- Preparation method of carboxylic ester compound
-
The invention relates to a preparation method of a carboxylic ester compound, which comprises the following steps: reacting carboxylic acid with methanol in air under the catalysis of nitrite to obtain an ester compound, the preparation method disclosed by the invention has the advantages of rich raw material sources, cheap and easily available catalyst, mild reaction conditions, simplicity and convenience in operation and the like, a series of fatty carboxylic acids can be modified with high yield, and particularly, the traditional esterification method is generally not suitable for esterification of drug molecules. By utilizing the method, a series of known drug molecules can be modified, so that a shortcut is provided for discovering new drug molecules.
- -
-
Paragraph 0046-0047
(2021/03/30)
-
- Green Esterification of Carboxylic Acids Promoted by tert-Butyl Nitrite
-
In this work, the green esterification of carboxylic acids promoted by tert-butyl nitrite has been well developed. This transformation is compatible with a broad range of substrates and exhibits excellent functional group tolerance. Various drugs and substituted amino acids are applicable to this reaction under near neutral conditions, with good to excellent yields.
- Cheng, Xionglve,Jiang, Gangzhong,Li, Xingxing,Tao, Suyan,Wan, Xiaobing,Zhao, Yanwei,Zheng, Yonggao
-
supporting information
p. 2713 - 2718
(2021/06/25)
-
- B(C6F5)3-catalyzed O-H insertion reactions of diazoalkanes with phosphinic acids
-
A highly efficient base-, metal-, and oxidant-free catalytic O-H insertion reaction of diazoalkanes and phosphinic acids in the presence of B(C6F5)3has been developed. This powerful methodology provides a green approach towards the synthesis of a broad spectrum of α-phosphoryloxy carbonyl compounds with good to excellent yields (up to 99% yield). The protocol features the advantages of operational simplicity, high atom economy, practicality, easy scalability and environmental friendliness.
- Jiang, Jun,Zhang, Xinzhi,Zhang, Yangyang,Zhao, Jincheng
-
supporting information
p. 5772 - 5776
(2021/07/12)
-
- B(C6F5)3-Catalyzed site-selective N1-alkylation of benzotriazoles with diazoalkanes
-
Alkylation of benzotriazoles is synthetically challenging, often leading to mixtures of N1 and N2 alkylation. Herein, metal-free catalytic site-selective N1-alkylation of benzotriazoles with diazoalkanes is described in the presence of 10 mol% of B(C6F5)3. These reactions provide N1-alkylated benzotriazoles in good to excellent yields and this protocol is successfully adapted to gram-scale syntheses as well as a derivative with antimicrobial activity.
- Guo, Jing,Mandal, Dipendu,Stephan, Douglas W.,Wu, Yile,Zhao, Yunbo
-
supporting information
p. 7758 - 7761
(2021/08/13)
-
- Insertion of Diazo Esters into C-F Bonds toward Diastereoselective One-Carbon Elongation of Benzylic Fluorides: Unprecedented BF3Catalysis with C-F Bond Cleavage and Re-formation
-
Selective transformation of C-F bonds remains a significant goal in organic chemistry, but C-F insertion of a one-carbon-atom unit has never been established. Herein we report the BF3-catalyzed formal insertion of diazo esters as one-carbon-atom sources into C-F bonds to accomplish one-carbon elongation of benzylic fluorides. A DFT calculation study revealed that the BF3 catalyst could contribute to both C-F bond cleavage and re-formation. This elongation provided α-fluoro-α,β-diaryl esters with a high level of diastereoselectivity. Various benzylic fluorides and diazo esters were applicable. The synthetic utility of this method was demonstrated by the synthesis of a fluoro analogue of a compound that is used as a transient receptor and potential canonical channel inhibitor.
- Wang, Fei,Nishimoto, Yoshihiro,Yasuda, Makoto
-
supporting information
p. 20616 - 20621
(2021/11/23)
-
- 2-azabicyclo [3.2.0] compound as well as synthesis method and application
-
The invention discloses a 2-azabicyclo [3.2.0] compound as well as a synthesis method and an application. The 2-azabicyclo [3.2.0] compound comprises a compound with a structure as shown in a formula I and pharmaceutically acceptable salts thereof, wherein R is a substituted or unsubstituted benzene ring, a C1-8 aliphatic group or trifluoromethyl, R1 and R2 are respectively a substituted or unsubstituted benzene ring, a hydrogen atom or a C1-8 aliphatic group, R3 is a substituted or unsubstituted benzene ring, a hydrogen atom, a C1-8 aliphatic group or a heterocyclic substituent, R4 is a heterocyclic substituent or a substituted or unsubstituted benzene ring, R5 is a C1-8 fatty group, a benzyl group or -COOR6, and R6 is a C1-4 fatty group or a benzyl group. The invention belongs to the technical field of pharmaceutical chemicals, and after the prepared 2-azabicyclo [3.2.0] compound acts on an animal body, anti-sedation and anti-hypnosis effects can be achieved by adjusting the intracerebral level of histamine.
- -
-
Paragraph 0107-0110; 0118; 0121-0123; 0126
(2021/07/17)
-
- Room Temperature Coupling of Aryldiazoacetates with Boronic Acids Enhanced by Blue Light Irradiation
-
A visible-light-promoted photochemical protocol is reported for the coupling of aryldiazoacetates with boronic acids. This photochemical reaction shows great enhancement compared to the same protocol performed in the absence of light. Except for a few cases, the room temperature coupling in the dark (thermal process) generally does not work. When it does, it is likely to also involve free carbenes as key intermediates. Alternatively, photochemical reactions show a broad scope, can be performed under air and tolerate a wide variety of functional groups. Reaction-evolution monitoring, DFT calculations and control experiments have been used to evaluate the main aspects of this intricate mechanistic scenario. Biologically active molecules Adiphenine, Benactyzine and Aprophen have been prepared as examples of synthetic applications.
- da Silva, Amanda F.,Afonso, Marco A. S.,Cormanich, Rodrigo A.,Jurberg, Igor D.
-
supporting information
p. 5648 - 5653
(2020/04/22)
-
- Pd-Catalyzed Decarboxylative Olefination: Stereoselective Synthesis of Polysubstituted Butadienes and Macrocyclic P-glycoprotein Inhibitors
-
The efficient and stereoselective synthesis of polysubstituted butadienes, especially the multifunctional butadienes, represents a great challenge in organic synthesis. Herein, we wish to report a distinctive Pd(0) carbene-initiated decarboxylative olefination approach that enables the direct coupling of diazo esters with vinylethylene carbonates (VECs), vinyl oxazolidinones, or vinyl benzoxazinones to afford alcohol-, amine-, or aniline-containing 1,3-dienes in moderate to high yields and with excellent stereoselectivity. This protocol features operational simplicity, mild reaction conditions, a broad substrate scope, and gram-scalability. Notably, a structurally unique allylic Pd(II) intermediate was isolated and characterized. DFT calculation and control experiments demonstrated that a rare Pd(0) carbene intermediate could be involved in this reaction. Moreover, the polysubstituted butadienes as novel building blocks were unprecedentedly assembled into macrocycles, which efficiently inhibited the P-glycoprotein and dramatically reversed multidrug resistance in cancer cells by 190-fold.
- Chen, Xiangyang,Hao, Jiping,Houk, K. N.,Li, Yingzi,Lou, Liguang,Quan, Haitian,Song, Bichao,Wang, Lu,Xia, Yuanzhi,Xie, Peipei,Xu, Zhongliang,Yang, Weibo
-
supporting information
p. 9982 - 9992
(2020/06/27)
-
- Palladium-catalyzed intermolecular C-H silylation initiated by aminopalladation
-
A Pd(ii)-catalyzed intermolecular C-H silylation reaction initiated by aminopalladation has been developed. The C-H bonds were activated by an alkyl Pd(ii) species generated through aminopalladation and then disilylated with hexamethyldisilane to form disilylated indolines as the final products. The reaction provides a new method for the introduction of silyl groups into complex organic molecules.
- Ji, Xiaoming,Wei, Feng,Wan, Bin,Cheng, Cang,Zhang, Yanghui
-
supporting information
p. 7801 - 7804
(2020/07/27)
-
- Macrolactam Synthesis via Ring-Closing Alkene-Alkene Cross-Coupling Reactions
-
Reported herein is a practical method for macrolactam synthesis via a Rh(III)-catalyzed ring closing alkene-alkene cross-coupling reaction. The reaction proceeded via a Rh-catalyzed alkenyl sp2 C-H activation process, which allows access to macrocyclic molecules of different ring sizes. Macrolactams containing a conjugated diene framework could be easily prepared in high chemoselectivities and Z,E stereoselectivities.
- Goh, Jeffrey,Loh, Teck-Peng,Maraswami, Manikantha
-
supporting information
p. 9724 - 9728
(2020/12/21)
-
- Photocatalytic Hydromethylation and Hydroalkylation of Olefins Enabled by Titanium Dioxide Mediated Decarboxylation
-
A versatile method for the hydromethylation and hydroalkylation of alkenes at room temperature is achieved by using the photooxidative redox capacity of the valence band of anatase titanium dioxide (TiO2). Mechanistic studies support a radical-based mechanism involving the photoexcitation of TiO2 with 390 nm light in the presence of acetic acid and other carboxylic acids to generate methyl and alkyl radicals, respectively, without the need for stoichiometric base. This protocol is accepting of a broad scope of alkene and carboxylic acids, including challenging ones that produce highly reactive primary alkyl radicals and those containing functional groups that are susceptible to nucleophilic substitution such as alkyl halides. This methodology highlights the utility of using heterogeneous semiconductor photocatalysts such as TiO2 for promoting challenging organic syntheses that rely on highly reactive intermediates.
- Zhu, Qilei,Nocera, Daniel G.
-
supporting information
p. 17913 - 17918
(2020/12/04)
-
- MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE
-
Provided are IDO inhibitor compounds of Formula I and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases. Formula I
- -
-
Page/Page column 21; 22
(2019/01/16)
-
- ARYL-SUBSTITUTED ACETAMIDE AND PYRROLIDIN-2-ONE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF SEIZURES
-
Aryl-substituted acetamide and pyrrolidin-2-one (γ-butyrolactam) derivatives have useful activity in the inhibition, prevention, or treatment of seizures. The derivatives may be useful in the treatment of epilepsy, including medically refractory epilepsy, and nerve agent poisoning.
- -
-
Paragraph 0064; 0065
(2019/06/09)
-
- Palladium-Catalyzed Domino Heck/C-H Activation/Decarboxylation: A Rapid Entry to Fused Isoquinolinediones and Isoquinolinones
-
A new palladium-catalyzed tandem cyclization of various alkene-tethered aryl iodides has been presented. In this protocol, o-bromobenzoic acids are employed as coupling parters to achieve the insertion of aromatic rings by the cleavage of C(sp2)-Br and decarboxylation, thus assembling various dibenzoisoquinolinediones and dibenzoisoquinolinones. In addition, a seven-membered ring can be constructed by the use of 8-bromo-1-naphthoic acid. Notably, this approach enables regioselective product formation and features broad substrate scope.
- Luo, Xiai,Zhou, Liwei,Lu, Haiyan,Deng, Guobo,Liang, Yun,Yang, Chunming,Yang, Yuan
-
supporting information
p. 9960 - 9964
(2019/12/24)
-
- Synthesis and bio-evaluation of natural butenolides-acrylate conjugates
-
A series of novel 3-aryl-4-hydroxy-2(5H) furanone-acrylate hybrids were designed and synthesized based on the natural butenolides and acrylates scaffolds. The structures of the prepared compounds were characterized by 1H-NMR, 13C-NMR and electrospray ionization mass spectrometry (ESI-MS), and the bioactivity of the target compounds against twelve phytopathogenic fungi was investigated. The preliminary in vitro antifungal activity screening showed that most of the target compounds had moderate inhibition on various pathogenic fungi at the concentration of 100 mg·L?1, and presented broad-spectrum antifungal activities. Further studies also indicated that compounds 7e and 7k still showed some inhibitory activity against Pestallozzia theae, Sclerotinia sclerotiorum and Gibberella zeae on rape plants at lower concentrations, which could be optimized as a secondary lead for further research.
- Bao, Longzhu,Wang, Shuangshuang,Song, Di,Wang, Jingjing,Cao, Xiufang,Ke, Shaoyong
-
-
- Efficient Synthesis of Spirooxindole Pyrrolones by a Rhodium(III)-Catalyzed C?H Activation/Carbene Insertion/Lossen Rearrangement Sequence
-
A rhodium(III)-catalyzed domino annulation of simple olefins with diazo oxindoles to give spirooxindole pyrrolone products is described. This reaction can be formally viewed as the result of an anomalous tandem C?H activation, carbene insertion, Lossen rearrangement, and a nucleophilic addition process. The potential utility of this reaction was further demonstrated by the late-stage diversification of drug molecules.
- Ma, Biao,Wu, Peng,Wang, Xing,Wang, Zhengyu,Lin, Hai-Xia,Dai, Hui-Xiong
-
supporting information
p. 13335 - 13339
(2019/08/20)
-
- A sustainable procedure toward alkyl arylacetates: Palladium-catalysed direct carbonylation of benzyl alcohols in organic carbonates
-
A sustainable procedure for the synthesis of various alkyl arylacetates from benzyl alcohols has been developed. With palladium as the catalyst and organic carbonates as the green solvent and in situ activator, benzyl alcohols were carbonylated in an efficient manner without any halogen additives.
- Li, Yahui,Wang, Zechao,Wu, Xiao-Feng
-
supporting information
p. 969 - 972
(2018/03/13)
-
- Palladium-Catalyzed C?H Silylation through Palladacycles Generated from Aryl Halides
-
A highly efficient palladium-catalyzed disilylation reaction of aryl halides through C?H activation has been developed for the first time. The reaction has broad substrate scope. A variety of aryl halides can be disilylated by three types of C?H activation, including C(sp2)?H, C(sp3)?H, and remote C?H activation. In particular, the reactions are also unusually efficient. The yields are essentially quantitative in many cases, even in the presence of less than 1 mol % catalyst and 1 equivalent of the silylating reagent under relatively mild conditions. The disilylated biphenyls can be converted into disiloxane-bridged biphenyls.
- Lu, Ailan,Ji, Xiaoming,Zhou, Bo,Wu, Zhuo,Zhang, Yanghui
-
supporting information
p. 3233 - 3237
(2018/02/23)
-
- Palladium-Catalyzed Tandem Reaction of Three Aryl Iodides Involving Triple C-H Activation
-
A novel palladium-catalyzed tandem reaction of N-(2-iodoaryl)acrylamides with two aryl iodides for the synthesis of spirooxindole has been achieved. The reaction underwent the process of triple C-H activation and four C-C bond formations based on the double trapping of transient spirocyclic palladacycles which are obtained through remote C-H activation.
- Luo, Xiai,Xu, Yankun,Xiao, Genhua,Liu, Wenjuan,Qian, Cheng,Deng, Guobo,Song, Jianxin,Liang, Yun,Yang, Chunming
-
supporting information
p. 2997 - 3000
(2018/05/28)
-
- Pd-Catalyzed Three-Component Domino Reaction of Vinyl Benzoxazinanones for Regioselective and Stereoselective Synthesis of Allylic Sulfone-Containing Amino Acid Derivatives
-
A Pd-catalyzed, highly regioselective and stereoselective three-component domino allylic substitution/N-H carbene insertion reaction under mild conditions is described. This reaction demonstrates a wide substrate scope and satisfactory functional group tolerance, providing a broad range of allylic sulfone-containing amino acid derivatives. Moreover, DBU mediates highly diastereoselective cross-dehydrogenative coupling annulation of allylic sulfones without using peroxides or any metal oxidants. This developed protocol affords 7-membered ring heterocyclic compounds incorporating both sulfone-containing amino acid esters and one quaternary carbon center. Mechanistic studies indicate that an unusual umpolung of glycine occurred in this annulation.
- Hao, Jiping,Xu, Yi,Xu, Zhongliang,Zhang, Zhiqiang,Yang, Weibo
-
supporting information
p. 7888 - 7892
(2019/01/04)
-
- Palladium-Catalyzed Carbonylative Direct Transformation of Benzyl Amines under Additive-Free Conditions
-
In this communication, we developed a new procedure for the direct carbonylative transformation of benzyl amines. Using dimethyl carbonate as the solvent, methyl 2-arylacetates can be produced in good to excellent yields from the corresponding primary, secondary, and tertiary benzyl amines with palladium as the catalyst. Notably, no base or any other additive is required here. In addition, our procedure can also be applied in the preparation of methylphenidate, which is a marketing drug and used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.
- Li, Yahui,Wang, Zechao,Wu, Xiao-Feng
-
p. 738 - 741
(2018/01/17)
-
- The computer-aided discovery of novel family of the 5-HT6 serotonin receptor ligands among derivatives of 4-benzyl-1,3,5-triazine
-
The work describes a discovery of new chemical family of potent ligands for the 5-HT6 serotonin receptors. During the search for new histamine H4 receptor antagonists among 1,3,5-triazine derivatives, compound 2 (4-benzyl-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine) was found. Compound 2, weakly active for the H4 receptor but fitted in 3/4 of pharmacophore features of the 5-HT6R ligand, occurred to be a moderate 5-HT6R agent, useful as a lead structure for further modifications. A series of new derivatives (3–19) of the lead 2 was synthesized, evaluated in the radioligand binding assay (RBA) and explored in comprehensive molecular modelling, including both pharmacophore- and structure-based approaches with docking to the homology model of 5-HT6R. The most active compounds displayed a potent affinity for the 5-HT6R in the nanomolar range (Ki?=?20–30?nM), some of them (4, 11 and 19) were tested in the rat forced swim test that revealed their antidepressant-like effect. SAR-analysis on the basis of both, RBA and docking results, indicated that action on the receptor is related to the hydrophobicity and the size of aromatic moiety substituted by a methylene linker at the position 4 of 1,3,5-triazine.
- ?a?ewska, Dorota,Kurczab, Rafa?,Wi?cek, Ma?gorzata,Kamińska, Katarzyna,Sata?a, Grzegorz,Jastrz?bska-Wi?sek, Magdalena,Partyka, Anna,Bojarski, Andrzej J.,Weso?owska, Anna,Kie?-Kononowicz, Katarzyna,Handzlik, Jadwiga
-
supporting information
p. 117 - 124
(2017/04/26)
-
- Water as a Hydride Source in Palladium-Catalyzed Enantioselective Reductive Heck Reactions
-
Pd-catalyzed intramolecular asymmetric carbopalladation of N-aryl acrylamides followed by reduction of C(sp3)-Pd intermediate using diboron–water as a hydride source afforded enantioenriched 3,3-disubstituted oxindoles in high yields and enantioselectivities. When heavy water was used as a deuterium donor in combination with bis(catecholato)diboron (Cat2B2), deuterium was incorporated into the products with high synthetic efficiency. The ligand determined both the enantioselectivity of the reaction and the reaction pathways, thereby affording either hydroarylation (reductive Heck) or carboborylation products.
- Kong, Wangqing,Wang, Qian,Zhu, Jieping
-
supporting information
p. 3987 - 3991
(2017/03/27)
-
- HETEROARYL COMPOUNDS AS IRAK INHIBITORS AND USES THEREOF
-
The present invention relates to compounds of Formula (I) and pharmaceutically acceptable compositions thereof, useful as IRAK inhibitors.
- -
-
Paragraph 00197
(2017/04/11)
-
- Discovery, synthesis, and structure-activity relations of 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-ones as potassium-competitive acid blockers
-
With the aim to discover a gastric antisecretory agent more potent than the existing proton pump inhibitors, novel 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-one derivatives, which could occupy two important lipophilic pockets (described as LP-1 and LP-2) of H+,K+-ATPase and can strongly bind to the K+-binding site, were designed based on a docking model. Among the compounds synthesized, compound 4d showed a strong H+,K+-ATPase-inhibitory activity and a high stomach concentration in rats, resulting in potent inhibitory action on histamine-stimulated gastric acid secretion in rats. Furthermore, 4d exerted significant inhibitory action on histamine-stimulated gastric-acid secretion in rats with a rapid onset and moderate duration of action after the administration. These findings may lead to a new insight into the drug design of potassium-competitive acid blockers.
- Imaeda, Toshihiro,Ono, Koji,Nakai, Kazuo,Hori, Yasunobu,Matsukawa, Jun,Takagi, Terufumi,Fujioka, Yasushi,Tarui, Naoki,Kondo, Mitsuyo,Imanishi, Akio,Inatomi, Nobuhiro,Kajino, Masahiro,Itoh, Fumio,Nishida, Haruyuki
-
p. 3719 - 3735
(2017/06/13)
-
- An approach to spirooxindoles: Via palladium-catalyzed remote C-H activation and dual alkylation with CH2Br2
-
A facile and efficient approach for the synthesis of spirooxindoles has been developed via the coupling of spirocyclic C,C-palladacycles with CH2Br2. The key spirocyclic palladacycles are generated catalytically via remote C-H activation. A range of spirooxindoles can be synthesized in good to excellent yields from readily available starting material.
- Shao, Changdong,Wu, Zhuo,Ji, Xiaoming,Zhou, Bo,Zhang, Yanghui
-
supporting information
p. 10429 - 10432
(2017/09/25)
-
- A 2 - (4 - fluorobenzyl) pyrrolidine preparation method (by machine translation)
-
The invention discloses a 2 - (4 - fluorobenzyl) pyrrolidine of preparation method, to the fluorophenyl acetic acid as the starting material, through esterification, coupling, open-loop, closed-loop, reduction to obtain the target product, the compound is an important medical intermediates. (by machine translation)
- -
-
Paragraph 0023; 0024
(2017/11/04)
-
- Synthesis and Biological Evaluation of New (-)-Gossypol-Derived Schiff Bases and Hydrazones
-
A series of 14 new (-)-gossypol Schiff bases and hydrazones have been synthesized via an in situ procedure in high yields. Structural data showed that all target compounds exist as the enamine tautomer. Bioassays showed that several compounds exhibited cytotoxic effects against three human cancer cell lines. Compound 8a showed the greatest cytotoxic effect against hepatocellular carcinoma (HepG2), lung carcinoma (LU-1), and breast cancer (MCF-7) cell lines with IC50 values of 20.93, 13.58, and 9.40 μM, respectively. However, in an antibacterial test, compounds 8a and 8b inhibited Staphylococcus aureus and Bacillus cereus and compound 8e inhibited only Staphylococcus aureus at the same MIC values of 1024 μg/ml.
- Vu, Vu Van,Nhung, Trinh Thi,Thanh, Nguyen Thi,Chinh, Luu Van,Tien, Vu Dinh,Thuy, Vu Thu,Thi Thao, Do,Nam, Nguyen Hai,Koeckritz, Angela,Vu, Tran Khac
-
-
- Synthesis of Benzo[a]carbazoles and an Indolo[2,3-a]carbazole from 3-Aryltetramic Acids
-
A simple and flexible approach to 3-pyrrolin-2-one fused carbazoles is disclosed. The key step involves the BF3-mediated electrophilic substitution of indoles with N-alkyl-substituted 3-aryltetramic acids, which provides access to indole-substituted 3-pyrrolin-2-ones. Scholl-type oxidative cyclizations of these materials led to the formation of the corresponding 3-pyrrolin-2-one-fused benzo[a]carbazoles and indolo[2,3-a]carbazoles. This work represents the first synthesis of the benzo[a]pyrrolo[3,4-c]carbazol-3(8H)-one ring system, while the indolo[2,3-a]pyrrolo[3,4-c]carbazol-5-one ring system is found in a number of biologically active compounds including the protein kinase C (PKC) inhibitor, staurosporine.
- Truax, Nathanyal J.,Banales Mejia, Fernando,Kwansare, Deborah O.,Lafferty, Megan M.,Kean, Maeve H.,Pelkey, Erin T.
-
p. 6808 - 6815
(2016/08/16)
-
- Synthesis of aryl anilinomaleimide based derivatives as glycogen synthase kinase-3β inhibitors with potential role as antidepressant agents
-
A series of aryl anilinomaleimide based derivatives has been synthesized and evaluated for in vitro glycogen synthase kinase-3β (GSK-3β) inhibitory activity. A large number of compounds from the series exhibited moderate to potent inhibitory activity against GSK-3β, with more than one-third of the compounds showing inhibition with IC50 values 50 values of 0.09, 0.12, 0.17, 0.19, 0.21 and 0.23 μM respectively), were further investigated for antidepressant activity by the widely accepted forced swim test and tail suspension test (FST and TST) models. All the tested compounds displayed antidepressant-like effects, particularly compounds 8j and 8b, which exhibited significant antidepressant activity, about 1.4-fold higher than fluoxetine, a standard antidepressant drug in both FST and TST. Preliminary structure-activity relationships have also been generated based on the experimental data obtained.
- Tantray, Mushtaq A.,Khan, Imran,Hamid, Hinna,Alam, Mohammad Sarwar,Dhulap, Abhijeet,Kalam, Abul
-
p. 6109 - 6119
(2016/07/16)
-
- Copper-mediated oxidative homocoupling and rearrangement of N-alkoxyamides: An efficient method for the preparation of aromatic esters
-
N-Alkoxyamides are successfully converted into their corresponding esters in a moderate to satisfactory yields via copper-catalyzed oxidative homocoupling and Heron rearrangement. The process tolerates a wide variety of functional groups and allows the synthesis of sterically hindered ester products not readily accessible by traditional acylation chemistry. A radical-mediated pathway has been tentatively proposed for the oxidative process.
- Duan, Xiyan,Yang, Kun,Tian, Shuang,Ma, Junying,Li, Yaning,Zou, Jiao,Zhang, Dongliang,Cui, Huanqing
-
p. 4634 - 4637
(2015/07/08)
-
- Higher-order cyclopropenimine superbases: Direct neutral br?nsted base catalyzed michael reactions with α-aryl esters
-
The synthesis and characterization of six new classes of higher-order superbases, including five that incorporate cyclopropenimine functionality, has been achieved. We propose a nomenclature that designates these as the CG2, GC2, PC3, PC1, C3, and GP2 classes of superbases. The pKBH+ values were measured to be between 29.0 and 35.6 in acetonitrile. Linear correlations of ten superbase basicities vs that of their substituents demonstrated the insulating effect of the cyclopropenimine core. The molecular structures of several of these materials were obtained by single-crystal X-ray analysis, revealing interesting aspects of conformational bias and noncovalent organization. The types of superbasic cores and substituents were each reliably shown to affect selectivity for deprotonation over alkylation. Higher-order cyclopropenimine and guanidine superbase stability to hydrolysis was found to correlate to basicity. Finally, a GC2 base was found to catalyze conjugate additions of α-aryl ester pronucleophiles, representing the first report of a neutral Br?nsted base to catalyze such reactions.
- Nacsa, Eric D.,Lambert, Tristan H.
-
supporting information
p. 10246 - 10253
(2015/09/01)
-
- Synthesis and biological evaluation of spirocyclic antagonists of CCR2 (chemokine CC receptor subtype 2)
-
Activation of chemokine CC receptors subtype 2 (CCR2) plays an important role in chronic inflammatory processes such as atherosclerosis, multiple sclerosis and rheumatoid arthritis. A diverse set of spirocyclic butanamides 4 (N-benzyl-4-(3,4-dihydrospiro[[2]benzopyran-1,4′-piperidin]-1′-yl)butanamides) was prepared by different combination of spirocyclic piperidines 8 (3,4-dihydrospiro[[2]benzopyran-1,4′-piperidines]) and γ-halobutanamides 11. A key step in the synthesis of spirocyclic piperidines 8 was an Oxa-Pictet-Spengler reaction of β-phenylethanols 5 with piperidone acetal 6. The substituted γ-hydroxybutanamides 11c-e were prepared by hydroxyethylation of methyl acetates 13 with ethylene sulfate giving the γ-lactones 14c and 14e. Aminolysis of the γ-lactones 14c and 14e with benzylamines provided the γ-hydroxybutanamides 15c-e, which were converted into the bromides 11c-e by an Appel reaction using polymer-bound PPh3. In radioligand binding assays the spirocyclic butanamides 4 did not displace the iodinated radioligand 125I-CCL2 from the human CCR2. However, in the Ca2+-flux assay using human CCR2 strong antagonistic activity of butanamides 4 was detected. Analysis of the IC50-values led to clear relationships between the structure and the inhibition of the Ca2+-flux. 4g (4-(3,4-dihydrospiro[[2]benzopyran-1,4′-piperidin]-1′-yl)-N-[3,5-bis(trifluoromethylbenzyl)]-2-(4-fluorophenyl)butanamide) and 4o (N-[3,5-bis(trifluoromethyl)benzyl]-2-cyclopropyl-4-(3,4-dihydrospiro[[2]benzopyran-1,4′-piperidin]-1′-yl)butanamide) represent the most potent CCR2 antagonists with IC50-values of 89 and 17 nM, respectively. Micromolar activities were found in the β-arrestin recruitment assay with murine CCR2, but the structure-activity-relationships detected in the Ca2+-flux assay were confirmed.
- Strunz, Ann Kathrin,Zweemer, Annelien J.M.,Weiss, Christina,Schepmann, Dirk,Junker, Anna,Heitman, Laura H.,Koch, Michael,Wünsch, Bernhard
-
p. 4034 - 4049
(2015/03/14)
-
- Antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives
-
In this study, a series of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives were synthesized and evaluated for their antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt caused by Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (R. solanacearum) via the turbidimeter test in vitro. Antibacterial bioassays indicated that most compounds demonstrated appreciable antibacterial bioactivities against Xoo and R. solanacearum. Among the title compounds, compound 4i demonstrated the best inhibitory effect against Xoo and R. solanacearum with half-maximal effective concentration (EC50) values of 14.69 and 15.14 μg/mL, respectively, which were even better than those of commercial agents Bismerthiazol and Thiodiazole Copper. In vivo antibacterial activities tests under greenhouse conditions revealed that the control efficiency of compound 4i against rice bacterial leaf blight and tobacco bacterial wilt were better than those of Bismerthiazol and Thiodiazole Copper. Meanwhile, field trials also indicated that compound 4i demonstrated appreciable control efficiency against rice bacterial leaf blight and tomato bacterial wilt.
- Li, Pei,Shi, Li,Gao, Man-Ni,Yang, Xia,Xue, Wei,Jin, Lin-Hong,Hu, De-Yu,Song, Bao-An
-
p. 481 - 484
(2015/02/18)
-
- Synthesis of Quinolines by Visible-Light Induced Radical Reaction of Vinyl Azides and α-Carbonyl Benzyl Bromides
-
A visible-light induced radical reaction of vinyl azides and α-carbonyl benzyl bromides was developed, which provides an efficient route to polysubstituted quinolines via a C-C and C-N bond formation sequence.
- Wang, Qile,Huang, Jun,Zhou, Lei
-
supporting information
p. 2479 - 2484
(2015/08/18)
-
- Design, synthesis, and antibacterial activity against rice bacterial leaf blight and leaf streak of 2,5-substituted-1,3,4-oxadiazole/thiadiazole sulfone derivative
-
A series of 2,5-substituted-1,3,4-oxadiazole/thiadiazole sulfone derivatives were synthesized and evaluated for their antibacterial activities against rice bacterial leaf blight and leaf streak caused by Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicolaby via the turbidimeter test in vitro. Antibacterial bioassay results indicated that most compounds demonstrated good inhibitory effect antibacterial bioactivities against rice bacterial leaf blight and leaf streak. Among the title compounds, compound 6c demonstrated the best inhibitory effect against rice bacterial leaf blight and leaf streak with half-maximal effective concentration (EC50) values of 1.07 and 7.14 μg/mL, respectively, which were even better than those of commercial agents such as Bismerthiazol and Thiediazole Copper. In vivo antibacterial activities tests at greenhouse conditions demonstrated that the controlling effect of compounds 6c (43.5%) and 6g (42.4%) against rice bacterial leaf blight were better than those of Bismerthiazol (25.5%) and Thiediazole Copper (37.5%).
- Li, Pei,Shi, Li,Yang, Xia,Yang, Lei,Chen, Xue-Wen,Wu, Fang,Shi, Qing-Cai,Xu, Wei-Ming,He, Ming,Hu, De-Yu,Song, Bao-An
-
p. 1677 - 1680
(2014/04/17)
-
- Palladium-catalyzed α-arylation of 2-chloroacetates and 2-chloroacetamides
-
A method has been developed for the Pd-catalyzed synthesis of α-(hetero)aryl esters and amides through a Suzuki-Miyaura cross-coupling reaction. This method avoids the use of strong base, does not necessitate inert or low temperature formation of reagents, and does not require the use of a large excess of organometallic reagent. Utilization of organotrifluoroborate salts as nucleophilic partners allows a variety of functional groups and heterocyclic compounds to be tolerated.
- Molander, Gary A.,Traister, Kaitlin M.,Barcellos, Thiago
-
p. 4123 - 4131
(2013/06/05)
-
- Amine Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands
-
The invention relates to amine substituted methanesulfonamide derivatives as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
- -
-
Paragraph 0668; 0669
(2013/04/10)
-
- AMINE SUBSTITUTED METHANESULFONAMIDE DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
-
The invention relates to amine substituted methanesulfonamide derivatives of formula (I) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
- -
-
Page/Page column 102
(2013/04/13)
-
- NOVEL ARYLAMIDE DERIVATIVES HAVING ANTIANDROGENIC PROPERTIES
-
The invention relates to novel arylamide derivatives having formula (I), and stereoisomers and pharmaceutically acceptable salts thereof, where RA, RB, RC, R', R", Z and X are as defined in the claims. The arylamide derivatives of formula (I) have antiandrogenic properties. The invention also relates to compounds of formula (I) for use as a medicament and to pharmaceutical compositions comprising them and to their preparation
- -
-
Page/Page column 23; 24
(2013/07/25)
-
- Palladium-catalyzed asymmetric synthesis of 2-pyrrolidinones with a quaternary carbon stereocenter
-
A palladium-catalyzed asymmetric synthesis of 2-pyrrolidinones with a quaternary stereocenter at the 3-position has been achieved by the reaction of γ-methylidene-δ-valerolactones with alkyl isocyanates. High enantioselectivity has been realized by employing a newly synthesized chiral phosphoramidite ligand. The Royal Society of Chemistry 2012.
- Shintani, Ryo,Ito, Tomoaki,Nagamoto, Midori,Otomo, Haruka,Hayashi, Tamio
-
supporting information
p. 9936 - 9938
(2012/10/29)
-
- Novel ether-functional spiro-tetronic acid derivatives: Molecule design, convenient synthesis and biological evaluation
-
A novel series of ether functionalization of spiro-tetronic acid derivatives have been designed and conveniently synthesized via three steps, including esterification, one-pot heterocyclization, and etherification reactions. The target molecules have been identified on the basis of analytical spectra data. All newly synthesized compounds have been screened for their potential insecticidal activity against Heliothis armigera and Plutella xylostella compared with spirodiclofen by standard method. Springer Science+Business Media B.V. 2012.
- Ke, Shaoyong,Zhang, Zhigang,Zhang, Ya-Ni,Shi, Liqiao,Zhou, Ronghua,Jiang, Aibing,Liang, Ying,Yang, Ziwen
-
p. 1827 - 1837
(2013/02/22)
-
- Synthesis and biological activities of some new 3,6-disubstituted 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole derivatives
-
A series of aromatic hydrazides 3a-j were prepared by refluxing esters 2a-j with hydrazine hydrate in methanol, which were prepared by the esterification of 1a-j. Acetohydrazides 3a-j upon treatment with carbon disulfide and methanolic potassium hydroxide yielded potassium dithiocarbazate salts 4a-j, which on refluxing with hydrazine hydrate yielded substituted 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones 5a-j. The target compounds 6a-j were synthesized by condensing furan-3-carboxylic acid in the presence of polyphosphoric acid under reflux. The structures of newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis and mass spectrometric studies. All the synthesized compounds were screened for their urease, acetylcholine esterase inhibition, antioxidant and alkaline phosphatase inhibition activity. Almost all of the compounds 6a-j showed good to excellent activities against urease and acetylcholine esterase more than the reference drugs. Compounds 6f and 6g were more potent scavenger of free radicals than the reference n-propyl gallate. Compound 6b and 6h showed excellent activities of alkaline phosphatase as compare to the reference KH 2PO4.
- Rafiq, Muhammad,Saleem, Muhammad,Hanif, Muhammad,Maqsood, Muhammad Rizwan,Rama, Nasim Hasan,Lee, Ki-Hwan,Seo, Sung-Yum
-
p. 3943 - 3949
(2013/08/23)
-
- Structural diversity-guided convenient construction of functionalized polysubstituted butenolides and lactam derivatives
-
A molecular diversity-oriented convenient access to multi-substituted butenolides and lactam scaffolds via four different methods from various phenylacetic acid derivatives is described. The target molecules have been identified on the basis of analytical spectra data, and are useful synthons in the fields of medicine and agrochemicals.
- Ke, Shaoyong,Zhang, Ya-Ni,Shu, Wenming,Zhang, Zhigang,Shi, Liqiao,Liang, Ying,Wang, Kaimei,Yang, Ziwen
-
scheme or table
p. 1071 - 1079
(2012/03/12)
-
- Fe(II)-catalyzed amination of aromatic C-H bonds via ring opening of 2 H-azirines: Synthesis of 2,3-disubstituted indoles
-
A general method for the synthesis of 2,3-disubstituted indoles is described. The key feature of this method is the amination of aromatic C-H bonds via FeCl2-catalyzed ring opening of 2H-azirines. The method tolerates a variety of functional groups such as Br, F, NO2, OMe, CF3, OTBS, alkenes, and OPiv. The method can also be extended to synthesize azaindoles.
- Jana, Samaresh,Clements, MacK D.,Sharp, Barry K.,Zheng, Nan
-
supporting information; scheme or table
p. 3736 - 3739
(2010/11/03)
-
- Spirodiclofen analogues as potential lipid biosynthesis inhibitors: A convenient synthesis, biological evaluation, and structure-activity relationship
-
Twenty spirodiclofen analogues have been designed and conveniently synthesized via three steps including esterification, one-pot heterocyclization, and acylation reactions. The target molecules have been identified on the basis of analytical spectra (1H NMR, 13C NMR and ESI-MS) data. All newly synthesized compounds have been screened for their potential insecticidal and herbicidal activity by standard method. The preliminary assays indicated that some of analogues displayed moderate to good insecticidal activity against Plutella xylostella compared with spirodiclofen, and some compounds showed obvious activity against Brassica chinensis. Structure-activity relationship (SAR) is also discussed based on the experimental data.
- Ke, Shaoyong,Sun, Tingting,Zhang, Zhigang,Zhang, Ya-Ni,Liang, Ying,Wang, Kaimei,Yang, Ziwen
-
experimental part
p. 2315 - 2321
(2010/11/16)
-
- Pd-catalyzed deoxygenation of mandelate esters
-
(Chemical Equation Presented) A new approach to the synthesis of phenylacetic acids and esters has been developed via the palladium-catalyzed deoxygenation of mandelate esters.
- Milne, Jacqueline E.,Murry, Jerry A.,King, Anthony,Larsen, Robert D.
-
supporting information; experimental part
p. 445 - 447
(2009/04/10)
-
- An improved bouveault-blanc ester reduction with stabilized alkali metals
-
Significantly improved Bouveault-Blanc conditions for ester reduction have been developed using sodium in silica gel (Na-SG), a free-flowing powder that can be easily handled in the open atmosphere. Primary alcohols were prepared in excellent yield from a variety of aliphatic esters under mild reaction conditions. The chemistry presented here is far safer than the classic Bouveault-Blanc reduction and is competitive with more modern hydride reduction methods.
- Bodnar, Brian S.,Vogt, Paul F.
-
supporting information; experimental part
p. 2598 - 2600
(2009/08/07)
-
- PROCESS FOR THE PREPARATION OF FLUOROPHENYLACETIC ACIDS AND DERIVATIVES THEREOF
-
The object of the present invention is a process for the preparation of fluorophenylacetic acids and derivatives thereof, particularly of 2,4, 5-trifluorophenylacetic acid, starting from the corresponding mandelic acids.
- -
-
Page/Page column 23
(2008/12/06)
-
- POLYMORPHS OF A HYDROISOINDOLINE TACHYKININ RECEPTOR ANTAGONIST
-
This application is directed to a novel polymorph of a hydroisoindoline tachykinin receptor antagonist having the following structural formula A.
- -
-
Page/Page column 13-14
(2008/12/05)
-