60547-97-9

Usage

InChI:InChI=1/C14H19N5O2/c1-20-11-7-9-10(8-12(11)21-2)17-14(18-13(9)15)19-5-3-16-4-6-19/h7-8,16H,3-6H2,1-2H3,(H2,15,17,18)

Upstream product

• 110-85-0 piperazine 
• 23680-84-4 2-chloro-6,7-dimethoxyquinazolin-4-amine 
• 16163-78-3 2,3-dihydro-2-methyl-1,4-benzodioxin-2-methyl 4-tolylsulfonate 
• 766532-56-3 4-(4-amino-6,7-dimethoxy-quinazolin-2-yl)-piperazine-1-carboxylic acid benzyl ester 
• 1260939-66-9 4-(4-amino-6,7-dimethoxy-quinazolin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester 

Downstream Products

• 117040-11-6 (Z)-1-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-2-fluoro-3-phenyl-propenone; hydrochloride 
• 117040-18-3 [4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-(3-chloromethyl-phenyl)-methanone 
• 117067-19-3 (E)-1-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-3-(3-fluoro-phenyl)-propenone 
• 117040-05-8 (E)-1-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-3-(4-fluoro-phenyl)-propenone 
• 117040-15-0 [4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-((2S,3R)-3-phenyl-oxiranyl)-methanone 
• 117040-12-7 (E)-1-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-4-phenyl-but-2-ene-1,4-dione 
• 107021-36-3 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(bicyclo[2,2,2]octa-2,5-diene-2-carbonyl)piperazine 
• 117040-07-0 (E)-1-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-3-(4-isothiocyanato-phenyl)-propenone 
• 117040-16-1 4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazine-1-carbothioic acid (4-azido-phenyl)-amide 
• 117040-19-4 [4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-(3-iodo-4-isothiocyanato-phenyl)-methanone 
• 117040-17-2 4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazine-1-carbothioic acid {4-[(aziridine-1-carbothioyl)-amino]-phenyl}-amide 
• 117040-08-1 N-(4-{(E)-3-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-3-oxo-propenyl}-phenyl)-2-bromo-acetamide 
• 117040-09-2 (E)-3-(4-{(E)-3-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-3-oxo-propenyl}-phenylcarbamoyl)-acrylic acid methyl ester 
• 117040-20-7 (E)-3-(4-{5-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-5-oxo-pentyl}-phenylcarbamoyl)-acrylic acid methyl ester 

Relevant academic research and scientific papers

Discovery of Fluorescence Polarization Probe for the ELISA-Based Antagonist Screening of α1-Adrenergic Receptors

High-throughput screening (HTS) of ligand library to find new active molecules for G protein-coupled receptors is still a major interest, as well as an actual challenge. Fluorescence polarization (FP) assay portrays an essential role in HTS; however, in many cases, it was restricted by the absence of FP probes, the narrow measurement window, and low signal-to-noise (S/N) ratio. Herein, based on the modification of our previous probe 1 (QFL), we discovered an FP probe 3 (QGGFL) for α1-adrenergic receptors (α1-ARs), which has satisfactory fluorescence intensity, specific binding ability to receptors, and suitable fluorescence properties that were compatible with the filters in the FP system. Meanwhile, an ELISA-like strategy was designed for FP-based HTS assay in which proteins were adhered into a solid phase to improve the measurement window and S/N ratio. With fluorescent antagonist QGGFL and the ELISA strategy, we succeeded in establishing the first competitive binding FP assay for α1-AR antagonists as the alternative of the radioligand binding assay.

PEPTIDE AND SMALL MOLECULE AGONISTS OF EPHA AND THEIR USES

A method of treating cancer in a subject includes administering to the subject a therapeutically effective amount of a compound, the small molecule having a general formula: A-L-X-Z (I).

Design and synthesis of small molecule agonists of EphA2 receptor

Ligand-independent activation of EphA2 receptor kinase promotes cancer metastasis and invasion. Activating EphA2 receptor tyrosine kinase with small molecule agonist is a novel strategy to treat EphA2 overexpressing cancer. In this study, we performed a lead optimization of a small molecule Doxazosin that was identified as an EphA2 receptor agonist. 33 new analogs were developed and evaluated; a structure?activity relationship was summarized based on the EphA2 activation of these derivatives. Two new derivative compounds 24 and 27 showed much improved activity compared to Doxazosin. Compound 24 possesses a bulky amide moiety, and compound 27 has a dimeric structure that is very different to the parental compound. Compound 27 with a twelve-carbon linker of the dimer activated the kinase and induced receptor internalization and cell death with the best potency. Another dimer with a six-carbon linker has significantly reduced potency compared to the dimer with a longer linker, suggesting that the length of the linker is critical for the activity of the dimeric agonist. To explore the receptor binding characteristics of the new molecules, we applied a docking study to examine how the small molecule binds to the EphA2 receptor. The results reveal that compounds 24 and 27 form more hydrogen bonds to EphA2 than Doxazosin, suggesting that they may have higher binding affinity to the receptor.

Discovery of the First Environment-Sensitive Near-Infrared (NIR) Fluorogenic Ligand for α1-Adrenergic Receptors Imaging in Vivo

Fluorescent ligands are gaining popularity as tools to aid GPCR research. Nonetheless, in vivo application of such tools is hampered due to their short excitation wavelengths in the visible range and lack of fluorogenic switch. Here we report the discovery of fluorescent ligands (3a-f) for α1-adrenergic receptors (α1-ARs) by conjugating the environment-sensitive fluorophore cyane 5 (Cy5) with the quinazoline pharmacophore. Among them, the conjugated compound 3a, with acylated piperazine and the shortest carbon chain spacer, exhibited potent binding and remarkable changes in fluorescence (10-fold) upon binding to α1-AR. Furthermore, it could be employed to selectively and specifically label α1-ARs with no washing procedures in single cells, prostate tissue slices, intact tumor xenografts and organs in living mice. Especially, the slice imaging results gave direct and visual evidence that there is a close relationship between α1-ARs and pathological prostate. It is anticipated that our fluorescent tools will find broad applications in the study of α1-AR pharmacology and physiology to aid development of novel therapeutics.

Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase

Novel quinazoline-type compounds were designed as inhibitors of the parasite specific enzyme trypanothione reductase (TR), and their biological activities were evaluated. Some of our compounds inhibited TR, showed selectivity for TR over human glutathione

Parallel synthesis of N-arylpiperazines using polymer-assisted reactions

A series of N-arylpiperazines were prepared in a parallel fashion using palladium-catalyzed cross-coupling, or nucleophilic aromatic displacement chemistries, and polymer-assisted sequestration and purification techniques as key steps.

NOVEL ANTITUMOUR AGENTS AND METHODS OF THEIR USE

Antitumor compounds based on the α1-adrenoceptor antagonist, doxazosin, as well as compositions and methods of use. The disclosed compounds induce apoptosis in cancer cells.

Pharmacological exploitation of the alpha1-adrenoreceptor antagonist doxazosin to develop a novel class of antitumor agents that block intracellular protein kinase B/Akt activation.

The alpha1-adrenoreceptor antagonist doxazosin induces apoptosis in malignant cells with moderate potency via an alpha1-adrenoreceptor-independent mechanism. Here, we demonstrate that the ability of doxazosin to induce apoptosis in PC-3 prostate cancer cells was, in part, attributable to the inhibition of protein kinase B (PKB)/Akt activation. The separation of the effect of doxazosin on apoptosis from its original pharmacological activity provides molecular underpinnings to develop novel antitumor agents. Replacement of the (2,3-dihydro-benzo[1,4]dioxane)-carbonyl moiety of doxazosin with aryl-sulfonyl functions dramatically improves the potency in facilitating Akt deactivation and inducing apoptosis. The optimal compounds, 33 and 44, were effective in apoptosis induction at low micromolar concentrations irrespective of androgen dependency and p53 functional status. Both agents were active in suppressing the growth of a panel of 60 cancer-cell lines with IC50 values of 2.2 and 1.5 microM, respectively. Together, these in vitro efficacy data suggest the translational potential of these agents in prostate cancer treatment.

A modified synthesis of iodoazidoaryl prazosin.

The antihypertension agent iodoazidoaryl prazosin (IAAP) has been made using a convergent route involving addition of an acylated piperazine 7 to 2-chloroquinazoline 5. IAAP has been shown to function as a multidrug resistance (MDR) reversal agent and bind to P-glycoprotein, a transmembrane transport protein. A study is also reported involving palladium-catalyzed substitution with amine heterocycles. With N,N-bis(2,6-diisopropyl)dihydroimidazolium chloride (10) as the ligand (2 mol %) for palladium(II) acetate (2 mol %) in THF at room temperature, morpholine added to 5 in 81% yield.

2,2-disubstitued 2,3-dihydro-1,4-benzodioxin derivatives having hypotensive activity

2,2-Disubstituted 2,3-dihydro-1,4-benzodioxin derivatives of formula (I): STR1 and pharmaceutically acceptable salts thereof having in vitro high affinity and selectively for α1 receptors and in vivo good and long lasting hypotensive activty, with negligible side-effects; processes for the preparation thereof and pharmaceutical compositions therefrom.