Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists: Part 2

Sasmal, Sanjita; Balasubrahmanyam, D.; Reddy, Hariprasada Reddy Kanna; Balaji, Gade; Gadipelli, Srinivas; Cheera, Srisailam; Abbineni, Chandrasekhar; Sasmal, Pradip K.; Khanna, Ish; Sebastián, Víctor; Jadhav, Vikram P.; Singh, Manvendra; Talwar, Rashmi; Joghee, Suresh; Shashikumar, Dhanya; Reddy, K. Harinder; Sihorkar, Vaibhav; Frimurer, Thomas M.; Rist, Øystein; Elster, Lisbeth; Högberg, Thomas

doi:10.1016/j.bmcl.2012.03.049

Cited by 23 publications

(12 citation statements)

References 18 publications

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“…Studies have shown that Quinazoline and its derivatives, which belong to organic heterocyclic compounds, possess a broad range of biopharmaceutical activities, including anti-inflammation [ 19 ], antimicrobial [ 20 , 21 ], antimetabolic syndrome [ 22 , 23 , 24 ], anti-convulsant [ 25 , 26 ] and anti-psychotics activity [ 27 ]. In recent years, quinazoline derivatives have been developed as drugs against different tumors, including FDA-approved erlotinib, gefitinib, vandetanib and lapatinib [ 28 , 29 , 30 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

2,4-Diamino-Quinazoline, a Wnt Signaling Inhibitor, Suppresses Gastric Cancer Progression and Metastasis

Chang

Hsieh

et al. 2020

IJMS

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Gastric cancer (GC) is among the most treatment-refractory epithelial malignancies. Aberrant activation of Wnt/β-catenin-signaling has been implicated in a variety of human cancers, including gastric cancer. Here we report that the elevated expression of lymphoid enhancer binding factor 1 (Lef1) is associated with the TNM (tumor– node–metastasis) stage of gastric cancer. Subsequently, 2,4-diamino-quinazoline (2,4-DAQ), a selective inhibitor of Lef1, was identified to suppress the expression of Wnt/β-catenin target genes such as AXIN2, MYC and LGR5 and result in the suppression of gastric cancer cell growth through the apoptotic pathway. The 2,4-DAQ also exhibited an inhibitory effect on the migration/invasion of gastric cancer cells. Importantly, the treatment of human gastric tumor xenograft with 2,4-DAQ suppressed tumor growth in a nude mouse model. Furthermore, 2,4-DAQ appears effective on patient-derived organoids (PDOs). Transcriptome sequencing analysis also revealed that 2,4-DAQ are more effective on the gastric cancers that exhibit higher expression levels of Wnt-signaling pathway-related genes than their adjacent normal gastric tissues.

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Section: Discussionmentioning

confidence: 99%

2,4-Diamino-Quinazoline, a Wnt Signaling Inhibitor, Suppresses Gastric Cancer Progression and Metastasis

Chang

Hsieh

et al. 2020

IJMS

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“…A series of quinazoline derivatives ( 104 – 106 ) are to be considered as an antagonist for melanin concentrating hormone receptor 1 (MCHR1) [ 90 ] (see Scheme 71 ).…”

Section: Biological Importance Of Quinazoline Derivativesmentioning

confidence: 99%

Chemical Characteristics, Synthetic Methods, and Biological Potential of Quinazoline and Quinazolinone Derivatives

Asif

2014

International Journal of Medicinal Chemistry

125

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The heterocyclic fused rings quinazoline and quinazolinone have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry. Quinazoline and quinazolinone are reported for their diversified biological activities and compounds with different substitutions bring together to knowledge of a target with understanding of the molecule types that might interact with the target receptors. Quinazolines and quinazolinones are considered as an important chemical for the synthesis of various physiological significance and pharmacological utilized molecules. Quinazolines and quinazolinone are a large class of biologically active compounds that exhibited broad spectrum of biological activities such as anti-HIV, anticancer, antifungal, antibacterial, antimutagenic, anticoccidial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant, antileukemic, and antileishmanial activities and other activities. Being considered as advantaged scaffold, the alteration is made with different substituent.

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“…Among these GW 856464 [211], AMG076 [212] and NGD-4715 [213] achieved phase 1 clinical investigations. Trials to optimize quinazolines [214][215][216][217][218][219], as (40) (Figure 9(a)), revealed GW 803430 (GW3430; [214]), ATC0175 and ATC0065 [215] which were shown efficacious in rodent depression models [197]. However, ATC0175 and ATC0065 are binding with high affinity not only to MCH1-R but also to subtypes of the 5 HT receptor [197] suggesting that the antidepressiv effect of the MCH1-R antagonist is not due to MCH1-R alone.…”

Section: Non-peptide Ligands Of Mch-receptorsmentioning

confidence: 99%

Non-peptide ligands in the characterization of peptide receptors at the interface between neuroendocrine and mental diseases

Pissarek¹,

Disko²

2013

WJNS

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Hypothalamic receptors for neuropeptide Y, melaninconcentrating hormone, melanocortins and orexins/ hypocretins as well as for the downstream signaling corticotrophic factor have been discussed broadly for their influence on food intake and reward but also on several psychiatric disorders. For the development of non-peptide ligands for the in vivo detection of alterations in density and affinity of such G-protein coupled (GPCRs) peptide receptors the requirements to affinity and pharmacokinetics have been shifted to thresholds markedly distict from classical GPCRs to dissociation constants < 0.5 nM, partition coefficients log P < 3.5 and transcellular transport ratios, e.g. for the permeability glycoprotein transporter, below 3. Nevertheless, a multitude of compounds has been reported originally as potential therapeutics in the treatment of obesity among which some are suitable candidates for labeling as PET or SPECT-tracers providing receptor affinities even below 0.1 nM. These could be unique tools not only for better understanding of the mechanism of obesity but also for investigations of extrahypothalamic role of "feeding receptors" at the interface between neuroendocrine and mental diseases.

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Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists: Part 2

Cited by 23 publications

References 18 publications

2,4-Diamino-Quinazoline, a Wnt Signaling Inhibitor, Suppresses Gastric Cancer Progression and Metastasis

2,4-Diamino-Quinazoline, a Wnt Signaling Inhibitor, Suppresses Gastric Cancer Progression and Metastasis

Chemical Characteristics, Synthetic Methods, and Biological Potential of Quinazoline and Quinazolinone Derivatives

Non-peptide ligands in the characterization of peptide receptors at the interface between neuroendocrine and mental diseases

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