- Synthesis of fluorinated cycloalkyl N-phenylcarbamates and their microbial defluorination/oxygenation by Beauveria bassiana
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Earlier investigations showed that cycloalkyl N-phenylcarbamates were hydroxylated by the fungus Beauveria bassiana predominantly in the 4-position relative to the electron-rich substituent. In cases involving fluorinated methylene groups potentially capable of hydroxylation, however, defluorination and formation of a ketone was observed. The formation of the ketone can be explained by primary hydroxylation to forman unstable geminal fluorohydrin, which is subsequently dehydrofluorinated. Wiley-VCH Verlag GmbH & Co. KGaAA, 69451 Weinheim, Germany, 2003.
- Haufe, Guenter,Pietz, Sylke,Woelker, Doerthe,Froehlich, Roland
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Read Online
- Decarboxylative Hydroxylation of Benzoic Acids
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Herein, we report the first decarboxylative hydroxylation to synthesize phenols from benzoic acids at 35 °C via photoinduced ligand-to-metal charge transfer (LMCT)-enabled radical decarboxylative carbometalation. The aromatic decarboxylative hydroxylation is synthetically promising due to its mild conditions, broad substrate scope, and late-stage applications.
- Ritter, Tobias,Su, Wanqi,Xu, Peng
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supporting information
p. 24012 - 24017
(2021/10/06)
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- Chromone dioxadiazole compound as well as preparation method and application thereof
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The preparation method comprises the following steps: adding an intermediate F and bis (acetoxy) iodobenzene to dichloromethane for reaction to obtain the chromone compound. The invention provides a novel chromone dioxadiazole compound and a preparation method thereof, and overcomes the defects of large toxicity and high preparation cost of the traditional method.
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Paragraph 0021-0023
(2021/10/30)
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- An efficient method to prepare aryl acetates by the carbonylation of aryl methyl ethers or phenols
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Synthesis of valuable chemicals from lignin based compounds is critical for the application of biomass. Here, we develop a method of preparing aryl acetates by the carbonylation of aryl methyl ethers or phenols under low CO pressure. Good to excellent yields of aryl acetates were obtained using different substrates, and a possible reaction mechanism was proposed by conducting a series of control experiments. This method may provide a potential way for the utilization of lignin.
- Zhang, Dejin,Yang, Guoqiang,Xiong, Junping,Liu, Jia,Hu, Xingbang,Zhang, Zhibing
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p. 2683 - 2687
(2021/02/16)
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- Synthesis of novel of 2, 5-disubstituted 1, 3, 4- oxadiazole derivatives and their in vitro anti-inflammatory, anti-oxidant evaluation, and molecular docking study
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A series of novel 2, 5-disubstituted 1, 3, 4-Oxadiazole derivatives as a potential anti-inflammatory, and anti-oxidant agent were synthesized via cyclisation. Hydrazide molecule treated with substituted acids in the presence of phosphorus oxychloride (POCl3) as an efficient reagent as well as solvent by conventional method with shorter reaction time and excellent yield. The newly synthesized 1, 3, 4- oxadiazole derivatives exhibited excellent to good anti-inflammatory and anti-oxidant activities compaired to the standard drugs. Molecular docking study on the crucial anti-inflammatory target–cyclooxygenase-2 (COX-2) revealed the ability of the scaffold to correctly recognize the active site and achieve significant bonded and non-bonded interactions with key residues therein. This study could identify potential compounds which can be pertinent starting points for structure-based drug design to obtain newer anti-inflammatory agents.
- Dongare, Balasaheb B.,Ghanwat, Anil A.,Kashid, Bharat B.,Khedkar, Vijay M.,More, Kishor R.,Salunkhe, Pravin H.
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supporting information
(2020/04/15)
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- Novel p-functionalized chromen-4-on-3-yl chalcones bearing astonishing boronic acid moiety as MDM2 inhibitor: Synthesis, cytotoxic evaluation and simulation studies
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Background: Novel 4-[3-(6/7/8-Substituted 4-Oxo-4H-chromen-3-yl)acryloyl]phenyl-boronic acid derivatives (5a-h) as well as other 6/7/8-substituted-3-(3-oxo-3-(4-substituted-phenyl)prop-1-enyl)-4H-chromen-4-one derivatives (3a-u) have been designed as p53-MDM2 pathway inhibitors and reported to possess significant cytotoxic properties against several cancer cell lines. Objectives: The current project aims to frame the structure-anticancer activity relationship of chromen-4-on-3-yl chalcones (3a-u/5a-h). In addition, docking studies were performed on these chromeno-chalcones in order to have an insight into their interaction possibilities with MDM2 pro-tein. Methods: Twenty-nine chromen-4-on-3-yl chalcone derivatives (3a-u/5a-h) were prepared by utilizing silica supported-HClO4 (green route with magnificent yield) and tested against four cancer cell lines (HCT116, MCF-7, THP-1, NCIH322). Results: Among the series 3a-u, compound 3b exhibited the highest anticancer activity (with IC50 values ranging from 8.6 to 28.4 μM) overall against tested cancer cell lines. Interestingly, para-Boronic acid derivative (5b) showed selective inhibition against colon cancer cell line, HCT-116 with an IC50 value of 2.35 μM. Besides the emblematic hydrophobic interactions of MDM2 inhibi-tors, derivative 5b was found to exhibit extra hydrogen bonding with GLN59 and GLN72 residues of MDM2 in molecular dynamics (MD) simulation. All the compounds were virtually nontoxic against normal fibroblast cells. Conclusion: Novel compounds were obtained with good anticancer activity especially 6-Chlorochromen-4-one substituted boronic acid derivative 5b. The molecular docking study proposed good activity as a MDM-2 inhibitor suggesting hydrophobic as well as hydrogen bonding interactions with MDM2.
- Bhatia, Richa Kaur,Coutinho, Evans C.,Garg, Ruchika,Kancherla, Satyavathi,Kaur, Maninder,Madan, Jitender,Pissurlenkar, Raghuvir R. S.,Singh, Lakhwinder,Yadav, Manmohan
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p. 212 - 228
(2020/03/10)
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- Mechanistic Insights into C(sp2)?C(sp)N Reductive Elimination from Gold(III) Cyanide Complexes
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A new family of phosphine-ligated dicyanoarylgold(III) complexes has been prepared and their reactivity towards reductive elimination has been studied in detail. Both, a highly positive entropy of activation and a primary 12/13C KIE suggest a late concerted transition state while Hammett analysis and DFT calculations indicate that the process is asynchronous. As a result, a distinct mechanism involving an asynchronous concerted reductive elimination for the overall C(sp2)?C(sp)N bond forming reaction is characterized herein, for the first time, complementing previous studies reported for C(sp3)?C(sp3), C(sp2)?C(sp2), and C(sp3)?C(sp2) bond formation processes taking place on gold(III) species.
- Genoux, Alexandre,González, Jorge A.,Merino, Estíbaliz,Nevado, Cristina
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supporting information
p. 17881 - 17886
(2020/08/19)
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- Preparation method for synthesis of phenolic ester through thiocarboxylic acid mediated visible light catalyzed phenol acylation reaction
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The invention discloses a preparation method for synthesis of phenolic ester through a thiocarboxylic acid mediated visible light catalyzed phenol acylation reaction. Thiocarboxylic acid compounds andphenol compounds are subjected to a site specific reaction under certain conditions to produce phenolic ester compounds, wherein the certain conditions are as follows: under the conditions of normaltemperature, normal pressure and visible light, K2CO3 is used as an alkaline catalyst, terpyridyl ruthenium dichloride hexahydrate is used as a photosensitizer and acetonitrile is used as a reaction solvent. Synthesis of phenolic ester under catalysis of visible light is realized, thiocarboxylic acid is used as an acylation reagent, and the site specific phenol esterification reaction is realizedefficiently under mild conditions of normal temperature, normal pressure and visible light. The method has mild reaction conditions, large substrate functional group tolerance, high applicability andhigh yield, and an efficient, reliable and economical preparation method is provided for synthesis of phenolic ester.
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Paragraph 0079; 0080; 0085; 0086; 0087
(2018/07/30)
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- Copper-Mediated Functionalization of Aryl Trifluoroborates
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This paper describes the Cu(OTf)2-mediated coupling of aryl and heteroaryl trifluoroborates with tetrabutylammonium or alkali metal salts to form C-O, C-N, and C-halogen bonds. The reactions proceed under mild conditions (often room temperature over 16 hours) with carboxylate, halide, and azide salts, all nucleophiles that have been underrepresented in the copper cross-coupling literature. Preliminary results show that copper salts bearing weakly coordinating X-type ligands are essential for enabling these transformations to proceed under mild conditions.
- Schimler, Sydonie D.,Sanford, Melanie S.
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supporting information
p. 2279 - 2284
(2016/10/06)
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- Synthesis and characterization of new N-alkylated pyridin-2(1H)-ones
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A series of novel N-substituted pyridin-2(1H)-one derivatives have been synthesized by reacting (E)-ethyl 3-(6-fluoro-4-oxo-4H-chromen-3-yl)acrylate, with various alkylamines, benzylamines, diaminoalkanes, propargyl amine, 2-amino-1,3-dihydroxypropane, etc. under basic conditions, in 60-83% yield. The structures of the compounds have been established on the basis of their physical and spectral characterization data (1H and 13C NMR, UV-Vis, FT-IR, and HRMS) and further confirmed by X-ray crystallographic analysis of a representative compound. Antibacterial activity of obtained 2-pyridones have been investigated against three human pathogen bacterial strains. Most of the compounds exhibit low activity as compared to the reference.
- Sharma, Atul Kumar,Yadav, Preeti,Chand, Karam,Sharma, Sunil K.
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p. 492 - 500
(2017/01/18)
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- Design, synthesis and docking studies of novel thienopyrimidine derivatives bearing chromone moiety as mTOR/PI3Kα inhibitors
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Two series of thienopyrimidine derivatives (10a-k, 16a-j) bearing chromone moiety were designed and synthesized. All the compounds were evaluated for inhibitory activity against mTOR kinase at a concentration of 10uM. Four selected compounds were further evaluated for the IC50 values against mTOR kinase, PI3Kα kinase and two cancer cell lines. Some of the target compounds exhibited moderate to excellent mTOR/PI3Kα kinase inhibitory activity and cytotoxicity. The most promising compound 16i showed good inhibitory activity against mTOR/PI3Kα kinase and good antitumor potency for H460 and PC-3 cell lines with IC50 values of 0.16 ± 0.03 μM, 2.35 ± 0.19 μM, 1.20 ± 0.23 μM and 0.85 ± 0.04 μM, which were 8.6, >5, 7.9 and 19.1 times more active than compound I (1.37 ± 0.07 μM, >10 μM, 9.52 ± 0.29 μM, 16.27 ± 0.54 μM), respectively. Structure-activity relationships (SARs) and docking studies indicated that the chromone moiety is necessary for the potent antitumor activity and cytotoxicity of these compounds. Substitution of the chromone moiety at the 6-position has a significant impact to the inhibitory activity, in particular a carboxylic acid group, produced the best potency.
- Zhu, Wufu,Chen, Chen,Sun, Chengyu,Xu, Shan,Wu, Chunjiang,Lei, Fei,Xia, Hui,Tu, Qidong,Zheng, Pengwu
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- Palladium-Catalyzed Desilylative Acyloxylation of Silicon-Carbon Bonds on (Trimethylsilyl)arenes: Synthesis of Phenol Derivatives from Trimethylsilylarenes
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A strategy for desilylative acetoxylation of (trimethylsilyl)arenes has been developed in which (trimethylsilyl)arenes are converted into acetoxyarenes. The direct acetoxylation is performed in the presence of 5 mol % of Pd(OAc)2 and PhI(OCOCF3)2 (1.5 equiv) in AcOH at 80°C for 17 h. The acetoxyarenes are obtained in good to high yields (67-98%). The synthetic utility is demonstrated with a one-pot transformation of (trimethylsilyl)arenes to phenols by successive acetoxylation and hydrolysis. Furthermore, desilylative acyloxylation of 2-(trimethylsilyl)naphthalene using several carboxylic acids has been conducted.
- Gondo, Keisuke,Oyamada, Juzo,Kitamura, Tsugio
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supporting information
p. 4778 - 4781
(2015/10/12)
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- Solventless acetylation of alcohols and phenols catalyzed by supported iron oxide nanoparticles
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Supported iron oxide nanoparticles on silicate catalysts were found to be efficient and easily recoverable materials in the acetylation of alcohols and phenols to their corresponding acetyl compounds using acetic anhydride under mild and solvent-less conditions. The supported iron oxide nanoparticles could be easily recovered from the reaction mixture and reused ten times without any loss in activity.
- Rajabi, Fatemeh,Luque, Rafael
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p. 129 - 132
(2014/01/06)
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- 3-Formylchromone based topoisomerase IIα inhibitors: Discovery of potent leads
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Substituted 3-formylchromones were synthesized and evaluated as inhibitors of the human DNA topoisomerase IIα (hTopo-IIα) enzyme. The results of the decatenation, relaxation and DNA intercalation assays revealed that the compounds (11b, 12a, 12b, 12d, 12e, 13a and 13b) exhibited potent inhibitory activity against the hTopo-IIα enzyme, and are nonintercalating agents. These compounds also possess significant in vitro cytotoxicity (LC50 ranges from 0.5-8.6 μM) against prostate (PC-3) cancerous cell line as seen in comparison to the standard drug etoposide. To further probe the plausible mode of action of 3-formylchromone derivatives, molecular docking studies have also been carried out, which showed that the compounds under investigation fitted well in the ATP binding pocket of hTopo-IIα enzyme with good docking scores and form nonbonding interactions with the crucial residues of the catalytic site. The Royal Society of Chemistry.
- Singh, Satyajit,Baviskar, Ashish Triambak,Jain, Vaibhav,Mishra, Nidhi,Chand Banerjee, Uttam,Bharatam, Prasad V.,Tikoo, Kulbhushan,Singh Ishar, Mohan Paul
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supporting information
p. 1257 - 1266
(2013/09/12)
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- A new ferrocene-based bulky pyridine as an efficient reusable homogeneous catalyst
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An effective approach to reusing a homogeneous catalyst has been demonstrated. A ferrocene-based bulky pyridine has been synthesized and utilized as a homogeneous catalyst for the synthesis of benzoylfumarates as well as for acetylation. After the reaction, the catalyst was separated by simple precipitation and reused without appreciable loss of activity. The Royal Society of Chemistry 2013.
- Kashyap, Bishwapran,Phukan, Prodeep
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p. 15327 - 15336
(2013/09/02)
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- Design and syntheses of novel N′-((4-oxo-4H-chromen-3-yl)methylene) benzohydrazide as inhibitors of cyanobacterial fructose-1,6-/sedoheptulose-1,7- bisphosphatase
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Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (Cy-FBP/SBPase) is an important target enzyme for finding inhibitors to solve harmful algal bloom (HAB). In this study, as potential inhibitors of Cy-FBP/SBPase, a series of novel chromone-connecting benzohydrazone compounds (Novel N′-((4-oxo-4H-chromen-3-yl)methylene)benzohydrazide) were designed and synthesized. Their inhibitory activities against Cy-FBP/SBPase were further examined in vitro. Some of these compounds, such as f6-f8, f11, f12 and f16, exhibit higher inhibitory activities (IC50 = 11.2-16.1 μM), especially, the compound f7 was identified as the most potent inhibitor with IC50 value of 11.2 μM. The probable binding-mode of compound f7 was further analyzed carefully by molecular docking methods. These results indicate that compound f7 could be used as a lead compound for further optimization and might have potential to be developed as a new algicide.
- Tu, Qi-Dong,Li, Ding,Sun, Yao,Han, Xin-Ya,Yi, Fan,Sha, Yibamu,Ren, Yan-Liang,Ding, Ming-Wu,Feng, Ling-Ling,Wan, Jian
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p. 2826 - 2831
(2013/06/27)
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- Comparisons of O-acylation and Friedel-Crafts acylation of phenols and acyl chlorides and Fries rearrangement of phenyl esters in trifluoromethanesulfonic acid: Effective synthesis of optically active homotyrosines
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Reactions involving phenol derivatives and acyl chlorides have to be controlled for competitive O-acylations and C-acylations (Friedel-Crafts acylations and Fries rearrangements) in acidic condition. The extent for these reactions in trifluoromethanesulfonic acid (TfOH), which is used as catalyst and solvent, is examined. Although diluted TfOH was needed for effective O-acylation, concentrated TfOH was required for effective C-acylations in mild condition. These results have been applied to the novel synthesis of homotyrosine derivatives. Both Fries rearrangement of N-TFA-Asp(OBn)-OMe and Friedel-Crafts acylation of phenol with N-TFA-Asp(Cl)-OMe in TfOH afforded the homotyrosine skeleton, followed by reduction and deprotection afforded homotyrosines maintaining stereochemistry of Asp as an optically pure form.
- Murashige, Ryo,Hayashi, Yuka,Ohmori, Syo,Torii, Ayuko,Aizu, Yoko,Muto, Yasuyuki,Murai, Yuta,Oda, Yuji,Hashimoto, Makoto
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experimental part
p. 641 - 649
(2011/03/19)
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- Mechanistic and computational studies of oxidatively-induced Aryl-CF 3 bond-formation at Pd: Rational design of room temperature aryl trifluoromethylation
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This article describes the rational design of first generation systems for oxidatively induced Aryl-CF3 bond-forming reductive elimination from PdII. Treatment of (dtbpy)PdII(Aryl)(CF3) (dtbpy = di-tert-butylbipyridine) with NFTPT (N-fluoro-1,3,5-trimethylpyridinium triflate) afforded the isolable PdIV intermediate (dtbpy)Pd IV(Aryl)(CF3)(F)(OTf). Thermolysis of this complex at 80 °C resulted in Aryl-CF3 bond-formation. Detailed experimental and computational mechanistic studies have been conducted to gain insights into the key reductive elimination step. Reductive elimination from this PdIV species proceeds via pre-equilibrium dissociation of TfO- followed by Aryl-CF3 coupling. DFT calculations reveal that the transition state for Aryl-CF3 bond formation involves the CF3 acting as an electrophile with the Aryl ligand serving as a nucleophilic coupling partner. These mechanistic considerations along with DFT calculations have facilitated the design of a second generation system utilizing the tmeda (N,N,N′,N′-tetramethylethylenediamine) ligand in place of dtbpy. The tmeda complexes undergo oxidative trifluoromethylation at room temperature.
- Ball, Nicholas D.,Gary, J. Brannon,Ye, Yingda,Sanford, Melanie S.
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scheme or table
p. 7577 - 7584
(2011/06/25)
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- An atom-efficient and powerful method for direct esterification of silyl ethers catalyzed by HClO4-SiO2
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An efficient and convenient procedure for direct esterification of alkyl and aryl silyl ethers with Ac2O and a catalyst system of perchloric acid immobilized on a silica gel (HClO4-SiO2) has been developed. The silyl protecting groups are directly replaced by acetyls and the protecting groups themselves are transformed into acetates as the sole byproducts, which can be readily recovered and converted back to silylchlorides, the original protecting agents, thus minimizing wastes.
- Du, Ti-Jian,Wu, Qin-Pei,Liu, Hai-Xia,Chen, Xi,Shu, Yi-Nan,Xi, Xiao-Dong,Zhang, Qing-Shan,Li, Yun-Zheng
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experimental part
p. 1096 - 1101
(2011/04/16)
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- Silver triflate catalyzed acetylation of alcohols, thiols, phenols, and amines
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A variety of alcohols, thiols, phenols, and amines were subjected to acetylation reaction using acetic anhydride in the presence of catalytic quantity of silver triflate. The method described has a wide range of applications, proceeds under mild conditions, does not involve cumbersome workup, and the resulting products are obtained in high yields within a reasonable time. Georg Thieme Verlag Stuttgart · New York.
- Das, Rima,Chakraborty, Debashis
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experimental part
p. 1621 - 1625
(2011/06/25)
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- Synthesis of 7-substituted-(2,3-dihydro-1,4-benzodioxin-5-yl)-piperazine
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A simple and versatile method for the synthesis of 7-substituted (2,3-dihydro-1,4-benzodioxin-5-yl)-piperazines starting from easy available class of derivatives has been developed. Copyright Taylor & Francis Group, LLC.
- Rancati, Fabio,Bromidge, Steven M.,Del Sordo, Simone,La Rosa, Salvatore,Parini, Carlo,Gagliardi, Stefania
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p. 2507 - 2520
(2008/12/22)
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- Al(OTf)3 as a highly efficient catalyst for the rapid acetylation of alcohols, phenols and thiophenols under solvent-free conditions
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Aluminium triflate (0.01-0.1 mol %) was found to be an efficient catalyst for the acylation of alcohols, phenols, thiols and sugars with acetic anhydride in high yields under solvent-free conditions in a short reaction time at room temperature. Racemization of optically active alcohols and epimerization of sugars were not observed. The acylation efficacy of various acyl donors was also investigated.
- Kamal, Ahmed,Khan, M. Naseer A.,Reddy, K. Srinivasa,Srikanth,Krishnaji
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p. 3813 - 3818
(2008/02/06)
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- Ruthenium(III) acetylacetonate [Ru(acac)3] -An efficient recyclable catalyst for the acetylation of phenols, alcohols, and amines under neat conditions
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A catalytic amount of ruthenium(III) acetylacetonate (2 mol%) [Ru(acac)3] enables solvent-free acetylation of phenols, alcohols, and amines at ambient temperature in good to excellent yields. Furthermore, the catalyst could be recovered and reused at least three times without a significant loss in yields.
- Varala, Ravi,Nasreen, Aayesha,Adapa, Srinivas R.
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p. 148 - 152
(2008/02/11)
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- Hydroxylated nebivolol metabolites
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Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.
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- A convenient synthesis of 1-[6-Fluoro-(2S)-3H,4H-dihydro-2H-2-chromenyl]- (1R)-1,2-ethanediol and 1-[6-fluoro-(2R)-3H,4H-dihydro- 2H-2-chromenyl]-(1R)-1, 2-ethanediol
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1-[6-Fluoro-(2S)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol and 1-[6-fluoro-(2R)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol, important pharmaceutical intermediates, were synthesized from natural chiral pool D-mannitol. Georg Thieme Verlag Stuttgart.
- Yu, An-Guang,Wang, Nai-Xing,Xing, Ya-Lan,Zhang, Jun-Ping,Yang, Yun-Xu,Wang, Wu-Wei,Sheng, Rui-Long
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p. 1465 - 1467
(2007/10/03)
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- HETEROCYCLIC COMPOUNDS THAT BLOCK THE EFFECTS OF ADVANCED GLYCATION END PRODUCTS (AGE)
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The present invention relates to novel compounds of Formula (Ia) or (Ib), their pharmaceutically acceptable salts and pharmaceutically acceptable compositions containing them. Formula (Ia), or Formula (Ib) in the above formulae L represents Formula (I), Formula (II) or -(CH2)1- Q represents Formula (III), or Formula (IV). The present invention also relates to a process for the preparation of the above said novel compounds, their pharmaceutically acceptable salts and pharmaceutical compositions containing them. The present invention also relates to methods and compositions comprising compounds that treat pathophysiological conditions arising from inflammatory responses. In particular, the present invention is directed to compounds that inhibit or block glycated protein produced induction of the signaling-associated inflammatory responses in tissues, including endothelial cells. The present invention relates to compounds that inhibit smooth muscle proliferation. The present invention also relates to compounds that act as modulators of Perlecan activity and expression. In particular, the present invention is directed to compounds that inhibit smooth muscle cell proliferation by modulating heparan sulfate proteoglycans (HSPG) such as Perlecan. The present invention further relates to the use of compounds to treat vascular occlusive conditions characterized by smooth muscle proliferation such as stenosis, restenosis, neointimal hyperplasia, and atherosclerosis. The compounds of Formula (I) are also useful for the treatment and/or prevention of cancer. The types of cancers include melanoma, prostate, leukemia, lymphoma, non-small lung cancers, cancer of the central nervous system, breast, colon, ovarian or renal cancer.
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Page/Page column 58
(2010/02/11)
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- 4,6-Disubstituted 2,2-dimethylchromans structurally related to the K ATP channel opener cromakalim: Design, synthesis, and effect on insulin release and vascular tone
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Five series (ureas, thioureas, carbamates, sulfonylureas, and amides) of 4,6-disubstituted-2,2-dimethylchromans structurally related to cromakalim were prepared and evaluated, as putative ATP-sensitive potassium channel activators, on rat pancreatic islets and rat aorta rings. The biological data indicate that most compounds were, like the reference molecule cromakalim, more active on the vascular smooth muscle tissue (myorelaxant effect on 30 mM KCl induced contractions of rat aorta rings) than on the pancreatic tissue (inhibition of 16.7 mM glucose induced insulin release from rat pancreatic islets). However, some drugs (8h, 8i, 9f, 9g, 9h, and 9i) markedly inhibited insulin release and exhibited an activity equivalent or greater than that of diazoxide. Compounds 9h and 9i were also found to be more active on pancreatic β-cells than on vascular smooth muscle cells. Last, the amide 6b was selected in order to examine its mechanism of action on vascular smooth muscle cells. Pharmacological results suggest that the compound acted as a KATP channel opener. In conclusion, the present data indicate that appropriate structural modifications can generate dimethylchromans with pharmacological profiles different from that of cromakalim.
- Sebille, Sophie,De Tullio, Pascal,Becker, Bénédicte,Antoine, Marie-Hélène,Boverie, Stéphane,Pirotte, Bernard,Lebrun, Philippe
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p. 614 - 621
(2007/10/03)
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- Sulfonamide-substituted chromans, processes for their preparation, their use as a medicament or diagnostic, and medicament comprising them
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Sulfonamide-substituted chromans, processes for their preparation, their use as a medicament or a diagnostic, and medicament comprising them Chromans of the formula I and of the formula 1a having the meanings R(A), R(B), R(C) and R(1) to R(8) indicated in the claims are outstandingly suitable for preparing a medicament for blocking the K+channel which is opened by cyclic adenosine monophosphate (cAMP); and further for preparing a medicament for inhibiting gastric acid secretion; for the treatment of ulcers of the stomach and of the intestinal region, in particular of the duodenum, for the treatment of reflux esophagitis, for the treatment of diarrheal illnesses, for the treatment and prevention of all types of arrhythmias including ventricular and supraventricular arrhythmias, and for the control of reentry arrhythmias and for the prevention of sudden heart death as a result of ventricular fibrillation.
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- Synthesis and in-vitro evaluation of platelet aggregation inhibitory activity of paeonol and its analogues
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Paeonol (1-(2-hydroxy-4-methoxyphenyl)ethanone) and a series of substituted 1-(2-hydroxyphenyl)ethanone derivatives were synthesized and screened as inhibitors of platelet aggregation. The compounds with the greatest anti-platelet potential among the series tested were 1-(2,5-dihydroxyphenyl)ethanone (65.36% inhibition at 300 μM against 5 μM ADP), paeonol(36.31%), 1-(2-hydroxy-5-methoxyphenyl)ethanone (24.47%), 1-(2-hydroxy-5-nitrophenyl) ethanone (30.40%) and 1-(5-chloro-2-hydroxy-4-methylphenyl)ethanone (24.43%).
- Akamanchi,Padmawar,Thatte,Rege,Dahanukar
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p. 323 - 329
(2007/10/03)
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- Synthesis and pharmacological evaluation of K(ATP)-channel openers related to cromakalim: Introduction of arylsulphonylurea moieties
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A series of 4-(arylsulphonylaminocarbonylamino)-3,4-dihydro-2,2-dimethyl-2 H-1-benzopyran derivatives were prepared and evaluated as potential ATP-sensitive potassium-channel activators. Pharmacological studies showed that some compounds expressed vasodilator efficacy on vascular smooth muscle. The compounds had no inhibitory activity on insulin secretion from pancreatic β-cells.
- Khelili,Nguyen,Lebrun,Delarge,Pirotte
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p. 189 - 193
(2007/10/03)
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- Benzopyran derivatives having leukotriene-antagonistic action
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The present invention relates to novel 4-oxo-4H-1-benzopyran compounds containing benzyloxymethyl, 3-phenylpropyl, or other araliphatic substituents in their 8-position. These compounds show a leukotriene-antagonistic activity. The compounds are characterized by good oral adsorption. The compounds of the present invention may be used as anti-inflammatory and antiallergic medicaments, and in the treatment of cardiovascular diseases.
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- Preparation of 4-fluorophenol and 4-fluorobenzoic acid by the Baeyer-Villiger reaction
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The possibility of preparing 4-fluorophenol or 4-fluorobenzoic acid via the Baeyer-Villiger reaction starting from unsymmetrical fluoroaryl ketones is disscussed.Several unsymmetrical 4-fluorobenzophenones having different substituents in the fluorine-free aryl group were prepared and converted to esters by treatment with peracetic acid.The electrophilicity of the substituents influenced the molecular structure of the ester formed as a result of a carbon-to-oxygen migration, and hence 4-fluorophenol or 4-fluorobenzoic acid formation.Electron-withdrawing substituents favoured the formation of 4-fluorophenol in good yields, while electron-donating substituents formed 4-fluorobenzoic acid preferentially.
- Conte, L.,Napoli, M.,Gambaretto, J. P.,Guerrato, A.,Carlini, F. M.
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- Acetylation of phenols in organic solvent catalyzed by a lipase from chromobacterium viscosum
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Lipase from Chromobacterium viscosum, absorbed on an inert support, was employed as catalyst for the esterification of monohydric phenols in organic solvent, with vinyl acetate as acyl donor. The effect of aromatic ring substitution on the initial rate of transesterification was investigated.
- Nicolosi,Piatelli,Sanfilippo
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p. 2477 - 2482
(2007/10/02)
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- An Open Transition State in Carbonyl Acyl Group Transfer in Aqueous Solution
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The second-order rate constants have been measured for the reaction of substituted phenolate ions with 2,4-dinitrophenyl acetate, 2,4-dinitrophenyl 4-methoxy-2,6-dimethylbenzoate and acetic anhydride in aqueous solution at 25 deg C.The data are over a wide range of phenolate ion basicity and obey good Broensted equations which have βnuc values of, respectively, 0.57 +/- 0.03, 0.15 +/- 0.07 and 0.59 +/- 0.05.The principal conclusion of this work is that the identity reaction of 2,4-dinitrophenolate ion with 2,4-dinitrophenyl 4-methoxy-2,6-dimethylbenzoate has anopen transition state, namely one with very weak bonds to entering and departing ligands.The transition state possesses a Kreevoy tightness parameter (τ) of 0.18.The open transition state arises from the stabilising effect of the acyl group substituents on the benzoylium ion and their destabilising effect on the putative tetrahedral intermediate as well as the weak basicities of the nucleophile and nucleofuge.This is the first example of an open transition state in an acyl group transfer which does not require the assistance of a negatively charged internal nucleophile.The data for 2,4-dinitrophenyl acetate may be employed to calculate an identity rate constant (kii) for the reaction of 2,4-dinitrophenolate ion with the ester.This data may be fitted to a theoretical Lewis-Kreevoy plot (log kii vs. pKi) possessing both positive and negative values of βii (slope of the line).Microscopic medium effects place a limit to the accuracy of predictions of rate constants, including kii, from linear free energy relationships.
- Ba-Saif, Salem A.,Colthurst, Matthew,Waring, Mark A.,Williams, Andrew
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p. 1901 - 1908
(2007/10/02)
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- Fungicidal azole derivatives
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A novel fungicidal compound of the formula: STR1 wherein R1 is hydrogen, alkyl having 1 to 12 carbon atoms, STR2 R2 and R3 are hydrogen, bromine or methyl; R4 is alkenyl having 2 to 9 carbon atoms or alkynyl having 2 to 9 carbon atoms; m is an integer of 0 to 2; n is an integer of 0 to 1; p and q are independently integers of 1 to 8; Az is imidazolyl or 1,2,4-triazolyl, Q is --CO--, --O-- or --CO--NR5 --; R5 is hydrogen or methyl, Y is hydrogen, fluorine, chlorine or phenyl; and Z is hydrogen, fluorine, chlorine or methyl, provided that, when Z is hydrogen or chlorine, n is 1, or its salt. A process for producing the compound (I) and a fungicide containing the compound (i) are also disclosed.
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- Concertedness in Acyl Group Transfer in Solution: A Single Transition State in Acetyl Group Transfer between Phenolate Ion Nucleophiles
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Rate constants have been measured for nucleophilic substitution of 4-nitrophenol from 4-nitrophenyl acetate by a series of phenolate anions.The Bronsted type plot is linear for unhindered phenolate ions with pKa values significantly above and below that of the displaced 4-nitrophenol: (log kArO = 0.75pKArOH - 7.28; n = 17, r = 0.984); this is consistent with a mechanism involving a single transition state or a mechanism with an intermediate that has a very low barrier to decomposition.A small change in effective charge on the carbonyl group from reactant to transition state (measured from βnuc and the known βeq for the overall reaction) points to an almost coupled concerted mechanism for the transfer of acetyl function between phenolate ion nucleophiles.The conclusions of this work are consistent with previous results that indicate relatively stable tetrahedral intermedates in reactions at reactive acyl centers; a spectrum of mechanisms exists for substitution reactions of acyl functions in solution that ranges from SN1 (or ElcB for an ester with an α-carbanion) through concerted to BAc2.
- Ba-Saif, Salem,Luthra, Ajay K.,Williams, Andrew
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p. 6362 - 6368
(2007/10/02)
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- The conformational properties of some phenyl esters. Molecular orbital and nuclear magnetic resonance studies
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Extensive, geometry-optimized, STO-3G MO computations on phenyl formate imply a strongly nonplanar Z conformer (C=O bond cis to the phenyl group) at ambient temperatures.The internal barrier to rotation about the C(1)-O bond in this conformer is computed as V/kJ mol-1=(-5.17+/-0.27)sin2θ - (2.42+/-0.27)sin22θ, θ being zero for the planar conformer; the twofold is nearly twice as large as the fourfold component.The expectation value of θ is 58 deg at 300 K.The spin-spin coupling constants over six bonds between (13)C and (19)F nuclei in 4-fluorophenyl formate, acetate, propionate, and isobutyrate, as well as in the 2,6-dichloro-4-fluorophenyl acetate, are adduced as evidence for nonplanar conformers of these molecules.The magnitudes of these six-bond coupling constants are consistent with internal barriers to rotation about the C(1)-O bonds, which are similar in magnitude to those given by the computations on the Z conformer of phenyl formate.The energies of the planar and nonplanar E conformers, as well as the interconversion energies for EZ isomerization, are computed.Small amounts of the nonplanar E conformer are predicted at ambient temperatures.The (13)C chemical shifts and the one-bond (13)C, (19)F coupling constants are consistent, respectively, with only minor variations in the conformational behavior of the ester moieties caused by the fluorine substituent and by changes in the structures of these moieties themselves.
- Schaefer, Ted,Penner, Glenn H.
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p. 2175 - 2178
(2007/10/02)
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