- Visible-Light-Induced Radical Difluoromethylation/Cyclization of Unactivated Alkenes: Access to CF2H-Substituted Quinazolinones
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A mild and efficient visible-light-induced radical difluoromethylation/cyclization of unactivated alkenes toward the synthesis of substituted quinazolinones with easily accessible difluoromethyltriphenylphosphonium bromide has been developed. The transformation has the advantages of wide functional group compatibility, a broad substrate scope, and operational simplicity. The benign protocol offers a facile access to pharmaceutically valuable difluoromethylated polycyclic quinazolinones.
- Chen, Xiaoyu,Liu, Bo,Pei, Congcong,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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supporting information
p. 7787 - 7791
(2021/10/20)
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- Design, synthesis and biological evaluation of novel pyrimidine, 3-cyanopyridine and m-amino-N-phenylbenzamide based monocyclic EGFR tyrosine kinase inhibitors
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36 new compounds with the typical skeleton of 4-anilino-5-vinyl/ethynyl pyrimidine, 4-anilino-3-cyano-5-vinyl/ethynyl/phenyl pyridine, and m-amino-N-phenylbenzamide, are designed, synthesized and selectively tested on EGFR, ErbB-2 kinases, and A-549, HL60 cells growth inhibition. Results from the bioactivity and chemical structures yield preliminary structure-activity relationships (SARs). The most potent 5-ethynylpyrimidine derivative 20a has an IC50 value of 45 nM to EGFR kinase. Several compounds of other series also show IC50 values 1 μM for EGFR and 5 μM for A-549 and HL60 cells growth inhibition.
- Mao, Yongjun,Zhu, Wenxiu,Kong, Xiaoguang,Wang, Zhen,Xie, Hua,Ding, Jian,Terrett, Nicholas Kenneth,Shen, Jingkang
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p. 3090 - 3104
(2013/07/11)
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- 5-Alkynyl-pyridines
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This invention relates to 5-alkynyl-pyridine of general formula (I) their use as inhibitors of the activity of PI3Kalpha, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer. The groups R1 to R6 and n have the meanings given in the claims and in the specification
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Paragraph 0175; 0176
(2013/03/26)
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- NEW 5-ALKYNYL-PYRIDINES
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5-alkynyl-pyridine of general formula (I) which are inhibitors of the activity of PI3K alpha, and their use in the treatment of diseases characterized by excessive or abnormal cell proliferation, such as cancer.
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Paragraph 0203; 0204
(2013/03/26)
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- 5-ALKYNYL-PYRIMIDINES
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The present invention encompasses compounds of general formula (1) wherein R1 to R4 R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.
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Page/Page column 8
(2012/02/06)
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- NEW 5-ALKYNYL-PYRIDINES
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This invention relates to 5-alkynyl-pyridine of general formula (I) their use as inhibitors of the activity of PI3Kalpha, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer. The groups R1 to R6 and n have the meanings given in the claims and in the specification.
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Page/Page column 50
(2012/08/08)
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- NEW 5-ALKYNYL-PYRIDINES
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This invention relates to 5-alkynyl-pyridine of general formula (I) their use as inhibitors of the activity of P13Kalpha, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer. The groups R1 to R6 and n have the meanings given in the claims and in the specification.
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Page/Page column 46
(2012/08/08)
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- 5-ALKYNYL-PYRIMIDINES
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The present invention encompasses compounds of general formula (1) wherein R1 to R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.
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Page/Page column 7
(2012/02/06)
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- Scalable synthesis of 4-substituted 5-bromo-6-methylpyrimidines
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Small halogenated heteroaromatic ring systems are valuable monomers, which can enable rapid access to novel and desirable chemical space, in part because of their ability to participate in established cross coupling chemistry such as the Heck, Stille, and Suzuki reactions. Described is a practical, scalable synthetic route towards the construction of a diverse array of 4-substituted 5-bromo-6-methylpyrimidine monomers. Georg Thieme Verlag Stuttgart · New York.
- Wang, Zhihan,Chi, Yushi,Harris, Anthony R.,Gray, David,Davoren, Jennifer E.
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experimental part
p. 1529 - 1531
(2011/06/23)
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- Synthesis and evaluation of novel pyrimidine-based dual EGFR/Her-2 inhibitors
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A structure-activity relationship study of 4-anilinopyrimidines for dual EGFR/Her-2 inhibitor has resulted in the identification of 4-anilino-5-alkenyl or 5-alkynyl-6-methylpyrimidine derivatives that have exhibited effective inhibitory activity against both enzymes. The presence of 5-alkenyl or 5-alkynyl moiety bearing terminal hydrophilic group played important role for inhibition of these enzymes. Selected compounds in the series demonstrated some activity against Her-2 dependent cell line (BT474).
- Suzuki, Naoyuki,Shiota, Takeshi,Watanabe, Fumihiko,Haga, Norihiro,Murashi, Takami,Ohara, Takafumi,Matsuo, Kenji,Oomori, Naoki,Yari, Hiroshi,Dohi, Keiji,Inoue, Makiko,Iguchi, Motofumi,Sentou, Jyunko,Wada, Tooru
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scheme or table
p. 1601 - 1606
(2011/05/11)
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- A method for the reductive scission of heterocyclic thioethers
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A mild, chemoselective, and generally high-yielding method for the reductive scission of heterocyclic thioethers is described. Suitable heterocycles have a thioether substituent at the 2-position relative to a ring heteroatom. The convenient and straightforward method is demonstrated with reactants which are not compatible with the standard Raney nickel conditions such as sulfides, sulfones, and thiophenes. In addition, benzyl esters, benzyl amides, and benzyl carbamates are tolerated by the reductive reaction conditions.
- Graham, Thomas H.,Liu, Wensheng,Shen, Dong-Ming
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supporting information; experimental part
p. 6232 - 6235
(2012/01/03)
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- 5-ALKYNYL PYRIMIDINES AND THEIR USE AS KINASE INHIBITORS
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The present invention encompasses compounds of general formula (1) wherein R1 to R4 R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.
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Page/Page column 21-22
(2011/08/21)
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- Xanthine oxidase-activated prodrugs of thymidine phosphorylase inhibitors
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Thymidine phosphorylase (TP) is over-expressed in various tumour types and plays an important role in tumour angiogenesis, growth, invasion and metastasis. The enzymatic activity of TP is required for the angiogenic effect of TP, therefore, inhibitors of TP are of significant interest in cancer chemotherapy. A series of xanthine oxidase (XO) activated prodrugs of known inhibitors of TP have been designed and synthesized with the ultimate intent of improving tumour selectivity and pharmacokinetic characteristics. These prodrugs were not inhibitors of TP, but were selectively oxidized by XO at C-2 and/or C-4 of the uracil ring moiety to generate the desired TP inhibitor. Molecular modelling of both the TP inhibitors and XO-activated prodrugs rationalized their binding in the active site of the human TP crystal structure.
- Reigan, Philip,Gbaj, Abdul,Stratford, Ian J.,Bryce, Richard A.,Freeman, Sally
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p. 1248 - 1260
(2008/09/21)
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- Unsymmetrical cyclic diamine compound
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A cyclic diamine compound of formula (1): wherein A is (CH2)n, (CH2)n—CH═CH, CO—(CH2)n or CO—(CH2)n—CH═CH, in which n is a number of 0 to 3; Z represents a formula (2) or (3): in which R1, R2, R4, R5 and R6 are individually a hydrogen atom, alkyl group, alkoxy group, halogen atom or nitro group; R3 is a hydrogen atom, alkyl group, alkoxy group, halogen atom, nitro group, naphthyl group, or phenyl group which may be substituted by 1 to 3 substituents selected from the group consisting of alkyl groups, alkoxy groups, halogen atoms, a nitro group and a phenyl group; and X and Y are individually CH or a nitrogen atom; and m is 1 or 2; an acid-addition salt thereof, or a hydrate thereof, and a medicine containing such a compound.
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- Cyclic diamine compound with 6-membered ring groups
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A cyclic diamine compound of formula (1): wherein A is a single bond or C≡C; X and Y are individually CH or a nitrogen atom; m is 1 or 2; and n is a number of 1 to 5; an acid-addition salt thereof, or a hydrate thereof. The compound has excellent inhibitory effects on both cell adhesion and cell infiltration and is useful as a medicine for prevention or treatment of diseases such as allergy, asthma, rheumatism, arteriosclerosis and inflammation.
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- Oxidation of substituted 2-thiouracils and pyrimidine-2-thione with ozone and 3,3-dimethyl-1,2-dioxirane
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Ozone and 3,3-dimethyl-1,2-dioxirane react with substituted 2-thiouracils and pyrimidine-2-thione to afford several interesting desulfurized products. The effect of the solvent, protic as opposed to nonprotic, on the course of oxidation was striking.
- Claudia, Crestini,Mincione, Enrico,Saladino, Raffaele,Nicoletti, Rosario
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p. 3259 - 3272
(2007/10/02)
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- Ozonation of substituted 2-thiouracils and pyrimidine-2-thione
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The ozonation of substituted 2-thiouracils and pyrimidine-2-thione is reported; this provides a new method for the synthesis of several pyrimidine derivatives.
- Crestini, Claudia,Saladino, Raffaele,Nicoletti, Rosario
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p. 1631 - 1634
(2007/10/02)
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- Process for preparing 4-hydroxypyrimidine
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A process for preparing a 4-hydroxypyrimidine of Formula III: STR1 wherein R1 and R2 each represent a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, a cycloalkyl group having 3 to 10 carbon atoms or an aralkyl group having 2 to 10 carbon atoms, and R4 represents hydrogen an alkyl group having 1 to 10 carbon atoms, a cycloalkyl group having 3 to 10 carbon atoms, an aralkyl group having 7 to 10 carbon atoms or an aryl group having 6 to 10 carbon atoms, which comprises subjecting a 3-amino-2-unsaturated carboxylate of Formula I: STR2 wherein R1 and R2 are as defined above and R3 represents an alkyl group having 1 to 10 carbon atoms, a cycloalkyl group having 3 to 10 carbon atoms or an aralkyl group having 7 to 10 carbon atoms, and a carboxylic acid amide of Formula II: wherein R4 is as defined above, to reaction with each other in the presence of a base.
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- The Chemistry of 4-Pyrimidinones: Acetylation and Ring-Opening Reactions
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4(3H)-Pyrimidinone, as well as its 5-acetoxy and 5-methoxy derivatives, undergoes selective acetylation at N-1 when treated with acetic anhydride.In the presence of water, these 1-acetylpyrimidines undergo spontaneous covalent hydration at C-2 and cleavage of the 1,2-bond to give crystalline cis-3-acetylamino-N-formylacrylamides, generally in good yield.In contrast, the 6-methyl derivative of 4(3H)-pyrimidinone forms an equilibrium mixture of acylated products that undergo the ring opening process to only a very limited extent, the major product (11percent) being the 3-formylamino-N-acetylacrylamide derivative formed via N-3 acetylation and cleavage of the 2,3-bond.
- Sodum, Rama S.,Klein, Robert S.,Otter, Brian A.
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p. 1239 - 1243
(2007/10/02)
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- EXTRUSION REACTIONS-VII. FORMATION OF 2,5-DIARYL-1,4-DITHIINS AND 2-ACETONYL THIAZOLES
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ω-(2,6-Dimethyl-4-pyrimidinylthio-(4), 2-methyl-4-quinazolinylthio-(9), and 4-oxo-2-quinazolinylthio)-(10) acetophenones with hydrochloric or perchloric acid provide 2,5-diaryl-1,4-dithiins (7) whereas ω-(6-methyl-4-pyrimidinylthio)acetophenones (11) with aq HCl/HClO4 or POCl3 followed by hydrolysis provide 1-(4-aryl-2-thiazolyl)-2-propanones (12).Likewise, 2-(6-methyl-4-pyrimidinylthio)cyclohexanone (13) give the thiazole derivative (14).
- Singh, Harjit,Aggarwal, Sunil K.,Malhotra, Nageshwar
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p. 4941 - 4946
(2007/10/02)
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- TAUTOMERIC EQUILIBRIA OF 2(4)-MONOOXOPYRIMIDINES IN THE GAS PHASE, IN LOW-TEMPERATURE MATRICES AND IN SOLUTION
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IR absorption spectra, including the NH, OH and C=O stretching regions, have been recorded for 4-oxo-6-methyl- and 2-oxo-4,6-dimethyl pyrimidines and several related derivatives, in the gas phase, in low-temperature inert matrices, and in several liquid solvents.All the 4-oxopyrimidines in the gas phase, and 4-oxo-6-methylpyrimidine in low-temperature matrices, exhibit comparable populations of the keto and enol forms.By contrast the 2-oxopyrimidines are predominantly in the enol forms.Both classes of compounds are predominantly in the keto form in liquid solvent systems.The tautomeric equilibrium constant (KT) in the vapour phase for 4-oxo-2,6-dimethylpyrimidine is about 2, and for the other 4-oxopyrimidines is about 1.For 4-oxo-6-methylpyrimidine, the equilibrium constant in inert matrices varies slightly with the activity of the matrix gas, with the keto tautomer favoured in the more active matrix.From the temperature-dependence of KT, the free energy difference between the two tautomeric forms of 4-oxo-6-methylpyrimidine in the vapour phase has been calculated.Heats of vaporization have also been calculated for the various compounds and related to their abilities to associate by hydrogen bonding in the condensed phase.The UV absorption spectra of some of the foregoing have also been recorded in the gas phase, but these were of only limited value in studies of tautomeric equilibria, as compared to the IR spectra.
- Nowak, M. J.,Szczepaniak, K.,Barski, A.,Shugar, D.
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