Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | ||||||
{[ item.p_purity ]} | {[ item.pr_size ]} | Inquiry |
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price) ]} |
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price) ]} | {[ item.pr_usastock ]} | in stock Inquiry - | {[ item.pr_chinastock ]} | {[ item.pr_remark ]} in stock Inquiry - | Login | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
Berg, Kaja ; Hegde, Pooja ; Pujari, Venugopal , et al. Eur. J. Med. Chem.,2023,249,115125. DOI: 10.1016/j.ejmech.2023.115125 PubMed ID: 36682292
More
Abstract: The electron transport chain (ETC) in the cell membrane consists of a series of redox complexes that transfer electrons from electron donors to acceptors and couples this electron transfer with the transfer of protons (H+) across a membrane. This process generates proton motive force which is used to produce ATP and a myriad of other functions and is essential for the long-term survival of Mycobacterium tuberculosis (Mtb), the causative organism of tuberculosis (TB), under the hypoxic conditions present within infected granulomas. Menaquinone (MK), an important carrier molecule within the mycobacterial ETC, is synthesized de novo by a cluster of enzymes known as the classic/canonical MK biosynthetic pathway. MenA (1,4-dihydroxy-2-naphthoate prenyltransferase), the antepenultimate enzyme in this pathway, is a verified target for TB therapy. In this study, we explored structure-activity relationships of a previously discovered MenA inhibitor scaffold, seeking to improve potency and drug disposition properties. Focusing our campaign upon three molecular regions, we identified two novel inhibitors with potent activity against MenA and Mtb (IC50 = 13-22 μM, GIC50 = 8-10 μM). These analogs also displayed substantially improved pharmacokinetic parameters and potent synergy with other ETC-targeting agents, achieving nearly complete sterilization of Mtb in combination therapy within two weeks in vivo. These new inhibitors of MK biosynthesis present a promising new strategy to curb the continued spread of TB.
Keywords: 1,4-dihydroxy-2-naphthoate prenyltransferase ; MenA ; MenA inhibitors ; Menaquinone ; Mtb ; Mycobacterium tuberculosis ; Piperidine derivatives ; SAR
Purchased from AmBeed: 25952-53-8 ; 90719-32-7 ; 872-85-5 ; 6457-49-4 ; 3769-41-3 ; 10338-57-5 ; 135-19-3 ; 135-19-3 ; 28177-48-2 ; 22246-18-0 ; 122334-37-6 ; 91914-06-6 ; 10040-98-9 ; 161975-39-9 ; 150-76-5 ; 371-41-5 ; 63754-96-1 ; 288-32-4 ; 3380-34-5 ; 1677-46-9 ; 166815-96-9 ; 700-57-2 ; 1204-86-0 ; 21725-69-9 ; 367-12-4 ; 1003-29-8 ; 627-35-0 ; 27292-49-5 ; 104324-16-5 ; 123855-51-6 ; 4328-13-6 ; 875401-70-0 ; 405272-71-1 ; 63614-86-8 ; 1420942-13-7 ; 25952-53-8 ; 1420895-21-1 ; 1078-18-8 ; 32363-45-4 ; 69564-68-7 ; 31519-22-9 ; 22246-18-0 ; 189618-33-5 ; 180847-24-9 ; 6264-98-8 ; 946680-75-7 ; 63608-38-8 ; 713-68-8 ; 62810-39-3 ; 189618-32-4 ; 180847-23-8 ; 63608-31-1 ; 15789-05-6 ; 63712-27-6 ; 63608-33-3 ; 63608-35-5 ...More
CAS No. : | 1204-86-0 | MDL No. : | MFCD00735826 |
Formula : | C11H13NO2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | FOAQOAXQMISINY-UHFFFAOYSA-N |
M.W : | 191.23 | Pubchem ID : | 291349 |
Synonyms : |
|
Chemical Name : | 4-Morpholinobenzaldehyde |
Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* 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 |
---|---|---|
With sodium ethanolate; In ethanol; at 20℃; | General procedure: Various aldehydes (1.0 equiv) were added to stirred solutions of indolin-2-one, 5-chloroindolin-2-one or <strong>[5654-97-7]7-azaoxindole</strong> (1.0equiv) in absolute ethanol. After stirring at room temperature for 5 min NaOEt/EtOH (0.5 mL) was added and the mixture was then stirred at room temperature overnight. The solvent was then removed under vacuum. The residue was washed with saturated sodium chloride solution and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under vacuum. The solid part was purified by chromatography over silica gel using ethyl acetate/petroleum ether as the eluent to afford desired compounds 1a-1g, 2a, 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation; | General procedure: A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized to give compounds 3-29. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10% | General procedure: Anthranilic amide 6 (1 eq), NaHSO3 (1.2 eq) and a corresponding aldehyde building block (1eq) were dissolved in DMAc and the solution stirred for 30 min. pTSA (0.1 eq) was added andthe mixture was stirred at 155°C for 18 h. After concentration of the reaction mixture in vacuoand separation between saturated NaHCO3 and DCM, the crude product was purified by flashcolumn chromatography to isolate the desired 2-arylquinazoline. |
[ 1049760-05-5 ]
2-(4-Morpholinophenyl)-2-oxoacetaldehyde hydrate
Similarity: 0.86
[ 53566-95-3 ]
4,4'-(Phenylazanediyl)dibenzaldehyde
Similarity: 0.82
[ 1049760-05-5 ]
2-(4-Morpholinophenyl)-2-oxoacetaldehyde hydrate
Similarity: 0.86
[ 53566-95-3 ]
4,4'-(Phenylazanediyl)dibenzaldehyde
Similarity: 0.82
[ 554448-63-4 ]
2-Fluoro-4-morpholinobenzaldehyde
Similarity: 0.79
[ 23351-05-5 ]
4-(1H-Pyrrol-1-yl)benzaldehyde
Similarity: 0.78
[ 1049760-05-5 ]
2-(4-Morpholinophenyl)-2-oxoacetaldehyde hydrate
Similarity: 0.86
[ 280556-71-0 ]
(4-Morpholin-4-yl-phenyl)methanol
Similarity: 0.80
[ 1049760-05-5 ]
2-(4-Morpholinophenyl)-2-oxoacetaldehyde hydrate
Similarity: 0.86