- Intramolecular Ring-Opening of Oxetanes: Access to Functionalised Hydroxymethyl 2,3-Dihydroimidazo[1,2- c ]quinazolines
-
An intramolecular oxetane ring-opening was developed, affording novel 2-(hydroxymethyl)-2,3-dihydroimidazo[1,2- c ]quinazolines from N -(3-methyloxetan-3-yl)quinazolin-4-amines under mild conditions. The resulting medicinally relevant tricyclic scaffolds were synthesised in good yields with diverse substituents. Moreover, reaction optimisation led to the development of a one-pot procedure.
- Bagal, Sharan K.,Bodnarchuk, Michael S.,King, Thomas A.,Luo, Xuehong,McKerrecher, Darren,Steward, Oliver R.,Wang, Peng
-
supporting information
p. 502 - 506
(2020/03/13)
-
- 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.
- Zhang, Yuchun,Niu, Pengpeng,Wen, Quanwu,Sun, Lin,Wang, Weili,Xu, Shengguang,Liu, Gang
-
p. 497 - 502
(2019/11/03)
-
- 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.
- Lan, Ta Thu,Anh, Duong Tien,Pham-The, Hai,Dung, Do Thi Mai,Park, Eun Jae,Jang, Sun Dong,Kwon, Joo Hee,Kang, Jong Soon,Thuan, Nguyen Thi,Han, Sang-Bae,Nam, Nguyen-Hai
-
-
- Hetero-aromatic compound and its use in medicine
-
The invention provides a hetero-aromatic compound or a stereisomer, geometric isomer, tautomer, despinner, nitrogen oxide, hydrate, solvate, metabolite, metabolism precursor and pharmaceutically acceptable salt or prodrug thereof, which is used for treating proliferative diseases. The invention also discloses a pharmaceutical composition containing the compound and an application of the compound or pharmaceutical composition thereof in preparation of a medicine for treating proliferative diseases.
- -
-
Paragraph 1729; 1732-1734
(2019/07/04)
-
- A process for preparing the lapatinib method and intermediate (by machine translation)
-
A through novel intermediate to prepare lapatinib or its pharmaceutically acceptable salt of the method, the method using 5 - bromo furfural and and 2 - nitrobenzene formic acid as the starting material through the Suzuki coupling reaction. This kind of synthetic pulls the handkerchief to raise nepal method can reach 32.2% overall yield. (by machine translation)
- -
-
Paragraph 0038; 0039
(2018/04/03)
-
- Novel compound having tumor diagnosis or tumor growth inhibitory activity on EGFR mutant and medical uses comprising the same
-
The present invention relates to a novel compound having activities of diagnosing a tumor having an epidermal growth factor receptor (EGFR) mutant and inhibiting tumor growth, a salt thereof, a contrast medium comprising the same, and a pharmaceutical composition for treating or preventing EGFR-related cancer diseases comprising the same as an active ingredient. The novel compound or the salt thereof according to the present invention does not inhibit a wild type EGFR but selectively inhibits an EGFR variant, and thus can treat and prevent EGFR-related cancer diseases, including lung cancer, colon cancer or breast cancer. Particularly, the compound or the salt thereof according to the present invention can effectively treat and prevent non-small cell lung cancer upon which Iressa or Tarceva cannot have any significant effect. In addition, the compound or the salt thereof according to the present invention responses with a target of Gefitinib-sensitive cancer cells or cancer cells showing EGFR T790M mutation rather than wild type EGFR over-expressed cancer cells, and thus can be used advisably as a contrast medium capable of clearly differentiating EGFR-related cancer cells by imaging.COPYRIGHT KIPO 2017
- -
-
Paragraph 0067; 0071; 0072
(2017/04/03)
-
- Compounds capable of inhibiting ErbB/HDAC and preparation method thereof, and pharmaceutical composition comprising compounds and application thereof
-
The invention relates to compounds capable of inhibiting ErbB/HDAC and a preparation method thereof, and a pharmaceutical composition comprising the compounds and application thereof. The compounds are disclosed as Formula 1. The compounds or pharmaceutically acceptable salts, solvates, esters, acids, metabolites or prodrugs thereof, or the pharmaceutical composition comprising the compounds can be used for preparing ErbB kinases and HDAC activity inhibitors and also preparing ErbB-kinase/HDAC-activated mediated disease curatives.
- -
-
Paragraph 0075; 0076; 0077; 0078
(2017/07/31)
-
- Synthesis and investigation of novel 6-(1,2,3-triazol-4-yl)-4-aminoquinazolin derivatives possessing hydroxamic acid moiety for cancer therapy
-
By merging the critical pharmacophore of EGFR/HER2 and HDAC inhibitors into one compound, a novel series of EGFR, HER-2, and HDAC multitarget inhibitors were synthesized. Compounds 9a–l contained 4-anilinoquinazolines with C-6 triazole-linked long alkyl chains of hydroxamic acid and displayed excellent inhibition against these enzymes (compound 9d exhibited the best inhibitory potency on wild-type EGFR, HDAC1, and HDAC6 with IC50values 0.12 nM, 0.72 nM and 3.2 nM individually). Furthermore, compounds 9b and 9d potently inhibited proliferation of five human cancer cell lines (with IC50values between 0.49 and 8.76 μM). Further mechanistic study revealed that compound 9d also regulated the phosphorylation of EGFR and HER2 and histone H3 hyperacetylation on the cellular level and induced remarkable apoptosis in BT-474 cells. Therefore, our study suggested that a system network-based multi-target drug design strategy might provided an alternate drug design method, by taking into account the synergy effect of EGFR, HER-2 and HDAC.
- Ding, Chao,Chen, Shaopeng,Zhang, Cunlong,Hu, Guangnan,Zhang, Wei,Li, Lulu,Chen, Yu Zong,Tan, Chunyan,Jiang, Yuyang
-
-
- Discovery of ErbB/HDAC inhibitors by combining the core pharmacophores of HDAC inhibitor vorinostat and kinase inhibitors vandetanib, BMS-690514, neratinib, and TAK-285
-
By combining the core pharmacophores of HDAC inhibitor vorinostat and kinase inhibitors vandetanib, BMS-690514, neratinib, and TAK-285 with 1,2,3-triazole as linker, eight novel 6-substituted-4-aminoquinazolin derivatives were synthesized and characterized by 1H NMR, 13C NMR, and high resolution mass spectrometry. Their inhibitory activities against five enzymes (VEGFR2, HER2, EGFR, HDAC1, and HDAC6) and five cancer cell lines (A549, BT-474, A431, SK-BR-3, and NCI-H1975) were evaluated. The bioassay results show that the introduction of triazole linked vorinostat-like segment dramatically changed the selectivity profiles of newly synthetic compounds relative to vandetanib, BMS-690514, neratinib, and TAK-285. Among them, compound 6b exerted outstanding enzymatic and cellular activities through its simultaneous and synergistic inhibitions on multiple pathways, which might have the great potential to confer the better benefits than single-targeted inhibitors in cancer therapy.
- Ding, Chao,Li, Dan,Wang, Yan-Wei,Han, Sai-Sai,Gao, Chun-Mei,Tan, Chun-Yan,Jiang, Yu-Yang
-
p. 1220 - 1227
(2017/06/19)
-
- Kuikui zuo lin kind of target anti- tumor compound and its preparation method and application (by machine translation)
-
The present invention provides a chemical formula (I) indicated by the kuikui zuo lin kind of target anti- tumor compound and its preparation method, in particular to EGFR, HER - 2 and DNA multi-target anti- tumor compounds, also provides a method for preparing the same and in the application of the anti-tumor medicament. Studies show that the compounds of the invention have significant anti-tumor activity, metabolic stability relative to the reference substance EMB - 3 is improved notably. (by machine translation)
- -
-
Paragraph 0012; 0113
(2017/08/31)
-
- Sulfur-containing 6 - furan [...] -4 - amine compound and process for preparation thereof and use
-
The invention belongs to the field of medicine synthesis, relates to a chemical compound containing sulphur-6-furan group chinazoline-4-amine with a general formula (I) shown in the Specification, in particular to a N-[3-chlorine-4-[(3-fluorophenyl) methoxyl] phenyl]-6-(2-furyl) chinazoline-4-amine chemical compound with a sulpho-quaternary heterocycle or a loop-coil structure, and a preparation method and medical application thereof. An external anti-tumour activity test result shows that the chemical compound has good anti-tumour acitivity, and can be further prepared into a new anti-tumour medicine.
- -
-
Paragraph 0017; 0027; 0028
(2016/10/09)
-
- AMINO QUINAZOLINES AS KINASE INHIBITORS
-
Disclosed are compounds having the formula (Formula I)): wherein R1, R2, R3 and Z are as defined herein, and methods of making and using the same.
- -
-
Paragraph 0156; 0157
(2016/12/12)
-
- 6-furan [...] -4-amine compound and process for preparation thereof and use
-
The invention belongs to the field of drug synthesis, and relates to 6-furyl quinazoline-4-amines in the general formula I (refer to the Specification), particularly to an N-[3-chlorine-4-[(3-fluorophenyl) methoxyl] phenyl]-6-(2-furyl) quinazoline-4-amine compound with a quaternary heterocyclic ring or a spiral structure, as well as a preparation method and medical application thereof. The compound provided by the invention is subjected to the in vitro EGFR and HER-2 kinase inhibitory activity and antineoplastic activity tests, and the result shows that the compound has excellent EGFR and HER-2 kinase inhibitory activity, and can be used for further preparing a novel antitumor drug.
- -
-
Paragraph 0054; 0055
(2017/04/03)
-
- INHIBITORS OF CDK8/19 FOR USE IN TREATING ESTROGEN RECEPTOR POSITIVE BREAST CANCER
-
The invention provides a selective inhibitor of CDK8/19 for use in a method of treating a patient having estrogen receptor positive (ER+) breast cancer, including breast cancer that is resistant to antiestrogen therapy. In some embodiments, the selective inhibitor of CDK8/19 is administered in combination with antiestrogen therapy. In some embodiments, the selective inhibitor of CDK8/19 is administered to ER + HER2+ breast cancer patients in combination with HER2-targeting drugs.
- -
-
Page/Page column 5
(2014/09/16)
-
- AMINO QUINAZOLINES AS KINASE INHIBITORS
-
Disclosed are compounds having the formula (Formula (I)): wherein R1, R2, R3, and Z are as defined herein, and methods of making and using the same.
- -
-
Page/Page column 55; 56
(2013/03/26)
-
- CDK8/CDK19 SELECTIVE INHIBITORS AND THEIR USE IN ANTI-METASTATIC AND CHEMOPREVENTATIVE METHODS FOR CANCER
-
The invention relates to the compounds and methods for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds and methods for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI -related diseases. The invention provides new compounds having improved solubility and/or potency, and methods for their use. In various aspects, the invention relates to the treatment of cancer. The invention provides methods for chemoprevention and prevention of tumor recurrence or metastasis. The invention further provides diagnostic techniques for treatment for certain cancer types. The invention utilizes specific inhibitors of CDK8/19 and/or measurement of CDK8 levels in a patient.
- -
-
Page/Page column 18
(2013/08/15)
-
- METHODS FOR DETECTING AND REDUCING IMPURITIES OF LAPATINIB AND SALTS THEREOF
-
Impurities of lapatinib such as N-{3-chloro-4-[(2-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl]quinazoline-4-amine compound of formula (I) or a salt thereof: and analytical methods for identifying and quantifying such impurities of Lapatinib and salts thereof are provided. Also provided is Lapatinib containing less than about 0.05 percent of this and related impurities and methods for preparing such pure forms of Lapatinib.
- -
-
-
- PHOSPHORUS CONTAINING QUINAZOLINE COMPOUNDS AND METHODS OF USE
-
Disclosed are novel quinazoline derivatives containing phosphorus substitutions and methods for the treatment of hyperproliferative diseases (e.g. cancer) using the compounds. These compounds are type I receptor protein kinase inhibitors useful in treating disorders related to abnormal protein kinase activities such as cancer and inflammation in mammals. Also disclosed are pharmaceutical compositions containing the compounds, methods for the preparation of the compounds and their pharmaceutically acceptable salts.
- -
-
Page/Page column 43
(2011/02/24)
-
- OPTICALLY PURE QUINAZOLINE COMPOUNDS
-
Optical pure quinazoline compounds, especially compounds of the general formula (I), wherein R1 and Y are defined as the specification, preparation methods of them, pharmaceutical compositions containing them and their uses are provided. Compounds of the general formula (VII), which are intermediates in the synthesis of the compounds of the general formula (I), wherein Ar, R2, R3, m, n, T and carbon atom with * are defined as the specification, are also provided.
- -
-
Page/Page column 7
(2011/11/30)
-
- Novel chimeric histone deacetylase inhibitors: A series of lapatinib hybrides as potent inhibitors of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and histone deacetylase activity
-
Reversible lysine-specific acetylation has been described as an important posttranslational modification, regulating chromatin structure and transcriptional activity in the case of core histone proteins. Histone deacetylases (HDAC) are considered as a promising target for anticancer drug development, with 2a as pan-HDAC inhibitor approved for cutanous T-cell lymphoma therapy and several other HDAC inhibitors currently in preclinical and clinical development. Protein kinases are a well-established target for cancer therapy with the EGFR/HER2 inhibitor 5 approved for treatment of advanced, HER2 positive breast cancer as a prominent example. In the present report, we present a novel strategy for cancer drug development by combination of EGFR/HER2 kinase and HDAC inhibitory activity in one molecule. By combining the structural features of 5 with an (E)-3-(aryl)-N-hydroxyacrylamide motif known from HDAC inhibitors like 1 or 3, we obtained selective inhibitors for both targets with potent cellular activity (target inhibition and cytotoxicity) of selected compounds 6a and 6c. By combining two distinct pharmacologically properties in one molecule, we postulate a broader activity spectrum and less likelihood of drug resistance in cancer patients.
- Mahboobi, Siavosh,Sellmer, Andreas,Winkler, Matthias,Eichhorn, Emerich,Pongratz, Herwig,Ciossek, Thomas,Baer, Thomas,Maier, Thomas,Beckers, Thomas
-
supporting information; experimental part
p. 8546 - 8555
(2011/02/28)
-
- Discovery and structure-activity relationships of a novel class of quinazoline glucokinase activators
-
We describe design, syntheses and structure-activity relationships of a novel class of 4,6-disubstituted quinazoline glucokinase activators. Prototype quinazoline leads (4 and 5) were designed based on the X-ray analyses of the previous 2-aminobenzamide lead classes. Modifications of the quinazoline leads led to the identification of a potent GK activator (21d).
- Iino, Tomoharu,Sasaki, Yasuhiro,Bamba, Makoto,Mitsuya, Morihiro,Ohno, Akio,Kamata, Kenji,Hosaka, Hideka,Maruki, Hiroko,Futamura, Mayumi,Yoshimoto, Riki,Ohyama, Sumika,Sasaki, Kaori,Chiba, Masato,Ohtake, Norikazu,Nagata, Yasufumi,Eiki, Jun-ichi,Nishimura, Teruyuki
-
scheme or table
p. 5531 - 5538
(2010/04/05)
-
- Processes and intermediates for the preparation of N4-phenyl-quinazoline-4-amine derivatives
-
This invention provides compounds of Formula (I), wherein B, G, A, E, R1, R2, R3, m and n are as defined herein, which are useful as type I receptor tyrosine kinase inhibitors, and methods of use thereof in the treatment of hyperproliferative disorders in mammals.
- -
-
Page/Page column 61
(2009/09/05)
-
- 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
- -
-
Page/Page column 69
(2009/06/27)
-
- 4-Aminoquinazoline derivatives and methods of use thereof
-
This invention relates to novel 4-aminoquinazolines, their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering inhibitors of the EGFR and HER-2.
- -
-
Page/Page column 13-14
(2008/06/13)
-
- MULTI-FUNCTIONAL SMALL MOLECULES AS ANTI-PROLIFERATIVE AGENTS
-
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.
- -
-
Page/Page column 169
(2008/06/13)
-
- CANCER TREATMENT METHOD
-
The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and at least one additional anti-neoplastic compound. In particular, the method relates to a methods of treating cancers by administration of N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2-(methanesulphonyl) ethyl]amino} methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof in combination with at least one additional anti-neoplastic compound.
- -
-
Page/Page column 23
(2008/12/06)
-
- Highly functionalised sulfur-based silica scavengers for the efficient removal of palladium species from active pharmaceutical ingredients
-
The use of multidentate sulfur-based silica scavengers 1,2, and 3 as highly effective adsorbents for the removal of precious metals, specifically palladium residues in this paper, from highly functionalised synthetic intermediates and APIs is described. The synthesis and purification of the polar and electron-rich reaction products, containing multiple functional groups, from palladium-catalysed removals of commonly used protecting groups such as benzyl, benzyloxycarbonyl, and allyloxycarbonyl and Sonogashira, Suzuki, Heck, and Buchwald-Hartwig coupling reactions is reported. The significant levels of residual palladium species, typically associated with these reaction products, are successfully and rapidly removed to below acceptable regulatory levels, of less than 5 ppm, by simple, unoptimised treatment with the designed silica scavengers at room temperature. Performance aspects, including broad solvent compatibility, excellent stability, and high metal affinity, combined with large-scale availability, ease of handling, and minimal loss of API make these silica scavengers particularly useful to process development groups.
- Galaffu, Nicola,Man, Siud Pui,Wilkes, Robin D.,Wilson, John R. H.
-
p. 406 - 413
(2012/12/31)
-
- ALKYLQUINOLINE AND ALKYLQUINAZOLINE KINASE MODULATORS
-
The invention is directed to alkylquinoline and alkylquinazoline compounds of Formula I: wherein R1, R2, R3, B, Z, G, Q and X are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of FLT3 and/or c-kit and/or TrkB, the use of such compounds to reduce or inhibit kinase activity of FLT3 and/or c-kit and/or TrkB in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 and/or c-kit and/or TrkB. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.
- -
-
Page/Page column 58-59
(2010/11/25)
-
- CANCER TREATMENT METHOD
-
The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and at least one additional EGFR and/or erbB-2 inhibitor. In particular, the method relates to methods of treating cancers by administration of N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2-(methanesulphonyl) ethyl]amino} methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof in combination with at least one additional EGFR and/or erbB-2 inhibitor.
- -
-
Page/Page column 23
(2010/10/20)
-
- Cyanoguanidines and cyanoamidines as ErbB2 and EGFR inhibitors
-
Cyanoguanidine quinazoline and cyanoamidine quinazolamine derivatives that are useful in the treatment of hyperproliferative diseases are disclosed. Methods of treating hyperproliferative diseases in mammals are also disclosed.
- -
-
Page/Page column 6
(2008/06/13)
-
- Evaluation of kilogram-scale Sonagashira, Suzuki, and Heck coupling routes to oncology candidate CP-724,714
-
The synthesis of the anti-cancer compound 2-methoxy-N-(3-{4-[3-methyl-4-(6- methyl-pyridin-3-yloxy)phenylamino]quinazolin-6-yl}-E-allyl)acetainide (CP-724,714) (1) on multikilogram scale using several different synthetic routes is described. Application of the Sonogashira, Suzuki, and Heck couplings to this synthesis was investigated to identify a safe, environmentally friendly, and robust process for the production of this drug candidate. A convergent and selective synthesis of the candidate was identified which utilizes a Heck coupling of a protected allylamine to install the critical olefin.
- Ripin, David H. Brown,Bourassa, Dennis E.,Brandt, Thomas,Castaldi, Michael J.,Frost, Heather N.,Hawkins, Joel,Johnson, Phillip J.,Massett, Stephen S.,Neumann, Karin,Phillips, James,Raggon, Jeffery W.,Rose, Peter R.,Rutherford, Jennifer L.,Sitter, Barbara,Stewart III, A. Morgan,Vetelino, Michael G.,Wei, Lulin
-
p. 440 - 450
(2012/12/25)
-
- CANCER TREATMENT METHOD
-
The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and at least one additional anti-neoplastic compound. In particular, the method relates to a methods of treating cancers by administration of N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2-(methanesulphonyl) ethyl]amino} methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof in combination with at least one additional anti-neoplastic compound.
- -
-
Page/Page column 23
(2008/06/13)
-
- CANCER TREATMENT METHOD
-
The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and pharmaceutical compositions containing the same. In particular, the method relates to a methods of treating cancers which are mediated by the tyrosine kinases EGFR and/or erbB2 by administration of N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2-(methanesulphonyl) ethyl]amino} methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof.
- -
-
Page/Page column 30
(2008/06/13)
-
- Anilinoquinazaolines as protein tyrosine kianse inhibitors
-
Heteroaromatic compounds are described, methods for their preparation, pharmaceutical compositions containing them, methods of use, and their use in medicines. In particular, the invention relates to quinazoline and pyridopyrimidine derivatives which exhibit protein tyrosine kinase inhibition.
- -
-
Page/Page column 45
(2008/06/13)
-
- PHENYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
-
The present invention is directed to phenylalanine derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
- -
-
-
- PROCESS FOR PRODUCING 4-AMINOQUINAZOLINE COMPOUND
-
A 4-aminoquinazoline derivative can be obtained by the steps of reacting quinazolin-4-one or its derivative with a chlorinating agent in a first organic solvent in the presence of an organic base, and subsequently reacting the reaction product with an amine compound represented by the formula R5-NH-R6 (each of R5 and R6 represents hydrogen or an optionally substituted hydrocarbyl group) in the presence of a second organic solvent.
- -
-
-
- Heteroaromatic bicyclic derivatives useful as anticancer agents
-
The invention relates to compounds of the formula 1 and to pharmaceutically acceptable salts and solvates thereof, wherein A, X, R1, R3and R4are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals by administering the compounds of formula 1 and to pharmaceutical compositions for treating such disorders which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.
- -
-
-
- Substituted bicyclic derivatives useful as anticancer agents
-
The invention relates to compounds of the formula 1 and to pharmaceutically acceptable salts and solvates thereof, wherein A, X, R1, R3and R4are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals with administering the compounds of formula 1 and to pharmaceutical compositions for treating such disorders which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.
- -
-
-