- Compounds containing pyrimidine heterocyclic structures and preparation methods and applications thereof
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Compounds containing pyrimidine heterocyclic structures and preparation methods and applications thereof, belonging to the field of pharmaceutical technology, the present invention relates to compounds containing pyrimidine heterocyclic structures shown i
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Paragraph 0177-0179
(2022/01/10)
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- ION CHANNEL INHIBITOR COMPOUNDS FOR CANCER TREATMENT
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The present invention concerns a compound of following general formula (I): where: either R is an R1 group and R′ is an -A1-Cy1 group, or R is an -A1-Cy1 group and R′ is an R1 group, R1 particularly being H or (C1-C6)alkyl group;A1 being an —NH— radical or —NH—CH2— radical;Cy1 particularly being a phenyl group,A is a fused (hetero)aromatic ring having 5 to 7 atoms, for use for treating cancer.
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Paragraph 0231; 0232
(2021/01/25)
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- Preparation method of heterocyclicpyrimidinedione compound
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The invention discloses a preparation method of a heterocyclicpyrimidinedione compound and relates to the technology of medicinal chemistry. The preparation method comprises the following steps: 1) mixing an o-amino formonitrile heterocyclic compound and a catalyst to form a mixture, wherein the catalyst is [HDBN][TFE]; 2) in a CO2 environment, heating the mixture and reacting; 3) when the temperature is reduced to room temperature, adjusting the pH value to neutrality, and extracting, separating and collecting the an organic phase; drying, filtering and then vaporizing; performing column chromatography separation to obtain the heterocyclicpyrimidinedione compound. The preparation method disclosed by the invention has the advantages of low cost, environmental friendliness, simple preparation process and wide application range of substrate.
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Paragraph 0030; 0031; 0032
(2018/03/26)
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- Ionic liquid promoted synthesis of heterocycle-fused pyrimidine-2,4(1H,3H)-diones utilising CO2
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An efficient ionic liquid system was developed for the preparation of various heterocycle-fused pyrimidine-2, 4(1H,3H)-diones in moderate to excellent yields (52–95%). It was found that [HDBN+][TFE?], a simple and easily prepared ionic liquid, could act as both the solvent and reaction promoter, and that the reactions could be efficiently carried out at atmospheric pressures of CO2.
- Li, Chun,Lu, Xunhua,Yang, Yuanyong,Yang, Shenggang,Zhang, Lin
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supporting information
p. 2463 - 2466
(2018/05/26)
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- Efficient synthesis of 2-oxazolidinones and quinazoline-2,4(1H,3H)-diones from CO2 catalyzed by tetrabutylammonium fluoride
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By employing tetrabutylammonium fluoride (TBAF) as a catalyst, the various carboxylative cyclizations of the propargylic amines having internal alkynes with CO2 proceeded to afford the corresponding 2-oxazolidinones. In this case, it was also found that the generated 2-oxazolidinones were tautomerized into the corresponding 2-oxazolones due to the basicity of TBAF. In addition, we performed the synthesis of quinazoline-2,4(1H,3H)-dione from 2-aminobenzonitrile and CO2 by using TBAF as a catalyst.
- Fujii, Akira,Matsuo, Hideaki,Choi, Jun-Chul,Fujitani, Tadahiro,Fujita, Ken-ichi
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p. 2914 - 2920
(2018/05/16)
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- Synthesis and Characterization of Amidato Divalent Lanthanide Complexes and Their Use in Forming 2,4-Quinazolidinones from CO2 and 2-Aminobenzonitriles
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Four amidato divalent lanthanide complexes, {LnLn[N(TMS)2]THF}2 [n = 1, Ln = Eu (1); n = 2, Ln = Eu (3), Yb (4); HL1 = tBuC6H4CONHC6H3(iPr)2; HL2 = C6H5CONHC6H3(iPr)2] and {L3Eu[N(TMS)2]THF}{L32Eu(THF)2} (2) [HL3 = ClC6H4CONHC6H3(iPr)2], were synthesized and extensively characterized. This is the first time that the amidato lanthanide amides 1-4 were used to catalyze the reactions of CO2 and 2-aminobenzonitriles to form quinazoline-2,4(1H,3H)-diones at atmospheric pressure. All the complexes efficiently catalyzed the transformation, with complex 3 showing the highest activity. This catalytic system gave good to excellent yields, and good functional group tolerance. Preliminary studies were conducted to investigate the reaction mechanism.
- Wang, Qianyu,Lu, Chengrong,Zhao, Bei,Yao, Yingming
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p. 2555 - 2559
(2016/06/01)
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- Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives
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Following the discovery of cell penetrant pyridine-4-carboxylate inhibitors of the KDM4 (JMJD2) and KDM5 (JARID1) families of histone lysine demethylases (e.g., 1), further optimization led to the identification of non-carboxylate inhibitors derived from pyrido[3,4-d]pyrimidin-4(3H)-one. A number of exemplars such as compound 41 possess interesting activity profiles in KDM4C and KDM5C biochemical and target-specific, cellular mechanistic assays.
- Westaway, Susan M.,Preston, Alex G. S.,Barker, Michael D.,Brown, Fiona,Brown, Jack A.,Campbell, Matthew,Chung, Chun-Wa,Drewes, Gerard,Eagle, Robert,Garton, Neil,Gordon, Laurie,Haslam, Carl,Hayhow, Thomas G.,Humphreys, Philip G.,Joberty, Gerard,Katso, Roy,Kruidenier, Laurens,Leveridge, Melanie,Pemberton, Michelle,Rioja, Inma,Seal, Gail A.,Shipley, Tracy,Singh, Onkar,Suckling, Colin J.,Taylor, Joanna,Thomas, Pamela,Wilson, David M.,Lee, Kevin,Prinjha, Rab K.
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p. 1370 - 1387
(2016/03/05)
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- 2,4-quinazolinediamine derivatives, and preparation method and application thereof
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The invention discloses 2,4-quinazolinediamine derivatives, and a preparation method and application thereof, belonging to the field of medicines and preparation and application thereof. The 2,4-quinazolinediamine derivatives comprises compounds as shown in a formula (I) which is described in the specification and a solvate, hydrate, tautomer and pharmaceutically acceptable salt thereof. Test results show that the 2,4-quinazolinediamine derivatives have strong Wolbachia resisting activity; and in the derivatives, 2-isopropylamido substitution has good effect, and compounds with better Wolbachia resisting activity can be obtained by changing a 4-amido group. The compounds have activity in resisting plasmodia, Wolbachia and bacteria.
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Paragraph 0211; 0212; 0213
(2017/04/18)
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- PIPERAZINYL PYRIMIDINE DERIVATIVES, PREPARATION METHOD AND USE THEREOF
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Provided are piperazinyl pyrimidine derivatives of formula I having CCR4 antagonism, and the preparation method, pharmaceutical composition and use thereof in the preparation of a medicament. The medicament is useful for the treatment and preve
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Paragraph 0135; 0136
(2015/05/13)
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- Novel Hinge-Binding Motifs for Janus Kinase 3 Inhibitors: A Comprehensive Structure-Activity Relationship Study on Tofacitinib Bioisosteres
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The Janus kinases (JAKs) are a family of cytosolic tyrosine kinases crucially involved in cytokine signaling. JAKs have been demonstrated to be valid targets in the treatment of inflammatory and myeloproliferative disorders, and two inhibitors, tofacitinib and ruxolitinib, recently received their marketing authorization. Despite this success, selectivity within the JAK family remains a major issue. Both approved compounds share a common 7H-pyrrolo[2,3-d]pyrimidine hinge binding motif, and little is known about modifications tolerated at this heterocyclic core. In the current study, a library of tofacitinib bioisosteres was prepared and tested against JAK3. The compounds possessed the tofacitinib piperidinyl side chain, whereas the hinge binding motif was replaced by a variety of heterocycles mimicking its pharmacophore. In view of the promising expectations obtained from molecular modeling, most of the compounds proved to be poorly active. However, strategies for restoring activity within this series of novel chemotypes were discovered and crucial structure-activity relationships were deduced. The compounds presented may serve as starting point for developing novel JAK inhibitors and as a valuable training set for in silico models.
- Gehringer, Matthias,Forster, Michael,Pfaffenrot, Ellen,Bauer, Silke M.,Laufer, Stefan A.
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supporting information
p. 2516 - 2527
(2015/08/24)
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- PIPERAZINYL PYRIMIDINE DERIVATIVES, PREPARATION METHOD AND USE THEREOF
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Provided are piperazinyl pyrimidine derivatives of formula I having CCR4 antagonism, and the preparation method, pharmaceutical composition and use thereof in the preparation of a medicament. The medicament is useful for the treatment and preve
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Paragraph 0082-0083
(2014/12/09)
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- Eco-efficient one-pot synthesis of quinazoline-2,4(1H,3H)-diones at room temperature in water
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An efficient one-pot synthesis of quinazoline-2,4(1H,3H)-diones was developed. First, the reactions of anthranilic acid derivatives with potassium cyanate afforded the corresponding urea derivatives. Then, cyclization of the urea derivatives with NaOH afforded the monosodium salts of benzoylene urea. Finally, HCl treatment afforded the desired products in near-quantitative yields. This is an eco-efficient method because all the reactions were carried out in water, and the desired products were obtained simply by filtration. The aqueous filtrate was the only waste generated from the reaction. We scaled up the reaction to 1 kg starting material, thus establishing an alternative approach for the green synthesis of quinazoline-2,4(1H,3H)-diones in the chemical and pharmaceutical industries.
- Tian, Xin-Chuan,Huang, Xing,Wang, Dan,Gao, Feng
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p. 824 - 829
(2016/10/06)
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- Alkali metal cations control over nucleophilic substitutions on aromatic fused pyrimidine-2,4-[1H,3H]-diones: Towards new PNA monomers
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In this paper we report synthesis of a series of aromatic fused pyrimidine-2,4(3H)-dione-1-yl acetic acid and new PNA monomers containing these polycyclic nucleobase analogues. Introduction of a fused aromatic ring onto the 5,6-positions of the pyrimidine-2,4-[1H,3H]-diones brings about the steric effects and the charge delocalization, both weakening the nucleophilic substitutions on the 1- and 3-positions. We found that alkali metal cations play an important role in this alkylation reaction. LiOH brings out a much more efficient alkylation than NaOH does, while KOH nearly does not work on this reaction. Such influences from the alkali metal cations are probably due to that the charge-pairing interactions between the pyrimidine-2,4-dioxide anions and the alkali metal cations rearrange the charge distribution around the whole aromatic system and increase the negative charge distribution on the 1- and 3-nitrogen atoms, which then strengthens the nucleophilic reactivity on these positions.
- Li, Pengfa,Zhan, Chuanlang,Zhang, Shanlin,Ding, Xunlei,Guo, Fengqi,He, Shenggui,Yao, Jiannian
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p. 8908 - 8915
(2012/10/29)
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- NOVEL MICROBICIDES
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Compounds of formula (I) wherein G1 represents together with the two ring atoms of the pyrimidine ring to which it is attached, a 5- to 6-membered aromatic heterocyclic ring system which contains one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and the other substituents are as defined in claim 1, are suitable for use as micro-biocides.
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Page/Page column 21
(2013/02/27)
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- Design and synthesis of a series of pyrido[2,3-d]pyrimidine derivatives as CCR4 antagonists
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A series of pyrido[2,3-d]pyrimidine derivatives were designed and synthesized based on known CC chemokine receptor 4 (CCR4) antagonists. The activities of all the newly synthesized compounds were evaluated using a chemotaxis inhibition assay. Compound 6b
- Gong, Hongwei,Qi, Hui,Sun, Wei,Zhang, Yang,Jiang, Dan,Xiao, Junhai,Yang, Xiaohong,Wang, Ying,Li, Song
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p. 9961 - 9970
(2012/11/13)
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- A facile and convenient approach for the one-pot synthesis of 2,4(1H,3H)-quinazolinediones
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A fast and efficient method is described for the one-pot synthesis of 2,4(1H,3H)-quinazolinediones by cyclization reaction of anthranilic acid derivatives with potassium cyanate and acetic acid in PEG. Good to high yields of the products obtain in short reaction times with simple work-up.
- Sharafi-Kolkeshvandi, Mahnaz,Nikpour, Farzad
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experimental part
p. 431 - 433
(2012/06/18)
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- NOVEL MICROBICIDES
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Compounds of formula (I) wherein G1 represents together with the two ring atoms of the pyrimidine ring to which it is attached, a 5-to 6-membered aromatic heterocyclic ring system which contains one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and the other substituents are as defined in claim 1, are suitable for use as microbiocides.
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Page/Page column 45
(2011/09/21)
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- Substituted pyrazolopyrimidines
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The present invention is related to chemical compositions, processes for the preparation thereof and uses of the composition. Particularly, the present invention relates to compositions that include substituted heterobicyclic pyrimidines of Formula (I): wherein R1, R2, R3, R4, R5, X, W, and ring A are as defined herein; pharmaceutical compositions of substituted heterobicyclic pyrimidines of Formula (I); and their use in the treatment of chronic neurodegenerative diseases, neurotraumatic diseases, depression and/or diabetes. More particularly, the present invention relates to substituted pyrazolopyrimidines of Formula (I).
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Page/Page column 100
(2008/06/13)
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- Synthesis and biological evaluation of heteroaryldiamides and heteroaryldiamines as cytotoxic agents, apoptosis inducers and caspase-3 activators
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The work described here involved the synthesis and biological evaluation of new heteroaryldiamides and heteroaryldiamines. A new general model in which the structures can be adjusted has been applied in this study. Three different structural units can be distinguished: a central nucleus and two symmetric terminal units. The central element is either an aliphatic chain of varying length and flexibility, piperazine, or a polyamine nucleus. However, the terminal units are pyridine, quinoline, indole, benzene or pyrido[2,3-d] pyrimidine with different substituents. The antitumoural activities of the compounds were evaluated in vitro by examining their cytotoxic effects against human breast, colon, and bladder cancer cell lines. Compounds that showed cytotoxic activity were subjected to both apoptosis and caspase-3 assays. With regard to selectivity, the cytotoxicity was also determined in cell cultures of two nontumoural lines. The most promising compounds are 4c, 5c and 7, which are amino-pyridinium, quinolyl-N-oxide, and pyridyl derivatives, respectively, and these reveal a significant in vitro cytotoxicity in at least two of the three cell lines tested. These compounds induced apoptosis and also produced a rapid dose-dependent increase in the caspase-3 level in HT-29 cells. Other encouraging profiles were found, such as those presented by 1k and 8d, which are cytotoxic and apoptotic but do not provoke an increase in the level of caspase-3, or those presented by 2f, 3c and 4a, which are slightly cytotoxic but do not show any other significant activity. The different types of behaviour of each compound are not necessarily parallel in the three cell lines tested.
- Echeverria, Mikel,Mendivil, Beatriz,Cordeu, Lucia,Cubedo, Elena,Garcia-Foncillas, Jesus,Font, Maria,Sanmartin, Carmen,Palop, Juan Antonio
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p. 182 - 192
(2007/10/03)
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- Compounds
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Compounds of formula I: [in-line-formulae]A-B-C??(I)[/in-line-formulae] and isomers, salts, solvates, chemically protected forms, and prodrugs thereof wherein: B is selected from the group consisting of: ?where RN is H or Me; or B is a divalent C5 heterocyclic residue containing one or two ring heteroatoms; A is: RA3 and RA5 are independently selected from halo, ORO and RAC, where RO is H or Me, and RAC is H or C1-4 alkyl; XA is selected from N and CRA4, where RA4 is selected from H, ORO, CH2OH, CO2H, NHSO2Me and NHCOMe; RA2 and RA6 are independently selected from H, halo and ORO; or RA3 and RA4 together with the carbon atoms to which they are attached, or RA2 and RA3 together with the carbon atoms to which they are attached, may form a C5-6 heterocylic or heteroaromatic ring, containing at least one nitrogen ring atom; where if X is not N, 1, 2, or 3 of RA2 to RA6 are not H; C is: ?where X is selected from N and CH, Y is selected from N and CH, and Z is selected from N and CRC6; RC3 is selected from H, halo and an optionally substituted N-containing C5-7 heterocyclic group; RC5 is a group selected from: ?which group may be selected by one or two C1-4 alkyl groups or a carboxy group; RC6 is H; or, when X and Y are N, RC5 and RC6 (when Z is CRC6) together with the carbon atoms to which they are attached may form a fused C6 aromatic ring selected from the group consisting of:
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Page/Page column 40
(2008/06/13)
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- Compounds
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Compounds of formula l: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof one of X1, X2 and X3 is N, and the others are CH; RN1 and RN2 together with the nitrogen atom to
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Page/Page column 13
(2008/06/13)
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- A green, facile, and one-pot synthesis of 2,4-(1H,3H)-quinazolinediones under microwave irradiations
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Quinazoline-2,4-diones are of considerable interest due to their wide pharmacological properties. Here, we have described an environmentally friendly method for the one-pot synthesis of 2,4-(1H,3H)-quinazolinediones from the reaction of anthranilic acid derivatives with urea in H2O media under microwave irradiations. This method is simple, safe, and fast which produces high yield of products without use of any catalyst. Copyright
- Nikpour, Farzad,Paibast, Touraj
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p. 1438 - 1439
(2007/10/03)
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- PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES
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Compounds of formula (I): and their use in the inhibition of Trk activity are described.
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Page/Page column 109-110
(2008/06/13)
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- Selective bifunctionalization of pyrido[2,3-d]pyrimidines in positions 2 and 4 by SNAr and palladium-catalyzed coupling reactions
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Selective disubstitution of 2,4-dichloropyrido[2,3-d]pyrimidine with various nucleophiles was investigated. Suzuki and Stille cross-coupling reactions on monosubstituted compound 4-tert-butylamino-2-chloro-pyrido[2,3-d] pyrimidine were performed in high yields.
- Lavecchia,Berteina-Raboin,Guillaumet
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p. 5851 - 5855
(2007/10/03)
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- Synthesis and biological evaluation of new symmetrical derivatives as cytotoxic agents and apoptosis inducers
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Based on the research of less toxic anticancer therapies, we have looked for novel compounds with anticancer activity based on a proapoptotic mechanism. The described compounds are derivatives of ether, carbamate, urea, amide, or amine. Some of the prepared compounds decreased cell viability of various tumor cell lines in a time- and dose-dependent manner, and also induced DNA fragmentation, which indicated cell apoptosis. The potential antitumoral activity of the compounds was evaluated in vitro by examining their cytotoxic effects against human mama, colon, and bladder cancer cell lines (MD-MBA-231, HT-29, and T-24). Compounds showing cytotoxic activity were subjected to an apoptosis assay. In addition, some of the synthesized compounds provoked a rapid and dose-dependent increase in the level of caspase-3, an enzyme, which is considered to be one of the principal executing caspases in which all of the biochemical routes involved in the apoptosis response converge. The most promising compounds, with respect to cytotoxicity and apoptosis induction capability, were the 4-nitrophenylcarbamate derivative of 2,2′- methylenebis(4-chlorophenyl) 3c, the naphthylurea derivative 4d, and the n-propylurea derivative 4c, from 4,4′-methylenebisphenyl, all of which displayed cytotoxic activity and showed very interesting levels of apoptosis. Furthermore, good levels of apoptosis induction were achieved for 3a and 4b in the T-24 cell line. Therefore, compounds such as 7b, a pyrido[2,3-d]pyrimidine derivative, show a significant in vitro cytotoxicity, with IC50 values between 3 and 8 μm in the three cell lines tested. This compound also produced a rapid and dose-dependent increase of the caspase-3 level and induced apoptosis in HT-29 cells. Other profiles have been found, such as those presented by 5c and 7c, which are cytotoxic and apoptotic but do not provoke an increase in the level of caspase-3, or those presented by 1c, 1d, and 2a, which are cytotoxic, without showing any other activity. The different types of behavior of each compound are not necessarily parallel in the three cell lines tested. A great number of these compounds of interest show no cytotoxicity in nontumoral human cells such as CRL-8799, a nontumoral line of mama. Subsequent modulation of these lead structures permits advances in the design of potent cytotoxic and proapoptotic anticancer drugs.
- Sanmartin, Carmen,Echeverria, Mikel,Mendivil, Beatriz,Cordeu, Lucia,Cubedo, Elena,Garcia-Foncillas, Jesus,Font, Maria,Palop, Juan Antonio
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p. 2031 - 2044
(2007/10/03)
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- PYRIMIDINES, XXXII: SYNTHESIS AND PROPERTIES OF PYRIDOPYRIMIDINE-2,4-DIONES (5-DEAZALUMAZINES)
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Pyridopyrimidine-2,4-dione (8) and its N-methyl derivatives (9-11) as well as the corresponding 6-nitro analogues (12-15) have been synthesized by condensation reactions from 6-aminouracils (4-7).Reduction of compound (4-7) led to the 6-aminopyrido
- Pfleiderer, Mathias,Pfleiderer, Wolfgang
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p. 905 - 929
(2007/10/02)
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- 2-Arylamino-4-oxo-3,4-dihydropyridopyrimidines: synthesis and diuretic activity
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The synthesis of a series of 19 new compounds, 2-arylamino-4-oxo-3,4-dihydropyridopyrimidines 9, and the results of a study of their potassium-sparing diuretic activity are reported.Compounds 9 were obtained by boiling in dimethylformamide a soluti
- Monge, Antonio,Martinez-Merino, Victor,Sanmartin, Carmen,Fernandez, Francisco J.,Ochoa, Maria C.
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p. 209 - 216
(2007/10/02)
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- Azaisatoic anhydrides
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A method for producing heterocyclic acid anhydrides and pyrimidinediones from the corresponding acids, dicarboxamides, 2,3-and 3,4-pyridinedicarboxamides, and N-monosubstituted 2,3-and 3,4-pyridinedicarboxamides, in which the aforesaid compounds are reacted with lead tetra-acetate in the presence of a suitable anhydrous inert solvent.
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