- New Reaction Mode of the Dieckmann-Type Cyclization under the Lewis Acid-Et3N Conditions
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Dieckmann-type cyclization reactions of various dicarboxylic acid derivatives were readily promoted by employing Lewis acids such as AlCl3, MgBr2, MgCl2, and Sn(OSO2CF3)2 in the presence of Et3N or N-ethylpiperidine.The cyclization reactions of half thiol
- Tamai, Satoshi,Ushirogochi, Hideki,Sano, Shigeki,Nagao, Yoshimitsu
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Read Online
- 2-Aryl-4-aromatic methylaminopyrimidine compounds and their applications
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The present invention relates to 2- aryl-4-aromatic methylaminopyrimidine compounds shown in general formula I and their applications, wherein substituents X,R1,R2 have the meaning given in the specification. The present invention al
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Paragraph 0057; 0059-0060
(2022/01/12)
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- Discovery of Novel Dihydrothiopyrano[4,3-d]pyrimidine Derivatives as Potent HIV-1 NNRTIs with Significantly Reduced hERG Inhibitory Activity and Improved Resistance Profiles
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Enlightened by the available structural biology information, a novel series of dihydrothiopyrano[4,3-d]pyrimidine derivatives were rationally designedviascaffold hopping and molecular hybridization strategies. Notably, compound 20a yielded exceptionally potent antiviral activities (EC50= 4.44-54.5 nM) against various HIV-1 strains and improved resistance profiles (RF = 0.5-5.6) compared to etravirine and rilpivirine. Meanwhile, 20a exhibited reduced cytotoxicity (CC50= 284 μM) and higher SI values (SI = 5210-63992). Molecular dynamics simulations were performed to rationalize the distinct resistance profiles. Besides, 20a displayed better solubility (sol. = 12.8 μg/mL) and no significant inhibition of the main CYP enzymes. Furthermore, 20a was characterized for prominent metabolic stability andin vivosafety properties. Most importantly, the hERG inhibition profile of 20a (IC50= 19.84 μM) was a remarkable improvement. Overall, 20a possesses huge potential to serve as a promising drug candidate due to its excellent potency, low toxicity, and favorable drug-like properties.
- Wang, Zhao,Zalloum, Waleed A.,Wang, Wenbo,Jiang, Xiangyi,De Clercq, Erik,Pannecouque, Christophe,Kang, Dongwei,Zhan, Peng,Liu, Xinyong
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p. 13658 - 13675
(2021/09/13)
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- Discovery of thiapyran-pyrimidine derivatives as potential EGFR inhibitors
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A series of novel thiapyran-pyrimidine derivatives (10a–10h, 11a–11g, 12a–12f, 13a–13f, 14a–14f) were synthesized and their antiproliferative activities were tested. Most of the target compounds showed good activity on one or more cancer cell lines but low activity on human normal cell LO2. The most promising compound 13a exhibited the similar IC50 values on A549 and H1975 cell lines to the lead drug Olmutinib, and exhibited excellent activity and selectivity on EGFRT790M/L858R in the kinase experiment. AO and Hoechst33258 staining indicated that 13a could effectively induce H1975 cells apoptosis. Cell cycle and apoptosis analysis suggested that 13a could block cancer cells in G2/M phase and induce into late apoptosis in a manner of concentration-dependent. The structure–activity relationship of 13a was analyzed to explore its mechanism. All the results showed that 13a was a promising EGFR inhibitor.
- Chu, Cilong,Xiao, Zhen,Xu, Shan,Yang, Feiyi,Yang, Zunhua,Zhang, Qian,Zheng, Pengwu,Zhou, Lingjia,Zhou, Zhihui,Zhu, Wufu
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- Preparation and application of 2-aminopyrimidine heterocyclic compounds containing 4-acylamino phenoxy
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The invention relates to preparation and application of 2-aminopyrimidine heterocyclic compounds containing 4-acylamino phenoxy as shown in general formulas I and II, and pharmaceutically acceptable salts, hydrates, solvates and prodrugs of the compounds. Substituents X, R1 and R2 have meanings given in the specification. The compounds shown in the general formulas I and II have a strong effect ofinhibiting EGFR, EGFRT790M/L858R and EGFRT790M kinase; the compounds have very low inhibitory activity on human normal hepatocyte LO2. The invention also relates to application of the compounds and pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof in preparation of drugs for treating diseases caused by abnormal activation and high expression of EGFR kinase and positive mutation of T790M and L858R, particularly application in preparing medicines for treating and/or preventing cancers.
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Paragraph 0076-0078
(2020/10/14)
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- Design, synthesis and 3D-QSAR analysis of novel thiopyranopyrimidine derivatives as potential antitumor agents inhibiting A549 and Hela cancer cells
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Four series of thiopyranopyrimidine AZD9291 derivatives containing acrylamide structure were designed, synthesized and evaluated for their antiproliferative activity against A549 and Hela cancer cells. Most of the compounds exhibited excellent antiproliferative activity against A549 cells. Moreover, the compounds with indole ring fluorine substituted exhibited better antiproliferative activity against Hela cells. The most promising compound 23g exhibited excellent enzymatic inhibitory activity and selectivity for EGFRL858R/T790M double mutations. The IC50 value against EGFRL858R/T790M kinase was 16 nM. The compound 23g inhibits selectively against the mutated form of EGFR, with the selectivity more than 125-fold. Furthermore, compound 23g also inhibited A549 cells, Hela cells and H1975 cells proliferation at a low concentration, and the IC50 values were 0.057 μM, 0.104 μM and 0.916 μM, respectively. To further investigate the QSARs of thiopyranopyrimidine derivatives, the CoMFA (q [2] = 0.765, r2 = 0.965) and CoMSIA (q [2] = 0.875, r2 = 0.956) models on Hela cancer cells were established. The generated 3D-QSAR model was validated to be reliable and can be used for further design and optimization of novel and selective EGFR inhibitors.
- Zhao, Bingbing,Zhao, Chengwu,Hu, Xiaohan,Xu, Shan,Lan, Zhou,Guo, Yuping,Yang, Zunhua,Zhu, Wufu,Zheng, Pengwu
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- A phenyl acrylamide structure containing substituted pyrimidine compound and use thereof (by machine translation)
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The invention discloses a containing substituted phenyl acrylamide structure of the pyridine compound, its geometric isomer and its pharmaceutically acceptable salt, hydrate, solvate or prodrug. The invention containing substituted phenyl acrylamide structure of pyrimidines, and its pharmaceutically acceptable salt, hydrate or solvate thereof as an active ingredient, with a pharmaceutically acceptable carrier or excipient mixed preparation composition in, and prepared into a clinically acceptable dosage form. The compounds of the invention in preparing and treating and/or preventing proliferative disorders application of the medicament, for treating and/or preventing cancer of application of the medicament, for treating and/or preventing lung cancer, prostate cancer, breast cancer and applied in the medicine of cervical cancer. (by machine translation)
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Paragraph 0056; 0093; 0094
(2019/02/10)
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- NOVEL COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Provided are 2-(piperidin-1-yl)pyrimidin-4(3H)-ones or pharmaceutically acceptable salts thereof, each characterized by having a 1,8-diazaspiro[4.5]deca-3-ene, 1-oxa-8-azaspiro[4.5]deca-3-ene, 2,8-diazaspiro[4.5]deca-3-ene, 2-oxa-8-azaspiro[4.5]deca-3-ene, 2,9-diazaspiro[5.5]undeca-3-ene, 1-oxa-9-azaspiro[5.5]undeca-3-ene, 1,9-diazaspiro[5.5]undeca-4-ene, or 3,9-diazaspiro[5.5]undeca-1-ene structure represented by the following general formula (1):
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Paragraph 0181; 0182
(2019/05/16)
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- 2-Azaadamantane N-oxyl (AZADO)/Cu Catalysis Enables Chemoselective Aerobic Oxidation of Alcohols Containing Electron-Rich Divalent Sulfur Functionalities
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The chemoselective oxidation of alcohols containing electron-rich sulfur functionalities (e.g., 1,3-dithianes and sulfides) into their corresponding carbonyl compounds with the sulfur groups can sometimes be a demanding task in modern organic chemistry. A reliable method for this transformation, which features azaadamantane-type nitroxyl radical/copper catalysis using ambient air as the terminal oxidant is reported. The superiority of the developed method was demonstrated by comparing it with various conventional alcohol oxidation methods.
- Sasano, Yusuke,Kogure, Naoki,Nagasawa, Shota,Kasabata, Koki,Iwabuchi, Yoshiharu
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supporting information
p. 6104 - 6107
(2018/09/27)
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- Rare aryl amide structure heterocyclic compound and its preparation method and application
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The invention discloses a biaryl amide structure containing heterocyclopyrimidine compound as well as a geometrical isomer, a pharmaceutically acceptable salt, a hydrate, a solvate or a prodrug and a preparation method of the heterocyclopyrimidine compound. The biaryl amide structure containing heterocyclopyrimidine compound as well as the pharmaceutically acceptable salt, the hydrate or the solvate of the heterocyclopyrimidine compound are taken as active components and mixed with a pharmaceutically acceptable carrier or excipient for preparation of composition and clinically acceptable dosage forms. The invention further discloses applications of the compound to preparation of drugs for treating and/or preventing hyperplastic diseases, preparation of drugs for treating and/or preventing cancer and preparation of drugs for treating and/or preventing prostate cancer, lung cancer and liver cancer.
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Paragraph 0134; 0165; 0166
(2017/08/26)
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- Synthesis and characterization of sulfide, sulfoxide and sulfone derivatives of thiopyran: antimicrobial evaluation
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Abstract: A series of thiopyran derivatives and their oxidized analogous forms were synthesized and characterized by FT-IR, 1H, 13C, 31P NMR and mass spectroscopy techniques. The antibacterial and antifungal activities of these synthesized materials were evaluated against Staphylococcus aureus and Bacillus subtilis, as Gram-positive bacteria, and Escherichia coli and Pseudomonas aeruginosa, as Gram-negative bacteria, as well as the fungus Candida albicans. The results revealed that thiopyran S,S-dioxides are the most effective against all the bacteria studied in this work. Furthermore, thiopyran S-oxides showed excellent antifungal activity against Candida albicans.
- Pasha, Ghasem Firouzzade,Asghari, Sakineh,Tajbakhsh, Mahmoud,Mohseni, Mojtaba
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p. 7291 - 7306
(2017/10/06)
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- [...] -containing heterocyclic structure and preparation and application of compound miazines
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The invention belongs to the field of chemic synthesis and relates to a heterocyclopyrimidine compound containing an aryl hydrazone structure, as well as a stereomer and pharmaceutically acceptable salt, hydrate, solvate or prodrug of the heterocyclopyrim
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Paragraph 0136; 0137
(2016/12/01)
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- Design, synthesis, biological evaluation and docking studies of novel 2-substituted-4-morpholino-7,8-dihydro-5 H -thiopyrano[4,3- d ]pyrimidine derivatives as dual PI3Kα/mTOR inhibitors
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Four series of 2-substituted-4-morpholino- 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives (9-28) were designed, synthesized and their structures were confirmed by 1H NMR, 13C NMR and MS spectrum. All compounds were evaluated for the IC50 values against three cancer cell lines (A549, PC-3 and MCF-7). And four selected compounds (10, 11, 24, 27) were further evaluated for the IC50 values against PI3Kα and mTOR kinases. Seven of the target compounds exhibited moderate to excellent antitumor activities against these three cancer cell lines. The most promising compound 11 showed good antitumor potency for A549, PC-3 and MCF-7 cell lines with IC50 values of 0.52 ± 0.10 1/4M, 1.41 ± 0.10 1/4M, 4.82 ± 0.24 1/4M and moderate antitumor activities against PI3Kα/mTOR with IC50 values of 6.72 ± 0.30 1/4M and 0.94 ± 0.10 1/4M. Structure-activity relationships (SARs) and docking studies indicated that aryl urea scaffolds had a significant impact on the antitumor activities, and aryl pyridine urea scaffolds produced the best potency. Variations in substitutions of the aryl group had a significant impact on the activity and 3-Cl-4-F or 3-CF3-4-Cl substitution was more preferred.
- Lei, Fei,Sun, Chengyu,Xu, Shan,Wang, Qinqin,Ouyang, Yiqiang,Chen, Chen,Xia, Hui,Wang, Linxiao,Zheng, Pengwu,Zhu, Wufu
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- Synthesis and anticancer activity of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety
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Herein, we designed and synthesized of a novel series of 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety (10a–j, 13a–j). All the compounds were evaluated for the IC50values against five cancer cell lines (A549, PC-3, MCF-7, Hela and HepG2). Seven of the target compounds exhibited moderate to excellent cytotoxicity. For these compounds, we tested their inhibitory activities against mTOR kinase, and four of them were tested their inhibitory activities against PI3Kα kinase in further. The results indicated that the optimized compound 10j showed excellent inhibitory activity and cytotoxicity against mTOR kinase, PI3Kα kinase and five cancer cell lines with IC50values of 1.1?μM, 0.92?μM and 8.77–14.3?μM. Structure–activity relationships (SARs) and docking studies indicated that the thiopyrano[4,3-d]pyrimidine scaffolds exerted little effect on antitumor activities of target compounds. Substitutions of chromone moiety at C-6 position with carboxyl were benefit to the antitumor activities.
- Sun, Chengyu,Chen, Chen,Xu, Shan,Wang, Jianqiang,Zhu, Yan,Kong, Dejia,Tao, Hong,Jin, Mengjia,Zheng, Pengwu,Zhu, Wufu
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p. 3862 - 3869
(2016/07/20)
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- Design, synthesis, anticancer activity and docking studies of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives as mTOR inhibitors
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A series of 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives (7a-q, 10a-q) were designed, synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR, MS and HRMS spectrum. All the compounds were evaluated for t
- Zhu, Wufu,Sun, Chengyu,Xu, Shan,Wu, Chunjiang,Wu, Jielian,Xu, Mengze,Zhao, He,Chen, Le,Zeng, Weipeng,Zheng, Pengwu
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p. 6746 - 6754
(2015/01/09)
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- Conformationally-restricted cyclic sulfones as potent and selective mTOR kinase inhibitors
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Novel conformationally-restricted mTOR kinase inhibitors with cyclic sulfone scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the mTOR potency and selectivity against class I PI3Kα kinase. PF-05139962 was identified with excellent mTOR biochemical inhibition, cellular potency, kinase selectivity and in vitro ADME properties.
- Liu, Kevin K.-C.,Bailey, Simon,Dinh, Dac M.,Lam, Hieu,Li, Chunze,Wells, Peter A.,Yin, Min-Jean,Zou, Aihua
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scheme or table
p. 5114 - 5117
(2012/09/07)
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- Synthesis and reduction kinetics of sterically shielded pyrrolidine nitroxides
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A series of sterically shielded pyrrolidine nitroxides were synthesized, and their reduction by ascorbate (vitamin C) indicate that nitroxide 3, a tetraethyl derivative of 3-carboxy-PROXYL, is reduced at the slowest rate among known nitroxides, i.e., at a 60-fold slower rate than that for 3-carboxy-PROXYL.
- Paletta, Joseph T.,Pink, Maren,Foley, Bridget,Rajca, Suchada,Rajca, Andrzej
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supporting information
p. 5322 - 5325
(2013/01/15)
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- Enantioselective direct aldol reactions of achiral ketones with racemic enolizable α-substituted aldehydes: Scope and limitations
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Aldol reactions of racemic enolizable dioxolan-protected α-substituted-β-ketoaldehydes with representative achiral ketones catalyzed by proline or 5-(2-pyrrolidine-2-yl)-1H-tetrazole in wet DMSO proceed with dynamic kinetic resolution (or via DYKAT with an α-substituted- β-alkoxyaldehyde) to give adducts with high dr and ee. Georg Thieme Verlag Stuttgart.
- Ward, Dale E.,Jheengut, Vishal,Beye, Garrison E.,Gillis, H. Martin,Karagiannis, Athanasios,Becerril-Jimenez, Fabiola
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supporting information; body text
p. 508 - 512
(2011/04/24)
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- Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors
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This Letter describes the de novo design of non-peptidic hydroxyethylamine (HEA) inhibitors of BACE-1 by elimination of P-gp contributing amide attachments. The predicted binding mode of the novel cyclic sulfone HEA core template was confirmed in a X-ray
- Rueeger, Heinrich,Rondeau, Jean-Michel,McCarthy, Clive,M?bitz, Henrik,Tintelnot-Blomley, Marina,Neumann, Ulf,Desrayaud, Sandrine
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scheme or table
p. 1942 - 1947
(2011/04/24)
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- NOVEL COMPOUNDS AND METHODS OF USING THEM
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The present invention relates to novel compounds and their pharmaceutically acceptable salts, prodrugs, solvates, polymorphs, tautomers and isomers. In some embodiments, the compounds described herein may be used to modulate sirtuins (SIRT). The present i
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Page/Page column 104
(2009/05/28)
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- NOVEL TRICYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to novel tricyclic derivatives having an excellent inhibitory activity on poly (ADP-ribose) polymerase, or pharmaceutically acceptable salts thereof, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The tricyclic derivatives of the present invention inhibit the activity of poly (ADP-ribose) polymerase, thereby being used for the prevention or treatment of diseases that are caused by excessive activation of PARP, in particular, neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathic pain, inflammatory diseases, osteoporosis, and cancer.
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Page/Page column 65
(2009/06/27)
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- Simple and efficient preparation of reagents for thiopyran introduction: Methyl tetrahydro-4-oxo-2H-thiopyran-3-carboxylate, tetrahydro-4H-thiopyran-4- one, and 3,6-dihydro-4-trimethylsilyloxy-2H-thiopyran
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Tetrahydro-4H-thiopyran-4-one was prepared in >75% yield by treatment of dimethyl 3,3′-thiobispropanoate with NaOMe (generated in situ) in THF solution and decarboxylation of the resulting methyl tetrahydro-4-oxo-2H- thiopyran-3-carboxylate in refluxing 10% aqueous H2SO4. Reaction of tetrahydro-4H-thiopyran-4-one with Me3SiCl and Et 3N in CHCl3 gave the corresponding trimethylsilyl enol ether in near quantitative yield. The prepared reagents are useful for the synthesis of thiopyran-containing compounds. Georg Thieme Verlag Stuttgart.
- Ward, Dale E.,Rasheed, M. Abdul,Gillis, H. Martin,Beye, Garrison E.,Jheengut, Vishal,Achonduh, George T.
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p. 1584 - 1586
(2008/02/08)
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- Influence of the β-alkoxy group on the diastereoselectivity of aldol reactions of tetrahydro-4H-thiopyran-4-one with 4-alkoxytetrahydro-2H-thiopyran-3-carboxaldehydes
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The diastereoselectivity of the aldol reaction of tetrahydro-4H-thiopyran-4-one (3) with 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde (9a) under a variety of conditions is examined. Under optimized conditions, three of the four possible diastereomers from this aldol reaction can be obtained selectively (3-16:1). Reactions of 9a with the Li, B, Mg(II), and Ti(IV) enolates of 3 and with the corresponding trimethylsilyl enol ether 4b in the presence of BF3·OEt2, SnCl4, or TiCl4 as promoters gave the Felkin adducts exclusively (>95%) as mixtures of syn (11a) and anti (12a) diastereomers. Use of the "amine-free" Li enolate of 3 gave 12a with a much higher diastereoselectivity (9:1) and yield (70%) than that obtained using the lithium diisopropylamide-generated Li enolate of 3 (2-3:1; 15-40%). The TiC14-promoted reaction of 4b with 9a gave 11a with excellent selectivity (16: 1). In contrast, the MgBr2·OEt2-promoted reaction of 4b with 9a gave the anti-Felkin adducts exclusively as a 3:1 mixture of syn (13a)/anti (14a) diastereomers. Similar aldol reactions of 3 with the cis and trans isomers of 4-(methoxy)methoxytetrahydro-2H-thiopyran-3-carboxaldehyde (9b and 9c) were examined to probe the influence of the ketal protecting group in 9a on the observed aldol diastereoselectivity. The results are rationalized by applying Evans' stereochemical model for merged 1,2- and 1,3-asymmetric induction (nonchelation), with the exception of the MgBr2· OEt2-promoted reactions of 4b with 9a, 9b, and 9c, which are accommodated by assuming chelation control. Comparison of the reactions of 9a, 9b, and 9c suggests that the ketal group in 9a uniquely allows high levels of either Felkin or anti-Felkin selectivity to be achieved.
- Ward, Dale E.,Sales, Marcelo,Man, Chuk C.,Shen, Jianheng,Sasmal, Pradip K.,Guo, Cheng
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p. 1618 - 1629
(2007/10/03)
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- Synthesis of 5 H-Imidazo[1,2-a]thiopyrano-[4',3':4,5]thieno[2,3-d]pyrimidin-5-one
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The enamino-ester, ethyl, 2-amino-4,7-dihydro-5H-thieno[2,3-c]thiopyrano-3-carboxylate (5) was prepared from tetrahydrothiopyran-4-one (4). Annelating reagent, 5-methyl-2-methylthioimidazoline (8) was prepared starting from 1, 2-diaminopropane (6) via 5-methyl-2-imidazolidinethione (7). The reaction of enamino-ester (5) with the annelating reagent (8) in HMPTA leaded to new 1,2,3,6,7,9-hexahydro-5H-imidazo[1,2-a]thiopyrano[4',3':4,5]thieno[2,3-d]pyrimidin-5-one (9) in good yield.
- Chowdhury, A. Z. M. Shaifullah,Khadker, M.M. Rahman,Bhuiyan, M. M. H.,Hossain, M. K.
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- POLY(ADP-RIBOSE) POLYMERASE INHIBITORS CONSISTING OF PYRIMIDINE DERIVATIVES
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A medicament for therapeutic and/or preventive treatment of a brain disease, which comprises a compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient: wherein R represents hydrogen atom, a C1-C8 alkyl group, a substituted C1-C8 alkyl group, an aryl group, a substituted aryl group, an aryl(C1-C8)alkyl group and the like; Y represents hydrogen atom or -C(R2)R3 (R2 and R3 represent hydrogen atom, a C1-C8 alkyl group, a C1-C8 alkoxy(C1-C8)alkyl group, a hydroxy(C1-C8)alkyl group and the like); symbol "a" represents single bond when Y represents hydrogen atom, or "a" represents double bound when Y represents -C(R2)R3; -A-B- represents -CH2-CH2-, -S-CH2-, -O-CH2-, -CH2-S-, -CH2-O-, -SO-CH2-, -CH2-SO-, -SO2-CH2-, or -CH2-SO2-; and Z represents -CH2- or single bond.
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- Using the electrostatic field effect to design a new class of inhibitors for cysteine proteases
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A new class of competitive inhibitors for the cysteine protease papain is described. These inhibitors are based upon a 4-heterocyclohexanone ring and are designed to react with the enzyme active site nucleophile to give a reversibly formed hemithioketal. The electrophilicity of the ketone in these inhibitors is enhanced by ring strain and by through-space electrostatic repulsion with the heteroatom at the 1-position of the ring. Equilibrium constants for addition of water and 3-mercaptopropionic acid to several 4- heterocyclohexanones were measured by 1H NMR spectroscopy. These reactions model addition of the active site nucleophile to the corresponding inhibitors. The equilibrium constants give a linear correlation with the field substituent constant F for the functional group at the 1-position of the heterocyclohexanone. These equilibrium constants also correlate well with the inhibition constants for the 4-heterocyclohexanone-based inhibitors, which range from 11 to 120 μM. Thus, the model system can be used to predict the potency of structurally related enzyme inhibitors.
- Conroy, Jeffrey L.,Sanders, Tanya C.,Seto, Christopher T.
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p. 4285 - 4291
(2007/10/03)
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- Syntheses of 4H-thiopyran-4-one 1,1-dioxides as precursors to sulfone-containing analogues of tetracyanoquinodimethane
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Synthetic routes to the unsubstituted 4H-thiopynan-4-one 1,1-dioxide (5a), 2,6-dialkyl-substituted, 2-aryl- or 2-heteroaryl-6-alkyl-substituted, 2,6-diaryl- or diheteroaryl-substituted, and 2-heteroaryl-6-aryl-substituted 4H-thiopyran-4-one 1,1-dioxides 5b-s are described. Sodium hydrosulfide hydrate in buffered aqueous alcohol can be used as a substitute for hydrogen sulfide gas for the introduction of sulfur to methyl acrylate, to 1,5-disubstituted-1,4-pentadien-3-ones 13, or to 1,5-disubstituted-1,4-pentadiyn-3-ones 17. The double dehydrogenation of 2,3,5,6-tetrahydrothiopyran-4-one 1,1-dioxides 13 with iodine-DMSO-sulfuric acid gives thiopyran-4-one 1,1-dioxides 5 in good yield and small amounts of 1,4-pentadien-3-ones 13. 2,3,5,6-Tetrahydrothiopyran-4-one 1,1-dioxide (9) and 5,6-dihydrothiopyran-4-one 1,1-dioxide (12), which lack aryl or heteroaryl substituents, give poor yields of 4H-thiopyran-4-one 1,1-dioxide (5a) with iodine-DMSO-sulfuric acid.
- Rule,Detty,Kaeding,Sinicropi
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p. 1665 - 1673
(2007/10/02)
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- Thiophene-2-carboxamidotetrazoles and pharmaceutical use thereof
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Thiophene-2-carboxamidotetrazoles inhibit the Mac-1 integrin and are thus useful for treating diseases mediated by Mac-1 adhesion, including inflammatory disorders.
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- Free Radical Ring-Expansion Leading to Novel Six- and Seven-Membered Heterocycles
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Free radical promoted ring-expansion of nitrogen-, oxygen- and sulfur-containing heterocyclic β-keto esters is described.Treatment of the derived phenylselenomethyl derivatives with tri-n-butyltin hydride leads to smooth one-carbon ring expansion.
- Dowd, Paul,Choi, Soo-Chang
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p. 4847 - 4860
(2007/10/02)
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- An improved procedure for the preparation of 3-carbomethoxy-4-oxotetrahydrothiopyran, 2- and 4-carbomethoxy-3-oxotetrahydrothiophene
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An improved procedure for the preparation of the title compounds 1-3 has been developed.Direct condensation of methyl 3-mercaptopropionate with methyl acrylate using sodium hydride as a base gave compound 1 in good yield.The reaction of methyl thioglycolate and methyl acrylate at 0 degC gave compound 2 as the major product whereas at lower temperature (-40 degC) isomer 3 was found as the major product.The condensation reactions of methyl thioglycolate with methyl metacrylate and crotonate were also carried out.
- Liu, Hsing-Jang,Ngooi, Teng Ko
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p. 437 - 439
(2007/10/02)
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