183319-38-2

Upstream product

• 183321-64-4 N-(3-ethynylphenyl)-6-nitroquinazolin-4-amine 
• 39263-34-8 N′-(2-cyano-4-nitrophenyl)-N,N-dimethylformimidamide 
• 19815-16-8 4-chloro-6-nitro-quinazoline 
• 54060-30-9 3-acetylenephenylamine 
• 17420-30-3 5-nitroanthranilonitrile 

Downstream Products

• 183319-48-4 (3-Ethynylphenyl)-[6-(4'-toluenesulfonylamino)-quinazolin-4-yl]-amine Hydrochloride 
• 183319-51-9 (3-Ethynylphenyl)-{6-[2'-phthalimido-ethan-1'-ylsulfonylamino]quinazolin-4-yl}-amine Hydrochloride 
• 1005194-68-2 tert-butyl 4-(2-(4-(3-ethynylphenylamino)quinazolin-6-ylamino)-2-oxoethylidene)piperidine-1-carboxylate 
• 1152132-25-6 (2-{4-[4-(3-ethynyl-phenylamino)-quinazolin-6-ylcarbamoyl]-benzoylamino}-phenyl)-carbamic acid tert-butyl ester 
• 1290545-43-5 1-(4-(bis(2-chloroethyl)amino)phenyl)-3-(4-(3-ethynylphenylamino)quinazolin-6-yl)urea 
• 1005194-69-3 N-(4-(3-ethynylphenylamino)quinazolin-6-yl)-2-(piperidin-4-ylidene)acetamide 
• 1005194-71-7 N-(4-(3-ethynylphenylamino)quinazolin-6-yl)-2-(1-methylpiperidin-4-ylidene)acetamide 
• 1428063-96-0 (E)-ethyl 3-[4-(3-ethynylphenylamino)quinazolin-6-ylamino]-2-cyanoacrylate 
• 1428064-17-8 C₂₄H₂₂N₄O₄ 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of cinnamamide-quinazoline derivatives as potential EGFR inhibitors to reverse T790M mutation

Gatekeeper T790M mutation in EGFR is the most common factor for acquired resistance. Acrylamide-bearing 4-anilinoquinazoline scaffold are powerful irreversible inhibitors for overcoming resistance. In this work, three series of EGFR inhibitors derived from incorporation of cinnamamide into the quinazoline scaffold were designed and synthesized to reverse resistance resulting from insurgence of T790M mutation. SAR studies revealed that methoxy and acetoxy substitutions on the cinnamic phenyl ring were found to elevate the activity. In particular, compound 7g emerged as the most potent derivative against mutant-type H1975 cells, which exhibited comparable activity to osimertinib (0.95 μM) towards H1975 cells with an IC50 value of 1.22 μM. Kinase inhibition studies indicated that 7g showed excellent inhibitory effect on EGFRT790M enzyme, which was 11 times more effective than gefitinib. Besides, selectivity index of 7g toward the EGFRT790M mutant over the EGFRWT is 2.72, hinting its effect of reducing off-target. Mechanism study indicated that 7g induced apoptosis of H1975 cells and arrest the cell cycle at G2/M phase in a dose-dependent manner. Moreover, 7g could significantly inhibit the expression of p-EGFR and its downstream p-AKT and p-ERK in H1975 cells. Molecular docking was also performed to gain insights into the ligand-binding interactions of 7g inside EGFRWT and EGFRT790M binding sites.

Quinazoline derivatives

no abstract published

Toward discovery of mutant EGFR inhibitors; Design, synthesis and in vitro biological evaluation of potent 4-arylamino-6-ureido and thioureido-quinazoline derivatives

A new series of 4-anilinoquinazolines with C-6 ureido and thioureido side chains and various substituents at the C-4 anilino moiety was designed, synthesized and evaluated as wild type (WT) and mutant EGFR inhibitors. Most of the compounds inhibited EGFR kinase wild type (EGFR WT) with IC50values in the low nanomolar range (50?=?1.76–2.38?μM) in these mutant lines and significant Her2 enzyme inhibition (IC50?=?19.2–40.6?nM) compared to lapatinib (60.1?nM). The Binding mode of compounds 6d, 6f, 7a, 7b and 8b were demonstrated. Furthermore, growth inhibition against gefitinib insensitive cell lines PC9-GR4 (Del19/T790M) were tested, compounds 6f and 7e showed about eight and three folds respectively greater potency than gefitinib. Our structure–activity relationships (SAR) studies suggested that presence of ethyl piperidino urea/thiourea at 6-position and bulky group of (3-chloro-4-(3-fluorobenzyloxy)phenyl)amino at 4-position of quinazoline may serve as promising scaffold for developing inhibitors against wild type and mutant EGFR.

Design, synthesis, and biological evaluation of novel quinazoline derivatives as anti-inflammatory agents against lipopolysaccharide-induced acute lung injury in rats

Quinazoline has been reported to exhibit multiple bioactivities. The aim of this study was to discover new quinazoline derivatives with preventive effect on lipopolysaccharide-induced acute lung injury via anti-inflammatory actions. Thirty-three 4-amino quinazolin derivatives were synthesized and screened for anti-inflammatory activities in lipopolysaccharide-induced macrophages. The most potent four compounds, 6h, 6m, 6p, and 6q, were shown dose-dependent inhibition against lipopolysaccharide-induced TNF-α and IL-6 release. Then, the preliminary structure-activity relationship and quantitative structure-activity relationship analyses were conducted. To further determine the effects of quinazolines on acute lung injury treatment, lipopolysaccharide-induced acute lung injury model was employed. Male Sprague Dawley rats were pretreated with 6m or 6q before instillation of lipopolysaccharide. The results showed that 6m and 6q, especially 6q, obviously alleviated lung histopathological changes, inflammatory cells infiltration, and cytokines mRNA expression initiated by lipopolysaccharide. Taken together, this work suggests that 6m and 6q suppressed the lipopolysaccharide-induced acute lung injury through inhibition of the inflammatory response in vivo and in vitro, indicating that quinazolines might serve as potential agents for the treatment of acute lung injury and deserve the continuing drug development and research.

Design, synthesis and in vitro anti-proliferative activity of 4,6-quinazolinediamines as potent EGFR-TK inhibitors

4-Anilino-6-substituted-quinazolines were designed, synthesized and evaluated for EGFR-TK and tumor growth inhibitory activities. The target compounds were designed with enamine ester or urea moieties appended at the C-6 of quinazoline as additional hydrogen bond acceptor functions. Most of the synthesized compounds displayed potent EGFR-TK inhibitory activity at 10 μM and the 6-ureido-anilinoquinazoline derivative 7a showed IC50 value of 0.061 μM. Moreover, six compounds were tested by National Cancer Institute (NCI), USA for their anti-proliferative activity at 10 μM in full NCI 60 cell panel. Compound 7a was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Non-Small Cell Lung Cancer EKVX (GI50 = 0.37 μM), NCI-H322M (GI50 = 0.36 μM), Renal Cancer A498 (GI50 = 0.46 μM), TK-10 (GI50 = 0.99 μM) and Breast Cancer MDA-MB-468 (GI50 = 1.096 μM) which are of high EGFR expression. Docking study was performed for the active compounds into ATP binding site of EGFR-TK which showed similar binding mode to gefitinib and additional binding with Cys-773 at the gatekeeper of EGFR-TK enzyme.

Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates

A series of N-mustard-quinazoline conjugates was synthesized and subjected to antitumor studies. The N-mustard pharmacophore was attached at the C-6 of the 4-anilinoquinazolines via a urea linker. To study the structure-activity relationships of these conjugates, various substituents were introduced to the C-4 anilino moiety. The preliminary antitumor studies revealed that these agents exhibited significant antitumor activity in inhibiting various human tumor cell growths in vitro. Compounds 21b, 21g, and 21h were selected for further antitumor activity evaluation against human breast carcinoma MX-1 and prostate PC-3 xenograft in animal model. These agents showed 54-75% tumor suppression with low toxicity (5-7% body-weight changes). We also demonstrate that the newly synthesized compounds are able to induce DNA cross-linking through alkaline agarose gel shift assay and inhibited cell cycle arrest at G2/M phase.

QUINAZOLINE DERIVATIVES

Quinazoline derivatives of the following formula: wherein R1, R2, R3, R4, R5, X, Y, and Z are defined herein. It also discloses a method of treating cancer with one of these compounds.

QUINAZOLINE AND QUINOLINE DERIVATIVES AS IRREVERSIBLE PROTEIN TYROSINE KINASE INHIBITORS

A compound of formula (I), a pharmaceutically acceptable salt, or hydrate thereof, and a method of preparing the same. A method of treating or preventing a physiological disorder caused by abnormal protein tyrosine kinase activity in a mammal comprising administering to said mammal a pharmaceutical composition comprising a compound of formula (I).

NOVEL BIFUNCTIONAL COMPOUNDS WHICH INHIBIT PROTEIN KINASES AND HISTONE DEACETYLASES

The present invention relates to a bifunctional compound of formula I or its pharmaceutically acceptable salts or solvates A-L-B (I) wherein A is a histone deacetylase (HDAC) inhibitory moiety, L is a single bond or a linker group and B is a protein kinase inhibitory moiety. The bifunctional compound according to formula (I) is useful for the treatment of malignant and non-malignant neoplasia and diseases related to abnormal cell growth

INREVERSIBLE PROTEIN TYROSINE KINASES INHIBITORS AND THE PREPARATION METHODS AND USES THEREOF

The compounds which could inhibit protein tyrosine kinases activity or the pharmaceutical acceptable salts or hydrates thereof. The uses of the compounds in treating or preventing physiological abnormal induced by protein tyrosine kinases overexpression in mammal. The preparation methods of the compounds.