6626-40-0

Usage

Uses

7,10-Dichloro-2-methoxybenzo[b][1,5]naphthyridine is used in the preparation of pyronaridine.

InChI:InChI=1/C13H8Cl2N2O/c1-18-11-5-4-9-13(17-11)12(15)8-3-2-7(14)6-10(8)16-9/h2-6H,1H3

Upstream product

• 6626-07-9 4-chloro-2-(6-methoxy-pyridin-3-yl-amino)-benzoic acid 
• 504-29-0 2-aminopyridine 
• 4214-76-0 5-nitro-pyridin-2-ylamine 
• 5418-51-9 5-nitro-2-hydroxypyridine 
• 4548-45-2 2-chloro-5-nitropyridine 
• 5446-92-4 2-methoxy-5-nitropyridine 
• 50-84-0 2,4 dichlorobenzoic acid 
• 6628-77-9 6-methoxy-pyridin-3-ylamine 

Downstream Products

• 81935-68-4 2-((7-chloro-2-methoxybenzo[b][1,5]naphthyridin-10-yl)amino)phenol 
• 74847-35-1 pyronaridine 
• 81935-60-6 2-methoxy-7-chloro-10-(4'-hydroxyphenyl)aminobenzo[b]-1,5-naphthyridine 
• 1269526-45-5 C₁₉H₁₃ClN₄O₃ 

Relevant academic research and scientific papers

ACRIDIN-9-YL-AMINE, QUINOLIN-9-YL-AMINE, 1 -AMINO-9H-THIOXANTHENE-9-ONE AND BENZO[B][1,5]NAPHTHYRI DIN-10-YL-AMINE DERIVATIVES AS AUTOPHAGY INHIBITORS FOR TREATING CANCER

This disclosure provides a cridin-9-yl-amine, quinolin-9-yl-amine, 1- amino-9H-thioxanthene-9-one and benzo[b][l,5]naphthyridin-10- yl-amine derivatives and structurally related compounds for use as autophagy inhibitors for treating cancer. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 77 to 155; examples 1 to 22; compound A; compounds 1 to 21; tables 1 to 3).

Design, synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents

In this study, we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors. MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation. In addition, all the compounds displayed Topo II inhibition activity at 10 mol/L, and also possessed good PARP-1 inhibitory activities. Subsequent mechanistic studies showed that compound 9a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells. Our study suggested that 9a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.

Methnaridine is an orally bioavailable, fast-killing and long-acting antimalarial agent that cures Plasmodium infections in mice

Background and Purpose: Malaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy. Experimental Approach: An integrated pharmacological approach was used to evaluate the antimalarial profile of methnaridine. The pharmacokinetic properties of methnaridine were investigated along with the associated safety profile. Host immune response patterns were also analysed. Key Results: Methnaridine exhibited potent antimalarial activity against P. falciparum (3D7: IC50 = 0.0066 μM; Dd2: IC50 = 0.0056 μM). In P. berghei-infected mice, oral administration effectively suppressed parasitemia (ED50 = 0.52 mg·kg?1·day?1) and cured the established infection (CD50 = 10.13 mg·kg?1·day?1). These results are equivalent to or better than those of other antimalarial agents in clinical use. Notably, a four-dose oral regimen at a dosage of 25 mg·kg?1 achieved a complete cure of P. berghei infection in mice. Methnaridine exhibited a rapid parasiticidal profile (PCT99 = 36.0 h) and showed no cross-resistance to chloroquine. Pharmacokinetic studies revealed that methnaridine is readily absorbed, long-lasting and slowly cleared. The safety profile of methnaridine is also satisfactory (maximum tolerated dose = 1,125 mg·kg?1). In addition, following methnaridine treatment, infection-induced Th1 immune response was almost fully alleviated in mice. Conclusion and Implications: Methnaridine is an orally bioavailable, fast-acting and long-lasting agent with excellent antimalarial properties. Our study highlights the potential of methnaridine for clinical development as a promising antimalarial candidate.

Highly sensitive and selective “naked eye” sensing of Cu(II) by a novel acridine-based sensor both in aqueous solution and on the test kit

A highly selective and sensitive acridine-based colorimetric sensor 2-((7-chloro-2-methoxybenzo[b][1,5]naphthyridin-10-yl)amino)phenol (NAP) was developed for detection of Cu2+ ions both in aqueous solution and on test papers. Sensor NAP responses to Cu2+ ions by changing its color from yellow to pink, which could be easily observed by the naked eyes. Furthermore, the mechanism of the binding model of NAP-Cu2+ complex was investigated by 1H NMR, HRMS analysis, and DFT calculations.

Synthesis and biological research of novel azaacridine derivatives as potent DNA-binding ligands and topoisomerase II inhibitors

DNA and DNA-related enzymes are one of the most effective and common used intracellular anticancer targets in clinic and laboratory studies, however, most of DNA-targeting drugs suffered from toxic side effects. Development of new molecules with good antitumor activity and low side effects is important. Based on computer aided design and our previous studies, a series of novel azaacridine derivatives were synthesized as DNA and topoisomerases binding agents, among which compound 9 displayed the best antiproliferative activity with an IC50 value of 0.57?μM against U937 cells, which was slightly better than m-AMSA. In addition, compound 9 displayed low cytotoxicity against human normal liver cells (QSG-7701), the IC50 of which was more than 3 times lower than m-AMSA. Later study indicated that all the compounds displayed topoisomerases II inhibition activity at 50?μM. The representative compound 9 could bind with DNA and induce U937 apoptosis through the exogenous pathway.

A method of preparing malaridine

The present invention relates to a method for preparing pyronaridine, and specifically, discloses a method for preparing high-purity pyronaridine. The method comprises the steps of: in an inert solvent, reacting a compound of formula II with acid salt of a compound of formula III to form pyronaridine of formula I, wherein n ranges from 1 to 3. The method according to the present invention has features of a short synthetic route, moderate reaction conditions, simple operations, a high product yield, high purity, low contents of an impurity 1 and an impurity 2, a low cost and the like, and is suitable for industrial production.

A novel process for antimalarial drug pyronaridine tetraphosphate

A novel process for preparation of pyronaridine tetraphosphate, an antimalarial drug substance, is reported. The overall yields are 54% and >99.8% (including five chemical steps). Formation and control of possible impurities are also described.

Improved manufacturing process for pyronaridine tetraphosphate

Pyronaridine tetraphosphate (1) is a well-known antimalarial drug. However, it required a carefully optimized production process for the manufacture of pyronaridine tetraphosphate. Each step of its manufacturing process was reinvestigated. For the cyclization of 4-chloro-2-(6-methoxy-pyridin-3-yl-amino) -benzoic acid 6 to 7,10- dichloro-2-methoxybenzo[b]-1,5-naphthyridine 5, an improved process was developed to eliminated critical process impurity (BIA). By the redesign of the formation of triphosphate salt, the purity as API grade was increased. Thus, a robust manufacturing process with an acceptable process performance has been developed to produce high quality pyronaridine tetraphosphate.

Novel synthetic azaacridine analogues as topoisomerase 1 inhibitors

Novel azaacridine analogues were synthesized and their antiproliferative activities against K562 and HepG-2 cell lines were evaluated, among which compound 5a was found to display good cytotoxicity. UVvisible spectral absorbance measurements showed that 5a can bind with calf thymus DNA (ct DNA). A relaxation assay indicated that 5a inhibits topoisomerase 1 activity.