Category: 5469-70-5

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Imidazole derivatives as promising agents for the treatment of Chagas disease

More than 100 years after being first described, Chagas disease remains endemic in 21 Latin American countries and has spread to other continents. Indeed, this disease, which is caused by the protozoan parasite Trypanosoma cruzi, is no longer just a problem for the American continents but has become a global health threat. Current therapies, i.e., nifurtimox and benznidazole (Bz), are far from being adequate, due to their undesirable effects and their lack of efficacy in the chronic phases of the disease. In this work, we present an in-depth phenotypic evaluation in T. cruzi of a new class of imidazole compounds, which were discovered in a previous phenotypic screen against different trypanosomatids and were designed as potential inhibitors of cAMP phosphodiesterases (PDEs). The confirmation of several activities similar or superior to that of Bz prompted a synthesis program of hit optimization and extended structure-activity relationship aimed at improving drug-like properties such as aqueous solubility, which resulted in additional hits with 50% inhibitory concentration (IC50) values similar to that of Bz. The cellular effects of one representative hit, compound 9, on bloodstream trypomastigotes were further investigated. Transmission electron microscopy revealed cellular changes, after just 2 h of incubation with the IC50 concentration, that were consistent with induced autophagy and osmotic stress, mechanisms previously linked to cAMP signaling. Compound 9 induced highly significant increases in both cellular and medium cAMP levels, confirming that inhibition of T. cruzi PDE(s) is part of its mechanism of action. The potent and selective activity of this imidazole-based PDE inhibitor class against T. cruzi constitutes a successful repurposing of research into inhibitors of mammalian PDEs.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N69 – PubChem

 

Reference of 5469-70-5, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 5469-70-5, molcular formula is C4H5N3, introducing its new discovery.

5-Ring Heteroaromatic compounds and their use as binding partners for 5-ht5 receptors

The invention relates to 5-ring heteroaromatic compounds of general formula (I), their use for the treatment and/or prevention of diseases, and medicaments containing same.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

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Design, synthesis, and evaluation of novel 4-thiazolylimidazoles as inhibitors of transforming growth factor-beta type i receptor kinase

A novel series of 4-thiazolylimidazoles was synthesized as transforming growth factor-beta (TGF-beta) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-beta-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. N-{[5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-2-yl] methyl}butanamide 20, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC50 = 8.2 nM) as well as inhibitory activity against TGF-beta-induced Smad2/3 phosphorylation at a cellular level (IC50 = 32 nM).

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Pyridazine – Wikipedia,
Pyridazine | C4H4N58 – PubChem

 

In heterogeneous catalysis, the catalyst is in a different phase from the reactants. category: pyridazine, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 5469-70-5, name is 3-Aminopyridazine. In an article£¬Which mentioned a new discovery about 5469-70-5

Design, structure-activity relationship, and in vivo characterization of the development candidate NVP-HSP990

Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.

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Pyridazine | C4H4N83 – PubChem

 

Chemistry is traditionally divided into organic and inorganic chemistry. Recommanded Product: 5469-70-5, The former is the study of compounds containing at least one carbon-hydrogen bonds.In a patent£¬Which mentioned a new discovery about 5469-70-5

NOVEL ETHYLENEDIAMINE DERIVATIVES

A compound represented by the following formula (1):Q1-Q2-To-N(R1)-Q3-N(R2)-T1-Q4 [wherein, R¹ and R² are hydrogen atoms or the like; Q¹ is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may have a substituent, or the like; Q² is a single bond or the like; Q³ represents the following group: -C(R^3a)(R^4a)-{C(R^3b)(R^4b)}m¹-{C(R^3c)(R^4c)}m²-{C(R^3d)(R^4d)}m³-{C(R^3e)(R^4e)}m⁴-C(R^3f)(R^4f)- (in which, R^3a to R^4e represent hydrogen or the like); T⁰ represents a carbonyl group or the like; and T¹ represents -COCONR- or the like]; or salt thereof, solvate thereof, or N-oxide thereof.The compound is useful as a preventive and/or therapeutic agent for cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger’s disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N34 – PubChem

 

In heterogeneous catalysis, the catalyst is in a different phase from the reactants. HPLC of Formula: C4H5N3, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 5469-70-5, name is 3-Aminopyridazine. In an article£¬Which mentioned a new discovery about 5469-70-5

NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS

The present invention provides compounds of formula (I) and compositions thereof, methods of making them, and methods of using them to modulate alpha7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N21 – PubChem

 

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Isoxazolines as potent antagonists of the integrin alpha(v)beta3

Starting with lead compound 2, we sought to increase the selectivity for alpha(v)beta3-mediated cell adhesion by examining the effects of structural changes in both the guanidine mimetic and the substituent alpha to the carboxylate. To prepare some of the desired aminoimidazoles, a novel reductive amination utilizing a trityl-protected aminoimidazole was developed. It was found that guanidine mimetics with a wide range of pK(a)’s were potent antagonists of alpha(v)beta3. In general, it appeared that an acylated 2-aminoimidazole guanidine mimetic imparted excellent selectivity for alpha(v)beta3-mediated adhesion versus alpha(IIb)beta3-mediated platelet aggregation, with selectivity of approximately 3 orders of magnitude observed for compounds 3g and 3h. It was also found in this series that the alpha- substituent was required for potent activity and that 2,6-disubstituted arylsulfonamides were optimal. In addition, the selective alpha(v)beta3 antagonist 3h was found to be a potent inhibitor of alpha(v)beta3-mediated cell migration.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N91 – PubChem

 

One of the major reasons for studying chemical kinetics is to use measurements of the macroscopic properties of a system, name: 3-Aminopyridazine, such as the rate of change in the concentration of reactants or products with time.In a article, mentioned the application of 5469-70-5, Name is 3-Aminopyridazine, molecular formula is C4H5N3

Easy and regioselective access to dimethyl acetal-protected heterocycles and their efficient allylation reactions mediated by allylaluminum reagent

This paper describes easy access to twelve examples of five- and six-membered heterocycles (monocyclic and fused) containing a dimethyl acetal aldehyde function and/or a trifluoromethyl substituent, in good to excellent yields (72-98%). The dimethyl acetal-protected heterocycles were obtained in one-step via regioselective cyclocondensation reactions of 4,6,6-trimethoxy-1,1, 1-trifluorohex-3-en-2-one with 1,2-, 1,3- and 1,5-dinucleophiles (hydrazines, hydrazides, hydroxylamine, 1-acetylguanidine and 1,8-diaminonaphthalene). Subsequently, to demonstrate a potential synthetic application, some pyrazole rings containing dimethyl acetal moiety were converted to the respective secondary homoallylic alcohols by efficient allylation reactions employing allylaluminum reagent in 84 to 90% yields.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N66 – PubChem

 

Synthetic Route of 5469-70-5, Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Patent, and a compound is mentioned, 5469-70-5, 3-Aminopyridazine, introducing its new discovery.

BENZOPHENONE DERIVATIVES USEFUL FOR INHIBITING FORMATION OF MICROTUBULE

Disclosed herein are novel benzophenone derivatives represented by formula I, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof, a pharmacological composition containing the same, and a use of the composition as therapeutic drugs. The benzophenone derivatives have an inhibition activity of microtubule formation and can be used to treat a normal proliferative state of a malignant tumor by killing the actively proliferating cells

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Pyridazine – Wikipedia,
Pyridazine | C4H4N35 – PubChem

 

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Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations

The native chemical ligation reaction (NCL) involves reacting a C-terminal peptide thioester with an N-terminal cysteinyl peptide to produce a native peptide bond between the two fragments. This reaction has considerably extended the size of polypeptides and proteins that can be produced by total synthesis and has also numerous applications in bioconjugation, polymer synthesis, material science, and micro- and nanotechnology research. The aim of the present review is to provide a thorough mechanistic overview of NCL and extended methods. The most relevant properties of peptide thioesters, Cys peptides, and common solvents, reagents, additives, and catalysts used for these ligations are presented. Mechanisms, selectivity and reactivity are, whenever possible, discussed through the insights of computational and physical chemistry studies. The inherent limitations of NCL are discussed with insights from the mechanistic standpoint. This review also presents a palette of O,S-, N,S-, or N,Se-acyl shift systems as thioester or selenoester surrogates and discusses the special molecular features that govern reactivity in each case. Finally, the various thiol-based auxiliaries and thiol or selenol amino acid surrogates that have been developed so far are discussed with a special focus on the mechanism of long-range N,S-acyl migrations and selective dechalcogenation reactions.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N55 – PubChem