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Usage

Nitroimidazole compound

A type of organic compound that contains a nitro group (-NO2) and an imidazole ring, which contributes to its potential biological activity.

Pharmaceutical and research applications

1-isopropyl-4-nitro-1H-imidazole is used in the development of new drugs and in various research projects due to its unique chemical structure and properties.

Potential anti-fungal and anti-bacterial properties

1-isopropyl-4-nitro-1H-imidazole has shown the ability to inhibit the growth of certain fungi and bacteria, making it a potential candidate for new drug treatments targeting these microorganisms.

Synthesis of organic compounds

1-isopropyl-4-nitro-1H-imidazole can be used as a starting material or intermediate in the synthesis of other organic compounds, contributing to its importance in chemical research.

Potential use in cancer treatment

Preliminary studies have shown that 1-isopropyl-4-nitro-1H-imidazole may have the ability to target and kill cancer cells, making it a possible candidate for further research and development in cancer therapy.

Need for further research

While 1-isopropyl-4-nitro-1H-imidazole has shown promise in various applications, more research is needed to fully understand its potential medical applications and to develop effective treatments using 1-isopropyl-4-nitro-1H-imidazole.

Upstream product

• 117836-30-3 1-(1-methyl-1-nitroethyl)-4-nitroimidazole 
• 75-30-9 2-iodo-propane 
• 3034-38-6 1H-4⁽⁵⁾-nitroimidazole 
• 19182-81-1 1,4-dinitro-1H-imidazole 
• 75-31-0 isopropylamine 
• 75-26-3 isopropyl bromide 

Relevant academic research and scientific papers

Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3

Fibroblast growth factor receptors (FGFR) 2 and 3 have been established as drivers of numerous types of cancer with multiple drugs approved or entering late stage clinical trials. A limitation of current inhibitors is vulnerability to gatekeeper resistance mutations. Using a combination of targeted high-throughput screening and structure-based drug design, we have developed a series of aminopyrazole based FGFR inhibitors that covalently target a cysteine residue on the P-loop of the kinase. The inhibitors show excellent activity against the wild-type and gatekeeper mutant versions of the enzymes. Further optimization using SAR analysis and structure-based drug design led to analogues with improved potency and drug metabolism and pharmacokinetics properties.

WDR5-MYC INHIBITORS

Substituted N-heteroaryl sulfonamide compounds inhibit WDR5-MYC interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject such as cancer cell proliferation.

Discovery of WD Repeat-Containing Protein 5 (WDR5)-MYC Inhibitors Using Fragment-Based Methods and Structure-Based Design

The frequent deregulation of MYC and its elevated expression via multiple mechanisms drives cells to a tumorigenic state. Indeed, MYC is overexpressed in up to ?50% of human cancers and is considered a highly validated anticancer target. Recently, we discovered that WD repeat-containing protein 5 (WDR5) binds to MYC and is a critical cofactor required for the recruitment of MYC to its target genes and reported the first small molecule inhibitors of the WDR5-MYC interaction using structure-based design. These compounds display high binding affinity, but have poor physicochemical properties and are hence not suitable for in vivo studies. Herein, we conducted an NMR-based fragment screening to identify additional chemical matter and, using a structure-based approach, we merged a fragment hit with the previously reported sulfonamide series. Compounds in this series can disrupt the WDR5-MYC interaction in cells, and as a consequence, we observed a reduction of MYC localization to chromatin.

NEW COMPOUNDS AND METHODS

The present invention relates to compounds of Formula (I) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, optical isomer, N-oxide, and/or prodrug thereof. The present invention also relates to pharmaceutical compositions comprising the compounds of the invention, and to their use in the treatment or prevention of medical conditions in which inhibition of c-ABL is beneficial. (I)

Structure-Based Design of 6-Chloro-4-aminoquinazoline-2-carboxamide Derivatives as Potent and Selective p21-Activated Kinase 4 (PAK4) Inhibitors

Herein, we report the discovery and characterization of a novel class of PAK4 inhibitors with a quinazoline scaffold. Based on the shape and chemical composition of the ATP-binding pocket of PAKs, we chose a 2,4-diaminoquinazoline series of inhibitors as a starting point. Guided by X-ray crystallography and a structure-based drug design (SBDD) approach, a series of novel 4-aminoquinazoline-2-carboxamide PAK4 inhibitors were designed and synthesized. The inhibitors' selectivity, therapeutic potency, and pharmaceutical properties were optimized. One of the best compounds, 31 (CZh226), showed remarkable PAK4 selectivity (346-fold vs PAK1) and favorable kinase selectivity profile. Moreover, this compound potently inhibited the migration and invasion of A549 tumor cells by regulating the PAK4-directed downstream signaling pathways in vitro. Taken together, these data support the further development of 31 as a lead compound for PAK4-targeted anticancer drug discovery and as a valuable research probe for the further biological investigation of group II PAKs.

Synthesis, limitations, and thermal properties of energetically- substituted, protonated imidazolium picrate and nitrate salts and further comparison with their methylated analogs

The possibility of forming simple energetic ionic liquids via the straightforward protonation of heterocyclic amines with nitric or picric acid was explored with 1-alkylimidazoles, 1-alkyl-2-methylimidazoles, and nitro, dinitro, and dicyano-substituted derivatives. The melting points of most of the prepared salts were lower than expected and of the 30 compounds prepared, more than half were found to melt below 100 °C. Limitations in the approach were found as a result of the use of energetic electron withdrawing substituents, such as nitro or cyano, which results in a reduction in nucleophilicity of the heterocycle and an inability to form salts with the acids studied. Interesting thermal behavior was observed with several of the new salts including supercooling and crystallization on heating. Comparison of the simple protonated imidazolium nitrate and picrate salts with their methylated analogs indicated that the protonated ionic liquids do not differ substantially in their melting points from the methylated analogs. However, the thermal stabilities of protonated imidazolium salts are much lower than their alkylated derivatives. Nitrate salts with alkylated cations tend to be more thermally stable than the corresponding picrate salts, but with protonated cations, the picrate salts tend to be approximately 70-80 °C more stable than the nitrate salts. Moreover, accelerating rate calorimetry (ARC) revealed that alkylated salts decompose much less exothermically (in some cases endothermically) than the protonated analogs, and that among all the analyzed salts, the most energetic materials found were protonated 1-methylimidazolium nitrate and 1,2-dimethylimidazolium picrate. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2012.

Potent and cellularly active 4-aminoimidazole inhibitors of cyclin-dependent kinase 5/p25 for the treatment of Alzheimer's disease

Utilizing structure-based drug design, a 4-aminoimidazole heterocyclic core was synthesized as a replacement for a 2-aminothiazole due to potential metabolically mediated toxicity. The synthetic route utilized allowed for ready synthesis of 1-substituted-4-aminoimidazoles. SAR exploration resulted in the identification of a novel cis-substituted cyclobutyl group that gave improved enzyme and cellular potency against cdk5/p25 with up to 30-fold selectivity over cdk2/cyclin E.

TRICYCLIC 2,4-DIAMIN0-L,3,5-TRIAZINE DERIVATIVES USEFUL FOR THE TREATMENT OF CANCER AND MYELOPROLIFERATIVE DISORDERS

The present invention relates to compounds of Formula (I): (I) and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds provide a treatment for myeloproliferative disorders and cancer.

PYRROLOTRIAZINE KINASE INHIBITORS

The invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity thereby making them useful as anticancer agents and for the treatment of Alzheimer's Disease.

Derives N-alkyles du 4-nitroimidazole. Synthese par chimie radicalaire (SRN1) et amenagements fonctionnels

Nucleophilic 4-nitroimidazole treated with variously functionalized gem-bromo-nitroalcanes under SRN1 conditions affords high yield of gem-nitro-(4-nitroimidazolyl) derivatives, the reactivity of which has been investigated.These compounds> i)