289628-76-8

Usage

Chemical properties

Indole-based heterocyclic compound with a pyrimidine ring structure

Usage

Synthetic intermediate in the preparation of pharmaceuticals and organic compounds

Application

Building block for the synthesis of biologically active molecules, including potential drug candidates

Study

Potential use in cancer treatment and therapeutic applications due to its interaction with biological targets and modulation of biochemical processes.

Upstream product

• 113-00-8 guanidine nitrate 
• 1538583-13-9 C₂₆H₃₆N₄O₆SSi 
• 487-89-8 Indole-3-carboxaldehyde 
• 50-01-1 guanidine hydrochloride 
• 99532-45-3 3-acetyl-1-benzenesulfonylindole 
• 120-72-9 indole 
• 104142-24-7 3-acetyl-N-(p-toluenesulfonyl)indole 
• 942070-45-3 tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate 
• 3993-78-0 2-amino-4-chloropyrimidine 
• 1207175-18-5 2-amino-4-ethynylpyrimidine 
• 586-96-9 Nitrosobenzene 
• 945016-63-7 3-(2-chloro-pyrimidin-4-yl)-1H-indole 
• 112677-04-0 3-dimethylamino-1-(1H-indol-3-yl)-propenone 
• 593-85-1 diguanidine carbonate 

Relevant academic research and scientific papers

Synthesis and antitumor activity of indolylpyrimidines: Marine natural product meridianin D analogues

Marine indole alkaloid meridianin D analogues have been synthesized starting from the appropriate 3-cyanoacetyl indole. A facile two-step conversion of 3-cyanoacetyl indole to the corresponding cyano meridianin D analogue by treatment with dimethylformamide-dimethylacetal and further cyclization of the resulting enaminonitrile with aminoguanidine is described. Then, alkaline hydrolysis of cyano meridianin D afforded the carboxylic acid analogue. The treatment of acid with 75% H2SO4 afforded the desired 6-debromomeridianin D. Simply treatment of cyano meridianin D analogue with hydrazine hydrate afforded the amidrazone analogue. The biological evaluation indicated that cyano analogue showed good cytotoxic activity with IC50 values of 0.85 and 2.65 μg (against MCF7 and HeLa, respectively), but acid and amidrazone analogues showed high cytotoxicity with IC50 values of 0.75 and 0.25 μg, respectively (against MCF7).

Metal-free carbonyl C(sp2)-H oxidative alkynylation of aldehydes using hypervalent iodine reagents leading to ynones

A new metal-free tert-butyl hydroperoxide (TBHP)-mediated carbonyl C(sp2)-H oxidative alkynylation of aldehydes with ethynyl benziodoxolones (EBX) for the synthesis of ynones is described. This method is based on a carbonyl C(sp2)-H

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.

Targeting the Gatekeeper MET146 of C-Jun N-Terminal Kinase 3 Induces a Bivalent Halogen/Chalcogen Bond

We target the gatekeeper MET146 of c-Jun N-terminal kinase 3 (JNK3) to exemplify the applicability of X···S halogen bonds in molecular design using computational, synthetic, structural and biophysical techniques. In a designed series of aminopyrimidine-ba

Iridium-catalyzed C-H borylation of heterocycles using an overlooked 1,10-phenanthroline ligand: Reinventing the catalytic activity by understanding the solvent-assisted neutral to cationic switch

The preformed catalyst [Ir(Cl)(COD)(1,10-phenanthroline)] (2; COD = cyclooctadiene) was found to be highly effective in a model reaction for the borylation of N-Boc-indole at the 3-position with B2pin2 (pin = pinacolato) as the borylating agent to give consistently 99% yield with 0.5 mol % catalyst loading. The corresponding in situ formed catalyst from [Ir(Cl)(COD)]2 and 1,10-phenanthroline provided very inconsistent results for the same reaction (0-94% conversion). We propose this to be due to the competing formation of a catalytically inactive cationic complex, [Ir(COD)(1,10-phenanthroline)]+Cl- (1), in a noncoordinating solvent such as octane. Complexes 1 and 2 were characterized using solid-state NMR (13C and 35Cl) in conjunction with XPS to be cationic and neutral, respectively. The X-ray crystal structure of a pentavalent neutral Ir complex, [Ir(Cl)(COD)(2,2′-bipyridine)] (3), was also obtained for comparison purposes. Using catalyst 2, the total synthesis of Meridianin G was accomplished in 87% overall isolated yield in a one-pot, three-step process.

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

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.

Rapid synthesis of bis(hetero)aryls by one-pot Masuda borylation-Suzuki coupling sequence and its application to concise total syntheses of meridianins A and G

3-(Hetero)aryl substituted indoles, 7-azaindoles, and pyrroles can be obtained in a very concise fashion via a one-pot Masuda borylation-Suzuki coupling sequence. The concise total syntheses of the marine natural products meridianins A (5) and G (4i) nice

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.