4498-68-4Relevant academic research and scientific papers
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.
The efficient synthesis of 3-[6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-indazole
Raut, Santosh,Hadi, Abdul,Pathan, Mohd Arif
, p. 1291 - 1305 (2020)
This study presents an efficient synthesis of 3-[6-(substituted-phenyl)-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazol-3-yl]-1H-indazole via dehydrative condensation with cyclization of 4-amino-5-(1H-indazol-3-yl)-4H-[1,2,4]triazole-3-thiol and fluorinated or nonfluorinated carboxylic acids in presence of phosphorous oxychloride. The multistep reaction pathway proceeds through different compounds. Present synthesis has the advantages of easily accessible starting materials, convenient synthesis, simple reaction condition, wider substrate scope, and higher yield (75% to 90% isolated).
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.
Optimization of N-benzoylindazole derivatives as inhibitors of human neutrophil elastase
Crocetti, Letizia,Schepetkin, Igor A.,Cilibrizzi, Agostino,Graziano, Alessia,Vergelli, Claudia,Giomi, Donatella,Khlebnikov, Andrei I.,Quinn, Mark T.,Giovannoni, Maria Paola
, p. 6259 - 6272 (2013/09/02)
Human neutrophil elastase (HNE) is an important therapeutic target for treatment of pulmonary diseases. Previously, we identified novel N-benzoylindazole derivatives as potent, competitive, and pseudoirreversible HNE inhibitors. Here, we report further development of these inhibitors with improved potency, protease selectivity, and stability compared to our previous leads. Introduction of a variety of substituents at position 5 of the indazole resulted in the potent inhibitor 20f (IC50 ～10 nM) and modifications at position 3 resulted the most potent compound in this series, the 3-CN derivative 5b (IC50 = 7 nM); both derivatives demonstrated good stability and specificity for HNE versus other serine proteases. Molecular docking of selected N-benzoylindazoles into the HNE binding domain suggested that inhibitory activity depended on geometry of the ligand-enzyme complexes. Indeed, the ability of a ligand to form a Michaelis complex and favorable conditions for proton transfer between Hys57, Asp102, and Ser195 both affected activity.
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.
Facile and efficient synthesis of indazole derivatives by 1,3-cycloaddition of arynes with diazo compounds and azomethine imides
Jin, Tienan,Yang, Fan,Yamamoto, Yoshinori
scheme or table, p. 957 - 972 (2010/01/19)
N-Unsubstituted indazoles 3 and 1-arylindazoles 4 are readily available in good to high yields through [3+2] cycloaddition of 2-(trimethylsilyI)aryl triflates 1 and diazo compounds in the presence of KF or CsF under mild reaction conditions. Furthermore, we found that azomethine imides also underwent cycloaddition reaction with 2-(trimethylsilyl)phenyl triflates (la) in the presence of KF to afford indazolone derivatives 6 in moderate yields.
Synthesis of indazoles by the [3+2] cycloaddition of diazo compounds with arynes and subsequent acyl migration
Liu, Zhijian,Shi, Feng,Martinez, Pablo D. G.,Raminelli, Cristiano,Larock, Richard C.
, p. 219 - 226 (2008/09/17)
(Chemical Equation Presented) The [3+2] cycloaddition of a variety of diazo compounds with o-(trimethylsilyl)aryl triflates in the presence of CsF or TBAF at room temperature provides a very direct, efficient approach to a wide range of potentially biologically and pharmaceutically interesting substituted indazoles in good to excellent yields under mild reaction conditions. Simple diazomethane derivatives afford N-unsubstituted indazoles or 1-arylated indazoles, depending upon the stoichiometry of the reagents and the reaction conditions, while dicarbonyl-containing diazo compounds undergo carbonyl migration to afford 1-acyl or 1-alkoxycarbonyl indazoles selectively.
An efficient, facile, and general synthesis of 1H-indazoles by 1,3-dipolar cycloaddition of arynes with diazomethane derivatives
Jin, Tienan,Yamamoto, Yoshinori
, p. 3323 - 3325 (2008/03/12)
(Chemical Equation Presented) Take your pick: Both N-unsubstituted and 1-aryl 1H-indazoles are available in good to high yields through the [3+2] cycloaddition of benzynes derived from o-silylaryl triflates with diazomethane derivatives (see scheme). In the presence of KF/[18]crown-6, the N-unsubstituted 1H-indazole is formed, whereas the 1-arylated product is obtained regioselectively with CsF and an excess of the triflate.
Nicotinamide derivatives useful as PDE4 inhibitors
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Page 15, (2010/02/10)
This invention relates to nicotinamide derivatives of general formula (I): in which R1, R2 and R3 have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.
