30489-43-1Relevant articles and documents
KIO4-mediated Selective Hydroxymethylation/Methylenation of Imidazo-Heteroarenes: A Greener Approach
Braga, Antonio Luiz,Franco, Marcelo Straesser,Rafique, Jamal,Saba, Sumbal
supporting information, p. 18454 - 18460 (2021/07/21)
Herein, we report a KIO4-mediated, sustainable and chemoselective approach for the one-pot C(sp2)?H bond hydroxymethylation or methylenation of imidazo-heteroarenes with formaldehyde, generated in situ via the oxidative cleavage of ethylene glycol or glycerol (renewable reagents) through the Malaprade reaction. In the presence of ethylene glycol, a series of 3-hydroxymethyl-imidazo-heteroarenes was obtained in good to excellent yields. These compounds are important intermediates to access pharmaceutical drugs, e.g., Zolpidem. Furthermore, by using glycerol, bis(imidazo[1,2-a]pyridin-3-yl)methane derivatives were selectively obtained in good to excellent yields.
Silver-catalyzed cyclization of N-(prop-2-yn-1-yl)pyridin-2-amines
Chioua, Mourad,Soriano, Elena,Infantes, Lourdes,Jimeno, M. Luisa,Marco-Contelles, Jose,Samadi, Abdelouahid
, p. 35 - 39 (2013/02/22)
We report herein the silver-catalyzed cycloisomerization of readily available N-(prop-2-yn-1-yl)pyridine-2-amines as a new and practical method for the synthesis of differently substituted 3-methylimidazo[1,2-a]pyridines. The isomerization reactions proce
Synthesis, stereochemistry and SAR of a series of minodronate analogues as RGGT inhibitors
B?aewska, Katarzyna M.,Ni, Feng,Haiges, Ralf,Kashemirov, Boris A.,Coxon, Fraser P.,Stewart, Charlotte A.,Baron, Rudi,Rogers, Michael J.,Seabra, Miguel C.,Ebetino, Frank H.,McKenna, Charles E.
, p. 4820 - 4826 (2011/11/13)
Phosphonocarboxylate (PC) analogues of bisphosphonates are of interest due to their selective inhibition of a key enzyme in the mevalonate pathway, Rab geranylgeranyl transferase (RGGT). The dextrarotatory enantiomer of 2-hydroxy-3-(imidazo[1,2-a]pyridin-3-yl)-2-phosphonopropanoic acid (3-IPEHPC, 1) is the most potent PC-type RGGT inhibitor thus far identified. The absolute configuration of (+)-1 in the active site complex has remained unknown due to difficulties in obtaining RGGT inhibitor complex crystals suitable for X-ray diffraction analysis. However, we have now succeeded in crystallizing (-)-1 and here report its absolute configuration (AC) obtained by X-ray crystallography, thus also defining the AC of (+)-1. An Autodock Vina 1.1 computer modeling study of (+)-1 in the active site of modified RGGT binding GGPP (3DSV) identifies stereochemistry-dependent interactions that could account for the potency of (+)-1 and supports the hypothesis that this type of inhibitor binds at the TAG tunnel, inhibiting the second geranylgeranylation step. We also report a convenient 31P NMR method to determine enantiomeric excess of 1 and its pyridyl analogue 2, using α- and β-cyclodextrins as chiral solvating agents, and describe the synthesis of a small series of 1 α-X (X = H, F, Cl, Br; 7a-d) analogues to assess the contribution of the α-OH group to activity at enzyme and cellular levels. The IC50 of 1 was 5-10× lower than 7a-d, and the LED for inhibition of Rab11 prenylation in vitro was 2-8× lower than for 7a-d. However, in a viability reduction assay with J774 cells, 1 and 7b had similar IC50 values, ~10× lower than those of 7a and 7c-d.