19155-93-2

Upstream product

• 51818-99-6 4-amino-3-nitro-benzaldehyde 
• 16588-34-4 4-chloro-3-nitro-benzaldehyde 
• 104-88-1 4-chlorobenzaldehyde 
• 3011-34-5 4-hydroxy-3-nitrobenzaldehyde 
• 459-57-4 4-fluorobenzaldehyde 
• 42564-51-2 4-fluoro-3-nitrobenzaldehyde 

Downstream Products

• 59660-56-9 benzo[c][1,2,5]oxadiazol-5-ylmethanol 
• 32863-33-5 5-formylbenzofurazan 

Relevant academic research and scientific papers

Arylethenylbenzofuroxan derivatives as drugs for chagas disease: Multigram batch synthesis ysubg a wuttug#bideb process

In the present work, we developed robust processes for the preparation of new antitrypanosomal benzofuroxans, E and Z isomers of 5-arylethenylbenzo[1,2-c] 1,2,5-oxadiazole p1N-oxide 1-6, in muhigram batch through Wittig-Boden conditions as the key synthetic step. In these conditions, the generation of the benzofurazans, as secondary byproduct, was minimized.

Design, Synthesis, and Characterization of N-Oxide-Containing Heterocycles with in Vivo Sterilizing Antitubercular Activity

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is the infectious disease responsible for the highest number of deaths worldwide. Herein, 22 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antitubercular potential against Mtb. Compound 8 was found to be the most promising compound, with MIC90 values of 1.10 and 6.62 μM against active and nonreplicating Mtb, respectively. Additionally, we carried out in vivo experiments to confirm the safety and efficacy of compound 8; the compound was found to be orally bioavailable and highly effective, leading to a reduction of Mtb to undetectable levels in a mouse model of infection. Microarray-based initial studies on the mechanism of action suggest that compound 8 blocks translation. Altogether, these results indicate that benzofuroxan derivative 8 is a promising lead compound for the development of a novel chemical class of antitubercular drugs.

Synthesis of nitrophenyl and fluorophenyl azides and diazides by SNAr under phase-transfer or microwave irradiation: Fast and mild methodologies to prepare photoaffinity labeling, crosslinking, and click chemistry reagents

Two fast and mild methodologies to prepare nitrophenyl and fluorophenyl azides are presented. These aryl azides are extensively used as crosslinking, photoaffinity labeling, and click chemistry reagents. Substituted aryl azides are prepared by performing a SNAr substitution on halogenated benzenes with a phase-transfer catalyst (PTC) such as tetraethylammonium tetrafluoroborate (TEATFB), the reaction proceeds in several hours under rather mild temperatures (25°C to 70°C). Furthermore, aryl azides are also prepared within minutes under microwave irradiation at slightly higher temperatures (50°C to 70°C). These procedures could be applied in the preparation of other aryl azides. In the case of substituted pentafluoro benzene (pF), the type of products obtained in each reaction depends on the amount of sodium azide and the strength and position of electron-withdrawing substituents (COH, COR, COOR, CN, NO2, or F). A discussion on the mechanisms and the products obtained in these SNAr reactions is presented.

Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity

Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly remarkable in this regard, with EC50 value of 3.6 μM against L. infantum amastigote forms and CC50 value superior to 500 μM against murine peritoneal macrophages. In vitro studies suggested that 4f may act by a dual effect, by releasing nitric oxide after biotransformation and by inhibiting cysteine protease CPB (IC50: 4.5 μM). In vivo studies using an acute model of infection showed that compound 4f at 7.7 mg/Kg reduced ~90% of parasite burden in the liver and spleen of L. infantum-infected BALB/c mice. Altogether, these outcomes highlight furoxan 4f as a promising compound for further evaluation as an antileishmanial agent.

Piperidine compound and preparation method and medical application thereof

The invention discloses a piperidine compound shown as a formula (I) and a preparation method and medical application thereof, and particularly relates to a piperidine USP7 inhibitor compound or pharmaceutically acceptable salt or ester or solvate thereof and a preparation method and application of the piperidine USP7 inhibitor compound or pharmaceutically acceptable salt or ester or solvate thereof. The compound provided by the invention can inhibit the activity of USP7 enzyme, has very good selectivity and druggability, and can be used for preparing medicines for preventing or treating tumor diseases or virus infectious diseases.

Biphenyl compound as well as preparation method and medical application thereof

The invention discloses a biphenyl compound as well as a preparation method and medical application thereof, the structure of the biphenyl compound is shown as a formula (I) or a formula (II), and thebiphenyl compound or pharmaceutically acceptable salt, tautomer, meso-isomer, raceme, stereoisomer, metabolite, metabolite precursor, prodrug or solvate thereof is a PD-L1 inhibitor. The compound hasa remarkable inhibiting effect on the interaction of PD-1 and PD-L1 protein, so that the compound can be applied to the preparation of PD-L1 inhibitors and immunomodulator drugs for preventing or treating tumors, autoimmune diseases, organ transplant rejection, infectious diseases and inflammatory diseases.

SNAr azidation of phenolic functions utilizing diphenyl phosphorazidate

A useful method for the synthesis of aryl azides via SNAr reaction of phenol derivatives using diphenyl phosphorazidate (DPPA) as an azidation reagent was developed. Various phenol derivatives bearing electron-withdrawing groups were converted into the corresponding aryl azides in a single step. This method is easy to perform and enables the preparation of aryl azides without the use of explosive azide sources.

Synthesis and preliminary evaluation of N-oxide derivatives for the prevention of atherothrombotic events

Thrombosis is the main outcome of many cardiovascular diseases. Current treatments to prevent thrombotic events involve the long-term use of antiplatelet drugs. However, this therapy has several limitations, thereby justifying the development of new drugs

Discovery of phenoxybutanoic acid derivatives as potent endothelin antagonists with antihypertensive activity

A series of phenoxybutanoic acid derivatives were synthesized and tested for their antagonistic activity on the contraction of the rat thoracic aortic ring induced by endothelin-1. Preliminary screening results showed that 6e and 6g with benzoheterocycles demonstrated significant antagonistic activities when compared to the reference compound BQ123. The results from additional assays for the binding affinity and selectivity for endothelin receptors showed that 6e was a selective ETA antagonist with a nanomolar IC50. Moreover, 6e was effective in relieving hypoxia-induced pulmonary arterial hypertension and right ventricular weight ratio. Therefore, 6e may have potential for further development as a therapeutic agent for the treatment of cardiovascular diseases.

Leishmanicidal activities of novel synthetic furoxan and benzofuroxan derivatives

A novel series of furoxan (1,2,5-oxadiazole 2-oxide) (compounds 3, 4a and -b, 13a and -b, and 14a to -f) and benzofuroxan (benzo[c][1,2,5]oxadiazole 1-oxide) (compounds 7 and 8a to -c) derivatives were synthesized, characterized, and evaluated for in vitro activity against promastigote and intracellular amastigote forms of Leishmania amazonensis. The furoxan derivatives exhibited the ability to generate nitric oxide at different levels (7.8% to 27.4%). The benzofuroxan derivative 8a was able to increase nitrite production in medium supernatant from murine macrophages infected with L. amazonensis at 0.75 mM after 48 h. Furoxan and benzofuroxan derivatives showed remarkable leishmanicidal activity against both promastigote and intracellular amastigote forms. Compounds 8a, 14a and -b, and 14d exerted selective leishmanicidal activities superior to those of amphotericin B and pentamidine. In vitro studies at pH 5.4 reveal that compound 8a is stable until 8 h and that compound 14a behaves as a prodrug, releasing the active aldehyde 13a. These compounds have emerged as promising novel drug candidates for the treatment of leishmaniasis. Copyright