224434-85-9

Upstream product

• 108-24-7 acetic anhydride 
• 189265-99-4 6-bromo-1-(4-methylphenylsulfonyl)-1H-indole 
• 98-59-9 p-toluenesulfonyl chloride 
• 316181-82-5 1-(6-bromo-1H-indol-3-yl)ethan-1-one 
• 52415-29-9 6-bromo-1H-indole 
• 75-36-5 acetyl chloride 

Downstream Products

• 341998-58-1 (E)-1-(6-bromo-1-tosyl-1H-indol-3-yl)-3-(dimethylamino)prop-2-en-1-one 
• 134029-45-1 Nortopsentin-C 
• 134029-43-9 nortopsentin A 
• 289503-27-1 2-amino-4-(N-tosyl-6'-bromo-3'-indolyl)pyrimidine 
• 1311395-35-3 4-(6-bromo-1H-indol-3-yl)-5-(3-methoxyphenyl)pyrimidin-2-amine 
• 1311395-31-9 4-(6-bromo-1H-indol-3-yl)-5-(4-trifluoromethylphenyl)pyrimidin-2-amine 
• 1311395-27-3 4-[2-amino-4-(6-bromo-1H-indol-3-yl)pyrimidin-5-yl]benzamide 
• 1311395-23-9 4-(6-bromo-1H-indol-3-yl)-5-(4-acetylphenyl)pyrimidin-2-amine 
• 290333-09-4 1-[1-[(4-methylphenyl)sulfonyl]-6-bromo-1H-indol-3-yl]-3-(dimethylamino)-2-propen-1-one 
• 224434-86-0 N-toluenesulfonyl-6-bromo-3-(2-bromoacetyl)indole 

Relevant academic research and scientific papers

A radical addition and cyclization relay promoted by Mn(OAc)3?2H2O: Synthesis of 1,2-oxaphospholoindoles and mechanistic study

Novel and efficient Mn(OAc)3?2H2O promoted radical addition-[4 + 1] cyclization relay of 3-indolymethanols and phosphites was disclosed, which afforded 1,2-oxaphospholoindole derivatives in moderate to good yields. Based on the experimental and computational studies, a mechanism involving radical addition and intramolecular cyclization cascade was proposed.

Second-Generation Meridianin Analogues Inhibit the Formation of Mycobacterium smegmatis Biofilms and Sensitize Polymyxin-Resistant Gram-Negative Bacteria to Colistin

Drug-resistant bacteria are rapidly becoming a significant problem across the globe. One element that factors into this crisis is the role played by bacterial biofilms in the recalcitrance of some infections to the effects of conventional antibiotics. Bacteria within a biofilm are highly tolerant of both antibiotic treatment and host immune responses. Biofilms are implicated in many chronic infections, including tuberculosis, in which they can act as bacterial reservoirs, requiring an arduous antibiotic regimen to eradicate the infection. A separate, compounding problem is that antibiotics once seen as last-resort drugs, such as the polymyxin colistin, are now seeing more frequent usage as resistance to front-line drugs in Gram-negative bacteria becomes more prevalent. The increased use of such antibiotics inevitably leads to an increased frequency of resistance. Drugs that inhibit biofilms and/or act as adjuvants to overcome resistance to existing antibiotics will potentially be an important component of future approaches to antibacterial treatment. We have previously demonstrated that analogues of the meridianin natural product family possess adjuvant and antibiofilm activities. In this study, we explore structural variation of the lead molecule from previous studies, and identify compounds showing both improved biofilm inhibition potency and synergy with colistin.

Optimization, Structure-Activity Relationship, and Mode of Action of Nortopsentin Analogues Containing Thiazole and Oxazole Moieties

Plant diseases seriously endanger plant health, and it is very difficult to control them. A series of nortopsentin analogues were designed, synthesized, and evaluated for their antiviral activities and fungicidal activities. Most of these compounds displayed higher antiviral activities than ribavirin. Compounds 1d, 1e, and 12a, with excellent antiviral activities, emerged as novel antiviral lead compounds, among which 1e was selected for further antiviral mechanism research. The mechanism research results indicated that these compounds may play an antiviral role by aggregating viral particles to prevent their movement in plants. Further fungicidal activity tests revealed that nortopsentin analogues displayed broad-spectrum fungicidal activities. Compounds 2p and 2f displayed higher antifungal activities against Alternaria solani than the commercial fungicides carbendazim and chlorothalonil. Current research has laid a foundation for the application of nortopsentin analogues in plant protection.

Marine-Natural-Product Development: First Discovery of Nortopsentin Alkaloids as Novel Antiviral, Anti-phytopathogenic-Fungus, and Insecticidal Agents

Nortopsentin alkaloids were found to have potent antiviral, anti-phytopathogenic-fungus, and insecticidal activities for the first time. Antiviral-activity tests revealed that these compounds were very sensitive to substituents, so a series of nortopsentin derivatives were designed, synthesized, and systematically evaluated for their antiviral activities against TMV, their fungicidal activities, and their insecticidal activities on the basis of a structural-diversity-derivation strategy. Compounds 2e (in vivo inactivation-, curative-, and protective-activity inhibitory rates of 50, 59, and 56%, respectively, at 500 μg/mL) and 2k (in vivo inactivation-, curative-, and protective-activity inhibitory rates of 60, 58, and 52%, respectively, at 500 μg/mL), with excellent antiviral activities and good physicochemical properties, emerged as new lead compounds for novel-antiviral-agent development. Further fungicidal-activity tests revealed that these alkaloids displayed broad-spectrum fungicidal activities. Compounds 2f, 2h, and 2j emerged as new lead compounds for antifungal-activity research. Additionally, all the compounds displayed good insecticidal activities against five kinds of insects, including Mythimna separate, Helicoverpa armigera, Ostrinia nubilalis, Plutella xylostella, and Culex pipiens pallens.

Meridianin D Analogues Display Antibiofilm Activity against MRSA and Increase Colistin Efficacy in Gram-Negative Bacteria

In the last 30 years, development of new classes of antibiotics has slowed, increasing the necessity for new options to treat multidrug resistant bacterial infections. Development of antibiotic adjuvants that increase the effectiveness of currently available antibiotics is a promising alternative approach to classical antibiotic development. Reports of the ability of the natural product meridianin D to modulate bacterial behavior have been rare. Herein, we describe the ability of meridianin D to inhibit biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) and to increase the potency of colistin against colistin-resistant and sensitive Gram-negative bacteria. Analogues were identified that are capable of inhibiting and dispersing MRSA biofilms and lowering the colistin MIC to below the CLSI breakpoint against Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli.

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.

Synthesis of the indole alkaloids meridianins from the tunicate Aplidium meridianum

The marine natural products meridianins A and C-E have been synthesized for the first time starting from the appropriate N-tosyl-3-acetylindole. A facile two-step conversion of N-tosyl-3-acetylindoles to the corresponding meridianins by treatment with dimethylformamide dimethylacetal and further cyclization of the resulting enaminone with aminoguanidine is described. This method has also been applied for the preparation of the 3-[(2-amino)pyrimidin-4-yl]-7-azaindole.

Syntheses and cytotoxicity evaluation of bis(indolyl)thiazole, bis(indolyl)pyrazinone and bis(indolyl)pyrazine: Analogues of cytotoxic marine bis(indole) alkaloid

2,4-Bis(3'-indolyl)thiazoles, 3,5-bis(3'-indolyl)-2(1H)pyrazinone and 3,6-bis(3'-indolyl)pyrazine were synthesized and evaluated for cytotoxic activity against diverse human cancer cell lines by the National Cancer Institute. These compounds demonstrated significant inhibitory effects in the growth of a range of cancer cell lines. 2,4-Bis(3'-indolyl)thiazole displayed selective cytotoxicity against certain leukemia cell lines with GI50 values in the low micromolar range while the substituted derivatives showed a broad spectrum of cytotoxic activity. 3,5-Bis(3'-indolyl)-2(1H)pyrazinone and 3,6- bis[3'-(N-methyl-indolyl)]pyrazine possessed strong inhibitory activity against a wide range of human tumor cell lines. The mechanism of action remained unknown. The results suggested that 2,4-bis(3'-indolyl)thiazoles, 3,5-bis(3'-indolyl)-2(1H)pyrazinone and 3,6-bis[3'-(N-methyl-indolyl)] pyrazine offer potential as lead compounds for the discovery of anticancer agents. (C) 2000 Elsevier Science Ltd.

Synthetic studies towards the 2-aminopyrimidine alkaloids variolins and meridianins from marine origin

A nine-step synthesis of 9-amino-4-methoxypyrido[3',2':4,5]pyrrolo[1,2- c]pyrimidine, a tricyclic ring system present in the marine alkaloids variolins is described. The natural marine products meridianins C-E have been synthesized for the first time starting from N-protected 3-acylindoles. (C) 2000 Elsevier Science Ltd.

Syntheses and biological activities of bis(3-indolyl)thiazoles, analogues of marine bis(indole)alkaloid nortopsentins

The thiazole analogues of the marine bis(indole)alkaloid nortopsentins, 2,4-bis(3-indolyl)thiazoles were synthesized using Hantzsch reaction between indole-3-thioamides and 3-(α-bromoacetyl)indoles as the key step, and these analogues showed potent cytotoxic activities against a variety of human cancer cell lines in vitro.