1908-01-6Relevant academic research and scientific papers
Preparation methods of 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine
-
Paragraph 0072-0077; 0116-0121, (2021/05/12)
The invention relates to preparation methods of a 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine. The 1H-indazol-3-carboxylic acid derivative is a compound with a structure shown in a formula (1) and a formula (2), and is mainly structurally characterized by having a 1H-indazol-3-carboxylic acid amide skeleton and a 1H-indazol-3-carboxylic ester skeleton. The 1H-indazol-3-carboxylic acid derivative can be synthesized by taking simple o-aminophenylacetic acid amide or o-aminophenylacetic acid ester as an initial raw material. The 1H-indazol-3-carboxylic acid derivative is a key intermediate for synthesizing a plurality of medicines, such as granisetron, lonidamine and the like. The synthesis method of the 1H-indazol-3-carboxylic acid derivative and the drug molecules glassetron and lonidamine is simple, the reaction condition is mild, the reaction speed is high, the yield is high, and purification is easy.
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.
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.
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.
