213473-00-8

Upstream product

• 50-01-1 guanidine hydrochloride 
• 341998-57-0 (E)-1-(5-bromo-1-tosyl-1H-indol-3-yl)-3-(dimethylamino)prop-2-en-1-one 
• 113-00-8 guanidine nitrate 
• 10075-50-0 5-bromo-1H-indole 
• 109-86-4 2-methoxy-ethanol 
• 1538583-15-1 C₂₆H₃₅BrN₄O₆SSi 
• 290333-07-2 (E)-1-(5-bromo-1-tosyl-1H-indol-3-yl)-3-(dimethylamino)prop-2-en-1-one 
• 593-84-0 guanidinium thiocyanate 
• 124-46-9 guanidine hydrogen carbonate 
• 1207175-18-5 2-amino-4-ethynylpyrimidine 
• 3623-23-2 4-bromonitrosobenzene 
• 19620-90-7 1-(5-bromo-1H-indol-3-yl)ethan-1-one 
• 265111-01-1 1-(5-bromo-1-tosyl-1H-indol-3-yl)ethan-1-one 
• 96546-77-9 N-tosyl-5-bromoindole 

Relevant academic research and scientific papers

Discovery of novel indoleaminopyrimidine NIK inhibitors based on molecular docking-based support vector regression (SVR) model

A set of NF-κB-inducing kinase (NIK) inhibitors was used to develop a molecular docking-based QSAR model by using nonlinear regression method. The accuracy of the QSAR model was remarkably improved by integrating the docking scores and key interaction pro

Discovery of Potent and Brain-Penetrant Tau Tubulin Kinase 1 (TTBK1) Inhibitors that Lower Tau Phosphorylation in Vivo

Structural analysis of the known NIK inhibitor 3 bound to the kinase domain of TTBK1 led to the design and synthesis of a novel class of azaindazole TTBK1 inhibitors exemplified by 8 (cell IC50: 571 nM). Systematic optimization of this series of analogs l

Meridianin derivatives as potent Dyrk1A inhibitors and neuroprotective agents

Meridianins are a group of marine-derived indole alkaloids which are reported to possess kinase inhibitory activities. In the present Letter, we report synthesis of N1-substituted and C-ring modified meridianin derivatives and their evaluation as Dyrk1A inhibitors and neuroprotective agents. Among the library of 52 compounds screened, morpholinoyl linked derivative 26b and 2-nitro-4-trifluoromethyl phenyl sulfonyl derivative 29v displayed potent inhibition of Dyrk1A with IC50 values of 0.5 and 0.53 μM, respectively. The derivative 26b also inhibited Dyrk2 and Dyrk3 with IC50 values of 1.4 and 2.2 μM, respectively showing 2.2 and 4.4 fold selectivity for Dyrk1A with respect to Dyrk2 and Dyrk3. The compound 26b was not cytotoxic to human neuroblastoma SH-SY5Y cells (IC50 >100 μM) and it displayed significant neuroprotection against glutamate-induced neurotoxicity in these cells at 10 μM. Molecular modelling studies of compound 26b led to identification of key interactions in the binding site of Dyrk1A and the possible reasons for observed Dyrk1A selectivity over Dyrk2.

Concise syntheses of meridianins and meriolins using a catalytic domino amino-palladation reaction

A synthesis of natural and synthetic members of the meridianin family of kinase inhibitory natural products has been developed. The sequence utilizes a variation of the Cacchi palladium-catalyzed domino reaction to efficiently construct the heterocyclic f

Pim kinase inhibitory and antiproliferative activity of a novel series of meridianin C derivatives

A novel series of meridianin C derivatives substituted at C-5 position were prepared. These derivatives were tested for their kinase inhibitory potencies against all three family members of the pim kinases (Pim-1, Pim-2 and Pim-3). In addition, their anti

Meridianin G and its analogs as antimalarial agents

The marine-derived indole alkaloids meridianin C and G and their N1-substituted and C-ring modified analogs were synthesized and screened for antiprotozoal and antimicrobial activities. Meridianin C and G showed antimalarial activity against both chloroquine-resistant (D6) as well as sensitive (W2) clones of Plasmodium falciparum with IC50 values in the range of 4.4 to 14.4 μM. Meridianin G showed better activity against the W2 clone, showing a higher selectivity index >24.1. Among the analogs, N1-morpholinoyl meridianin C analog displayed antimalarial activity against both clones, showing selectivity indices up to 25.1. Meridianin C along with a few other analogs showed weak to moderate antileishmanial activity against Leishmania donovani promastigotes, the best analog being a C-ring modified 5-iodo meridianin showing an IC50 of 9.17 μM. A few compounds also showed mild antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus, and antifungal activity against Cryptococcus neoformans.

Synthesis, protein kinase inhibitory potencies, and in vitro antiproliferative activities of meridianin derivatives

The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as well as some of their synthetic intermediates were tested for their kinase inhibitory potencies and for their in vitro antiproliferative activities. We found that this series of compounds is particularly interesting in the development of new inhibitors of DYRK1A and CLK1 kinases. The most effective compounds toward these two kinase families are the 6- and 7-bromo derivatives 30, 33, and 34 that showed more than 45-fold selectivity toward DYRK1A/CLK1 kinases over the other kinases tested. Meridianin derivatives could thus be developed toward potent and selective inhibitors of key RNA splicing regulators and potential therapeutic agents.

One-pot synthesis of meridianins and meridianin analogues via indolization of nitrosoarenes

Meridianins, marine alkaloids known as kinase inhibitors with an indole skeleton, and meridianin analogues were produced regioselectively and in moderate to good yields by thermal annulation of nitrosoarenes with 2-amino-4-ethynylpyrimidine and 2-chloro-4-ethynylpyrimidine, respectively, through a novel and atom-economical indolization process.

Towards the syntheses of N-H and N-alkylated derivatives of meridianins

(Chemical Equation Presented) Novel N-H and N-alkylated derivatives of meridianins have been synthesized as potential antitumor agents by a two-step conversion of N-tosyl-3-acetylindoles or N-alkyl-3-acetylindoles to the corresponding enaminones using DMF-DMA, with or without added pyrrolidine. Further cyclization with guanidine gave the corresponding 2-aminopyrimidines. The structures of the compounds, thus obtained, were proved by 1H and 13C NMR spectroscopy, NOE experiments and X-ray analysis.

Concise syntheses of meridianins by carbonylative alkynylation and a four-component pyrimidine synthesis

(Chemical Equation Presented) In one go: (Hetero)aryl iodides, alkynes, carbon monoxide, and amidines can be assembled in a consecutive four-component reaction to give pyrimidines by a sequence of carbonylative alkynylation and cyclocondensation. Carbonyl