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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Synonyms: m-Nitrobenzyldehyde
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Robenidine derivatives as potential antischistosomal drug candidates
Christian N. Lotz ; Alina Krollenbrock ; Lea Imhof ; Michael Riscoe ; Jennifer Keiser ;
Abstract: Schistosomiasis caused by Schistosoma spp. is a disease that causes a considerable health burden to millions of people worldwide. The limited availability of effective drugs on the market and the increased risk of resistance development due to extensive usage, highlight the urgent need for new antischistosomal drugs. Recent studies have shown that robenidine derivatives, containing an aminoguanidine core, exhibit promising activities against Plasmodium falciparum, motivating further investigation into their efficacy against Schistosoma mansoni, due to their similar habitat and the resulting related cellular mechanisms like the heme detoxification pathway. The conducted phenotypic screening of robenidine and 80 derivatives against newly transformed schistosomula and adult Schistosoma mansoni yielded 11 candidates with low EC50 values for newly transformed schistosomula (1.12–4.63 μM) and adults (2.78–9.47 μM). The structure-activity relationship revealed that electron-withdrawing groups at the phenyl moiety, as well as the presence of methyl groups adjacent to the guanidine moiety, enhanced the activity of derivatives against both stages of Schistosoma mansoni. The two compounds 2,2′-Bis[(3-cyano-4-fluorophenyl)methylene] carbonimidic Dihydrazide Hydrochloride (1) and 2,2′-Bis[(4-difluoromethoxyphenyl) ethylidene] carbonimidic Dihydrazide Hydrochloride (19), were selected for an in vivo study in Schistosoma mansoni-infected mice based on their potency, cytotoxicity, pharmacokinetic-, and physicochemical properties, but failed to reduce the worm burden significantly (worm burden reduction <20%). Thus, robenidine derivatives require further refinements to obtain higher antischistosomal specificity and in vivo activity.
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Keywords: Robenidine derivative ; Aminoguanidine ; Schistosoma mansoni ; Drug discovery ; Structure-activity relationship
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Purchased from AmBeed: 101048-76-4 ; 90-98-2 ; 36062-19-8 ; 99-61-6 ; 1261759-41-4 ; 218301-22-5 ; 67-36-7 ; 35714-48-8
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Are β-Lactones Involved in Carbon-Based Olefination Reactions?
Jan Nowak ; Michał Tryniszewski ; Michał Barbasiewicz ;
Abstract: Heteroatom-based olefinating reagents (e.g., organic phosphonates, sulfonates, etc.) are used to transform carbonyl compounds into alkenes, and their mechanism of action involves aldol-type addition, cyclization, and fragmentation of four-membered ring intermediates. We have developed an analogous process using ethyl 1,1,1,3,3,3-hexafluoroisopropyl methylmalonate, which converts electrophilic aryl aldehydes into α-methylcinnamates in up to 70% yield. The reaction plausibly proceeds through the formation of β-lactone that spontaneously decarboxylates under the reaction conditions. The results shed light on the Knoevenagel–Doebner olefination, for which decarboxylative anti-fragmentation of aldol-type adducts is usually considered.
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Keywords: olefination ; carbonyl compounds ; reaction mechanism ; lactones ; malonates ; Knoevenagel ; Doebner reaction
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Arylnitro monocarbonyl curcumin analogues: Synthesis and in vitro antitubercular evaluation
du Preez, Charne ; Legoabe, Lesetja J. ; Jordaan, Audrey ; Jesumoroti, Omobolanle J. ; Warner, Digby F. ; Beteck, Richard M.
Abstract: Curcumin is a natural product that has been reported to exhibit myriad pharmacol. properties, one of which is antitubercular activity. It demonstrates antitubercular activity by directly inhibiting Mycobacterium tuberculosis (M.tb) and also enhances immune responses that ultimately lead to the elimination of M.tb by macrophages. This natural product is, however, unstable, and several analogs, noticeably monocarbonyl analogs, have been synthesized to overcome this challenge. Curcumin and its monocarbonyl analogs reported so far exhibit moderate antitubercular activity in the range of 7 to 16 μM. Herein, we report a straightforward synthesis of novel monocarbonyl curcumin analogs, their antitubercular activity, and the structure-activity relationship. The hit compound from this study, 3a, exhibits potent MIC90 values in the range of 0.2 to 0.9 μM in both ADC and CAS media.
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Keywords: analogues ; aryl nitro ; curcumin ; synthesis ; tuberculosis
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Purchased from AmBeed: 552-89-6 ; 458-37-7 ; 698-63-5 ; 99-61-6 ; 30626-03-0 ; 30625-98-0 ; 1675220-86-6 ; 30625-99-1
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CAS No. : | 99-61-6 |
Formula : | C7H5NO3 |
M.W : | 151.12 |
SMILES Code : | O=CC1=CC=CC([N+]([O-])=O)=C1 |
Synonyms : |
m-Nitrobenzyldehyde
|
MDL No. : | MFCD00007249 |
InChI Key : | ZETIVVHRRQLWFW-UHFFFAOYSA-N |
Pubchem ID : | 7449 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H412 |
Precautionary Statements: | P501-P273-P264-P280-P337+P313-P305+P351+P338-P302+P352-P332+P313-P362 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.6% | In ethanol;Reflux; | General procedure: solutionof acid hydrazide (0.01 mol) and appropriate benzaldehyde/acetophenone (0.01 mol) in ethanol was refluxed for 5-6 h. The precipitated title compounds were then filtered off, washed with water and recrystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With dimethyl amine; In ethanol; isopropyl alcohol; | a) 200 kg of 2-methoxyethyl acetoacetate and 185.1 kg of 3-nitrobenzaldehyde are suspended in 800 l of isopropanol. Then 5.65 kg of p-anisic acid and 5.05 kg of 33percent dimethylamine in ethanol are added, heating for about 30' at about 35° C. to obtain a solution. The reaction mixture is left to cool at 20/25° C. and then it is cooled for about 12 hours with running water and for a further 24 hours at about 0° C. with brine, then is centrifuged, washing with isopropanol. After drying, 327 kg of 2-methoxyethyl 2-(3-nitrobenzylidene) acetoacetate are obtained, in an about 91percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | General procedure: To a solution of the corresponding aromatic aldehyde (0.27 mmol) in EtOH (0.5 mL) was added urea (0.54 mmol) and CuSO4·5H2O (0.054 mmol). The mixture was stirred at 80 °C for 15 minutes before tetrahydrocurcumin or tetrahydrodemethoxycurcumin (0.27 mmol) was added. The reaction mixture was continued stirring for 24 hours and quenched with water (2 mL). The solution was washed with water (10 mL) and extracted with EtOAc (415 mL). The combined organic phases were washed with brine, dried over MgSO4 and concentrated under reduced pressure to afford crude product as a yellow brown oil. Purification was accomplished by column chromatography eluting with 60percent-75percent EtOAc/hexane to furnish compounds 8-17. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; at 60℃; for 0.5h; | General procedure: A mixture of corresponding hydrazinylpyridazine 1 or 5 (1 mmol) and aldehyde 2 (1.1 mmol) in ethanol (5 mL) was heated at 60 oC for 0.5 h. The formation of hydrazone was checked by TLC and the reaction mixture was cooled to rt. Oxone (1.5 mmol) was added to the mixture at rt followed by tetramethyl ammonium bromide (0.2 mmol) and the resulting mixture was heated at 60 oC for another 5 h. The mixture was cooled to rt and extracted with dichloromethane (2 × 25 mL), dried over anhydrous sodium sulphate and concentrated to obtain a residue which was purified by column chromatography using hexane/ethyl acetate as eluent to furnish the desired triazolopyridazines 4 and 7. | |
In ethanol; at 60℃; for 0.5h; | General procedure: A mixture of corresponding hydrazinylpyridazine 1 or 5 (1 mmol) and aldehyde 2 (1.1 mmol) in ethanol (5 mL) was heated at 60 C for 0.5 h. The formation of hydrazone was checked by TLC and the reaction mixture was cooled to rt. Oxone (1.5 mmol) was added to the mixture at rt followed by tetramethyl ammonium bromide (0.2 mmol) and the resulting mixture was heated at 60 C for another 5 h. The mixture was cooled to rt and extracted with dichloromethane (2 × 25 mL), dried over anhydrous sodium sulfate and concentrated to obtain a residue which was purified by column chromatography using hexane/ethyl acetate as eluent to furnish the desired triazolopyridazines 4 and 7 (See reference no; 7 for supporting information). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | for 0.166667h;Microwave irradiation; | General procedure: Second step consists of condensation of <strong>[6761-52-0]3-aminopyrazine-2-carbohydrazide</strong> (0.5 gm, 0.003 mol) with aromatic aldehydes (0.5 gm, 0.008 mol) using microwaveirradiation (8 - 10 min, 350 W). After cooling and filtration,the product was recrystallized using ethanol [6, 9] (Fig. 1). |
In ethanol;Microwave irradiation; | General procedure: Asolution of aromatic/substituted aldehydes (0.008 mole, 0.9gm) in 25ml ethanolwas added to a solution of compound 2(0.003 mol, 0.5gm) in 10 ml ethanol and wasirradiated in a microwave oven for 8-10 min (350 W). The resultanthydrazone was precipitated by addition of water (30 ml). The product wasfiltered and purified using ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; at 70 - 80℃; for 3h; | General procedure: The mixture of <strong>[78364-55-3]6-fluoro-2-hydrazinylbenzo[d]thiazole</strong> (2) (0.01 mol) and benzalde-hyde/substituted benzaldehyde (0.01 mol) was reuxed in ethanol (15 ml) at 70?80 °C for 3 h. The separated product obtained was ltered off, washed withdistilled water and recrystallized from methanol to give the correspondinghydrazone. The product obtained was further dissolved in acetic acid (20 ml) atroom temperature followed by the addition of sodium acetate (0.5 g). Bromine(2 mmol) in acetic acid (10 ml) was added dropwise to the reuxing reactionmixture. After 1 h, the mixture was poured onto crushed ice (100 g). The precipitateobtained was ltered off and crystallized from ethanol-dimethylformamide (1:1) togive crystals of (3a?3t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With chitosan; In neat (no solvent); at 75℃; for 0.0333333h;Microwave irradiation; Green chemistry; | General procedure: An equimolar mixture of <strong>[54396-44-0]2-methyl-3-(trifluoromethyl)aniline</strong> (0.351 g, 0.002 mol), corresponding aldehyde (0.002 mol), dimethyl phosphite (0.18 ml, 0.002 mol) and chitosan catalyst (10 molpercent) were taken in a reaction glass tube, degassed for 10 min and microwave irradiated at 180 W for 2 min at 60 °C. The progress of the reaction was monitored by TLC using petroleum ether and ethyl acetate (3:7) as solvent. After completion of the reaction, the mixture was diluted with ethyl acetate, washed with water (2 x 15 ml) followed by brine (1 x 10 ml), dried over Na2SO4 and evaporated to dryness. The crude mass was purified by column chromatography on silicagel (100-200 mesh) by using a 7:3 mixture of ethyl acetate in hexane to afford the pure alpha-aminophosphonates. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | General procedure: Trans-2-phenylcyclopropylamine hydrochloride (1.0 eq.), acetic acid (1.0eq.) and the appropriate aldehyde (0.9 eq.) were dissolved in around bottom flask in 10 mL dry DCE. The reaction mixture was stirred gently at room temperature for 2 h before sodium triacetoxyborohydride (3.0 eq.) was added in small portions to the reaction vessel. The reaction was monitored by TLC and quenched using 10 mL of an aqueous (5%) NaHCO3 solution. The organic layer was separated and the aqueous layer extracted three times with10 mL of DCE. All organic layers were combined, dried over anhydrous Na2SO4, concentrated in vacuo and purified using flash chromatography (silica gel; cyclohexane/ethyl acetate) to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 2-(3-phenylthioureido)ethylprolinamide; In water; for 0.25h;Reflux; | General procedure: To an equimolar solution of 6-amino-1,3-dimethyluracil(0.155g, 1mmol), aldehyde(1 mmol) and 4-hydroxycoumarin(0.162g, 1mmol) in 1mL of water, 5mol% of thioureacatalyst was added and the solution wasstirred underreflux condition. In about 5min, the product started forming(as evident from TLC). The stirring was continued untilcompletion of the reaction (monitored by TLC). The resultingmixture was cooled to room temperature and the solid that precipitated out of the solution was filtered off, washedwith water and then with ethanol twice to remove any unreactedstarting materials and trace of catalyst present. Thesolid crudeproduct was then dissolved in ethanol and keptovernight to get thepure recrystallized product. |
Tags: 3-Nitrobenzaldehyde | m-Nitrobenzyldehyde | Benzene Compounds | Nitroes | Aryls | Aldehydes | Organic Building Blocks | 99-61-6
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