120372-85-2

Upstream product

• 26717-39-5 [[(3,4-Dimethoxyphenyl)amino]methylene]malonic acid,diethyl ester 
• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 6315-89-5 3,4-dimethoxyaniline 

Downstream Products

• 26893-22-1 1,4-Dihydro-6,7-dimethoxy-4-oxo-3-quinolinecarboxylic acid 
• 347151-53-5 4-(6,7-Dimethoxyquinolin-4-yloxy)phenylcarbamic acid phenyl ester 
• 190728-25-7 4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline 
• 35654-56-9 6,7-dimethoxy-4-chloroquinoline 
• 127285-54-5 1,4-dihydro-6,7-dimethoxy-4-oxoquinoline 
• 190728-24-6 6,7?dimethoxy?4?(4?nitrophenoxy)quinoline 
• 202917-04-2 3-((6,7-dimethoxyquinolin-4-yl)oxy)aniline 

Relevant academic research and scientific papers

A novel series of 4-phenoxyquinolines: Potent and highly selective inhibitors of PDGF receptor autophosphorylation

A novel series of 4-phenoxyquinolines some of which showed potent and highly selective inhibitory activities for PDGF receptor autophosphorylation, was discovered. Interestingly, their structures were very similar to those of the selective inhibitors for EGF receptor autophosphorylation.

Structural development of a type-1 ryanodine receptor (RyR1) Ca2+-release channel inhibitor guided by endoplasmic reticulum Ca2+ assay

Type-1 ryanodine receptor (RyR1) is a calcium-release channel localized on sarcoplasmic reticulum (SR) of the skeletal muscle, and mediates muscle contraction by releasing Ca2+ from the SR. Genetic mutations of RyR1 are associated with skeletal muscle diseases such as malignant hyperthermia and central core diseases, in which over-activation of RyR1 causes leakage of Ca2+ from the SR. We recently developed an efficient high-throughput screening system based on the measurement of Ca2+ in endoplasmic reticulum, and used it to identify oxolinic acid (1) as a novel RyR1 channel inhibitor. Here, we designed and synthesized a series of quinolone derivatives based on 1 as a lead compound. Derivatives bearing a long alkyl chain at the nitrogen atom of the quinolone ring and having a suitable substituent at the 7-position of quinolone exhibited potent RyR1 channel-inhibitory activity. Among the synthesized compounds, 14h showed more potent activity than dantrolene, a known RyR1 inhibitor, and exhibited high RyR1 selectivity over RyR2 and RyR3. These compounds may be promising leads for clinically applicable RyR1 channel inhibitors.

Lead optimization of 3-carboxyl-4(1 H)-quinolones to deliver orally bioavailable antimalarials

Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multidrug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization.

ANTIVIRAL AGENTS

The present invention is directed to compounds that are antiviral agents. Specificially the compounds of the present invention inhibit replication of HCV and are therefore useful in treating hepatitis C infections. The present invention is also directed t

Identification of potent and selective inhibitors of PDGF receptor autophosphorylation

We report the structure-activity relationship of quinoline and quinazoline derivatives, which include urea, thiourea, urethane, and acylthiourea groups, as inhibitors of the platelet-derived growth factor (PDGF) receptor autophosphorylation. Our previous studies showed that the quinoline and quinazoline derivatives including urea, thiourea, and carbamate groups were highly potent compounds as the PDGF receptor autophosphorylation inhibitor, but these compounds did not exhibit receptor selectivity between the PDGF receptor and the c-kit receptor. As a result of further synthesis and biological evaluation, we have found that the quinoline and quinazoline-acylthiourea derivatives showed not only good inhibitory activity for the PDGF receptor but also receptor selectivity between the PDGF receptor and the c-kit receptor. Furthermore N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2- methylbenzoyl)thiourea exhibited potent oral efficacy in in vivo assay using the rat carotid balloon injury model. Therefore, the quinoline and quinazoline-acylthiourea derivatives may be expected to have potential as therapeutic agents for the treatment of restenosis.

Synthesis and structure-activity relationship for new series of 4-phenoxyquinoline derivatives as specific inhibitors of platelet-derived growth factor receptor tyrosine kinase

We discovered a new series of 4-phenoxyquinoline derivatives as potent and selective inhibitors of the platelet-derived growth factor receptor (PDGFr) tyrosine kinase. We researched the highly potent and selective inhibitors on the basis of both PDGFr and epidermal growth factor receptor (EGFr) inhibitory activity. First, we found a compound, Ki6783 (1), which inhibited PDGFr autophosphorylation at 0.13 μM, but it did not inhibit EGFr autophosphorylation at 100 μM. After extensive explorations, we found the two desired compounds, Ki6896 (2) and Ki6945 (3), which are substituted by benzoyl and benzamide at the 4-position of the phenoxy group on 4-phenoxyquinoline, respectively. These inhibitory activities were 0.31 and 0.050 μM, respectively, but neither of them inhibited EGFr autophosphorylation at 100 μM. We further investigated the profile of both compounds toward various tyrosine and serine/threonine kinases. The three compounds specifically inhibited PDGFr rather than the other kinases.

4-anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor kinase and their bioisosteric relationship to the 4-anilino-6,7-dialkoxyquinazoline inhibitors

The synthesis and SAR of a series of 4-anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor (EGF-R) kinase are described. Condensation of 3,4-dialkoxyanilines with ethyl (ethoxymethylene)cyanoacetate followed by thermal cyclization gave, regiospecifically, 6,7-dialkoxy-4-oxo-1,4-dihydroquinoline-3-carbonitriles. Chlorination (POCl3) followed by the reaction with substituted anilines furnished the 4-anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of EGF-R kinase. An alternate synthesis of these compounds starts with a methyl 3,4-dialkoxybenzoate. Nitration followed by reduction (Fe, NH4Cl, MeOH-H2O) gave a methyl 2-amino-4,5-dialkoxybenzoate. Amidine formation using DMF-acetal followed by cyclization using LiCH2CN furnished a 6,7-dialkoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile, which was transformed as before. Compounds containing acid, ester, amide, carbinol, and aldehyde groups at the 3-position of the quinoline ring were also prepared for comparison, as were several 1-anilino-6,7-dimethoxyisoquinoline-4-carbonitriles. The compounds were evaluated for their ability to inhibit the autophosphorylation of the catalytic domain of EGF-R. The SAR of these inhibitors with respect to the nature of the 6,7-alkoxy groups, the aniline substituents, and the substituent at the 3-position was studied. The compounds were further evaluated for their ability to inhibit the growth of cell lines that overexpress EGF-R or HER-2. It was found that 4-anilinoquinoline-3-carbonitriles are effective inhibitors of EGF-R kinase with activity comparable to the 4-anilinoquinazoline-based inhibitors. A new homology model of EGF-R kinase was constructed based on the X-ray structures of Hck and FGF receptor-1 kinase. The model suggests that with the quinazoline-based inhibitors, the N3 atom is hydrogen-bonded to a water molecule which, in turn, interacts with Thr 830. It is proposed that the quinoline-3-carbonitriles bind in a similar manner where the water molecule is displaced by the cyano group which interacts with the same Thr residue.

Bicyclic compounds as ring-constrained inhibitors of protein-tyrosine kinase p56(lck)

A study was undertaken to prepare inhibitors of the lymphocyte protein- tyrosine kinase p56(lck). Using the known p56(lck) inhibitor 3,4-dihydroxy- α-cyanocinnamamide (4) as a lead compound, bicyclic analogues were designed as conformationally constrained

4(1H)-quinolone derivatives

Quinolone derivatives having a quinolone structure: STR1 where Yo is O or S are disclosed, which are useful as cardiotonic agents. Typical examples of the quinolone derivatives include: 6,7-dimethoxy-4 (1H) quinolone (compound 6) and 5-hydroxy-6-methoxy-4(1H) quinolone (compound 1) as typical compounds of the formulae[I] and [I'], respectively, shown in the specification.

2-oxo-1-[[(substituted sulfonyl)amino]-carbonyl]azetidines

Antibacterial activity is exhibited by 3-acylamino-2-oxoazetidines having in the 1-position an activating group of the formula STR1 wherein R is STR2 and R4 is STR3