- Synthesis and biological evaluation of N4-hydrazone derivatives of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one as novel anticancer agents with antimetastatic adjunct efficacy
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To obtain new anticancer agents with antimetastatic adjunct efficacy, a series of novel N4-hydrazone derivatives of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one were designed and synthesized by an eight-step reaction, with appropriate yields. All the synthesized compounds were evaluated for their antiproliferative activity against A549 and MCF-7 cells and for antiplatelet aggregation activity in vitro. The results showed that compounds 25 and 35 not only showed potent antiproliferative activity against the A549 (IC50 = 15.3 and 21.4 μM) and MCF-7 (IC50 = 15.6 and 10.9 μM) cell lines but also showed certain antiplatelet aggregation activity (inhibition rates: 47.0% and 45.8%). These results indicated that the structural modification on the N4-hydrazone moiety of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one is promising to obtain novel anticancer compounds with antimetastatic adjunct efficacy. In addition, a molecular docking study was performed to investigate the possible targets, and these results indicated that compounds 25 and 35 have the potential to target EGFR, HER2, and P2Y12.
- Zhao, Zhichang,Wang, Hongjun,Tian, Nana,Yan, Hong,Wang, Juan
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- Design, synthesis and biological evaluation of 4-Aryl-5,7-dihydro- 6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives as a PI3Kα inhibitor
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A novel series of 4-aryl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives were designed as a phosphoinositide 3-kinase α (PI3Kα) inhibitor by scaffold hopping. The target compounds, characterized by 1H-NMR, 13C-NMR and high resolution (HR)-MS, were synthesized from diethyl malonate and ethyl chloroacetate by nucleophilic substitution, ring-closure, chlorination and Suzuki reaction, etc. The biological activities were evaluated with cytotoxic activity in vitro on Uppsala 87 Malignant Glioma (U87MG) and prostate cancer-3 (PC-3) by Cell Counting Kit-8 (CCK-8). The results showed that compound 9c displayed the higher inhibition than the positive control PI-103, and high PI3Kα inhibitory activity with IC50 of 113 ± 9 nM in the same order of magnitude as BEZ235. In addition, the Log Kow values and molecular docking studies were performed to further investigate the drug-like properties of target compounds and interactions between 9c and PI3Kα.
- Hu, Shengquan,Zhao, Zhichang,Ni, Yeming,Xin, Hongxing,Yan, Hong,Song, Xiuqing
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- Discovery and optimization of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives as mTORC1/mTORC2 dual inhibitors
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New potent mTORC1/mTORC2 dual inhibitors, 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives, were obtained by optimizing functional groups on our previously reported PI3Kα inhibitor. All the target compounds were synthesized and structural optimization on the structure of the lead compound based on cytotoxic activity. The results showed that some of the target compounds exhibited moderate to high cytotoxic activity against cell line U87MG and PC-3. The activities against mTOR kinase were investigated and the compound 12q showed excellent activity with an IC50 value of 54 nM in the same level of the positive control BEZ235 with IC50 value of 55 nM under the same test conditions. The western blot and cell cycle results demonstrate that compound 12q is a candidate as an mTORC1/mTORC2 dual-target inhibitor. The theoretical calculations were also performed to better understanding the binding modes of the compound 12q in the mTOR active site.
- Hu, Shengquan,Zhao, Zhichang,Yan, Hong
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- A New Approach to the Synthesis of Diethyl 2,3-Diisobutylsuccinate, a Component of Titanium–Magnesium Catalysts for Propylene Polymerization
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A procedure was developed for preparing 2,3-dialkyl-substituted succinates by condensation of a succinic acid diester with two isobutyraldehyde molecules, followed by esterification and hydrogenation of the sum of dienes. Diethyl 2,3-diisobutylsuccinate of 75%–99% purity was prepared by this procedure in a good yield. The use of the synthesized diethyl 2,3-diisobutylsuccinate as a stereoregulating component of titanium–magnesium catalysts allows synthesis of polypropylene with broad molecular-mass distribution. The catalysts prepared using >95% pure diethyl 2,3-diisobutylsuccinate demonstrated the best characteristics and allowed polypropylene synthesis with high isotacticity index in a high yield.
- Barabanov, A. A.,Bukatov, G. D.,Mainagashev, I. Ya.,Mats’ko, M. A.,Nechepurenko, I. V.,Salakhutdinov, N. F.,Sergeev, S. A.,Volcho, K. P.,Zakharov, V. A.
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p. 715 - 725
(2021/08/13)
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- 5. 7 - Dihydro - 6H - pyrrolo [2, 3 - d] pyrimidine -6 - ketone derivatives preparation method and application (by machine translation)
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5. 7 - Dihydro - 6 H - pyrrolo [2, 3 - d] pyrimidine - 6 - ketone derivatives preparation method and application, which belongs to the new compound preparation and pharmaceutical application field, in particular to immune dysfunction and technical field of tumor diseases, in particular relates to a 5, 7 - dihydro - 6 H - pyrrolo [2, 3 - d] pyrimidine - 6 - ketone derivative compounds of the general formula I as the structure of the PI3K/mTOR inhibitor compound. The structure of the compound of the general formula I . The invention discloses the general formula I indicated by the 5, 7 - dihydro - 6 H - pyrrolo [2, 3 - d] pyrimidine - 6 - ketone derivatives of the preparation method, and also relates to the compounds in the immune disorders and neoplastic diseases, the compounds of the antiproliferative in the treatment of diseases related to the application of the medicament. (by machine translation)
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Paragraph 0061-0064
(2019/04/09)
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- Preparation method of 1,1,2-triethyl ethane triformate
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The invention relates to a preparation method of 1,1,2-triethyl ethane triformate. The method mainly comprises the following steps: adding first inorganic alkaline into a first organic solvent, addingdiethyl malonate into a reaction system, adding a catalyst 1, generating heating reaction for a period of time, adding ethyl acetate, and generating heating reaction to obtain a final product. The product has a high value, can be applied to multiple fields, and is high in conversion rate, easy to separate and purify and high in reaction controllability, and the raw material cost is low.
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Paragraph 0017; 0018; 0019; 0022; 0025
(2018/10/11)
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- Preparation method of tetrahydro-3-furanmethanol
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The invention relates to the field of preparation of insecticides, in particular to a preparation method of tetrahydro-3-furanmethanol. The method comprises the steps as follows: 13.6 g of sodium ethoxide and 0.5 g of sodium iodide are dissolved in 120 mL of absolute ethyl alcohol, 32 g of diethyl malonate is dropwise added in an ice-water bath, the temperature is controlled at 20 DEG C or below,stirring is performed continuously for 1 h after addition, then 30.3 g of ethyl bromoacetate is slowly added, the temperature is increased to 50-60 DEG C after addition, stirring is performed for about 8 h, ethyl bromoacetate is detected to be used up through gas chromatography, a heating reaction is stopped, the system is cooled to the room temperature, 10 mL of a saturated ammonium chloride solution is added with stirring, the system is adjusted to be neutral or slightly acid, solvent ethyl alcohol is evaporated, residues are dissolved in 100 mL of water and 100 mL of ethyl acetate for extraction, solution separation is performed, an organic phase is separated, the solvent ethyl acetate is removed from the organic phase, reduced pressure distillation is performed through an oil pump, andthe first fraction point, namely, a triethyl 1,1,2-ethanetricarboxylate product, is collected. The process is simple, safety in actual production is guaranteed, and the product with higher yield is obtained.
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Paragraph 0007; 0008
(2018/04/02)
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- Preparation method and applications of a class of electrophilic enol salts
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The invention relates to a preparation method and applications of a class of electrophilic enol salts, and belongs to the technical field of metal organic catalysis, wherein an alkynyl terminated compound, a nitrogen oxide and a proton supplying agent are subjected to an addition reaction in an organic solvent by using a silver salt as a catalyst to obtain the electrophilic enol salt, and the electrophilic enol salt is used for preparing a functionalized carbonyl compound. According to the present invention, with the synthesis method, by using various commercially availaboe monovalent silver salts as the catalyst and using various alkynyl terminated compounds as the starting raw material, the alkynyl terminated compound can be added by the protonated nitrogen oxide so as to achieve the synthesis of the special enol salt; the obtained enol salt has characteristics of diverse structure, high tolerance of the functional group, and good yield; and the electrophilic enol salts with the characteristic of easy separation is synthesized.
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Paragraph 0102; 0103; 0104
(2017/10/07)
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- 3-tetrahydrofurfuryl alcohol intermediate synthesis method
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The present invention discloses a 3-tetrahydrofurfuryl alcohol intermediate synthesis method, wherein under a condition of a weak base acid-binding agent, dialkyl malonate and halogenated alkyl acetate are adopted as raw materials and are subjected to a dehydration reaction in a solvent under the effects of a catalyst and a phase transfer catalyst, and post-treatment is performed to obtain 2-alkoxy acyl-dialkyl succinate. According to the present invention, the weak base acid-binding agent is used to replace metal sodium, sodium hydride, potassium hydride and other strong bases; and compared with the traditional methods, the method of the present invention has advantages of high yield, mild and easily-controlled reaction conditions, easy post-treatment and environmental protection, and is suitable for industrial large-scale production.
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Paragraph 0031
(2016/10/09)
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- COMPOUNDS FOR IMPROVING MRNA SPLICING
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Provided herein are compounds useful for improving mRNA splicing in a cell. Exemplary compounds provided herein are useful for improving mRNA splicing in genes comprising at least one exon ending in the nucleotide sequence CAA. Methods for preparing the compounds and methods of treating diseases of the central nervous system are also provided.
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Page/Page column 220
(2016/08/10)
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- PROCESS FOR PREPARING DI-SUBSTITUTED SUCCINATES
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The invention relates to a process for preparing (2,3) disubstituted succinates that allows (2,3) disubstituted succinates to be obtained in good purity and with acceptabel reaction yields. The (2) and (3) substitutions may be the same or different. The process comprises reacting a haloacetate with a malonic acid ester into a tricarboxylate, which is further reacted to a (2,3) disubstituted tricarboxylate, hydrolysed, decarboxylated and optionally esterified. Esterified (2,3) disubstituted succinic esters may be used as internal donor in Ziegler-Natta type catalysts for the polymerisation of olefins.
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Page/Page column 16; 17
(2013/03/28)
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- 2,4-DIAMINO-6,7-DIHYDRO-5H-PYRROLO[2,3]PYRIMIDINE DERIVATIVES AS FAK/Pyk2 INHIBITORS
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The invention relates to a novel class of 2,4-diamino-6,7-dihydro-5H-pyrrolo[2,3]pyrimidine derivatives as a FAK and/or Pyk2 inhibitor, to a process for their preparation, and to a composition thereof, as well as to use of the compounds for the inhibiting FAK and/or Pyk2 and method for the treatment of a FAK and/ or Pyk2 mediated disorder or disease.
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Page/Page column 45-46
(2012/07/27)
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- AKT AND P70 S6 KINASE INHIBITORS
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The present invention provides AKT and p70 S6 kinase inhibitors of the formula: The present invention also provides pharmaceutical compositions comprising compounds of Formula I, uses of compounds of Formula I and methods of using compounds of Formula I.
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Page/Page column 60-61
(2010/06/11)
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- Heterocyclic Compounds Useful as RAF Kinase Inhibitors
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The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.
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Page/Page column 17
(2009/01/24)
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- BIOACTIVE COMPOUNDS FOR TREATMENT OF CANCER AND NEURODEGENERATIVE DISEASES
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The invention provides bioactive compounds for the treatment of various malconditions such as cancer and neurodegenerative diseases including Alzheimer's disease. The chemical compounds as disclosed herein are found to show bioactivity in bioassays related to these conditions. Pharmaceutical compositions, combinations and methods of synthesis are provided, as are methods of using the compound, compositions and combinations in the treatment of the diseases.
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Page/Page column 96
(2009/12/23)
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- PREVENTION AND TREATMENT OF CANCER AND OTHER DISEASES
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Nucleoside chemical compounds, which interact with specific structures of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) are disclosed. The compounds interfere with the activities of telomerase and reverse transcriptase, and are useful as antivirals, antibacterials and anticancer agents. Methods of treating or preventing cancers in patients involving administration of a therapeutically effective amount of a composition having an inhibitor or antagonist of the reverse transcriptases (RTs) expressed in cells of the patients are also disclosed. Method of using nucleoside analogs and other inhibitors of RTs in conjunction with DNA damaging agents such as genotoxic agents or radiation or photodynamic therapy or combinations these for the treatment of various cancers are also disclosed.
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Page/Page column 67-68
(2008/06/13)
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- DUTPASE INHIBITORS
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Deoxyuridine derivatives of the formula (I) where R1 is H or various substituents; D is -NHCO-, -CONH-, -0-, -C(=O)-, -CH=CH, -CΞC-, -NR5-; R4 is hydrogen or various substituents; R5 is H, C1-C4 alkyl, C1-C4 alkanoyl; E is Si or C; R6, R7 and R8 are independently selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl or a stable monocyclic, bicyclic or tricyclic ring system; G is -O-, -S-, -CHR10-, -C(=O)-; J is -CH2-, or when G is CHR10 may also be -O- or -NH-; R10 is H, F, -CH3, -CH2NH2, -CH2OH; -OH R11 is H, F, -CH3, -CH2 NH2, -CH2OH, CH(OH)CH3, CH(NH3)CH3; or R10 and R11 together define an olefinic bond, or together form a -CH2-group, thereby defining a cis or trans cyclopropyl group; have utility in the prophylaxis or treatment of protozoal diseases such as malaria.
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Page/Page column 39-40
(2008/06/13)
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- Surface-mediated Solid-phase Reaction. Part 2. Highly Selective Mono- and Di-C-alkylation of 1,3-Dicarbonyl Compounds on the Surface of Alumina
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Highly selective mono- and di-C-alkylation of 1,3-dicarbonyl compounds with different, structurally varied alkyl halides has been achieved in high yields through a simple solvent-free reaction on the surface of alumina impregnated with sodium or potassium alkoxide.
- Ranu, Brindaban C.,Bhar, Sanjay
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p. 365 - 368
(2007/10/02)
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- SYNTHESIS OF POLYFUNCTIONAL ALIPHATIC CARBONYL COMPOUNDS UNDER PHASE-TRANSFER CONDITIONS
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We have studied mono- and dialkylation of malonic, acetoacetic, and cyanoacetic esters with esters of haloacetic and β-halopropionic acids and addition of the CH acids mentioned and their analogues to methyl and ethyl acrylate under phase-transfer catalysis conditions, and also deethoxycarbonylation of the obtained products.We have demonstrated for the first time the possibility of Dieckmann cyclization under phase-transfer catalysis conditions and have developed a simple method for the synthesis of 2,3-di(ethoxycarbonyl)cyclopentanone, a key intermediate in the synthesis of deoxyprostaglandins, by cyclization of triethyl 1,2,4-butanetricarboxylate.
- Sizov, A. Yu.,Dombrovskii, V. A.,Yanovskaya, L. A.
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p. 955 - 961
(2007/10/02)
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- Reduction-alkylation with organocopper(I) reagents-alkyl halydes: Highly regioselective α-alkylation of γ-acetoxy-α,β-enoates with lithium dibutylcuprate-alkyl halides and difference in the reactivity of electron-deficient olefins with organocopper(I)-Lewis acid reagents
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Reaction of γ-acetoxy-α,β-enoates with lithium dialkylcuprate followed by alkyl halides results in the predominant or exclusive formation of α-alkyl-β,γ-enoates in high yields under mild conditions, and a synthetic application to (+-)-α-vetispirene is presented.Treatment of diethyl fumarate and triethoxycarbonylethylene with Bu2CuLi*AlCl3 led to 1,4-addition to give conjugate adducts in high yields.In sharp contrast, diethyl maleate and tetraethoxycarbonylethylene predominantly gave the respective reduction products.Evidence for a presumed dianionic intermediate, based on trapping with some electrophyles, is also presented.Keywords - γ-oxygenated α,β-enoate; β,γ-enoate; deconjugative reduction; α-vetispirene; lithium dialkylcuprate; organocopper(I)-Lewis acid.
- Ibuka, Toshiro,Aoyagi, Takeshi,Yamamoto, Yoshinori
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p. 2417 - 2427
(2007/10/02)
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- DIFFERENCES IN THE REACTION OF ELECTRON DEFICIENT OLEFINS WITH ORGANOCOPPER(I)-LEWIS ACID REAGENTS AND EVIDENCE FOR A DIANIONIC EQUIVALENT
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Treatment of diethyl fumarate and triethoxycarbonylethylene with Bu2CuLi*AlCl3 led to 1,4-addition to give butylated products in high yields.In sharp contrast, diethyl meleate and tetraethoxycarbonylethylene predominantly gave the respective reduction products.The first evidence for a presumed dianionic intermediate by trapping with some electrophiles was also presented.
- Ibuka, Toshiro,Aoyagi, Takeshi,Kitada, Kazuko,Yoneda, Fumio,Yamamoto, Yoshinori
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p. C18 - C22
(2007/10/02)
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- One-Pot Synthesis of cis Fixed β-Diketones of Bicycloalkanes, 2
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Starting from 2-cycloalken-1-ones 1 the substituted cis fixed β-diketones of bicycloalkanes 4 have been obtained by a combined Michael addition of α,α,ω-alkanetricarboxylates (and related species) 2 and Dieckmann cyclization of the intermediates 3.Reactions of the β-diketone system as well as modifications of the disubstituted malonate system of 4 are reported.
- Schank, Kurt,Lorig, Werner
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p. 112 - 136
(2007/10/02)
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- AN EFFICIENT SYNTHESIS OF BISLACTONE SKELETON LEADING TO d,l-CANADENSOLIDE
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A novel, stereoselective total synthesis of d,l-canadensolide by application of the two-phase reaction (Bu4NBr, benzene-H2O) of 2-bromohexanal with 1,1,2-ethanetricarboxylic acid 2-tert-butyl, 1-ethyl ester, 1-potassium salt (6a) is described.
- Sakai, Takashi,Yoshida, Masanori,Kohmoto, Shoichi,Utaka, Masanori,Takeda, Akira
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p. 5185 - 5188
(2007/10/02)
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- Anthracycline synthesis
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A process for synthesizing doxorubicin and related compounds from aloe-emodin is disclosed. Intermediates useful in the preparation of doxorubicin and related compounds are also disclosed.
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