16959-59-4

Upstream product

• 87281-44-5 methyl 5,6,7,8-tetrahydroindolizine-2-carboxylate 
• 16959-62-9 methyl indolizine-2-carboxylate 
• 131211-78-4 methyl 2-[acetoxy(pyridin-2-yl)methyl]acrylate 
• 118488-74-7 2-(hydroxy-pyridin-2-yl-methyl)-acrylic acid methyl ester 
• 1121-60-4 pyridine-2-carbaldehyde 
• 3189-48-8 indolizine-2-carboxylic acid 

Downstream Products

• 1346672-96-5 3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-1(2H)-one 
• 1346672-97-6 2-bromo-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)benzyl acetate 
• 1346672-98-7 2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)-6-(4-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 
• 1346669-67-7 2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)phenyl)-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-1(2H)-one 
• 1433820-64-4 2-[5-fluoro-2-(hydroxymethyl)-3-[6-[4-[4-(oxetan-3-yl)piperazin-1-yl]anilino]-9H-purin-2-yl]phenyl]-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-1-one 
• 1433824-32-8 4-fluoro-2-(6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenylamino)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-2-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)benzyl acetate 
• 1433824-29-3 4-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 
• 1433824-25-9 2-bromo-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]-indolizin-2(1H)-yl)benzyl acetate 
• 1433990-47-6 2-bromo-4-fluoro-6-(1-oxo-6,7,8,9-tetrahydropyridazino[4,5-b]indolizin-2(1H)-yl)benzaldehyde 
• 1433990-45-4 methyl 3-formyl-5,6,7,8-tetrahydroindolizine-2-carboxylate 

Relevant academic research and scientific papers

Discovery of fused heterocyclic carboxamide derivatives as novel α7-nAChR agonists: Synthesis, preliminary SAR and biological evaluation

The α7 nicotinic acetylcholine receptor (α7 nAChR) has emerged as a promising therapeutic target for schizophrenia. In our previous work, a novel series of α7-nAChR agonists bearing scaffold of indolizine were discovered. To explore the effect of aromaticity on the activity and find more active agents, herein, fused heterocyclic carboxamide derivatives were designed and synthesized in this study. Based on the evaluation by two-electrode voltage clamp in Xenopus oocytes, 27 of the synthesized compounds showed obvious agonism of α7 nAChR. Particularly, compounds 10a and 10e showed significantly higher Emax than EVP-6124. The result illustrated the importance of aromaticity to the activity of agonism. Compound 10a, which showed EC50 of 1.88 μM and Emax of 72.4%, was further characterized comprehensively, including co-application with type II positive allosteric modulator PNU-120596, selectivity with other closely related ligand-gated ion channel, etc. The results showed that 10a showed moderate selectivity over other subtypes such as α4β2 and α3β4 nAChR. 10a evoked α7-like currents that were inhibited by MLA and enhanced in the presence of the α7 PAM PNU-120596. The analysis of binding mode and understanding of structure-activity relationship provided insights to develop more potent novel α7-nAChR agonists.

INDOLIZINE CARBOXAMIDES AND THE AZA AND DIAZA DERIVATIVES THEREOF

The invention relates to neuroreceptor-active carboxamide-substituted indolizine derivatives of general formula (I) wherein X represents a group of general formula (X1).