- Novel pyrrol-2(3H)-ones and pyridazin-3(2H)-ones carrying quinoline scaffold as anti-proliferative tubulin polymerization inhibitors
-
A novel quinolinyl pyrrolone and quinolinyl pyridazinone derivatives has been synthesized and characterized using different spectroscopic and elemental analysis techniques. Most of the target compounds displayed promising antiproliferative activity; In general, the pyrrolone derivatives 4a-f exhibited higher antiproliferative activity than their corresponding pyridazinone. The pyrrolone 4f showed outstanding antiproliferative activity with moderate selectivity against CNS and renal cancer with selectivity ratio of 3.49 and 3.56, respectively. Compound 4e and 5d experienced tubulin polymerization inhibitory activity comparable to that of vincristine while 4c, 4e and 4d showed good BRAF kinase inhibition compared to Erlotinib. Docking of compound 4e into colchicine binding site and biological assay results revealed that these compounds act mainly through tubulin polymerization inhibitory mechanism and can exhibit pre G1 apoptosis and cell cycle arrest at G2/M phase.
- Abdelbaset, Mahmoud S.,Abuo-Rahma, Gamal El-Din A.,Abdelrahman, Mostafa H.,Ramadan, Mohamed,Youssif, Bahaa G.M.,Bukhari, Syed Nasir Abbas,Mohamed, Mamdouh F.A.,Abdel-Aziz, Mohamed
-
-
Read Online
- Design and synthesis of butenolide-based amide derivatives as anti-inflammatory agents
-
Butenolide-based eighteen new amide derivatives (1-18) have been synthesized and evaluated for anti-inflammatory activity. The compounds 9, 17 and 4 exhibited significant in vivo inhibition of 84.69, 76.52 and 76.22 % inflammation, respectively, after 5 h without causing any damage to stomach and liver in comparison with the standard drug indomethacin which showed 79.04 % inhibition. The compounds showing potent anti-inflammatory activity were further evaluated for ex vivo TNF-α suppression. Compounds 9, 17 and 4 significantly suppressed TNF-α concentration to 74.83, 71.74 and 67.11 % as compared to indomethacin which exhibited a suppression of 69.01 %. Compounds 9 and 17 were also found to suppress the expression of COX-2 and NF-κB in the paw tissue. Moreover, compound 9 showed significant analgesic activity (57.03 %) which was comparable to indomethacin (61.03 %).
- Ali, Yakub,Alam, Mohammad Sarwar,Hamid, Hinna,Husain, Asif,Dhulap, Abhijeet,Bano, Sameena,Kharbanda, Chetna,Nazreen, Syed,Haider, Saqlain
-
-
Read Online
- Insight into the mechanism and stereochemistry of the transformations of alkyltitanium Ate-Complexes. An enhanced enantioselectivity in the cyclopropanation of the carboxylic esters with titanacyclopropane reagents
-
The dependence of the stereoselectivity of the cyclopropanation reaction of g,g-diphenyl-g-butyrolactone and carboxylic esters with alkylmagnesium bromides in the presence of titanium(IV) TADDOLates on the structure of the reactants has been examined in d
- Kulinkovich, Oleg G.,Kananovich, Dzmitry G.,Lopp, Margus,Snieckus, Victor
-
-
Read Online
- A simple procedure for the isolation of γ-oxobenzenebutanoic acid derivatives: Application to the synthesis of fenbufen
-
A simple, convenient, and industrially viable process for the isolation of 4-oxobutanoic acid derivatives resulting from Friedel-Crafts acylation products of aromatic hydrocarbons with succinic anhydride is reported. The isolation procedure involves simple quenching of the reaction mixture followed by filtration of the product in good yield and with excellent purity. The generality of the procedure has been demonstrated with representative examples of aromatic hydrocarbon precursors and has also been applied to the isolation of fenbufen. The quantity of aluminum chloride used in the reaction has also been optimized to reduce the load on effluent.
- Srinivas,Haricharan Raju,Acharyulu, Palle V. R.
-
-
Read Online
- Design, synthesis, and bioactive screen in vitro of cyclohexyl (E)-4-(Hydroxyimino)-4-phenylbutanoates and their ethers for anti-Hepatitis B Virus agents
-
A series of oxime Cyclohexyl (E)-4-(hydroxyimino)-4-phenylbutanoates and their ethers were designed, synthesized, and evaluated for anti-hepatitis B virus (HBV) activities with HepG 2.2.15 cell line in vitro. Most of these compounds possessed anti-HBV activities, and among them, compound 4B-2 showed significant inhibiting effects on the secretion of HBsAg (IC50 = 63.85 ± 6.26 μM, SI = 13.41) and HBeAg (IC50 = 49.39 ± 4.17 μM, SI = 17.34) comparing to lamivudine (3TC) in HBsAg (IC50 = 234.2 ± 17.17 μM, SI = 2.2) and HBeAg (IC50 = 249.9 ± 21.51 μM, SI = 2.07). Docking study of these compounds binding to a protein residue (PDB ID: 3OX8) from HLA-A2 that with the immunodominant HBcAg18-27 epitope (HLA-A2.1- restricted CTL epitope) active site was carried out by using molecular operation environment (MOE) software. Docking results showed that behaviors of these compounds binding to the active site in HLA-A protein residue partly coincided with their behaviors in vitro anti-HBV active screening.
- Cui, Xinhua,Zhou, Min,Tan, Jie,Wei, Zhuocai,Wei, Wanxing,Luo, Peng,Lin, Cuiwu
-
-
Read Online
- Kinetic and thermodynamic study for the oxidation of 4-oxo-4-phenyl butanoic acid by tripropylammonium fluorochromate in aqueous acetic acid medium
-
Tripropylammonium fluorochromate (TriPAFC) in acetic acid-water medium oxidizes 4-oxo-4-phenyl butanoic acid (4-Oxo acid) in the presence of perchloric acid. The reaction is first order each in [TriPAFC], [4-Oxo acid] and [H+]. From the observed kinetic results a suitable mechanism has been proposed.
- Yogananth,Mansoor, S. Sheik
-
-
Read Online
- Visible Light-Driven, Copper-Catalyzed Aerobic Oxidative Cleavage of Cycloalkanones
-
A visible light-driven, copper-catalyzed aerobic oxidative cleavage of cycloalkanones has been presented. A variety of cycloalkanones with varying ring sizes and various α-substituents reacted well to give the distal keto acids or dicarboxylic acids with moderate to good yields.
- Xin, Hong,Duan, Xin-Hua,Yang, Mingyu,Zhang, Yiwen,Guo, Li-Na
-
p. 8263 - 8273
(2021/06/30)
-
- In silico designing, in vitro and in vivo evaluation of potential PPAR-γ agonists derived from aryl propionic acid scaffold
-
Attributed to several side effects, especially on hepatic tissues and body weight, there is always an urge of innovation and upgrading in already existing medication being used in maintaining diabetic condition. Therefore, in the present work, forty-eight molecules derived from arylpropionic acid scaffold were synthesized and their evaluation against diabetes was carried out. The synthesis of these molecules attributed to excellent dock score displayed by all the structures performed against PPAR-γ receptor site. Subsequently, all the derivatives were primarily deduced for their antidiabetic potential by OGTT. The compounds that showed significant antidiabetic activity in OGT Test and also exhibited high dock scores were assessed further by in vitro PPAR transactivation assay to assure analogy between in vivo and in vitro studies. The antidiabetic activity of these active compounds was then evaluated on STZ induced diabetic model in vivo. The most active compounds were scrutinized for its effect on PPAR-γ gene expression and hepatotoxic effect. Finally, it was recapitulated that these derivatives can provide a new prospect towards the development of antidiabetic agents with fewer side effects.
- Kharbanda, Chetna,Alam, Mohammad Sarwar,Hamid, Hinna,Ali, Yakub,Nazreen, Syed,Dhulap, Abhijeet,Alam, Perwez,Pasha
-
-
- Design, synthesis, and biological evaluation of new series of pyrrol-2(3H)-one and pyridazin-3(2H)-one derivatives as tubulin polymerization inhibitors
-
A potential microtubule destabilizing series of new thirty-five Pyrrol-2-one, Pyridazin-3(2H)-one and Pyridazin-3(2H)-one/oxime derivatives has been synthesized and tested for their antiproliferative activity against a panel of 60 human cancer cell lines. Compounds IVc, IVg and IVf showed a broad spectrum of growth inhibitory activity against cancer cell lines representing renal, cancer of lung, colon, central nervous system, ovary, and kidney. Among them, compound IVg was found to have broad spectrum anti-tumor activity against the tested nine tumor subpanels with selectivity ratios ranging between 0.21 and 3.77 at the GI50 level. In vitro assaying revealed tubulin polymerization inhibition by all active compounds IVc, IVg and IVf. The results of the docking study revealed nice fitting of compounds IVc, IVf, and IVg into CA-4 binding site in tubulin. The three compounds exhibited high binding affinities (ΔGb = ?12.49 to ?12.99 kcal/mol) toward tubulin compared to CA-4 (?8.87 kcal/mol). Investigation of the binding modes of the three compounds IVc, IVf, and IVg revealed that they interacted mainly hydrophobically with tubulin and similar binding orientations to that of CA-4. These observations suggest that tubulin is a possible target for these compounds.
- Abdelbaset, Mahmoud S.,Abdelrahman, Mostafa H.,Bukhari, Syed Nasir Abbas,Gouda, Ahmed M.,Youssif, Bahaa G.M.,Abdel-Aziz, Mohamed,Abuo-Rahma, Gamal El-Din A.
-
-
- Brine Shrimp (Artemia salina) Lethality Bioassay of Some 2-(Alkyl/Aryl)-6-Phenyl-4,5-Dihydropyridazin-3(2H)-one Derivatives
-
A series of pyridazinone derivatives, 2-(alkyl/aryl)-6-phenyl-4,5-dihydropyridazin-3(2H)-ones (3a-h), was synthesized from 6-phenyl-4,5-dihydropyridazin-3(2H)-one (2). Compound 2 was synthesized from benzoylpropionic acid (1). The synthesized compounds were characterized on the basis of their spectral (infrared, proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and mass spectra) and elemental analytical data. The compounds 2 and 3a-h and potassium dichromate (as reference drug) were tested at the dose level of 10, 20, and 30 μg/mL. Compounds 3d and 3b exhibited potent brine shrimp lethality with LC50values of 4.023 μg and 4.20 μg. Other compounds 3g, 3f, 3c, 3h, 2, 3a, and 3e also showed significant cytotoxic activity with LC50values of 13.91, 12.58, 11.91, 11.76, 10.58, 9.76, and 7.46 μg, respectively. The present study supports that brine shrimp bioassay is a simple, reliable, and suitable method for estimation of bioactivity of synthesized compounds and provides support for their use in medicine.
- Acharya, Mrityunjoy,Asif, Mohammad,Imran, Mohd,Kamal, Mehnaz
-
-
- Nickel-Mediated Photoreductive Cross Coupling of Carboxylic Acid Derivatives for Ketone Synthesis**
-
A simple visible light photochemical, nickel-catalyzed synthesis of ketones from carboxylic acid-derived precursors is presented. Hantzsch ester (HE) functions as a cheap, green and strong photoreductant to facilitate radical generation and also engages in the Ni-catalytic cycle to restore the reactive species. With this dual role, HE allows for the coupling of a large variety of radicals (1°,2°, benzylic, α-oxy & α-amino) with aroyl and alkanoyl moieties, a new feature in reactions of this type. With both precursors deriving from abundant carboxylic acids, this protocol is a welcome addition to the organic chemistry toolbox. The reaction proceeds under mild conditions without the need for toxic metal reagents or bases and shows a wide scope, including pharmaceuticals and complex molecular architectures.
- Brauer, Jan,Quraishi, Elisabeth,Kammer, Lisa Marie,Opatz, Till
-
p. 18168 - 18174
(2021/11/30)
-
- Tunable Trifunctionalization of Tertiary Enaminones for the Regioselective and Metal-Free Synthesis of Discrete and Proximal Phosphoryl Nitriles
-
This paper reports an unprecedented trifunctionalization of tertiary enaminones for the synthesis phosphoryl nitriles by the reactions of enaminones with diarylphosphine oxides and trimethylsilyl cyanide (TMSCN) without the use of any metal reagent. Emplo
- Xu, Zhongrong,Fu, Leiqing,Fang, Xia,Huang, Bin,Zhou, Liyun,Wan, Jie-Ping
-
p. 5049 - 5053
(2021/07/19)
-
- Visible-Spectrum Solar-Light-Mediated Benzylic C-H Oxygenation Using 9,10-Dibromoanthracene As an Initiator
-
We report a visible-light-mediated benzylic C-H oxygenation reaction. The reaction is initiated by solar light or the blue LED activation of 9,10-dibromoanthracene in a reaction with oxygen and takes place at ambient temperature and air pressure. Secondary benzylic positions are oxygenated to ketones, while tertiary benzylic carbons are oxygenated to give hydroperoxides. Notably, cumene hydroperoxide is produced in a higher yield and at milder conditions than the currently employed industrial conditions.
- Santra, Sourav K.,Szpilman, Alex M.
-
p. 1164 - 1171
(2020/12/23)
-
- Iridium-Catalyzed Asymmetric Hydrogenation of ?- A nd ?-Ketoacids for Enantioselective Synthesis of ?- A nd ?-Lactones
-
A highly efficient asymmetric hydrogenation of ?- A nd ?-ketoacids was developed by using a chiral spiro iridium catalyst (S)-1a, affording the optically active ?- A nd ?-hydroxy acids/lactones in high yields with excellent enantioselectivities (up to >99% ee) and turnover numbers (TON up to 100000). This protocol provides an efficient and practical method for enantioselective synthesis of Ezetimibe.
- Hua, Yun-Yu,Bin, Huai-Yu,Wei, Tao,Cheng, Hou-An,Lin, Zu-Peng,Fu, Xing-Feng,Li, Yuan-Qiang,Xie, Jian-Hua,Yan, Pu-Cha,Zhou, Qi-Lin
-
supporting information
p. 818 - 822
(2020/02/15)
-
- Development of Nitrolactonization Mediated by Iron(III) Nitrate Nonahydrate
-
The nitrolactonization of alkenyl carboxylic acids mediated by Fe(NO3)3·9H2O has been developed. Nitrolactones were obtained in up to 93% yield by treatment of alkenyl carboxylic acids with Fe(NO3)3·9H2O. Mechanistic studies disclosed that the reaction proceeded through a radical intermediate generated from addition of NO2 to alkenyl carboxylic acids.
- Yoshimura, Tomoyuki,Umeda, Yuki,Takahashi, Risako,Matsuo, Jun-Ichi
-
p. 1220 - 1225
(2020/12/17)
-
- Synthesis, anti-convulsant activity and molecular docking study of novel thiazole pyridazinone hybrid analogues
-
Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.
- Khisal, Subuhi,Mishra, Ravinesh,Partap, Sangh,Siddiqui, Aness Ahmad,Yar, Mohammad Shahar
-
-
- Chemoselective Hydrosilylation of the α,β-Site Double Bond in α,β- And α,β,γ,δ-Unsaturated Ketones Catalyzed by Macrosteric Borane Promoted by Hexafluoro-2-propanol
-
The B(C6F5)3-catalyzed chemoselective hydrosilylation of α,β- and α,β,γ,δ-unsaturated ketones into the corresponding non-symmetric ketones in mild reaction conditions is developed. Nearly 55 substrates including those bearing reducible functional groups such as alkynyl, alkenyl, cyano, and aromatic heterocycles are chemoselectively hydrosilylated in good to excellent yields. Isotope-labeling studies revealed that hexafluoro-2-propanol also served as a hydrogen source in the process.
- Zhan, Xiao-Yu,Zhang, Hua,Dong, Yu,Yang, Jian,He, Shuai,Shi, Zhi-Chuan,Tang, Lei,Wang, Ji-Yu
-
p. 6578 - 6592
(2020/07/17)
-
- Organocatalyzed Aerobic Oxidation of Aldehydes to Acids
-
The first example organocatalyzed aerobic oxidation of aldehydes to carboxylic acids in both organic solvent and water under mild conditions is developed. As low as 5 mol % N-hydroxyphthalimide was used as the organocatalyst, and molecular O2 was used as the sole oxidant. No transition metals or hazardous oxidants or cocatalysts were involved. A wide range of carboxylic acids bearing diverse functional groups were obtained from aldehydes, even from alcohols, in high yields.
- Dai, Peng-Fei,Qu, Jian-Ping,Kang, Yan-Biao
-
supporting information
p. 1393 - 1396
(2019/02/26)
-
- Aryl Boronic Acid Catalysed Dehydrative Substitution of Benzylic Alcohols for C?O Bond Formation
-
A combination of pentafluorophenylboronic acid and oxalic acid catalyses the dehydrative substitution of benzylic alcohols with a second alcohol to form new C?O bonds. This method has been applied to the intermolecular substitution of benzylic alcohols to form symmetrical ethers, intramolecular cyclisations of diols to form aryl-substituted tetrahydrofuran and tetrahydropyran derivatives, and intermolecular crossed-etherification reactions between two different alcohols. Mechanistic control experiments have identified a potential catalytic intermediate formed between the aryl boronic acid and oxalic acid.
- Estopi?á-Durán, Susana,Donnelly, Liam J.,Mclean, Euan B.,Hockin, Bryony M.,Slawin, Alexandra M. Z.,Taylor, James E.
-
supporting information
p. 3950 - 3956
(2019/02/16)
-
- NOVEL PYRIDAZINONE DERIVATIVES AND PROCESS FOR THEIR PREPARATION
-
The present invention relates to a compound of formula I, wherein R is selected from the group consisting of -H, -F, -Cl, -Br, -I, -NO2, -CH3, and -C2H5; X is selected from the group consisting of -F, -Cl, -Br, and –I; and pharmaceutically acceptable salts thereof. The present invention also relates to processes for the preparation of the compound of formula I.
- -
-
Page/Page column 8
(2019/11/12)
-
- Metal-Free Arylation-Lactonization Sequence of γ-Alkenoic Acids Using Anilines as Aryl Radical Precursors
-
The presence of salicylic acid (10 mol-%) and H2O (10 equiv.) significantly improves the arylation-lactonization sequence of γ-alkenoic acids with in situ formed diazonium salts (from bench stable anilines). The reaction is finished in less than 5 h without thermal or photochemical activation, giving access to a variety of γ,γ-disubstituted butyrolactones. The protocol is user-friendly and can be used at gram-scale or adapted to transform alkenols into phthalanes. Control experiments revealed that aryl radicals participate in the reaction and a plausible mechanism is proposed to include this and other mechanistic investigations, for the catalyzed and the background reaction.
- Felipe-Blanco, Diego,Gonzalez-Gomez, Jose C.
-
supporting information
p. 7735 - 7744
(2019/12/24)
-
- Organocatalytic Reductive Propargylation: Scope and Applications
-
An amino acid-catalyzed three-component reductive coupling protocol has been developed for the selective high-yielding synthesis of nearly fifty examples of propargylated cyclic/acyclic systems from the various propargyl aldehydes, cyclic/acyclic CH acids, and Hantzsch ester under ambient conditions. It is an economical, efficient, catalytic, metal-free protocol for the quick gram-scale synthesis of propargylated cyclic/acyclic compounds, and many of these coupling compounds were purified by a simple precipitation-filtration technique instead of column chromatography. Functionally rich propargylated cyclic-1,3-diketones were specifically transformed into dihydropyrans found in natural products and drugs through an annulative etherification reaction by using Lewis-acid (AgOTf) catalysis. Further, we developed the C-methylation reactions on propargylated cyclic-1,3-diketones, which are prolific synthons in natural products and medicinal chemistry.
- Pasha, Mohammed Anif,Krishna, A. Vamshi,Ashok, Etikala,Ramachary, Dhevalapally B.
-
p. 15399 - 15416
(2019/12/04)
-
- Convenient and easy access to 2-hydroxycyclopent-2-enones from acylcyanohydrins
-
A convenient access to 2-hydroxycyclopentenones was designed from acylcyanohydrins, by using titanacyclopropane complexes as nucleophilic partners and an intramolecular aldol condensation in basic conditions. The development of a one-pot procedure allows a step- and atom-economic process, and the use of Grignard reagents other than ethylmagnesium bromide provided valuable 3,4-disubstituted 2-hydroxycyclopentenones. The utility of the hydroxy group was illustrated by further functionalization of the α-position using palladium-mediated cross-coupling reactions.
- Pantin, Mathilde,Bodinier, Florent,Saillour, Jordan,Youssouf, Yassine M.,Boeda, Fabien,Pearson-Long, Morwenna S.M.,Bertus, Philippe
-
p. 4657 - 4662
(2019/07/16)
-
- A aldehyde or mellow directly converted into the carboxylic acid (by machine translation)
-
The invention discloses a aldehyde or mellow oxidation can be directly transformed into carboxylic acid, is characterized in that the pure oxygen environment, in N - hydroxy imide compound under the catalysis of the imide compound or N - hydroxy and nitrous acid ester compound common under the catalysis, the CH2 OH and CHO oxidation directly converted into the carboxylic acid compounds. The invention using oxygen as the oxidizing agent, does not add any metal catalyst, environment-friendly, high catalytic efficiency, simple and convenient operation. With the previous metal catalytic system complex and different catalytic system, has some metal catalytic system in the process, the use of transition metal will cause the transition metal of the residual, the invention adopts the non-metallic catalytic system, environmental protection, preventing the metal residue problem, this to the solution of the drug in the synthesis of transition metal residue problem and provides a new method of thinking. (by machine translation)
- -
-
Paragraph 0050-0052
(2018/08/03)
-
- Method for synthesizing intermediate 4-oxo-4-phenylbutyric acid
-
The invention discloses a method for synthesizing an intermediate 4-oxo-4-phenylbutyric acid. According to the method, butanedioic anhydride, benzene, aluminum trichloride, CsPW/CNT, phosphotungstic acid, cesium carbonate and CNT are taken as main raw materials. The synthetic process disclosed by the invention comprises the step: carrying out a Friedel-Crafts acylation reaction on dicarboxylic anhydride and anhydrous benzene in the presence of a catalyst CsPW/CNT so as to obtain 4-oxo-4-phenylbutyric acid. Under the effect of the catalyst, acyl cation is produced and carries out an electrophilic substitution reaction with an aromatic ring, any by-product is not produced, the separation and purification process is reduced, the catalyst can be repeatedly utilized after recovery, the production cost is reduced, and the purity and yield of the product are improved.
- -
-
Paragraph 0008; 0010-0029
(2018/12/12)
-
- Synthesis of plasmodione metabolites and 13C-enriched plasmodione as chemical tools for drug metabolism investigation
-
Malaria is a tropical parasitic disease threatening populations in tropical and sub-tropical areas. Resistance to antimalarial drugs has spread all over the world in the past 50 years, thus new drugs are urgently needed. Plasmodione (benzylmenadione series) has been identified as a potent antimalarial early lead drug, acting through a redox bioactivation on asexual and young sexual blood stages. To investigate its metabolism, a series of plasmodione-based tools, including a fully 13C-labelled lead drug and putative metabolites, have been designed and synthesized for drug metabolism investigation. Furthermore, with the help of UHPLC-MS/MS, two of the drug metabolites have been identified from urine of drug-treated mice.
- Feng, Liwen,Lanfranchi, Don Antoine,Cotos, Leandro,Cesar-Rodo, Elena,Ehrhardt, Katharina,Goetz, Alice-Anne,Zimmermann, Herbert,Fenaille, Fran?ois,Blandin, Stephanie A.,Davioud-Charvet, Elisabeth
-
supporting information
p. 2647 - 2665
(2018/04/27)
-
- An Electrophilic Trifluoromethylthiolation of Silylenol Ethers and β-Naphthols with Diethylaminosulfur Trifluoride and (Trifluoromethyl)trimethylsilane
-
An efficient and general trifluoromethylthiolation of silylenol ethers and β-naphthols have been accomplished employing the combination of diethylaminosulfur trifluoride (DAST) and (trifluoromethyl)trimethylsilane (CF3TMS) as source of electrophilic trifluoromethylthio moiety for the synthesis of α-trifluoromethylthiolated carbonyl compounds and β-naphthols in good yields. Important features of this method include wide functional group tolerance and use of readily available DAST/CF3TMS. Potential of the methodology was demonstrated via the synthesis of α-trifluoromethylthiolated (+)-4-cholesten-3-one and naphthoquinone. (Figure presented.).
- Saravanan, Perumal,Anbarasan, Pazhamalai
-
supporting information
p. 2894 - 2899
(2018/08/17)
-
- Mechanistic analysis of a copper-catalyzed C-H oxidative cyclization of carboxylic acids
-
We recently reported that carboxylic acids can be oxidized to lactone products by potassium persulfate and catalytic copper acetate. Here, we unravel the mechanism for this C-H functionalization reaction using desorption electrospray ionization, online electrospray ionization, and tandem mass spectrometry. Our findings suggest that electron transfer from a transient benzylic radical intermediate reduces Cu(ii) to Cu(i), which is then re-oxidized to Cu(ii) in the catalytic cycle. The resulting benzylic carbocation is trapped by the pendant carboxylate group to give the lactone product. Formation of the putative benzylic carbocation is supported by Hammett analysis. The proposed mechanism for this copper-catalyzed oxidative cyclization process differs from earlier reports of analogous reactions, which posit a substrate carboxylate radical as the reactive oxidant.
- Banerjee, Shibdas,Sathyamoorthi, Shyam,Du Bois,Zare, Richard N.
-
p. 7003 - 7008
(2017/10/05)
-
- Efficient Hydrogenation of Biomass Oxoacids to Lactones by Using NHC–Iridium Coordination Polymers as Solid Molecular Catalysts
-
A series of NHC–iridium coordination polymers have proven to be robust, efficient and recyclable solid molecular catalysts toward the hydrogenation of biomass levulinic acid (LA) to γ-valerolactone. Along with quantitative yields attained at 0.01 mol % catalyst loading under 50 atm of H2, the solid molecular catalyst was readily recovered and reused for 12 runs without obvious loss of the selectivity and activity. Remarkably, up to 1.2×105 TON, an unprecedented value could be achieved in this important transformation. In addition, a number of LA homologues, analogues and derivatives were well tolerated to deliver various intriguing and functional lactones in good to excellent yields, which further confirmed the feasibility of the solid molecular catalysts.
- Liu, Yaoqi,Sun, Zheming,Huang, Changyu,Tu, Tao
-
p. 355 - 360
(2017/02/05)
-
- Oxime and oxime ether compounds with anti-hepatitis B virus activity
-
The invention discloses oxime and oxime ether compounds with anti-hepatitis B virus activity. The structural general formula of the compound is shown in the following description; a HepG 2.2.15 cell experiment proves that the oxime and oxime ether compounds have a certain inhibition function on HBV surface antigens (HBsAg) and e antigens (HBeAg). Under the same condition, the inhibition rate of positive control group lamivudine on HBsAg is only 55.51%, the highest inhibition rate of the oxime and oxime ether compound on HBsAg can achieve 98.67%, and the oxime and oxime ether compounds have the characteristic of low toxicity. The novel oxime and oxime ether compounds disclosed by the invention are one class of nonnucleosides anti-hepatitis B virus activity compound, and are hopefully developed into the new medicine for resisting hepatitis b viruses.
- -
-
Paragraph 0056
(2017/04/20)
-
- Design, Synthesis, and Pharmacological Screening of Pyridazinone Hybrids as Anticonvulsant Agents
-
A series of new hybrid benzimidazole containing pyridazinones derivatives were designed and synthesized in accordance with the pharmacophoric requirements essential for the anticonvulsant activity. The synthesized compounds were evaluated for anticonvulsant activity on mice by the gold standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models. Among the compounds tested, SS-4F showed significant anticonvulsant activity in both the screens with ED50 values of 25.10 and 85.33 mg/kg in the MES and scPTZ screens, respectively. Compound SS-4F emerged as safer and effective anticonvulsant due to its several-fold higher protective indices. Further, the gamma-aminobutyric acid (GABA) estimation result showed a marked increase in the GABA level (1.7-fold) as compared to the control, which was further confirmed by good binding properties with the GABAA receptor.
- Partap, Sangh,Yar, Mohammad Shahar,Hassan, Md. Zaheen,Akhtar, Md. Jawaid,Siddiqui, Anees A.
-
-
- Solubility and thermodynamics of 6-phenyl-4,5-dihydropyridazin-3(2H)-one in various neat solvents at different temperatures
-
Pyridazinone derivatives have been investigated either pre-clinically or clinically in the treatment of various cardiovascular diseases. The main problems associated with these drugs are the poor aqueous solubility and toxicity. Therefore, in the current study, the solubility of pyridazinone derivative i.e. 6-phenyl-4,5-dihydropyridazin-3(2H)-one [coded as PDP-6] was determined in eleven different neat solvents at temperatures “T?=?293.2?K to 313.2?K” and “atmospheric pressure p?=?0.1?MPa”. Experimental mole fraction solubilities of PDP-6 were correlated well with van't Hoff and Apelblat models with mean percent deviation of ??1) followed by 2-(2-ethoxyethoxy) ethanol (Transcutol) (5.24?×?10??1), polyethylene glycol-400 [PEG-400] (8.47?×?10??2), ethyl acetate [EA] (1.45?×?10??2), ethylene glycol [EG] (1.09?×?10??2), propylene glycol [PG] (1.03?×?10??2), 2-butanol (7.78?×?10??3), 1-butanol (7.68?×?10??3), ethanol (6.96?×?10??3), isopropyl alcohol [IPA] (6.51?×?10??3) and water (1.61?×?10??6) and similar trend was also recorded at all five different temperatures investigated. “Apparent thermodynamic analysis” on mole fraction solubilities of PDP-6 indicated an endothermic dissolution of PDP-6 in all neat solvents studied. Based on these data, PDP-6 has been proposed as practically insoluble in water, sparingly soluble in ethanol, IPA, EG, PG, EA, 1-butanol and 2-butanol, soluble in PEG-400 and very soluble in DMSO and Transcutol.
- Imran, Mohd,Haq, Nazrul,Abida,Alanazi, Fars K.,Alsarra, Ibrahim A.,Shakeel, Faiyaz
-
supporting information
p. 455 - 461
(2017/05/19)
-
- Kinetics and thermodynamics of oxidation of some para-substituted 4-oxo-4-phenyl butanoic acids by tripropylammonium fluorochromate in aqueous acetic acid medium
-
The kinetics of oxidation of 4-oxo-4-phenyl butanoic acid (4-oxo acid), p-methoxy (p-OCH3), p-ethoxy (p-OC2H5), p-methyl (p-CH3), p-chloro (p-Cl), p-bromo (p-Br) and p-acetyl (p-COCH3) 4-oxo acids by tripropylammonium fluorochromate (TriPAFC) in aqueous acetic acid medium in the presence of perchloric acid have been described. The reaction is first order with respect to 4-oxo acid, TriPAFC and perchloric acid. The order of reactivity among the studied 4-oxoacids is: p-OCH3 > p-OC2H5 > p-CH3 > p-H > p-Cl > p-Br > p-COCH3. The effect of changes on the electronic nature of the substrate reveals that there is a development of positive charge in the transition state. The activation parameters have been computed from Arrhenius and Eyring plots. Based on the kinetic results, a suitable mechanism has been proposed.
- Yogananth,Asghar, Basim H.,Sheik Mansoor
-
p. 1617 - 1621
(2017/05/29)
-
- Preparation γ - carbonyl carboxylic acid, amino acid, amino acid ester and amide compounds
-
The invention discloses a method for preparing gamma-carbonyl carboxylic acid, amino acid, amino acid ester and amide compounds. The method comprises the following steps: uniformly mixing a methylene-containing compound, an oxidizing agent and water to perform selective methylene carbon-hydrogen bond oxidation, so as to obtain at least one of gamma-carbonyl carboxylic acid, gamma-carbonyl amino acid and gamma-carbonyl amide compounds after the reaction is finished. The method is a methylene selective oxidation reaction which does not need a catalyst for catalysis and employs a persulfate as an oxidizing agent, and the reaction is successfully applied to oxidation of methylene carbon-hydrogen bonds of carboxylic acids, amino acids and amide compounds, excellent selectivity is obtained, and the method has important application value.
- -
-
Paragraph 0053; 0054; 0055; 0056; 0058
(2017/06/21)
-
- Copper-Catalyzed Oxidative Cyclization of Carboxylic Acids
-
A method for converting C-H to C-O bonds through oxidative cyclization of carboxylic acids to generate lactone products is described. The reaction employs catalytic amounts of Cu(OAc)2 and potassium persulfate as the terminal oxidant and is performed open to air in an aqueous acetic acid solvent system. Preliminary mechanistic studies suggest that substrate oxidation likely proceeds by sulfate radical anion and that the Cu catalyst has no influence on the product-determining step. These conclusions differ from related investigations that propose the intermediacy of a carboxylate radical.
- Sathyamoorthi, Shyam,Du Bois
-
supporting information
p. 6308 - 6311
(2016/12/23)
-
- Synthesis and antihypertensive activity of some novel pyridazinones
-
Four pyridazinones (2-5) were synthesized by the reaction of 3-benzoylpropionic acid with the corresponding hydrazines. These pyridazinones were further derivatized with appropriate aromatic aldehydes in the presence of piperidine to obtain the desired compounds (6-13). The chemical structures of the synthesized pyridazinones were elucidated on the basis of their spectral analysis (IR, 1H-NMR, and 13C-NMR). Molecular docking studies were carried out to identify the most active antihypertensive pyridazinone compound by using the crystal structure of human Angiotensin Converting Enzyme (ACE), the enzyme implicated in the pathogenesis of hypertension. The compound (6) was identified as the most active inhibitor of the Angiotensin Converting Enzyme (ACE). This compound was further assessed for its ACE inhibitory activity using Dojindo ACE Kit-WST test kit. The enzymatic ACE inhibitory activity revealed that the compound (6) had IC50 value of 5.78 μg/mL, wherein the standard drug Lisinopril had IC50 value of 0.85 μg/mL. It has been concluded that incorporation of free amino groups and free carboxylic acid groups in the structure of the synthesized pyridazinone (6-13) may provide more active and potent ACE inhibitors.
- Imran, Mohd,Nayeem, Naira
-
p. 267 - 274
(2016/05/09)
-
- Cobalt-catalyzed oxidative cyclization of gem-disubstituted conjugated alkenols
-
Aryl gem-disubstituted conjugated alkenols underwent oxidative cyclization affording 2,5,5-trisubstituted tetrahydrofurans in reasonable yields and good diastereoselectivities using the reductive termination variation of the Mukaiyama aerobic oxidative reaction. Under oxidative termination, the same alkenols produced diols and ketonic by-products via the double hydration and beta-scission competing pathways. Furthermore, the differences in alkenol reactivity under the reductive and oxidative termination conditions were investigated.
- Alves, Tania M.F.,Costa, Mateus O.,Bispo, Beatriz A.D.,Pedrosa, Fabiana L.,Ferreira, Marco A.B.
-
supporting information
p. 3334 - 3338
(2016/07/11)
-
- Synthesis of the novel tetrahydropyrazolo[3,4- c ]pyridin-5-one scaffold
-
We report an efficient synthesis of the novel 1,4,6,7-tetra-hydropyrazolo[3,4-c]pyridin-5-one scaffold with the potential for incorporation of alkyl or aryl substituents at the C-3 and N-6 positions. The route utilises a Dieckmann condensation to install the lactam ring, followed by a hydrazine cyclisation to build the fused pyrazole ring.
- Howe, Nicholas J.,Blades, Kevin,Lamont, Gillian M.
-
supporting information
p. 228 - 232
(2015/03/03)
-
- Discovery of phenoxybutanoic acid derivatives as potent endothelin antagonists with antihypertensive activity
-
A series of phenoxybutanoic acid derivatives were synthesized and tested for their antagonistic activity on the contraction of the rat thoracic aortic ring induced by endothelin-1. Preliminary screening results showed that 6e and 6g with benzoheterocycles demonstrated significant antagonistic activities when compared to the reference compound BQ123. The results from additional assays for the binding affinity and selectivity for endothelin receptors showed that 6e was a selective ETA antagonist with a nanomolar IC50. Moreover, 6e was effective in relieving hypoxia-induced pulmonary arterial hypertension and right ventricular weight ratio. Therefore, 6e may have potential for further development as a therapeutic agent for the treatment of cardiovascular diseases.
- Cai, Jin,Liu, Ligang,Hong, Kwon Ho,Wang, Peng,Li, Lushen,Cao, Meng,Sun, Chunlong,Wu, Xiaoqing,Zong, Xi,Chen, Junqing,Ji, Min
-
p. 657 - 667
(2015/02/19)
-
- Diastereo- and enantioselective direct vinylogous Michael addition of γ-substituted butenolides to 2-enoylpyridines catalyzed by chiral bifunctional amine-squaramides
-
The diastereo- and enantioselective direct vinylogous Michael addition reaction of γ-substituted butenolides to 2-enoylpyridines has been achieved. A range of γ,γ-disubstituted butenolide derivatives, bearing two consecutive tri- and tetrasubstituted stereogenic centers, were readily obtained in good yields with excellent stereoselectivities (up to >99:1 dr and >99% ee).
- Wang, Zhen-Hua,Wu, Zhi-Jun,Huang, Xue-Qun,Yue, Deng-Feng,You, Yong,Xu, Xiao-Ying,Zhang, Xiao-Mei,Yuan, Wei-Cheng
-
supporting information
p. 15835 - 15838
(2015/11/10)
-
- Chiral Surfactant-Type Catalyst: Enantioselective Reduction of Long-Chain Aliphatic Ketoesters in Water
-
A series of amphiphilic ligands were designed and synthesized. The rhodium complexes with the ligands were applied to the asymmetric transfer hydrogenation of broad range of long-chained aliphatic ketoesters in neat water. Quantitative conversion and excellent enantioselectivity (up to 99% ee) was observed for α-, β-, γ-, δ- and ε-ketoesters as well as for α- and β-acyloxyketone using chiral surfactant-type catalyst 2. The CH/π interaction and the strong hydrophobic interaction of long aliphatic chains between the catalyst and the substrate in the metallomicelle core played a key role in the catalytic transition state. Synergistic effects between the metal-catalyzed site and the hydrophobic microenvironment of the core in the micelle contributed to high stereoselectivity. (Chemical Equation Presented).
- Lin, Zechao,Li, Jiahong,Huang, Qingfei,Huang, Qiuya,Wang, Qiwei,Tang, Lei,Gong, Deying,Yang, Jun,Zhu, Jin,Deng, Jingen
-
p. 4419 - 4429
(2015/05/13)
-
- Ultrasound-promoted Friedel-Crafts acylation of arenes and cyclic anhydrides catalyzed by ionic liquid of [bmim]Br/AlCl3
-
A simple and efficient method of Friedel-Crafts acylation of arenes with succinic anhydride, phthalic anhydride and glutaric anhydride under the action of 1-butyl-3-ethylimidazolium ([bmim]Br/AlCl3 ([bmim]+) cation (ionic liquid) and ultrasound irradiation is presented. Thy purity of products was tested by GC-MS and their structures evaluated by IR and 1H NMR spectroscopy.
- Fekri, Leila Zare,Nikpassand, Mohammad
-
p. 1825 - 1829
(2015/01/09)
-
- Efficient synthesis, anticonvulsant and muscle relaxant activities of new 2-((5-amino-1,3,4-thiadiazol-2-yl)methyl)-6-phenyl-4,5-dihydropyridazin-3(2H) -one derivatives
-
A series of 2-(2-(3-(4-chlorophenyl)-6-oxo-5,6-dihydropyridazin-1(4H)yl) acetyl)hydrazine carbothioamide and 2-((5-amino-1,3,4-thiadiazol-2-yl)methyl)-6- (4-chlorophenyl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized, characterized, and evaluated for anticonvulsant activity and muscle relaxant activity. The synthesized compounds 5d (82.75 %) and 5e (85.44 %) showed promising anticonvulsant activity by protection against tonic hind limb extensor phase in maximal electroshock model (MES) at (50 mg/kg) compared to standard drug phenytoin and also compounds 5d (82.75 %), and 5e (85.44 %) showed significant anticonvulsant activity by protection against pentylenetetrazole- induced generalized convulsions in pentylenetetrazole model (PTZ) at (100 mg/kg) compared to standard drug diazepam. On the other hand, compound 5e showed significant muscle relaxant activity (84.57 %) by rotarod and traction test model comparing with diazepam as a standard drug.
- Sharma, Bhawna,Verma, Amita,Sharma, Upendra Kumar,Prajapati, Sunil
-
p. 146 - 157
(2014/03/21)
-
- Remote activation of the nucleophilicity of isatin
-
The concept of the remote activation of reactivity was first applied in asymmetric organocatalysis. An isatin 3-phenylimine derivative acts as a donor in the thiourea catalyzed asymmetric addition to unsaturated 1,4-ketoesters, affording aza-Michael adducts in high enantiomeric purity and yield.
- Zari, Sergei,Kudrjashova, Marina,Pehk, Tonis,Lopp, Margus,Kanger, Tonis
-
supporting information
p. 1740 - 1743
(2014/04/17)
-
- Iron-catalyzed arene alkylation reactions with unactivated secondary alcohols
-
A simple, iron-based catalytic system allows for the inter- and intramolecular arylation of unactivated secondary alcohols. This transformation expands the substrate scope beyond the previously required activated alcohols and proceeds under mild reaction conditions, tolerating air and moisture. Furthermore, the use of an enantioenriched secondary alcohol provides an enantioenriched product for the intramolecular reaction, thereby offering a convenient approach to nonracemic products.
- Jefferies, Latisha R.,Cook, Silas P.
-
supporting information
p. 2026 - 2029
(2014/05/06)
-
- Design, synthesis and antihypertensive screening of novel pyridazine substituted s-triazin-2-imine/one/thione derivatives
-
Some new 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine/one/thione derivatives were synthesized by a sequence of reactions starting from appropriate aryl hydrocarbons. The final compounds were screened for antihypertensive activities by non-invasive method using Tail Cuff method. All the test compounds showed significant antihypertensive activity; 7-(biphenyl-4-yl)-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine (4p) exhibited antihypertensive activity more than the reference standard drugs.
- Mishra, Ravinesh,Siddiqui, Anees A.,Husain, Asif,Rashid, Mohd.,Goda, Chirag
-
p. 552 - 559
(2015/02/19)
-
- Enzymatic synthesis of chiral γ-amino acids using ω-transaminase
-
In this study, we successfully synthesized enantiomerically pure (R)- and (S)-γ-amino acids (>99% ee) using ω-transaminase (ω-TA) through kinetic resolution and asymmetric synthesis respectively. The present study demonstrates the high potentiality of ω-TA reaction for the production of chiral γ-amino acids.
- Shon, Minsu,Shanmugavel, Ramachandran,Shin, Giyoung,Mathew, Sam,Lee, Sang-Hyeup,Yun, Hyungdon
-
supporting information
p. 12680 - 12683
(2015/05/20)
-
- Biotransformation of aromatic ketones and ketoesters with the non-conventional yeast Pichia glucozyma
-
The non-conventional yeast Pichia glucozyma CBS 5766 has been used for the biotransformation of different aromatic ketones and ketoesters. The growth and biotransformation conditions were optimised for the reduction of acetophenone and under optimised conditions, propiophenone, butyrophenone and valerophenone were reduced to the corresponding (S)-alcohols with high yields and enantioselectivity. Ketoreductase(s) of Pichia glucozyma showed high catalytic activities also towards aromatic β- and γ-ketoesters, being often competitive with esterase(s). These concurrent activities allowed for the preparation of hydroxyesters, hydroxyacids and lactones often in a very selective manner.
- Contente, Martina Letizia,Molinari, Francesco,Zambelli, Paolo,De Vitis, Valerio,Gandolfi, Raffaella,Pinto, Andrea,Romano, Diego
-
supporting information
p. 7051 - 7053
(2015/02/02)
-
- A simple and efficient approach to realize difunctionalization of arylketones with malonate esters via electrochemical oxidation
-
A facile difunctionalization of arylketones with malonate esters via electrochemical oxidation was achieved under mild conditions. A variety of difunctionalized products were obtained in good to excellent yields.
- Gao, Huihui,Zha, Zhenggen,Zhang, Zhenlei,Ma, Huanyue,Wang, Zhiyong
-
p. 5034 - 5036
(2014/05/06)
-
- Methods for the synthesis of chiral sulfur heterocycles and their application in the asymmetric Baylis-Hillman reactions
-
Enantiomerically pure (2S,6S)-2,6-diphenyltetrahydro-2H-thiopyran, (2S)-2-phenyltetrahydro thiophene, and (2S)-2-phenyltetrahydro-2H-thiopyran were prepared in 70-72% yields and with 86-99% ee via cyclization of the corresponding dimesylate in an SN2 cyclization reaction using sodium sulfide nonahydrate. The results on the application of various chiral sulfides in asymmetric Baylis-Hillman reactions are also described.
- Periasamy, Mariappan,Gurubrahamam, Ramani,Muthukumaragopal, Gopal P.
-
p. 568 - 574
(2013/06/27)
-