- Synthesis of alkylamino quinazolines and anti-tumor activity thereof
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The present invention provides a compound represented by formula (I), or a pharmaceutically acceptable salt, or ester, or prodrug thereof. The invention further provides a compound represented by the formula (I) or a pharmaceutically acceptable salt or ester, or a synthetic method of the prodrug and an application of the compound in preparation of a medicament for treating tumors.
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Paragraph 0060-0062; 0064
(2021/09/08)
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- Synthesis and pharmacological evaluation of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as sigma-2 receptor ligands
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Increasing evidences have implicated that sigma-2 receptor is a biomarker and significantly over-expressed in many proliferative cancer cells with no or low expression in normal cells. Sigma-2 receptor selective ligands have been successfully used as valuable tools to study its pharmacological functions, tumor imaging, and cancer therapeutics or adjuvants. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolinylalkyl benzamides are among a few categories of structures that have demonstrated high affinities and selectivities for sigma-2 receptor and been used extensively as study tools in various tumor imaging and therapy. As a continuous effort, we have synthesized a new series of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and evaluated their affinities for both sigma-1 and sigma-2 receptors. Most of these newly developed analogs showed good to excellent binding affinities for sigma-2 receptor with no or low affinities for sigma-1 receptor. In particular, compounds 3b, 3e, 4b, and 4e demonstrated Ki values of 5–6 nM affinities and excellent selectivities for sigma-2 receptor. In addition, these analogs also demonstrated moderate anticancer activities against human liver Huh-7 tumor cells and human esophagus KYSE-140 cancer cells. But their cytotoxicities seem not to be correlated with their sigma-2 receptor affinities.
- Sun, Yu-Tong,Wang, Gui-Fei,Yang, Yi-Qiu,Jin, Fujun,Wang, Yifei,Xie, Xiao-Yang,Mach, Robert H.,Huang, Yun-Sheng
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p. 227 - 237
(2018/02/14)
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- Tetrahydroisoquinoline derivatives preparation and application of (by machine translation)
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The invention mainly relates to a series of containing tetrahydroisoquinoline structure the synthesis of the compounds and in the medical field of application. Specifically, the invention relates to a series of tetrahydroisoquinoline structure compound, it can inhibit the polymerization of A β, antagonizing A β O in combination and in nerve cells caused by the cytotoxic, therapeutic or improve AD has application prospect. (by machine translation)
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Paragraph 0133; 0134; 0135
(2018/09/21)
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- Phenyl [...] compound and its preparation method, pharmaceutical composition, drug use (by machine translation)
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The invention provides a phenylurea coupling quinazoline compound or a pharmaceutically acceptable salt thereof represented by formula (I), wherein R1 represents H, represents Br, Cl or F, represents -CH3, -CH2-CH3, -CH2(CH3)2 or -CF3, represents -O-CH3, -O-CH2-CH3 or -O-CH2(CH3)2, or represents -C[triple bond]CH or -C[triple bond]N; n1 is 1, 2, 3, 4 or 5; one of R2 and R3 is a group represented by formula (II); R4 represents H, represents Br, Cl or F, represents -CH3, -CH2-CH3, -CH2(CH3)2 or -CF3, represents -O-CH3, -O-CH2-CH3 or -O-CH2(CH3)2, represents -NH2, or represents -NO2; n2 is 1, 2, 3, 4 or 5; and the other one of R2 and R3 represents H, -O-CH3, -O-CH2-CH3, -O-CH2(CH3)2, or the following groups.
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Paragraph 0272; 0273; 0276; 0277
(2016/10/27)
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- Artemisin derivative and its preparation and use
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Provided are artemisinin derivatives of formula (I) or pharmaceutically acceptable salts thereof, or enantiomers, diastereomers, and racemic bodies thereof, and a pharmaceutical composition of the compounds, the preparation process and uses thereof. Artemisinin derivatives of formula (I) have excellent effects in the treatment of tumours.
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Paragraph 0303; 0304; 0307
(2016/10/08)
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- Synthesis, biological evaluation and QSAR study of a series of substituted quinazolines as antimicrobial agents
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A novel series of 1-N-substituted-3-(4-(5-(pyridin-3-yl)-1,3,4-oxadiazol-2- ylthio)quinazolin-6-yl)urea/thiourea derivatives (6a-6r) and 1-N-substituted-3-(7-(4-methylpiperazin-1-yl)-4-(5-(pyridin-3-yl)-1,3, 4-oxadiazol-2-ylthio)quinazolin-6-yl)urea/thiourea derivatives (14a-14s) were synthesized and screened for antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli. Biological results indicated that the synthesized compounds showed a broad-spectrum activity against tested microorganisms at MIC values between 6.25 and 100 μg/mL. Compound 6r showed a broad spectrum of activity and was found to be active against all tested species. A quantitative structure-activity relationship study has been carried out on the synthesized compounds to get better insights into pharmacophoric features responsible for the antibacterial activity. Genetic function approximation technique was used to identify descriptors that influence biological activity. Hydrophobic (AlogP98), electronic (atomic polarizability), and topological (radius of gyration) descriptors were found to affect the activity significantly. Generated model was found to be statistically significant (r 2 = 0.86, predictive index = 0.96) and predictive as indicated by very low residuals in internal and external cross-validation.
- Buha, Vipul M.,Rana, Dharmaraj N.,Chhabria, Mahesh T.,Chikhalia, Kishor H.,Mahajan, Bhushan M.,Brahmkshatriya, Pathik S.,Shah, Nisha K.
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p. 4096 - 4109
(2013/09/02)
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- Design, synthesis and biological evaluation of novel 4-anilinoquinazolines with C-6 urea-linked side chains as inhibitors of the epidermal growth factor receptor
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A novel series of anilinoquinazoline compounds with C-6 urea-linked side chains was designed and synthesized as reversible inhibitors of epidermal growth factor receptor (EGFR) based on the structure-activity relationships (SARs) of anilinoquinazoline inhibitors. All compounds demonstrated good inhibition of EGFR wild type (EGFR wt) (IC50 = 0.024-1.715 μM) and inhibited proliferation of A431cell line (IC50 = 0.116-22.008 μM). The binding mode of compounds 8a, 8d, 8k and 8o was consistent with the biological results. Moreover, compounds 8k and 8l almost completely blocked the phosphorylation of EGFR in A431 cell line at 0.01 μM. Interestingly, all of the compounds also demonstrated moderate inhibition of EGFR/T790M/L858R (IC 50 = 0.049-5.578 μM). In addition, compounds 8f and 8h blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (10 μM), and compound 8f was confirmed to be an irreversible inhibitor through the dilution method. Importantly, the compounds with C-6 urea-linked side chains which did not contain Michael acceptors demonstrated moderate to strong irreversible EGFR inhibition.
- Zhang, Xu,Peng, Ting,Ji, Xun,Li, Jian,Tong, Linjiang,Li, Zeng,Yang, Wei,Xu, Yungen,Li, Mengyuan,Ding, Jian,Jiang, Hualiang,Xie, Hua,Liu, Hong
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p. 7988 - 7998
(2014/01/06)
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- Irreversible inhibition of epidermal growth factor receptor activity by 3-aminopropanamides
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Irreversible epidermal growth factor receptor (EGFR) inhibitors contain a reactive warhead which covalently interacts with a conserved cysteine residue in the kinase domain. The acrylamide fragment, a commonly employed warhead, effectively alkylates Cys797 of EGFR, but its reactivity can cause rapid metabolic deactivation or nonspecific reactions with off-targets. We describe here a new series of irreversible inhibitors containing a 3-aminopropanamide linked in position 6 to 4-anilinoquinazoline or 4-anilinoquinoline-3- carbonitrile driving portions. Some of these compounds proved to be as efficient as their acrylamide analogues in inhibiting EGFR-TK (TK = tyrosine kinase) autophosphorylation in A549 lung cancer cells. Moreover, several 3-aminopropanamides suppressed proliferation of gefitinib-resistant H1975 cells, harboring the T790M mutation in EGFR, at significantly lower concentrations than did gefitinib. A prototypical compound, N-(4-(3-bromoanilino)quinazolin-6- yl)-3-(dimethylamino)propanamide (5), did not show covalent binding to cell-free EGFR-TK in a fluorescence assay, while it underwent selective activation in the intracellular environment, releasing an acrylamide derivative which can react with thiol groups.
- Carmi, Caterina,Galvani, Elena,Vacondio, Federica,Rivara, Silvia,Lodola, Alessio,Russo, Simonetta,Aiello, Stefania,Bordi, Fabrizio,Costantino, Gabriele,Cavazzoni, Andrea,Alfieri, Roberta R.,Ardizzoni, Andrea,Petronini, Pier Giorgio,Mor, Marco
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p. 2251 - 2264
(2012/05/20)
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- TARTRATE SALTS OF QUINAZOLINE BASED EGFR INHIBITORS CONTAINING A ZINC BINDING MOIETY
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The present invention relates to tartrate salts of quinazoline containing zinc-binding moiety based derivatives that are inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and their use in the treatment of EGFR-TK related diseases and disorders such as cancer. The tartrate salts may further act as HDAC inhibitors.
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Page/Page column 74
(2009/04/24)
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- FORMULATION OF QUINAZOLINE BASED EGFR INHIBITORS CONTAINING A ZINC BINDING MOIETY
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The present invention relates to a composition comprising an inclusion complex of a cyclodextrin and quinazoline containing zinc-binding moiety based derivatives. The cyclodextrin is preferable a β-cyclodextrin or a derivative thereof. The quinazolines have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and their use in the treatment of EGFR-TK related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors.
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Page/Page column 73
(2009/05/29)
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- MULTI-FUNCTIONAL SMALL MOLECULES AS ANTI-PROLIFERATIVE AGENTS
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The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.
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Page/Page column 129
(2008/06/13)
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- QUINAZOLINE DERIVATIVES,PREPARATION METHODS AND USES THEREOF
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The present invention has disclosed a compound of formula I and a pharmaceutically acceptable salt or a solvate thereof, wherein the substituents are as defined in the description. The invention has also disclosed a method for preparing the compound of formula I, the pharmaceutical compositions comprising the same and their uses in the preparation of an anti- tumor medicament.
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Page/Page column 11
(2008/12/08)
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- Quinazoline Derivatives, Preparation Methods and Uses Thereof
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The present invention has disclosed a compound of formula I and a pharmaceutically acceptable salt or a solvate thereof, wherein the substituents are as defined in the description. The invention has also disclosed a method for preparing the compound of formula I, the pharmaceutical compositions comprising the same and their uses in the preparation of an anti-tumor medicament.
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Page/Page column 7
(2009/01/20)
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- PROCESS FOR PRODUCING QUINAZOLIN-4-ONE DERIVATIVE
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A process for producing a quinazolin-4-one compound having the formula: [wherein R1, R2, R3 and R4 each represents a group not participating in the below-mentioned reaction, and R1, R2, R3 and R4 can be combined together to form a ring] which comprises reacting an anthranilic acid derivative having the formula: [wherein R5 is a hydrogen atom or a hydrocarbyl group] with a formic acid derivative in the presence of an ammonium carboxylate.
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- NOVEL QUINAZOLINE DERIVATIVES
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Quinazoline derivatives represented by the general formula (1) or a pharmaceutically acceptable salt thereof in said formula R1is nitro or halogen; R2and R4are each hydrogen, C1-4alkyl, carboxyl, or C2-5alkoxycarbonyl; R3is hydrogen, amino, optionally substituted C1-4alkyl, C1-4alkanoyl, or C2-5alkoxycarbonyl; W is carbon or nitrogen; and m is 0 to 2.
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- Structure-activity relationships of quinazoline derivatives: Dual-acting compounds with inhibitory activities toward both TNF-α production and T cell proliferation
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We synthesized 4-chlorophenethylaminoquinazoline derivatives and evaluated their inhibitory activities toward both TNF-α production and T cell proliferation responses. Compound 2f, containing a piperazine ring at the C(7)-position of the quinazoline ring, exhibited more potent inhibitory activities toward both than the lead compound 1a. A smaller N-substituent in the piperazine ring was required for inhibition of TNF-α production.
- Tobe, Masanori,Isobe, Yoshiaki,Tomizawa, Hideyuki,Matsumoto, Mitsuhiro,Obara, Fumihiro,Nagasaki, Takahiro,Hayashi, Hideya
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p. 545 - 548
(2007/10/03)
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- Aniline derivatives
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The invention concerns aniline derivatives of formula I STR1 wherein m is 1, 2 or 3, n is 0, 1, 2 or 3, Q is phenyl or naphthyl or a 5- or 6-membered heteroaryl moiety containing 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulfur, and X, R1 and R2 are defined in the claims; or pharmaceutical compositions containing them, and the methods of using the compounds as tyrosine kinase inhibitors and for the treatment of proliferative diseases such as cancer.
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- Tricyclic derivatives
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The invention concerns tricyclic derivatives of the formula I STR1 wherein R 1 and R 2 together form an optionally substituted group of the formula --N CH--NH--, --N CH--O--, --N CH--S--, --N N--NH--, --NH--N CH--, --NH--CH CH--. --NH--CO--NH--, --NH--CO--O--, --NH--CO--S--, --NH--NH--CO--, --N CH--CH N--, --N N--CH CH--, --N CH--N CH--, --N CH--CH N--, --NH--CO--CH CH-- or --N CH--CO--NH--; m is 1, 2 or 3 and R 3 includes hydrogen, halogeno and (1-4C)alkyl; or a pharmaceutically-acceptable salt thereof;processes for their preparation; pharmaceutical compositions containing them; and the use of the receptor tyrosine kinase inhibitory properties of the compounds. in the treatment of cancer.
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- Quinazoline derivatives
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The invention concerns quinazoline derivatives of the formula I STR1 wherein R 1 includes hydroxy, amino, hydroxyamino, (1-4C)alkoxy, (1-4C)alkylamino and di-[(1-4C)alkyl]amino;R 3 is halogeno;n is 1, 2 or 3 and R 2 includes hydrogen, hydroxy, halogeno and (1-4C)alkyl;or a pharmaceutically-acceptable salt thereof;processes for their preparation; pharmaceutical compositions containing them; and the use of the receptor tyrosine kinase inhibitory properties of the compounds in the treatment of cancer.
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