- Design, synthesis and biological evaluation of novel pyrrolidone-based derivatives as potent p53-MDM2 inhibitors
-
Inhibition of the interactions of the tumor suppressor protein p53 with its negative regulators MDM2 in vitro and in vivo, representing a valuable therapeutic strategy for cancer treatment. The natural product chalcone exhibited moderate inhibitory activity against MDM2, thus based on the binding mode between chalcone and MDM2, a hit unsaturated pyrrolidone scaffold was obtained through virtual screening. Several unsaturated pyrrolidone derivatives were synthesized and biological evaluated. As a result, because the three critical hydrophobic pockets of MDM2 were occupied by the substituted-phenyl linked at the pyrrolidone fragment, compound 4 h demonstrated good binding affinity with the MDM2. Additionally, compound 4 h also showed excellent antitumor activity and selectivity, and no cytotoxicity against normal cells in vitro. The further antitumor mechanism studies were indicated that compound 4 h could successfully induce the activation of p53 and corresponding downstream p21 proteins, thus successfully causing HCT116 cell cycle arrest in the G1/M phase and apoptosis. Thus, the novel unsaturated pyrrolidone p53-MDM2 inhibitors could be developed as novel antitumor agents.
- Si, Dongjuan,Luo, Huijuan,Zhang, Xiaomeng,Yang, Kundi,Wen, Hongmei,Li, Wei,Liu, Jian
-
-
- Enantioselective Synthesis of Nitrogen-Nitrogen Biaryl Atropisomers via Copper-Catalyzed Friedel-Crafts Alkylation Reaction
-
Nitrogen-nitrogen bonds containing motifs are ubiquitous in natural products and bioactive compounds. However, the atropisomerism arising from a restricted rotation around an N-N bond is largely overlooked. Here, we describe a method to access the first enantioselective synthesis of N-N biaryl atropisomers via a Cu-bisoxazoline-catalyzed Friedel-Crafts alkylation reaction. A wide range of axially chiral N-N bisazaheterocycle compounds were efficiently prepared in high yields with excellent enantioselectivities via desymmetrization and kinetic resolution. Heating experiments showed that the axially chiral bisazaheterocycle products have high rotational barriers.
- Guo, Chang-Qiu,Liu, Ren-Rong,Lu, Chuan-Jun,Wang, Xiao-Mei,Xu, Qi,Zhang, De-Bing,Zhang, Peng
-
supporting information
p. 15005 - 15010
(2021/09/30)
-
- Asymmetric Transfer Hydrogenation: Dynamic Kinetic Resolution of α-Amino Ketones
-
A series of α-amino ketones were reduced using asymmetric transfer hydrogenation (ATH) through a dynamic kinetic resolution (DKR). The protecting group was matched to the reducing agent, and following optimization, a series of substrates were investigated, giving products in high diastereoselectivity, over 99% ee in several cases and full conversion. The methodology was applied to the enantioselective synthesis of an MDM2-p53 inhibitor precursor.
- Gediya, Shweta K.,Clarkson, Guy J.,Wills, Martin
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p. 11309 - 11330
(2020/10/12)
-
- 3D-QSAR assisted identification of FABP4 inhibitors: An effective scaffold hopping analysis/QSAR evaluation
-
Following on the recent publication of pharmacologically relevant effects, small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have attracted high interest. FABP4 is mainly expressed in macrophages and adipose tissue, where it regulates fatty acid storage and lipolysis, being also an important mediator of inflammation. In this regard, FABP4 recently demonstrated an interesting molecular target for the treatment of type 2 diabetes, other metabolic diseases and some type of cancers. In the past years, hundreds of effective FABP4 inhibitors have been synthesized. In this paper, a quantitative structure-activity relationship (QSAR) model has been produced, in order to predict the bioactivity of FABP4 inhibitors. The methodology has been combined with a scaffold-hopping approach, allowing to identify three new molecules that act as effective inhibitors of this protein. These molecules, synthesized and tested for their FABP4 inhibitor activity, showed IC50 values between 3.70 and 5.59 μM, with a high level of agreement with the predicted values.
- Floresta, Giuseppe,Cilibrizzi, Agostino,Abbate, Vincenzo,Spampinato, Ambra,Zagni, Chiara,Rescifina, Antonio
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p. 276 - 284
(2018/12/11)
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- NBS-mediated synthesis of β-keto sulfones from benzyl alcohols and sodium arenesulfinates
-
An efficient synthetic route towards the synthesis of β-keto sulfones has been developed from secondary benzyl alcohols using N-bromosuccinimide (NBS). The present protocol utilizes NBS as oxidant as well as brominating agent, readily accessible benzyl alcohols and sodium arenesulfinates as the sulfonylating reagent under mild conditions. The control experiments revealed that the reaction proceeds via oxidation of alcohol to ketone, α-bromination of ketone and nucleophilic substitution by sodium arenesulfinate. Furthermore, the efficiency of the methodology was tested with a gram scale reaction and also shown the synthetic utility.
- Muneeswara, Madithedu,Sundaravelu, Nallappan,Sekar, Govindasamy
-
supporting information
p. 3479 - 3484
(2019/05/21)
-
- A Method for the Catalytic Enantioselective Synthesis of Chiral α-Azido and α-Amino Ketones from Racemic α-Bromo Ketones, and Its Generalization to the Formation of Bonds to C, O, and S
-
A new and practical method has been developed for the transformation of racemic α-bromo ketones to chiral α-azido and α-amino ketones with high enantioselectivity using phase transfer, ion-pair mediated reactions with a recoverable chiral quaternary salt (10 mol %) as catalyst in fluorobenzene-water. The process has been generalized to a variety of other attachments including of C, O, S, and NHR.
- Da Silva Gomes, Roberto,Corey
-
supporting information
p. 20058 - 20061
(2019/12/27)
-
- High yield preparation method of selexipag intermediate compound under middle conditions
-
The invention relates to a high yield preparation method of a selexipag intermediate compound under middle conditions. According to the method, styracitol and halogen acid carry out halogenation reactions, and the reaction product and N-aminoacetyl-N-isopropyl n-butanol carry out condensation, ammoxidation, and ring forming reactions to obtain 2-(N-isopropyl-N-4-hydroxylbutyl)amino-5,6-diphenylpyrazine. The compound can be used to prepare selexipag. The raw materials are cheap and easily available, the operation is simple, convenient and safe, the reaction selectivity is good, the yield and purity are high, and the cost is low.
- -
-
Paragraph 0054-0055; 0061-0062
(2019/03/15)
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- 2-Amino-4-arylthiazoles through One-Pot Transformation of Alkylarenes with NBS and Thioureas
-
Treatment of alkylarenes with N-bromosuccinimide in a mixture of ethyl acetate and water at 60 °C, a mixture of acetonitrile and water at 80 °C, or a mixture of diethyl carbonate and water under irradiation with a tungsten lamp, followed by a reaction with thioureas or arenethioamides provided the corresponding 2-amino- 4-arylthiazoles or 2,4-diarylthiazoles in good to moderate yields, respectively, in one pot. The present reaction is an efficient one-pot transformation method of alkylarenes into 2-amino-4-arylthiazoles and 2,4-diarylthiazoles directly under mild and transition-metal-free conditions.
- Shibasaki, Kaho,Togo, Hideo
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p. 2520 - 2527
(2019/04/04)
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- Efficient sulfonylation of ketones with sodium sulfinates for the synthesis of β-keto sulfones
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The oxidative sulfonylation of ketones with sodium sulfinates as the sulfone source and DMSO as the oxidant is reported. A series of β-keto sulfones were obtained in good to excellent yields. The advantages of this efficient protocol include the low cost of DMSO and HBr, and a broad scope.
- Deng, Siqi,Liang, En,Wu, Yinrong,Tang, Xiaodong
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supporting information
p. 3955 - 3957
(2018/09/27)
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- BF3·OEt2-mediated [1,2]-aryl shift: Synthesis of functionalized α-arylnitriles via the bromination/cyanation/deformylation of substituted deoxybenzoin
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A new sequential, tandem synthesis of functionalized α-arylnitriles via the bromination/cyanation/deformylation of substituted deoxybenzoin has developed. CuBr2-promoted bromination of substituted deoxybenzoins gives 2-bromo-2-arylacetophenne 3. The cyanation of 3 with sodium cyanide (NaCN) generates epoxynitrile. Then, a treatment of epoxynitrile with BF3·OEt2 results in the formation of functionalized α-arylnitriles 4 via a 1,2-aryl shift.
- Chan, Chieh-Kai,Chang, Meng-Yang
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p. 5207 - 5213
(2017/07/28)
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- Vicinal diaryl azole-based urea derivatives as potential cholesterol lowering agents acting through inhibition of SOAT enzymes
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A novel series of vicinal diaryl azole-urea derivatives were synthesized and evaluated for their potential to inhibit SOAT enzyme. Among the reported compounds, compound (12d) emerged as the most potent compound with an IC50value of 2.43?μM. In polaxamer-407 induced lipoprotein lipase inhibition model, compound (12d) reduced triglyceride turnover in?vivo. Compound (12d) also showed dose-dependent prevention of serum total cholesterol and prevention of LDL-C elevation at a dose of 30?mg/kg. Furthermore, compound (12d) showed potential to stop falling levels of serum HDL-C dose-dependently and improved the atherogenic index. Effect of 12d on body weight, plaque formation and development of atherogenic lesions were studied. Toxicological study of compound (12d) indicated that at a dose of 2000?mg/kg, 12d was devoid of any signs of toxicity or mortality.
- Pal, Palash,Gandhi, Hardik P.,Kanhed, Ashish M.,Patel, Nirali R.,Mankadia, Niraj N.,Baldha, Satish N.,Barmade, Mahesh A.,Murumkar, Prashant R.,Yadav, Mange Ram
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supporting information
p. 107 - 123
(2017/03/02)
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- Water-controlled selective preparation of α-mono or α,α′-dihalo ketones: Via catalytic cascade reaction of unactivated alkynes with 1,3-dihalo-5,5-dimethylhydantoin
-
The control of a reaction that can produce multiple products from the same starting material is a highly attractive and challenging concept in organic synthesis. An efficient protocol for the selective synthesis of α-mono or α,α′-dihalo ketones via a water-controlled three-component thiourea-catalyzed cascade reaction of unactivated alkynes, 1,3-dihalo-5,5-dimethylhydantoin and water has been developed. α-Monohaloketones were obtained in aqueous acetone at 45 °C; conversely, α,α′-dihalo ketones were formed with pure water as the sole solvent at room temperature.
- Wu, Chao,Xin, Xiu,Fu, Zhi-Min,Xie, Long-Yong,Liu, Kai-Jian,Wang, Zheng,Li, Wenyi,Yuan, Zhi-Hui,He, Wei-Min
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p. 1983 - 1989
(2017/06/09)
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- Copper nitrate-catalyzed α -bromination of aryl ketones with hydrobromic acid
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An efficient method for α-bromination of aryl ketones, using the combination of molecular oxygen and aqueous hydrobromic acid as a brominating agent in the presence of the copper nitrate, has been developed. This catalytic system, which uses cheap and readily available reactants, shows good atom economy with water as the only by-product.
- Wang, Jianqiang,Wang, Xiaolei,Niu, Zong-Qiang,Wang, Jian,Zhang, Man,Li, Jing-Hua
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p. 165 - 168
(2016/02/23)
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- Unexpected Role of p-Toluenesulfonylmethyl Isocyanide as a Sulfonylating Agent in Reactions with α-Bromocarbonyl Compounds
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The reactions of p-toluenesulfonylmethyl isocyanide (TosMIC) with α-bromocarbonyl compounds leading efficiently to α-sulfonated ketones, esters, and amides were reported, in which an explicit new role of TosMIC as the sulfonylating agent was uncovered for the first time. Mechanistic study by control experiments and DFT calculations suggested that the reaction is initiated by Cu(OTf)2-catalyzed hydration of TosMIC to form a formamide intermediate, which undergoes facile C-S bond cleavage under the mediation of a Cs2CO3 additive.
- Chen, Jiajia,Guo, Wei,Wang, Zhenrong,Hu, Lin,Chen, Fan,Xia, Yuanzhi
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p. 5504 - 5512
(2016/07/13)
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- A metal-free hydrogenation of 3-substituted 2H-1,4-benzoxazines
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A metal-free hydrogenation of 3-substituted 2H-1,4-benzoxazines has been successfully realized with 2.5 mol% of B(C6F5)3 as a catalyst to furnish a variety of 3,4-dihydro-2H-1,4-benzoxazines in 93-99% yields. Up to 42% ee was also achieved for the asymmetric hydrogenation with the use of a chiral diene and HB(C6F5)2.
- Wei, Simin,Feng, Xiangqing,Du, Haifeng
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supporting information
p. 8026 - 8029
(2016/09/09)
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- Metal-free protocol for the synthesis of α-bromo ketones from olefins using TsNBr2
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TsNBr2 reacts readily with olefins to produce α-bromo ketones at room temperature. The synthesis was carried out by treating an olefin with TsNBr2 in acetone-water mixture in 30:1 ratio. Excellent yield of corresponding α-bromo ketone could be achieved within a short time.
- Rajbongshi, Kamal Krishna,Hazarika, Debojit,Phukan, Prodeep
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supporting information
p. 356 - 358
(2015/04/27)
-
- Synthesis, cytotoxic evaluation, and molecular docking study of 4,5-diaryl-thiazole-2-thione analogs of combretastatin A-4 as microtubule-binding agents
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A series of combretastatin A-4 analogs in which cis-olefinic bond replaced by thiazole ring were prepared by reaction of α-bromo-1,2-(p-substituted) diaryl-1-ethanones and dithiocarbamate derivatives. The cytotoxicity of these compounds was determined against three cancer cell lines (HT-29), (MCF-7), (AGS) as well as fibroblastic cell line (NIH-3T3) using MTT assay. Inhibition of tubulin polymerization for some potent compounds was evaluated. These biological studies proved that 6j and 6o were the most potent compounds in this series. Furthermore 2-(methylthio)-substituted compounds show moderate or no activity. Docking studies involving 6j and 6o demonstrated that this analogs could be successfully docked in the colchicine binding site of α,β-tubulin.
- Salehi, Marjan,Ostad, Seyed Nasser,Riazi, Gholam Hossein,Assadieskandar, Amir,Cheraghi-Shavi, Tayebeh,Shafiee, Abbas,Amini, Mohsen
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p. 1465 - 1473
(2014/03/21)
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- Three-component access to pyrroles promoted by the CAN-silver nitrate system under high-speed vibration milling conditions: A generalization of the Hantzsch pyrrole synthesis
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A sequential multicomponent process involving the high-speed vibration milling of ketones with N-iodosuccinimide and p-toluenesulfonic acid, followed by addition of a mixture of primary amines, β-dicarbonyl compounds, cerium(iv) ammonium nitrate and silver nitrate afforded polysubstituted, functionalized pyrroles. This one-pot, solid-state process can be considered as the coupling of an α-iodoketone preparation with a general version of the classical Hantzsch pyrrole synthesis.
- Estevez, Veronica,Villacampa, Mercedes,Menendez, J. Carlos
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supporting information
p. 591 - 593
(2013/02/22)
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- Magnetic-nanoparticle-supported 2,2′-bis[3-(triethoxysilyl)propyl] imidazolium-substituted diethyl ether bis(tribromide): A convenient recyclable reagent for bromination
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A new magnetic-nanoparticle-supported bromination reagent was synthesized by anchoring a 2,2′-bis[3-(triethoxysilyl)propyl]imidazolium-substituted diethyl ether bis(tribromide) onto the surface of γ-Fe2O 3 nanoparticles and subsequently treating this new ionic liquid with bromine. The nanoparticle reagent was obtained with good loading levels and has been successfully used for the efficient bromination of a wide range of alkenes, alkynes, ketones, and aromatic substrates. More importantly, the reagent could be easily recovered by an external magnet and reused six times without significant loss of activity. A new maghemite nanoparticle bromination reagent has been prepared. The nanoparticle reagent was obtained with good loading levels and has been successfully used for the efficient bromination of a wide range of alkenes, alkynes, ketones, and aromatic substrates. Copyright
- Wu, Liqiang,Yin, Zhikui
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p. 6156 - 6163
(2014/01/06)
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- Reactivity of a-trifluoromethanesulfonyl esters, amides and ketones: Decarboxylative allylation, methylation, and enol formation
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The impact of α-trifluoromethanesulfonyl groups on the chemistry of various carbonyl groups is reported. Allylic α, α-dialkylated- α-trifluoromethanesulfonyl esters readily underwent decarboxylative allylation. α-Trifluoromethylsulfonyl esters, ketones, and amides were all methylated in the presence of trimethylsilyldiazomethane. Esters afforded a mixture of O-and C-methylation; however, ketones and amides offered exclusively O-methylation, with varying degrees of E/Z selectivity, thus affording ambiphilic alkenes. α-Trifluoromethanesulfonyl ketones also exhibited keto-enol tautomerism.
- Kong, Han Il,Gill, Monica A.,Hrdina, Amy H.,Crichton, Jennifer E.,Manthorpe, Jeffrey M.
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p. 151 - 161
(2013/11/06)
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- Stereoselective synthesis of ambiphilic alkenes via regioselective methylation of α-trifluoromethanesulfonyl carbonyl compounds with trimethylsilyldiazomethane
-
α-Trifluoromethanesulfonyl esters, ketones and amides are C-H acids capable of reacting with trimethylsilyldiazomethane to afford the corresponding ambiphilic alkenes. While esters were found to be non-selective, ketones were highly regioselective for O-methylation and displayed variable E/Z stereoselectivity. Amides were observed to be both highly regio- and stereoselective, affording O-methylation with exclusive formation of the Z-alkene.
- Kong, Han Il,Crichton, Jennifer E.,Manthorpe, Jeffrey M.
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supporting information; experimental part
p. 3714 - 3717
(2011/08/06)
-
- Utilization of natural sunlight and air in the aerobic oxidation of benzyl halides
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Chemical equations presented. A novel, efficient oxidation of α-aryl halogen derivatives to the corresponding α-aryl carbonyl compounds at room temperature has been disclosed. Natural sunlight and air are successfully utilized in this approach through the combination of photocatalysis and organocatalysis. A plausible mechanism was proposed on the basis of the mechanistic studies.
- Su, Yijin,Zhang, Liangren,Jiao, Ning
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supporting information; body text
p. 2168 - 2171
(2011/06/21)
-
- Synthesis of a series of novel 2,4,5-trisubstituted selenazole compounds as potential PLTP inhibitors
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Based on a homology-modeled structure of PLTP and characteristic structural features of reported cholesteryl ester transfer protein (CETP) inhibitors, we designed and synthesized a novel series of 2,4,5-trisubstituted selenazole compounds. Biological evaluation reveals that compounds 12 and 17 exhibit favorable PLTP activity, and their IC50s are 8 μM and 10 μM, respectively.
- Ling, Cui,Zheng, Zhibing,Jiang, Xian Cheng,Zhong, Wu,Li, Song
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scheme or table
p. 5123 - 5125
(2010/10/19)
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- Azole derivatives as histamine H3 receptor antagonists, Part I: Thiazol-2-yl ethers
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Most human histamine H3 receptor (hH3R) antagonists follow a general structural blueprint, containing a basic moiety linked by a spacer to a substituted core element. In this investigation the acceptance of thiazol-2-yl ether moieties in the core region is proved with some ether derivatives showing hH3R binding affinities in the nanomolar concentration range. A diversity of structural motifs is used as substituents to enhance the in vitro hH3R binding affinity.
- Walter,Von Coburg,Isensee,Sander,Ligneau,Camelin,Schwartz,Stark
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supporting information; experimental part
p. 5879 - 5882
(2010/11/18)
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- Facile aerobic photo-oxidative synthesis of phenacyl iodides and bromides from styrenes using I2 or aqueous HBr
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We report a useful method for facile synthesis of phenacyl iodides and bromides from styrene derivatives by aerobic photo-oxidation using I2 or 48% aqueous HBr in the presence of water. Georg Thieme Verlag Stuttgart - New York.
- Nobuta, Tomoya,Hirashima, Shin-Ichi,Tada, Norihiro,Miura, Tsuyoshi,Itoh, Akichika
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experimental part
p. 2335 - 2339
(2010/11/04)
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- Direct synthesis of α-bromoketones from alkylarenes by aerobic visible light photooxidation
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The direct synthesis of α-bromoketones from alkylarenes by aerobic photooxidation with hydrobromic acid is reported. The key success for this direct oxidative reaction is due to control of bromination with acetic acid and ethanol, which are generated in situ by solvolysis of ethyl acetate in the course of the reaction.
- Tada, Norihiro,Ban, Kazunori,Hirashima, Shin-Ichi,Miura, Tsuyoshi,Itoh, Akichika
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supporting information; experimental part
p. 4701 - 4704
(2010/11/17)
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- A facile synthesis of two series of multifunctional carbon compounds from α,α-dihalo ketones using allylsamarium bromide
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The use of allylsamarium bromide to effect two different reactions on the common starting material, a,a-dihalo ketones, is presented. With DMF, α-halo-α-allyl aldehydes were obtained, while α-hydroxy- α-allyl aldehyde acetals were obtained in the presence of NaOMe/MeOH. Georg Thieme Verlag Stuttgart.
- Liu, Xiaodan,Zhang, Songlin,Di, Jucai
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experimental part
p. 2749 - 2755
(2010/01/21)
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- Facile one-pot synthesis of α-bromoketones from olefins using bromide/bromate couple as a nonhazardous brominating agent
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A new method for the preparation of α-bromoketones from olefins using bromide/bromate couple as a nonhazardous brominating agent has been developed. Several α-bromoketones were successfully prepared from a variety of olefins by this method. This procedure is an alternative to conventional molecular bromine.
- Patil, Rajendra D.,Joshi, Girdhar,Adimurthy, Subbarayappa,Ranu, Brindaban C.
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experimental part
p. 2529 - 2532
(2009/09/06)
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- Halogenation of ketones with N-halosuccinimides under solvent-free reaction conditions
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Several aryl substituted ketones, cyclic ketones, 1,3-diketones and a β-ketoamide were halogenated with N-halosuccinimides under solvent-free reaction conditions (SFRC) at various temperatures (20-80 °C), whereas less enolized ketones required the presence of an acid catalyst (p-toluenesulfonic acid, PTSA). Bromination of substituted acetophenones obeys first order kinetics v=kBr[ketone] and the following correlation with the keto-enol equilibrium constant: log kBr=0.3pKE+C1, less enolized substrates being more reactive; the moderate positive charge developed in the rate determining step was confirmed by the Hammett correlation (ρ=-0.5). On the other hand, in cyclic ketones an opposite relation was observed: log kBr=-0.6pKE+C2, indicating higher reactivity of substrates with higher enolization constant (KE). The important role of the nature of the solvent (MeCN, MeOH) in preorganization of the ketone-NBS-PTSA mixture prior to SFRC bromination was found.
- Pravst, Igor,Zupan, Marko,Stavber, Stojan
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p. 5191 - 5199
(2008/09/21)
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- A facile one-pot synthesis of a?-halo-a?-allyl-aldehydes from a?,a?-Dihaloketoncs Using Allylsamarium Bromide and DMF
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A convenient, one-pot synthesis of a range of a?-halo-a?-allyl aldehydes is described. The protocol involves the reaction of allylsamarium bromide with various a?,a?-dihalo ketones. A possible mechanism of the transformation is proposed.
- Di, Jucai,Zhang, Songlin
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experimental part
p. 1491 - 1494
(2009/04/07)
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- Directed regioselectivity of bromination of ketones with NBS: solvent-free conditions versus water
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The reaction conditions employed directed the site of functionalisation of ketones with NBS: under solvent-free conditions α-bromination was the exclusive process, while in water, ring functionalisation occurred in the case of methoxy substituted aromatic ketones.
- Pravst, Igor,Zupan, Marko,Stavber, Stojan
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p. 4707 - 4710
(2007/10/03)
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- Non-peptidic small molecule inhibitors of XIAP
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Non-peptidic small molecule SMAC mimetics were designed and synthesized that bind to the BIR3 domain of XIAP using structure-based design. Substituted five-membered heterocycles such as thiazoles and imidazoles were identified that serve as replacements for peptide fragments of the lead.
- Park, Cheol-Min,Sun, Chaohong,Olejniczak, Edward T.,Wilson, Alan E.,Meadows, Robert P.,Betz, Stephen F.,Elmore, Steven W.,Fesik, Stephen W.
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p. 771 - 775
(2007/10/03)
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- A novel synthesis of arylpyrrolo[1,2-a]pyrazinone derivatives
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Some aryl-2-methyl-1-pyrrolo[1,2-a]pyrazinones were designed and prepared to study the Structure-Activity Relationships (SAR) of pyrrolo[1,2-a]pyrazinone derivatives. With methyl pyrrole-2-carboxylate as the starting material, the title compounds were prepared through N-alkylation and two novel cyclizations. Eleven aryl-2-methyl-1-pyrrolo[1,2-a]pyrazinone derivatives not previously reported in the literature are presented in this paper. Some of them show potent anti-inflammatory and analgesic activities.
- Wang, Fei,Wang, Jiawei,Zhang, Shoufang
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p. 574 - 582
(2007/10/03)
-
- Acid-mediated cyclization of 3-benzoyl-2-cyanobutyronitrile to 2-amino-4-methyl-5-phenylfuran-3-carbonitrile
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Cyclization of 3-benzoyl-2-cyanobutyronitrile to 2-amino-4-methyl-5-phenylfuran-3-carbonitrile was effected under acidic conditions, rather than the basic conditions previously reported. Since treatment with trifluoroacetic acid (TFA) at room temperature is very mild, 2-amino-4-methyl-5-phenylfuran-3-carbonitriles containing various functional groups can be accessed via this route.
- Watanuki, Susumu,Sakamoto, Shuichi,Harada, Hironori,Kikuchi, Kazumi,Kuramochi, Takahiro,Kawaguchi, Ken-Ichi,Okazaki, Toshio,Tsukamoto, Shin-Ichi
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p. 127 - 130
(2007/10/03)
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- DERIVATIVES OF CHROMEN-2-ONE AS INHIBITORS OF VEGF PRODUCTION IN MAMMALIAN CELLS
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The compounds of formula (I) wherein A and R1-R5 are as defined in the description, are inhibitors of Vascular Endothelial Growth Factor and are useful as angiogenesis inhibitors and antiproliferative agents.
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-
- A simple route to new phenanthro- and phenanthroid-fused thiazoles by a PIFA-mediated (hetero)biaryl coupling reaction
-
An application of the PIFA-mediated [PIFA: phenyliodine(III) bis(trifluoroacetate) biaryl coupling reaction is presented and extended to the formation of heterobiaryl connections. A preliminary study of the scope and limitations of this procedure was carried out in the synthesis of phenanthroids 11 from a series of phenethyl-substituted heterocycles 10, It was observed that in some cases a competitive dimerization process took place. It was also found that the coupling step could be efficiently extended to a larger number of examples if an aromatic ring were situated fused to the 1,2-diarylethane skeleton, as in 23 and 30. The synthesis of a series of 4,5-diarylthiazoles 23a-g was therefore carried out to explore the electronic requirements and the regioselectivity of the PIFA-mediated non-phenolic coupling reaction. When the same procedure was applied to aryl-heteroarylthiazoles 30, a series of phenanthroid-fused thiazoles 31 was obtained in good overall yields. To the best of our knowledge, no oxidative aryl-heteroaryl coupling reaction of this type had previously been reported. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
- Moreno, Isabel,Tellitu, Imanol,Dominguez, Esther,SanMartin, Raul
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p. 2126 - 2135
(2007/10/03)
-
- Compounds and compositons for treating C1s-mediated diseases and conditions
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Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4, X, Y and Z are defined in the specification.
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- Triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone as a new, selective and neutral system for the facile conversion of alcohols, thiols and selenols to alkyl halides in the presence of halide ions
-
A mixture of triphenylphosphine (Ph3P) and 2,3-dichloro-5,6-dicyanobenzoquinone in CH2Cl2 affords a complex which in the presence of R4NX (X=Cl, Br, I) converts alcohols, thiols and selenols into their corresponding alkyl halides in high yields at room temperature. The method is highly selective for the conversion of 1° alcohols in the presence of 2° ones and also 1° and 2° alcohols in the presence of 3° alcohols, thiols, epoxides, trimethylsilyl- and tetrahydropyranyl ethers, 1,3 dithianes, disulfides, and amides.
- Iranpoor,Firouzabadi,Aghapour,Vaez zadeh
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p. 8689 - 8693
(2007/10/03)
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- Heteroaryl amidines, methylamidines and guanidines, preparation thereof, and use thereof as protease inhibitors
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The present invention is directed to compounds of Formula I: wherein X is O, S or NR7and R1-R7, Y and Z are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, plasmin and urokinase. Certain of the compounds exhibit direct, selective inhibition of urokinase, or are intermediates useful for forming compounds having such activity.
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- Synthesis and properties of some novel anti-calmodulin drugs
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The preparation and properties of some novel inhibitors of calmodulin function are described. The compounds are cationic derivatives of phenyl-substituted thiazoles which inhibit the calmodulin stimulation of cyclic-AMP phosphodiesterase and are active against animal tumor cells in culture. These derivatives form the basis for the preparation of new, more potent inhibitors of calmodulin function which could take advantage of the reported elevated levels of calcium-bound calmodulin in tumor cells and show preferential anti-tumor activity. Copyright (C) 1999 Elsevier Science Ltd.
- Sakai, Ted T.,Krishna, N. Rama
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p. 1559 - 1565
(2007/10/03)
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- Preparation of 2-alkylselenobenzothiazoles by the reaction of alcohols with 2-(2-oxoethylseleno)benzothiazoles in the presence of tertiary phosphines
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Reactions of alcohols with 2-(1,2-diphenyl-2- oxoethylseleno)benzothiazole in the presence of Bu3P gave the corresponding 2-alkylselenobenzothiazoles, where inversion of the secondary carbinol center of the alcohols took place. 1,3-Butanediol reacted at the primary hydroxyl group, while 1-phenyl-1,2-ethanediol reacted at the secondary hydroxyl group.
- Shibata, Koichi,Yamaga, Hiko,Mitsunobu, Oyo
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p. 947 - 966
(2007/10/03)
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- Organophosphorous chemistry: Selective transformation of benzoin to benzil, desyl bromide, or benzyl phenyl ketone
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Reaction of benzoin with dibromotriphenylphosphorane under various conditions has been closely investigated. Benzoin was selectively converted to desyl bromide by treatment with dibromotriphenylphosphorane in the presence of triethylamine, while benzyl phenyl ketone was formed in the presence of an excess amount of triphenylphosphine. On the other hand, benzoin was effectively oxidized to benzil by treatment with only bromine. The mechanism of producing these was also proposed. Desyl bromide was formed from the reaction of benzoin with dibromotriphenylphosphorane as a primary product and converted to benzyl phenyl ketone via the Perkow reaction, and benzil was formed by the oxidation of benzoin by bromine. When triethylamine or triphenylphosphine was used as an added base, these bases trapped free bromine, and the oxidation product, benzil, was formed in low yield. In the presence of triphenylphosphine as a base, the Perkow reaction of desyl bromide proceeded smoothly to give benzyl phenyl ketone preferentially, while in the presence of triethylamine, replacement of the hydroxy group to bromide occurred mainly.
- Furukawa, Isao,Sasaki, Mitsuhiro,Inoue, Takeshi,Ohta, Tetsuo
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- Synthesis and Anti-tetrabenazine Activity of C-3 Analogues of Dimethyl-2-phenylmorpholines
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A series of analogues of 2-phenylmorpholines with alkyl substituents at the C-3 position were synthesized for anti-tetrabenazine (anti-TBZ) testing in mice.The target compounds were prepared by reaction of (2-bromoalkyl) phenyl ketones 21a-h with the appropriate aminoalcohol 20a-b to form morpholinols 22a-h.Hydride reduction of the morpholinols gave aminodiols 23a-h which were cyclized to morpholines 6, 8, 10-12, 14-16, 18 and 19 by acid catalysis.Compounds 7, 9, 13 and 17 were prepared by reductive formylation.The smaller straight chain substituents of 6, 8, 12 and 15, and the beta branching of the iso-butyl group of 16 were well tolerated; anti-tetrabenazine ED50's were comparable to compounds 2-5.The α-branched, N-methylated, and side chain aryl derivatives were less active.
- Boswell, G. Evan,Musso, David L.,Kelley, James L.,Soroko, Francis E.,Cooper, Barret R.
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- Diastereoselective synthesis and optical resolution of 3,4-substituted tetrahydroisoquinolin-4-ols
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Trans-3,4-substituted 1,2,3,4-tetrahydroisoquinolin-4-ols were prepared diastereoselectively by an insertion reaction with zerovalent nickel and by Barbier reaction with butyllithium of N-(2-iodobenzyl)phenacylamines. The isoquinolin-4-ols were resolved by means of HPLC method and the absolute configurations were determined.
- Kihara, Masaru,Ikeuchi, Motoki,Jinno, Kaori,Kashimoto, Minoru,Kobayashi, Yoshimaro,Nagao, Yoshimitsu
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p. 1017 - 1024
(2007/10/02)
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- SELENIUM CATALYZED CONVERSION OF VINYL HALIDES INTO α-ALKOXY ACETALS
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The reaction of vinyl halides with phenylselenenyl chloride in alcohols affords α-alkoxy acetals and diphenyl diselenide which can be oxidized to PhSe cations by nitrate or persulfate anions.The reaction can be carried out with catalytic amounts of PhSeCl or PhSeSePh.The reaction proceeds through the formation of the methoxyselenenylation product which then suffers solvolysis.Under controlled conditions, the 1-phenyl-1-methoxy-2-bromo-2-phenylselenenyl ethane was isolated from the reaction of β-bromostyrene and PhSeCl in methanol.Several deselenenylation reactions of this α-halogenoselenide are reported.
- Tiecco, Marcello,Testaferri, Lorenzo,Tingoli, Marco,Chianelli, Donatella,Bartoli, Donatella
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p. 2273 - 2282
(2007/10/02)
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- Destabilized Carbenium Ions. Secondary and Tertiary α-Acetylbenzyl Cations and α-Benzoylbenzyl Cations
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The secondary α-acetylbenzyl and α-benzoylbenzyl cations, as well as their tertiary analogues, have been generated in a mass spectrometer by electron impact induced fragmentation of the corresponding α-bromoketones.These ions belong to the interesting family of destabilized α-acylcarbenium ions.While primary α-acylcarbenium ions appear to be unstable, the secondary and tertiary ions exhibit the usual behaviour of stable entities in a potential energy well.This can be attributed to a 'push-pull' substitution at the carbenium centre by an electron-releasing phenyl group and an electron-withdrawing acyl substituent.The characteristic unimolecular reaction of the metastable secondary and tertiary α-acylbenzyl cations is the elimination of CO by a rearrangement reaction involving a 1,2-shift of a methyl group and a phenyl group, respectively.The loss of CO is accompanied by a very large kinetic energy release, which gives rise to a broad and dish-topped peaks for this process in the mass-analysed ion kinetic energy spectra of the corresponding ions.This behaviour is attributed to the rigid critical configuration of a corner-protonated cyclopropanone derivative and a bridged phenonium ion derivative, respectively, for this reaction.For the tertiary α-acetyl-α-methylbenzyl cations, it has been shown by deuterium labelling and by comparison of collisional activation spectra that these ions equilibrate prior to decomposition with their 'protomer' derivatives formed by proton migration from the α-methyl substituent to the carbonyl group and to the benzene ring.
- Dommroese, Anne-Marie,Gruetzmacher, Hans-Friedrich
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p. 437 - 443
(2007/10/02)
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- Synthesis of Bromoacetyl Derivatives by Use of Tetrabutylammonium Tribromide
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Orange ccrystalline tetrabutylammonium tribromide was prepared using a simple method.The reaction of acetyl dervivatives with an eqimolar amount of the tribromide in dichloromethane-methanol at room temperature bave bromoacetyl derivatives in fairly good yields.
- Kajigaeshi, Shoji,Kakinami, Takaaki,Okamoto, Tsuyoshi,Fujisaki, Shizuo
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p. 1159 - 1160
(2007/10/02)
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- Triazolyl-alkanones or triazolyl-alkanols
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Triazolyl-alkanones or triazolyl-alkanols of the formula STR1 in which R1 is alkyl, cycloalkyl, aryl or substituted aryl, and R2 is hydrogen, alkyl, cycloalkyl, aryl or substituted aryl, or R1 and R2 are joined to form an aliphatic ring, and A is a keto group or a CH(OH) group, or a salt thereof which possess fungicidal, microbicidal and plant-growth regulating properties.
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- Pyridazine derivatives having a psychotropic action and compositions
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This invention relates to pyridazine derivatives substituted in the 4-position by a cyano group having psychotropic activity. It also relates to a process for the preparation of these products and their application as medicaments. STR1
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- Synthesis of some Thiazole Schiff Bases and Their Derivatives
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Synthesis of some Schiff bases derived from 4,5-diaryl-2-aminothiazoles have been described.Cycloaddition of the Schiff bases with thioglycolic acid gave the corresponding thiazolidone derivatives.Reaction with cyclohexanone gave the secondary amines.The compounds have been characterised by ir and mass spectra, and screened for antifungal activity.
- Dash, B.,Patra, M.,Mohapatra, P. K.
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p. 460 - 464
(2007/10/02)
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