1011711-52-6Relevant articles and documents
Room-Temperature and Transition-Metal-Free Intramolecular α-Arylation of Ketones: A Mild Access to Tetracyclic Indoles and 7-Azaindoles
Adouama, Chérif,Budén, María E.,Guerra, Walter D.,Puiatti, Marcelo,Joseph, Beno?t,Barolo, Silvia M.,Rossi, Roberto A.,Médebielle, Maurice
, (2018)
A novel approach for the synthesis of tetracyclic indoles and 7-azaindoles is reported. The strategy involves four steps, with a fast rt intramolecular α-arylation of ketones as key step. The reaction was inspected synthetically to achieve the synthesis of 11 novel tetracyclic structures with moderate to very good yields (39-85%). Theoretical combined with experimental studies led us to propose a probable polar mechanism (concerted SNAr).
Method for synthesizing Meriolin
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Paragraph 0009; 0041; 0046-0047; 0054; 0059-0060; 0067; 0073, (2019/07/01)
The invention belongs to the field of medicinal chemistry, and concretely relates to a method for synthesizing Meriolin. The method comprises the following steps: 7-azaindole used as a raw material undergoes an oxidation reaction to generate an intermediate 2; the intermediate 2 undergoes a halogenations reaction to generate an intermediate 3; the intermediate 3 is subjected to a Friedel-Crafts acylation to generate an intermediate 4; and the amino group of the intermediate 4 is protected to obtain an intermediate 5, the intermediate 5 undergoes an alkylation reaction to generate an intermediate 6, and the intermediate 6 is cyclized to obtain the target products Merilin 10 and Meriolin 7. The method adopting the inexpensive 7-azaindole as the raw material has the advantages of simple operation steps, mild reaction conditions, avoiding the use of CO, high temperature, high pressure and expensive Pd catalytic reagent and hazardous chemicals, obtaining of the Meriolin 10 and Meriolin 7 ata high yield, and provision of a new idea for the synthesis of Meriolins series new derivatives.
Room-Temperature and Transition-Metal-Free Intramolecular α-Arylation of Ketones: A Mild Access to Tetracyclic Indoles and 7-Azaindoles
Adouama, Chérif,Budén, María E.,Guerra, Walter D.,Puiatti, Marcelo,Joseph, Beno?t,Barolo, Silvia M.,Rossi, Roberto A.,Médebielle, Maurice
supporting information, p. 320 - 324 (2019/01/10)
A novel approach for the synthesis of tetracyclic indoles and 7-azaindoles is reported. The strategy involves four steps, with a fast rt intramolecular α-arylation of ketones as key step. The reaction was inspected synthetically to achieve the synthesis of 11 novel tetracyclic structures with moderate to very good yields (39-85%). Theoretical combined with experimental studies led us to propose a probable polar mechanism (concerted SNAr).
Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors
Liu, Bin,Yuan, Xia,Xu, Bo,Zhang, Han,Li, Ridong,Wang, Xin,Ge, Zemei,Li, Runtao
, p. 1 - 15 (2019/03/17)
Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy.
PYRROLO[2,3-B]PYRIDINE COMPOUNDS, AZAINDOLE COMPOUNDS USED FOR SYNTHESIZING SAID PYRROLO[2,3-B]PYRIDINE COMPOUNDS, METHODS FOR THE PRODUCTION THEREOF, AND USES THEREOF
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Page/Page column 6, (2010/08/07)
The invention relates to pyrrolo[2,3-b]pyridine compounds and azaindole compounds used for the synthesis thereof. The invention also relates to methods for the production thereof and the uses thereof. Said novel pyrrolo[2,3-b]pyridine compounds according to the invention have great antiproliferative, apoptotic, and neuroprotective activities. The invention particularly applies to the pharmaceutical field.
Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): Synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/Cyclin A/meriolin complex
Echalier, Aude,Bettayeb, Karima,Ferandin, Yoan,Lozach, Olivier,Clément, Monique,Valette, Annie,Liger, Fran?ois,Marquet, Bernard,Morris, Jonathan C.,Endicott, Jane A.,Joseph, Beno?t,Meijer, Laurent
, p. 737 - 751 (2008/09/19)
We report the synthesis and biological characterization of 3-(pyrimidin-4-yl)-7-azaindoles (meriolins), a chemical hybrid between the natural products meridianins and variolins, derived from marine organisms. Meriolins display potent inhibitory activities toward cyclin-dependent kinases (CDKs) and, to a lesser extent, other kinases (GSK-3, DYRK1A). The crystal structures of 1e (meriolin 5) and variolin B (Bettayeb, K.; Tirado, O. M.; Marionneau-Lambert, S.; Ferandin, Y.; Lozach, O.; Morris, J.; Mateo-Lozano, S.; Drückes, P.; Sch?chtele, C.; Kubbutat, M.; Liger, F.; Marquet, B.; Joseph, B.; Echalier, A.; Endicott, J.; Notario, V.; Meijer, L. Cancer Res. 2007, 67, 8325-8334) in complex with CDK2/cyclin A reveal that the two inhibitors are orientated in very different ways inside the ATP-binding pocket of the kinase. A structure-activity relationship provides further insight into the molecular mechanism of action of this family of kinase inhibitors. Meriolins are also potent antiproliferative and proapoptotic agents in cells cultured either as monolayers or in spheroids. Proapoptotic efficacy of meriolins correlates best with their CDK2 and CDK9 inhibitory activity. Meriolins thus constitute a promising class of pharmacological agents to be further evaluated against the numerous human diseases that imply abnormal regulation of CDKs including cancers, neurodegenerative disorders, and polycystic kidney disease.
