1447607-84-2Relevant academic research and scientific papers
In vitro identification of imidazo[1,2-a]pyrazine-based antileishmanial agents and evaluation of L. major casein kinase 1 inhibition
Bazin, Marc-Antoine,Cojean, Sandrine,Pagniez, Fabrice,Bernadat, Guillaume,Cavé, Christian,Ourliac-Garnier, Isabelle,Nourrisson, Marie-Renée,Morgado, Cathy,Picot, Carine,Leclercq, Olivier,Baratte, Blandine,Robert, Thomas,Sp?th, Gérald F.,Rachidi, Najma,Bach, Stéphane,Loiseau, Philippe M.,Le Pape, Patrice,Marchand, Pascal
, (2021)
Leishmaniasis constitutes a severe public health problem, with an estimated prevalence of 12 million cases. This potentially fatal disease has a worldwide distribution and in 2012, the fatal Visceral Leishmaniasis (VL) was declared as new emerging disease in Europe, mainly due to global warming, with expected important public health impact. The available treatments are toxic, costly or lead to parasite resistance, thus there is an urgent need for new drugs with new mechanism of action. Previously, we reported the discovery of CTN1122, a potent imidazo[1,2-a]pyrazine-based antileishmanial hit compound targeting L-CK1.2 at low micromolar ranges. Here, we described structurally related, safe and selective compounds endowed with antiparasitic properties, better than miltefosine, the reference therapy by oral route. L-CK1.2 homology model gave the first structural explanations of the role of 4-pyridyl (CTN1122) and 2-aminopyrimidin-4-yl (compound 21) moieties, at the position 3 of the central core, in the low micromolar to nanomolar L-CK1.2 inhibition, whereas N-methylpyrazole derivative 11 remained inactive against the parasite kinase.
Molecular Design Strategy of Thermally Activated Delayed Fluorescent Emitters Using CN-Substituted Imidazopyrazine as a New Electron-Accepting Unit
Kothavale, Shantaram,Lee, Kyung Hyung,Lee, Jun Yeob
, p. 122 - 128 (2020)
Thermally activated delayed fluorescence (TADF)-based organic light-emitting diodes (OLEDs) have attracted enormous attention recently due to their capability to replace conventional phosphorescent organic light-emitting diodes for practical applications. In this work, a newly designed CN-substituted imidazopyrazine moiety was utilized as an electron-accepting unit in a TADF emitter. Two TADF emitters, 8-(3-cyano-4-(9,9-dimethylacridin-10(9H)-yl)phenyl)-2-phenylimidazo[1,2-a]pyrazine-3-carbonitrile (Ac-CNImPyr) and 8-(3-cyano-4-(10H-phenoxazin-10-yl)phenyl)-2-phenylimidazo[1,2-a]pyrazine-3-carbonitrile (PXZ-CNImPyr), were developed based on the CN-substituted imidazopyrazine acceptor combined with acridine and phenoxazine donor, respectively. A CN-substituted phenyl spacer was introduced between the donor and acceptor for a sufficiently small singlet-triplet energy gap (ΔEST) and molecular orbital management. Small ΔEST of 0.07 eV was achieved for the phenoxazine donor-based PXZ-CNImPyr emitter. As a result, an organic light-emitting diode based on the PXZ-CNImPyr emitter exhibited a high external quantum efficiency of up to 12.7 %, which surpassed the EQE limit of common fluorescent emitters. Hence, the CN-modified imidazopyrazine unit can be introduced as a new acceptor for further modifications to develop efficient TADF-based OLEDs.
Synthesis, antileishmanial activity and cytotoxicity of 2,3-diaryl- and 2,3,8-trisubstituted imidazo[1,2-a]pyrazines
Marchand, Pascal,Bazin, Marc-Antoine,Pagniez, Fabrice,Rivière, Guillaume,Bodero, Lizeth,Marhadour, Sophie,Nourrisson, Marie-Renée,Picot, Carine,Ruchaud, Sandrine,Bach, Stéphane,Baratte, Blandine,Sauvain, Michel,Pareja, Denis Castillo,Vaisberg, Abraham J.,Le Pape, Patrice
, p. 381 - 395 (2015/09/28)
A series of original 2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyrazines and the 3-iodo precursors, bearing a polar moiety at the C-8 position, was synthesized and evaluated for their antileishmanial activities. Two derivatives exhibited very good activity a
Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility
Cao, Xufeng,Sun, Zhaoshuan,Cao, Yongbing,Wang, Ruilian,Cai, Tongkai,Chu, Wenjing,Hu, Wenhao,Yang, Yushe
supporting information, p. 3687 - 3706 (2014/05/20)
Triazoles with fused-heterocycle nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SAR of antifungal triazoles. Tetrahydro-[1,2,4] triazolo[1,5-a]pyrazine and tetrahydro-thiazolo[5,4-c]pyridine nuclei were preferable to the other four fused-heterocycle nuclei investigated. Potent in vitro activity, broad spectrum and better water solubility were attained when triazoles containing nitrogen aromatic heterocycles were attached to these two nuclei. The most potent compounds 27aa and 45x, with low hERG inhibition and hepatocyte toxicity, both exhibited excellent activity against Candida, Cryptococcus, and Aspergillus spp., as well as selected fluconazole-resistant strains. A high water-soluble compound 58 (the disulfate salt of 45x) displayed unsatisfactory in vivo activity because of its poor PK profiles. Mice infected with C.alb. SC5314 and C.alb. 103 (fluconazole-resistant strain) and administered with 27aa displayed significantly improved survival rates. 27aa also showed favorable pharmacokinetic (PK) profiles.
