56128-66-6

Epidermal growth factor receptor (EGFR) is the most attractive target for drug research in non-small cell lung cancer (NSCLC). The first-generation EGFR tyrosine kinase inhibitors (TKIs) Gefetinib and Elotinib showed good clinical efficacy on lung adenocarcinoma tumors, but almost all patients developed resistance to these inhibitors over time. Quinazoline and quinoline derivatives are common targeted inhibitors of EGFR kinase, and their structural optimization is an important direction for the development of effective targeted anticancer drugs. Based on these facts, a series of heterocyclic 2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline derivatives have been designed and synthesized and their structures were confirmed by spectral analyses. The cytotoxic activity of the newly synthesized compounds was evaluated against the human kidney epithelial T293 cell line, normal lung cell lines WI-38, non-small cell lung cancer A549 and NCI-H157 cell lines using MTT. The tested compounds showed an evident anticancer activity against the tested cell lines, especially compound 13c, which was the most potent anticancer agent with half maximal inhibitory concentrations (IC50) between 8.82 and 10.24 μM. Docking study showed that compound 13b could be nicely bound to the ATP binding pocket of EGFR. In addition, the inhibitory activity of the target compounds against epidermal growth factor receptor tyrosine kinase (EGFR-TK) was evaluated. Results indicated the ability of the target compounds to inhibit EGFR-TK with half maximal inhibitory concentrations (IC50) in the range of 10.29 nM to 652.3 nM. In view of the reported compound activity, the structure deserves further optimization as cancer treatment agents.

The DPPH radical-scavenging abilities of the naturally occurring phenolic acid, 2,3,4-trihydroxybenzoic acid, and its methyl ester were evaluated. Both compounds in acetonitrile scavenged as many as four radicals compared to three or fewer radical consump

A novel series of 2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline derivatives were designed, synthesized and evaluated as reversible and noncovalent epidermal growth factor receptor (EGFR) inhibitors. Most of the compounds exhibited good potency against EGFRwt and some showed moderate to excellent potency against EGFRT790M/L858R mutant. The half-maximal inhibitory concentration (IC50) values of twenty-one compounds against EGFRwt were less than 50 nM, and those of six compounds were less than 10 nM. The IC50 values of eleven compounds against EGFRT790M/L858R were less than 100 nM. Among these, compound b1 displayed the most potent inhibitory activity against EGFRwt (IC50 = 2.0 nM) and EGFRT790M/L858R (IC50 = 6.9 nM). Compounds with excellent inhibitory activities against EGFRwt and EGFRT790M/L858R kinase inhibitory activities showed good antiproliferative activities against H358 and A549 cells. Docking study was performed to position compound b1 into the EGFR active pocket to determine the probable binding conformation.

A catalyst-controlled enantiodivergent bromolactonization of olefinic acids has been developed. Quinine-derived amino-amides bearing the same chiral core but different achiral aryl substituents were used as the catalysts. Switching the methoxy substituent in the aryl amide system from meta- to ortho-position results in a complete switch in asymmetric induction to afford the desired lactone in good enantioselectivity and yield. Mechanistic studies, including chemical experiments and density functional theory calculations, reveal that the differences in steric and electronic effects of the catalyst substituent alter the reaction mechanism.

The present invention relates to an N-substituted-phenyl-5-substituted-alkoxy-2,3-dihydro-[1,4]dioxane[2,3-f]quinazolin-10-amine (I) or 4-substituted-arylamino-6-substituted-alkyl-6H-[1,4]oxazino[3,2-g]quinazoline-7(8H)-one (II) type compounds, a preparation method thereof and an application thereof as an inhibitor for epidermal growth factor receptor (EGFR) (comprising some mutant forms of EGFR) to treat cancer. These compounds and salts thereof can be used to treat or prevent various cancer diseases.

The invention discloses 3-methoxymethyl-2,3-dihydro-[1,4]dioxano[2,3-f]quinazoline-10-amine compound and a preparation method thereof, and application of the compound as an epidermal growth factor receptor inhibitor for treating cancers, belonging to the field of biology. The compound is an N-substituted phenyl-5-substituted alkoxy-3-methoxymethyl-2,3-dihydro-[1,4]dioxano[2,3-f]quinazoline-10-amine compound as shown in a formula (I) which is described in the specification, or a pharmaceutically acceptable salt or a prodrug molecule thereof. In the formula (I), R is selected from a group consisting of -H, C1-5 straight-chain or branched-chain alkyl groups, alkyloxy groups, alkyloxy-substituted C1-5 straight-chain or branched-chain alkyl groups, etc.; R is selected from a group consisting of -H, halogen, aromatic alkyloxy groups, C1-3 alkyl groups, and C1-3 straight-chain or branched-chain alkoxy groups; and R is selected from a group consisting of -H, halogen, C1-4 unsaturated alkyl groups, nitro groups, cyano groups and C1-3 straight-chain or branched-chain alkoxy groups. The compound provided by the invention can be applied to treatment or prevention a variety of cancers.

This invention provides hydroxybenzoic acids, their esters and analogues thereof that are useful for the prevention and/or treatment of virus infection such as HBV, papillomavirus and/or herpes virus infection.

Compounds are provided corresponding to the following general formula (I): in which:--R1 and R2, independently of each other, represent an alkyl group with 1 to 3 carbon atoms, or a group of formula --CH2 --ORa, Ra representing a hydrogen atom or a methyl group Rx represents: an alkyl group with 1 to 3 carbon atoms, in particular a methyl group, or an --ORx1 group, Rx1 representing an alkyl group with 1 to 3 carbon atoms, in particular a methoxy group, or a group of formula --CH2 --X in which X represents a halogen atom, in particular chlorine, or a group of formula (a) STR1 in which: R3 and R5, independently of each other, represent a hydrogen atom, or an --OH group, or an --OCH3 group, R4 represents a hydrogen atom, or an --ORb group, Rb representing a hydrogen atom or a methyl group, or R4 represents a group of formula --Orc, Rc representing a group of formula --CH2 --CO--C6 H4 R'. The present compounds are benzoxazine derivatives which are used for treating pathological conditions associated with the presence of free radicals, such as Alzheimer's disease, and methods are provided for preparation of these compounds.

Candida cylindracea lipase (CCL) and porcine pancreatic lipase (PPL) have been used for deacetylation of peracetates of methyl and ethyl esters of six different polyphenolic acids in organic solvents. Exclusive de-esterification of the ester groups derived from the phenolic hydroxy and aliphatic acid over the ester group of the aromatic acid and aliphatic alcohol has been achieved affording the corresponding esters of phenolic acids in as high yields as 90-97%. The results have been corroborated with the mechanism of lipase action.

Bioactivity-directed fractionation of an ethanolic extract of the stems of Kadsura interior led to the isolation and identification of 12 known lignans (1-12). Seven of these compounds (1, 6, 8-12) were active as anti-HIV agents. Gomisin-G (11) exhibited

Disclosed herein are derivatives of 4,4''-dimethoxy-5,6,5''6''-bimethylenedioxy 2,2''-dimethoxycarbonyl biphenyl (DDB) which were synthesized and found to have anti-HIV activity. Of the compounds studied, 3,3''-dibromo DDB and 3-bromo-DDB initially exhibi

Benzohydroxamic acids inhibit mammalian ribonucleotide reductase and exhibit antineoplastic activity in L1210 leukemic mice. Five new hydroxy- and amino-substituted benzohydroxamic acids (3,4- and 3,5-OH,3,4-NH2, 2,3,4-, and 3,4,5-OH) were prepared and tested along with 12 previously reported benzohydroxamic acids (BHA) for enzyme inhibition and antitumor activity. The most potent enzyme inhibitor in this series was 2,3,4-OH-BHA (ID50=3.5 μM), which is 140 times more potent than hydroxyurea, but its toxicity limited the antitumor activity to a 30% increase in life span of L1210 bearing mice at 125 (mg/kg) day ip for 8 days. The most effective antitumor agent in this series was 3,4-OH-BHA which prolonged the life span of L1210 bearing mice 103% at 600 (mg/kg)/day ip for 8 days.