38267-96-8

Usage

Uses

Used in Pharmaceutical Industry:
6-Bromo-4-chloroquinazoline is used as a key intermediate in the synthesis of various pharmaceuticals for its unique reactivity and structural properties. It contributes to the development of new drugs with potential therapeutic applications.
Used in Agrochemical Industry:
In the agrochemical sector, 6-Bromo-4-chloroquinazoline is utilized as a building block for the synthesis of agrochemicals, such as pesticides and herbicides. Its unique properties enable the creation of effective compounds for crop protection and management.
Used in Organic Synthesis:
6-Bromo-4-chloroquinazoline is employed as a versatile intermediate in organic synthesis for the development of a wide range of organic compounds. Its reactivity and structural features allow for the creation of new molecules with various applications in the chemical industry.
Used in Chemical Research:
As a compound with distinct properties, 6-Bromo-4-chloroquinazoline is used in chemical research to explore novel reactions, mechanisms, and the synthesis of new compounds. It aids in advancing the understanding of organic chemistry and the development of innovative chemical processes.

InChI:InChI=1/C8H4BrClN2/c9-5-1-2-7-6(3-5)8(10)12-4-11-7/h1-4H

Upstream product

• 32084-59-6 6-bromoquinazolin-4(3H)-one 
• 5794-88-7 5-Bromo-2-aminobenzoic acid 
• 32084-59-6 6-bromo-4-hydroxyquinazoline 
• 32084-59-6 6-bromo-4-quinazolone 
• 134-20-3 2-carbomethoxyaniline 
• 52727-57-8 5-bromo-2-aminobenzoic acid methyl ester 
• 118-92-3 anthranilic acid 
• 16313-66-9 5-bromoanthranilamide 

Downstream Products

• 102467-63-0 1-(6-bromo-quinazolin-4-yl)-5-(4-chloro-phenyl)-biguanide 
• 195457-61-5 6-bromo-N-(3-chloro-4-fluorophenyl)-4-quinazolinamine 
• 474707-54-5 6-bromo-4-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}quinazoline 
• 307538-54-1 6-bromo-4-(4-N-methylpiperazin-1-yl)quinazoline 
• 474710-32-2 methyl 3-[4-(6-bromo-4-quinazolinyl)piperazino]benzoate 
• 474710-17-3 methyl-{3-[4-(6-bromo-4-quinazolinyl)-1,4-diazepan-1-yl]phenyl}sulfone 
• 474710-10-6 6-Bromo-4-[4-(2-fluoro-5-methylsulfonylphenyl)piperazin-1-yl]quinazoline 
• 179246-97-0 (4-benzyloxyphenyl)-(6-bromoquinazolin-4-yl)-amine hydrochloride 
• 32084-59-6 6-bromo-4-quinazolone 
• 307538-52-9 4-(6-bromoquinazolin-4-yl)morpholine 
• 307538-20-1 6-bromo-N-(3-chlorophenyl)quinazolin-4-amine 
• 944549-41-1 N-[3-chloro-4-[(3-fluorobenzyl)oxy]phenyl]-6-bromo-quinazolin-4-amine 
• 1135238-69-5 C₁₆H₁₄BrN₃O 
• 307538-42-7 SMER28 

Relevant academic research and scientific papers

UiO-66-NH2as an effective solid support for quinazoline derivatives for antibacterial agents against Gram-negative bacteria

Nanomaterials have been widely used as a class of antibacterial drugs. However, the bottlenecks of this class of materials are their significant aggregation and accumulation, as well as toxicity resulting from excessive metal leaching. Metal-organic frameworks (MOFs) have inspired researchers owing to their distinct characteristics of robust architecture and tunable pore structures, which may help overcome the above challenges. We, herein, synthesize UiO-66-NH2 and use it as a solid support for loading quinazoline derivatives that are specifically designed and active against Gram-negative bacteria. The quinazoline derivatives were adsorbed on UiO-66-NH2 nanoparticles to form new UiO-66-NH2-quinazoline formulations which have a large inhibitory zone against Gram-negative bacteria, compared to that of free quinazoline compounds. This work has the potential for increasing antibacterial activity while also broadening the antibacterial range, and thus opens a pathway for new medical applications using MOFs. This journal is

Discovery of New 4-Indolyl Quinazoline Derivatives as Highly Potent and Orally Bioavailable P-Glycoprotein Inhibitors

The major drawbacks of P-glycoprotein (P-gp) inhibitors at the clinical stage make the development of new P-gp inhibitors challenging and desirable. In this study, we reported our structure-activity relationship studies of 4-indolyl quinazoline, which led to the discovery of a highly effective and orally active P-gp inhibitor, YS-370. YS-370 effectively reversed multidrug resistance (MDR) to paclitaxel and colchicine in SW620/AD300 and HEK293T-ABCB1 cells. YS-370 bound directly to P-gp, did not alter expression or subcellular localization of P-gp in SW620/AD300 cells, but increased the intracellular accumulation of paclitaxel. Furthermore, YS-370 stimulated the P-gp ATPase activity and had moderate inhibition against CYP3A4. Significantly, oral administration of YS-370 in combination with paclitaxel achieved much stronger antitumor activity in a xenograft model bearing SW620/Ad300 cells than either drug alone. Taken together, our data demonstrate that YS-370 is a promising P-gp inhibitor capable of overcoming MDR and represents a unique scaffold for the development of new P-gp inhibitors.

Discovery of BPR1R024, an Orally Active and Selective CSF1R Inhibitor that Exhibits Antitumor and Immunomodulatory Activity in a Murine Colon Tumor Model

Colony-stimulating factor-1 receptor (CSF1R) is implicated in tumor-associated macrophage (TAM) repolarization and has emerged as a promising target for cancer immunotherapy. Herein, we describe the discovery of orally active and selective CSF1R inhibitors by property-driven optimization of BPR1K871 (9), our clinical multitargeting kinase inhibitor. Molecular docking revealed an additional nonclassical hydrogen-bonding (NCHB) interaction between the unique 7-aminoquinazoline scaffold and the CSF1R hinge region, contributing to CSF1R potency enhancement. Structural studies of CSF1R and Aurora kinase B (AURB) demonstrated the differences in their back pockets, which inspired the use of a chain extension strategy to diminish the AURA/B activities. A lead compound BPR1R024 (12) exhibited potent CSF1R activity (IC50 = 0.53 nM) and specifically inhibited protumor M2-like macrophage survival with a minimal effect on antitumor M1-like macrophage growth. In vivo, oral administration of 12 mesylate delayed the MC38 murine colon tumor growth and reversed the immunosuppressive tumor microenvironment with the increased M1/M2 ratio.

Discovery of quinazoline derivatives as a novel class of potent and in vivo efficacious LSD1 inhibitors by drug repurposing

Histone lysine-specific demethylase 1 (LSD1) is an important epigenetic modulator, and is implicated in malignant transformation and tumor pathogenesis in different ways. Therefore, the inhibition of LSD1 provides an attractive therapeutic target for cancer therapy. Based on drug repurposing strategy, we screened our in-house chemical library toward LSD1, and found that the EGFR inhibitor erlotinib, an FDA-approved drug for lung cancer, possessed low potency against LSD1 (IC50 = 35.80 μM). Herein, we report our further medicinal chemistry effort to obtain a highly water-soluble erlotinib analog 5k (>100 mg/mL) with significantly enhanced inhibitory activity against LSD1 (IC50 = 0.69 μM) as well as higher specificity. In MGC-803 cells, 5k suppressed the demethylation of LSD1, indicating its cellular activity against the enzyme. In addition, 5k had a remarkable capacity to inhibit colony formation, suppress migration and induce apoptosis of MGC803 cells. Furthermore, in MGC-803 xenograft mouse model, 5k treatment resulted in significant reduction in tumor size by 81.6% and 96.1% at dosages of 40 and 80 mg/kg/d, respectively. Our findings indicate that erlotinib-based analogs provide a novel structural set of LSD1 inhibitors with potential for further investigation, and may serve as novel candidates for the treatment of LSD1-overexpressing cancers.

Discovery of novel quinazoline derivatives as potent PI3Kδ inhibitors with high selectivity

Inhibition of PI3Kδ has been proved to be an efficacious strategy for the treatment of hematological malignancies where the PI3K/Akt signaling pathway is hyperactive. Herein, a series of quinazoline derivatives bearing acrylamide fragment were prepared using skeleton-deconstruction strategy. The preliminary bioactivity evaluation resulted in the discovery of lead compound 15c. Compound 15c exhibited excellent enzyme activity against PI3Kδ (IC50 = 27.5 nM) compared with BEZ235 as well as the significant anti-proliferation activities. With the high selectivity over other PI3K isoforms and potent effects on PI3K/Akt pathway, 15c can be identified as a promising PI3Kδ inhibitor worthy of further profiling.

Design, synthesis, and anticancer activities of sodium quinazolin-4-diselenide compounds

Substituted 4-chloroquinazoline reacted with sodium diselenide to give novel sodium quinazoline-4-diselenide compounds. The reaction provides an efficient and facile approach to the synthesis of sodium quinazoline-4-diselenide compounds. Structures of title compounds were confirmed by IR, 1H NMR, 13C NMR, and elemental analysis. MTT assay was adopted to show anticancer activities of the compounds. Compounds 5a and 5h showed good activities against cancer-cell lines MDA-MB-435, MDA-MB-231, A549, SiHa, and HeLa. In addition, 5a exhibited quite good anticancer effects on relative above cell lines with 10μM concentration compared with oxaliplatin and gefitinib of the commercial anticancer drugs.

SUBSTITUTED IMIDAZOLES FOR THE INHIBITION OF TGF-BETA AND METHODS OF TREATMENT

This disclosure relates to low molecular weight substituted imidazoles that inhibit the TGF-b signaling pathway. More specifically, this disclosure relates to methods of using said imidazoles for the treatment of diseases related to the TGF-b signaling pathways including, but not limited to, atherosclerosis, Marfan syndrome, Loeys-Dietz syndrome, obesity, diabetes, multiple sclerosis, keratoconus, idiopathic pulmonary fibrosis, Alzheimer's Disease, chronic kidney disease, and scleroderma.

Design, Synthesis and Bioevaluation of Two Series of 3-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-ones and N-(1-Benzylpiperidin-4-yl)quinazolin-4-amines

Two series of 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-ones and N-(1-benzylpiperidin-4-yl)quinazolin-4-amines were designed initially as potential acetylcholine esterase inhibitors. Biological evaluation demonstrated that N-(1-benzylpiperidin-4-yl)quinazolin-4-amines significantly inhibited AChE activity. Especially, two compounds of them were found to be the most potent with relative AChE inhibition percentages of 87 percent in comparison to donepezil. The docking studies with AChE showed similar interactions between donepezil and four derivatives. N-(1-Benzylpiperidin-4-yl)quinazolin-4-amines also exhibited significant DPPH scavenging effects. The two series of compound also exerted moderate to good cytotoxicity against three human cancer cell lines, including SW620 (human colon cancer), PC-3 (prostate cancer), and NCI?H23 (lung cancer), with 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one being the most cytotoxic agent. 3-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one significantly induced early apoptosis and arrested the SW620 cells at G2/M phase. From this study, two compounds of N-(1-benzylpiperidin-4-yl)quinazolin-4-amines could serve as new leads for further design and AChE inhibitors, while 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one could serve as a new lead for the design and development of more potent anticancer agents.

Alkylsulfonamide-containing quinazoline derivatives as potent and orally bioavailable PI3Ks inhibitors

Phosphoinositide 3-kinases (PI3Ks) are regarded as promising targets for treatment of various cancers due to their roles in regulating cell proliferation, differentiation, migration, and survival. Here we report our efforts to develop potent and orally bioavailable PI3K inhibitors for the treatment of cancers. The alkylsulfonamide-containing quinazoline derivatives A1–A18 significantly inhibited PI3Kα, and cell proliferation among HCT-116, MCF-7 and SU-DHL-6 cell lines. The optimal compound A1 displayed potent inhibitory activity against PI3Kα (IC50 = 4.5 nM), PI3Kβ (IC50 = 4.5 nM), PI3Kγ (IC50 = 4.5 nM), PI3Kδ (IC50 = 4.5 nM) and significantly inhibited the growth of HCT-116, MCF-7 and SU-DHL-6 cell lines with IC50 values of 0.82 μM, 0.99 μM and 0.19 μM, respectively. Western blot analysis demonstrated A1 significantly suppressed the phosphorylation of AKTS473 in a dose-dependent manner. Furthermore, A1 could markedly inhibit cancer growth at the dose of 25 mg/kg in nude mouse HCT-116 xenograft model in vivo without causing significant weight loss or toxicity.

Benzopyrimidine compound, preparation method, and applications thereof

The invention provides a benzopyrimidine compound, and a pharmaceutically acceptable salt and an isotope labeled product thereof, and applications of the benzopyrimidine compound and the derivatives of the benzopyrimidine compound in preparation of Btk or PI3K kinases inhibitors used in treatment or prevention of diseases related with the activity of protein kinase, for example, diseases such as tumor including leukemia and lymphoma can be treated through inhibiting Btk or PI3K.