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271-34-1Relevant academic research and scientific papers
A medicine intermediate 5 - aza indole synthesis method (by machine translation)
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, (2019/03/28)
The present invention discloses a pharmaceutical intermediate 5 - aza indole synthesis method, comprises the following steps: the 3 - methyl - 4 - aminopyridine with acetone after mixing, heating to 40 - 60 °C, adding catalyst after adding the oxalate, under stirring conditions, refluxing reaction 1 - 2 h, filtering, the filtrate by reduced pressure distillation, recrystallization, prepared 4 - aminopyridine - 3 - pyruvate ester; in its entry into the DMA, adding salicylic acid then adding the FeO, heated to 60 - 70 °C, stirring reflux reaction for 2 - 3 h, filter, the filtrate is distilled under reduced pressure, to obtain 5 - aza indole - 2 - carboxylic acid; and after mixing with the carbon tetrachloride, heating to 70 - 90 °C, adding ZnO mixing, stirring reflux reaction for 2 - 3 h after, filtering, the filtrate is distilled under reduced pressure, to obtain 5 - azaindole. The application of the synthesis method is simple in operation, mild condition, less by-products, the product has high purity, product yield is relatively high. (by machine translation)
Synthesis method of 5-azaindole
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Paragraph 0020-0031; 0032-0037; 0038-0043; 0044-0049, (2018/05/01)
The invention discloses a synthesis method of 5-azaindole. The synthesis method of the 5-azaindole comprises the following steps of after mixing 3-chloro-4-aminopyridine and tetrahydrofuran, adding into a reaction kettle, heating to 100 to 130 DEG C, adding diethyl ether and Ni(COD)2, adding a catalyst, adding acetylene under a stirring condition, carrying out microwave radiation for 20 to 30min,then continuously carrying out reflux reaction for 4 to 6h, filtering after finishing reaction, removing the tetrahydrofuran from a filter liquor, extracting by using ethyl acetate, recrystallizing byusing water, carrying out suction filtration, drying, and obtaining 5-azaindole. The synthesis method provided by the invention is simple to operate, mild in conditions, less in byproducts, high in product purity, and higher in product yield.
Preparation method of5-diazaindene
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Paragraph 0016; 0017; 0018; 0019; 0020; 0021-0039, (2017/04/26)
The invention discloses apreparation method of 5-diazaindene. 3-methyl-4-aminopyridine is evenly stirred and mixed with acetic anhydride and a catalyst for reaction, the obtained product is evenly mixed with pyrrolidine and DMF-DMA, reaction is performed at the temperature of 80-90 DEG Cunder the condition of the catalyst for 2-3 hours to obtain the final product 5-diazaindene. The method produces fewer by-products and is high in productpurity.In addition, the added novel catalyst makes reaction temperaturemore moderate, and reaction time is shortened greatly. In a word, the steps of the whole production process are simple, operation is easy, the cost of large-scale industrial production is low, and implementation is easy.
HETEROCYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS
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Paragraph 0435, (2014/06/23)
The present invention provides a heterocyclic compound of formula (I), a pharmaceutically acceptable salt thereof, a prodrug thereof or a hydrate thereof, wherein A, A′ B, D, R1, R2 and R3 are as defined herein, a pharmaceutical composition comprising a compound of formula (I) as an active ingredient, methods of production, and methods of use thereof. Particularly, the present invention provides a compound of formula (I) useful for treating or preventing a disease, condition or disorder associated with protein kinases, preferably Janus Kinase family.
Design, synthesis and antiproliferative activity evaluation of new 5-azaisoindigo derivatives
Zhao, Ping,Yan, Yun,Li, Yanzhong,Zhang, Aiying,Zhan, Xiaoping,Liu, Zenglu,Mao, Zhenmin,Chen, Shaoxiong,Wang, Liqun
, p. 1923 - 1932 (2014/08/18)
New 5-azaisoindigo derivatives were synthesized with two key intermediates 5-azaoxindole (7) and substituted indole-2,3-dione (10) in this paper. Intermediate 7 was prepared from 3-methylpyridine (1) through 6 steps containing oxidation reaction and so on. Intermediate 10 was obtained by a convenient Sandmeyer's method. The target compounds 5-azaisoindigo derivatives 11a-f were obtained by condensation of these two intermediates 7 and 10 in acidic condition. All target compounds were evaluated for their antiproliferative activity against seven cell lines by SRB assay. Compounds 11e and 11f showed significant antiproliferative activity against K562 cells (IC50: 8.9 μM and 13.6 μM, respectively).
HETEROCYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS
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Page/Page column 72, (2012/12/13)
The present invention provides a heterocyclic compound of formula (I), a pharmaceutically acceptable salt thereof, a prodrug thereof or a hydrate thereof, wherein A, A' B, D, R1, R2 and R3 are as defined herein, a pharmaceutical composition comprising a compound of formula (I) as an active ingredient, methods of production, and methods of use thereof. Particularly, the present invention provides a compound of formula (I) useful for treating or preventing a disease, condition or disorder associated with protein kinases, preferably Janus Kinase family.
Novel 3-azaindolyl-4-arylmaleimides exhibiting potent antiangiogenic efficacy, protein kinase inhibition, and antiproliferative activity
Ganser, Christopher,Lauermann, Eva,Maderer, Annett,Stauder, Torsten,Kramb, Jan-Peter,Plutizki, Stanislav,Kindler, Thomas,Moehler, Markus,Dannhardt, Gerd
, p. 9531 - 9540 (2013/01/16)
Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.
Molecular recognition at the active site of catechol-O-methyltransferase (COMT): Adenine replacements in bisubstrate inhibitors
Ellermann, Manuel,Paulini, Ralph,Jakob-Roetne, Roland,Lerner, Christian,Borroni, Edilio,Roth, Doris,Ehler, Andreas,Schweizer, W. Bernd,Schlatter, Daniel,Rudolph, Markus G.,Diederich, Francois
supporting information; experimental part, p. 6369 - 6381 (2011/08/06)
L-Dopa, the standard therapeutic for Parkinson's disease, is inactivated by the enzyme catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of an activated methyl group from S-adenosylmethionine (SAM) to its catechol substrates, such as L-dopa, in the presence of magnesium ions. The molecular recognition properties of the SAM-binding site of COMT have been investigated only sparsely. Here, we explore this site by structural alterations of the adenine moiety of bisubstrate inhibitors. The molecular recognition of adenine is of special interest due to the great abundance and importance of this nucleobase in biological systems. Novel bisubstrate inhibitors with adenine replacements were developed by structure-based design and synthesized using a nucleosidation protocol introduced by Vorbrueggen and co-workers. Key interactions of the adenine moiety with COMT were measured with a radiochemical assay. Several bisubstrate inhibitors, most notably the adenine replacements thiopyridine, purine, N-methyladenine, and 6-methylpurine, displayed nanomolar IC50 values (median inhibitory concentration) for COMT down to 6 nM. A series of six cocrystal structures of the bisubstrate inhibitors in ternary complexes with COMT and Mg2+ confirm our predicted binding mode of the adenine replacements. The cocrystal structure of an inhibitor bearing no nucleobase can be regarded as an intermediate along the reaction coordinate of bisubstrate inhibitor binding to COMT. Our studies show that solvation varies with the type of adenine replacement, whereas among the adenine derivatives, the nitrogen atom at position 1 is essential for high affinity, while the exocyclic amino group is most efficiently substituted by a methyl group. Copyright
NOVEL COMPOUNDS
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Page/Page column 47-48, (2011/02/18)
The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R1, R2, R3 and R4 are defined as in the description, the tautomers, the isomers, the diastereomers, the enantiomers, the hydrates, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, their use and processes for preparing them.
Novel indole and azaindole (pyrrolopyridine) cannabinoid (CB) receptor agonists: Design, synthesis, structure-activity relationships, physicochemical properties and biological activity
Blaazer, Antoni R.,Lange, Jos H.M.,Van Der Neut, Martina A.W.,Mulder, Arie,Den Boon, Femke S.,Werkman, Taco R.,Kruse, Chris G.,Wadman, Wytse J.
, p. 5086 - 5098 (2011/11/29)
The discovery, synthesis and structure-activity relationship (SAR) of a novel series of cannabinoid 1 (CB1) and cannabinoid 2 (CB 2) receptor ligands are reported. Based on the aminoalkylindole class of cannabinoid receptor agonists, a biphenyl moiety was introduced as novel lipophilic indole 3-acyl substituent in 11-16. Furthermore, the 3-carbonyl tether was replaced with a carboxamide linker in 17-20 and the azaindole (pyrrolopyridine) nucleus was designed as indole bioisostere with improved physicochemical properties in 21-25. Through these SAR efforts, several high affinity CB1/CB2 dual cannabinoid receptor ligands were identified. Indole-3-carboxamide 17 displayed single-digit nanomolar affinity and ～80 fold selectivity for CB1 over the CB2 receptor. The azaindoles displayed substantially improved physicochemical properties (lipophilicity; aqueous solubility). Azaindole 21 elicited potent cannabinoid activity. Cannabinoid receptor agonists 17 and 21 potently modulated excitatory synaptic transmission in an acute rat brain slice model of cannabinoid receptor-modulated neurotransmission.
