51387-92-9

Upstream product

• 121-78-8 N-{3-[(diethylamino)methyl]-4-hydroxyphenyl}acetamide 
• 50-00-0 formaldehyd 
• 123-30-8 4-amino-phenol 
• 109-89-7 diethylamine 
• 103-90-2 4-acetaminophenol 
• 100-02-7 4-nitro-phenol 

Downstream Products

• 110147-33-6 4-(5-chloro-8-methoxy-[4]quinolylamino)-2-diethylaminomethyl-phenol 
• 114277-11-1 6-chloro-2-methoxy-9-(3'-diethylamino methyl-4'-hydroxyanilino)acridine 
• 109472-72-2 2-diethylaminomethyl-4-(4,6-diamino-2,2-dimethyl-2H-[1,3,5]triazin-1-yl)-phenol; dihydrochloride 
• 107399-96-2 Benzofuran-2-carboxylic acid (3-diethylaminomethyl-4-hydroxy-phenyl)-amide 
• 86-42-0 amodiaquin 
• 76005-41-9 2-Diethylaminomethyl-4-[2-(4-diethylamino-1-methyl-butylamino)-quinazolin-4-ylamino]-phenol; hydrochloride 
• 76004-73-4 2-Diethylaminomethyl-4-[4-(2-pyrrolidin-1-yl-ethylamino)-quinazolin-2-ylamino]-phenol 
• 106052-10-2 1-(3-diethylaminomethyl-4-hydroxyanilino)-3-methyl-6-(p-methylphenoxy)benzo<1,8>naphthyridine 
• 108731-42-6 4-(4-Hydroxy-3-diethylaminomethylphenyl)amino-1,2-naphthoquinone 
• 689299-97-6 (3-diethylaminomethyl-4-hydroxy-phenyl)-carbamic acid tert-butyl ester 
• 959007-23-9 C₁₇H₂₃N₃O 
• 1174988-10-3 C₁₇H₂₃N₃O 
• 1174988-11-4 C₁₆H₂₂N₄O₃S 

Relevant academic research and scientific papers

Antiplasmodial imidazopyridazines: structure-activity relationship studies lead to the identification of analogues with improved solubility and hERG profiles

3,6-Diarylated imidazopyridazines have recently been shown to possess good in vitro antiplasmodial and in vivo antimalarial activity. However, frontrunner compounds have been associated with poor solubility and a hERG (human ether-a-go-go-related gene) inhibition liability raising concerns for potential cardiotoxicity risks. Herein, we report the synthesis and structure-activity relationship studies of new imidazopyridazines aimed at improving aqueous solubility and countering hERG inhibition while maintaining antiplasmodial potency. While we identified new analogues with potent antiplasmodial activity (IC50 = 0.031 μM against the NF54 drug-sensitive strain, and IC50 = 0.0246 μM against the K1 multidrug resistant strain), hERG inhibition remained an issue. Excitingly, on the other hand, new analogues with a substantially improved hERG inhibition profile (IC50 = 7.83-32.3 μM) with sub-micromolar antiplasmodial activity (NF54, IC50 = 0.151-0.922 μM) were identified. Similarly, the introduced molecular features also resulted in analogues with moderate to high solubility (60-200 μM) while also displaying sub-micromolar antiplasmodial potency (NF54, IC50 = 0.136-0.99 μM).

Continuous preparing method for amodiaquine hydrochloride

The invention provides a continuous preparing method for amodiaquine hydrochloride. The method is a continuous three-step reaction preparing method and has the advantages that an intermediate product prepared in the reaction step is not separated, and amodiaquine hydrochloride is directly prepared. The method is simple in technology, less equipment is occupied, operation is simple, water serves as reaction solvent, pollution of a system is small, and the method is suitable for industrial production.

Aromatic amino analogues of artemisinin: Synthesis and in vivo antimalarial activity

Nine orally active novel artemisinin derivatives were prepared from artemisinin by four-step synthesis, and the compounds were evaluated in the rodent model using multidrug resistant Plasmodium yoelii nigeriensis. All of the compounds exhibited antimalarial activities with the ED50 ranging from 5.41 mg/kg-12.4 mg/kg. Among them, artemisinin derivative bearing N-(4-hydroxy-3- ((4-phenylpiperazin-1-yl)methyl)phenyl) moiety (5f) was found to be the most active compound and was found to be three times more potent than artemisinin (ED50 16.4 mg/kg). Birkhaeuser Boston 2009.

Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials

(1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) strains. The most active of these derivatives, 4m, had an IC50 of 1 μM against W2 and 3 μM against FCR3. Molecular modeling studies suggest that (1H-pyridin-4-ylidene)amines may bind to the ubiquinol oxidation Qo site of cytochrome bc1.

Aminocyanopyridine inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)

A class of inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2) was discovered. These compounds have demonstrated activity against the enzyme with IC50 values as low as 130 nM and suppress the expression of TNFα in U

Microwave-induced Mannich reaction - Synthesis of some Mannich derivatives of p-aminophenol

Mono and bis substituted dialkylamino alkyl-p-aminophenol 3 are prepared by treating paracetamol 1 with formaldehyde and appropriate secondary amines followed by deacetylation using 6 M HCI in unmodified domestic microwave oven in unsealed borosil vessels

Synthesis of new arylaminoquinoxalines and their antimalarial activity in mice

2-Arylaminoquinoxalines were prepared by the condensation of 2-chloroquinoxaline with the appropriate Mannich bases in the presence of HCI. To synthesize the Mannich bases, 4-acetamidophenol was reacted with formaldehyde and dialkylamine to yield 3-[(dial

X-ray crystal structure of N-[3-(diethylaminomethyl)-4- hydroxyphenyl]acetamide and its hydrochloride salt. Two forms of an important precursor in the synthesis of anti-tuberculosis drugs

N-[3-(Diethylaminomethyl)-4-hydroxyphenyl]acetamide (dmhpa) and its hydrochloride salt (dmhpaH+ Cl-) have been prepared and their X-ray crystal structures determined. The structure of dmhpa comprises an intramolecular hydrogen bond b

The Effect of Fluorine Substitution on the Metabolism and Antimalarial Activity of Amodiaquine

Amodiaquine (AQ) (2) is a 4-aminoquinoline antimalarial which causes adverse side effects such as agranulocytosis and liver damage.The observed drug toxicity is believed to be related to the formation of an electrophilic metabolite, amodiaquine imine (AQQI), which can bind to cellular macro-molecules and initiate hypersensitivity reactions. 5'-Fluoroamodiaquine (5'-FAQ, 3), 5',6'-difluoroamodiaquine (5',6'-DIFAQ, 4), 2',6'-difluoroamodiaquine (2',6'-DIFAQ, 5), 2',5',6'-trifluoroamodiaquine (2',5',6'-TRIFAQ, 6) and 4'-dehydroxy-4'-fluoroamodiaquine (4'-deOH-4'-FAQ, 7) have been synthesized to assess the effect of fluorine substitution on the oxidation potential, metabolism, and in vitro antimalarial activity of amodiaquine.The oxidation potentials were measured by cyclic voltammetry, and it was observed that substitution at the 2',6'- and 4'-positions (2',6'-DIFAQ and 4'-deOH'4'-FAQ) produced analogues with significantly higher oxidation potentials than the parent drug.Fluorine substitution at the 2',6'-positions and 4'-position also produced analogues that were more resistant to bioactivation.Thus 2',6'-DIFAQ and 4'-deOH-4'-FAQ produced thioether conjugates corresponding to 2.17percent (SD: +/-0.27percent) and 0percent of the dose compared with 11.87percent (SD: +/-1.31percent) of the dose for amodiaquine.In general the fluorinated analogues had similar in vitro antimalarial activity to amodiaquine against the chloroquine resistant K1 strain of Plasmodium falciparum and the chloroquine sensitive T9-96 strain of P. falciparum with the notable exception of 2',5',6'-TRIFAQ (6).The data presented indicate that fluorine substitution at the 2',6'-positions and replacement of the 4'-hydroxyl of amodiaquine with fluorine produces analogues ( 5 and 7) that maintain antimalarial efficacy in vitro and are more resistant to oxidation and hence less likely to form toxic quinone imine metabolites.

Studies in Potential Filaricides: Part XI - Synthesis of 2-Dialkylaminomethyl-4-substitutedamino-phenols as Amodiaquine Analogs

A number of 4,7-disubstituted quinazolines (11-17) and 2-dialkylaminomethyl-4-acetylaminophenols (19-30) have been synthesized and tested for their antifilarial activity against Litosomoides carinii in cotton rat (Sigmodon hispidus).Of the compounds tested 19-21 and 26 cause 60percent fall in microfilarial count at a dose of 30 mg/kg given intraperitoneally daily for 6 days.None of the compounds possesses any macrofilaricidal activity.