudo-cross-conjugated mesomeric betaine. According to the calculations, the carbene adopts a singlet ground state. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
Stereoselective Direct N-Trifluoropropenylation of Heterocycles with a Hypervalent Iodonium Reagent
Csenki, János T.,Mészáros, ádám,Gonda, Zsombor,Novák, Zoltán
supporting information, p. 15638 - 15643 (2021/10/08)
The availability and synthesis of fluorinated enamine derivatives such as N-(3,3,3-trifluoropropenyl)heterocycles are challenging, especially through direct functionalization of the heterocyclic scaffold. Herein, a stereoselective N-trifluoropropenylation method based on the use of a bench-stable trifluoropropenyl iodonium salt is described. This reagent enables the straightforward trifluoropropenylation of various N-heterocycles under mild reaction conditions, providing trifluoromethyl enamine type moieties with high stereoselectivity and efficiency.
Design, synthesis and evaluation of N-benzoylindazole derivatives and analogues as inhibitors of human neutrophil elastase
Crocetti, Letizia,Giovannoni, Maria Paola,Schepetkin, Igor A.,Quinn, Mark T.,Khlebnikov, Andrei I.,Cilibrizzi, Agostino,Piaz, Vittorio Dal,Graziano, Alessia,Vergelli, Claudia
scheme or table, p. 4460 - 4472 (2011/09/12)
Human neutrophil elastase (HNE) plays an important role in tumour invasion and inflammation. A series of N-benzoylindazoles was synthesized and evaluated for their ability to inhibit HNE. We found that this scaffold is appropriate for HNE inhibitors and that the benzoyl fragment at position 1 is essential for activity. The most active compounds inhibited HNE activity with IC50 values in the submicromolar range. Furthermore, docking studies indicated that the geometry of an inhibitor within the binding site and energetics of Michaelis complex formation were key factors influencing the inhibitor's biological activity. Thus, N-benzoylindazole derivatives and their analogs represent novel structural templates that can be utilized for further development of efficacious HNE inhibitors.
