- Coordination chemistry of [methyl-3-(4-benzyloxyphenyl)methylene] dithiocarbazate with divalent metal ions: Crystal structures of the N,S Schiff base and of its bis-chelated nickel(II) complex
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The condensation of 4-benzyloxybenzaldehyde with S-methyldithiocarbazate (SMDTC) yielded the Schiff base methyl-3-[(4-benzyloxyphenyl)methylene] dithiocarbazate (HL) that, upon reaction with different metal ions, afforded bis-chelated complexes, ML2
- Islam, M. Al-Amin A. A.,Tarafder, M. Tofazzal H.,Chanmiya Sheikh,Ashraful Alam,Zangrando, Ennio
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- Synthesis and pharmacological evaluation of pyrazole derivatives containing sulfonamide moiety
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A new series of N-[4-[N-[4-[5-[4-(benzyloxy)phenyl]-1-(substituted phenyl)-1H-pyrazol-3-yl]phenyl]sulfamoyl]phenyl]acetamide derivatives were synthesized and elucidated by spectral data. All the compounds were subjected to in vitro evaluation for anti-inflammatory (BSA anti-denaturation assay), antioxidant (DPPH radical scavenging assay) and in vivo screening for anti-inflammatory (carrageenan induced rat paw edema inhibition)?activities. Selected active compounds were evaluated for ulcerogenic, lipid peroxidation, and LPS induced TNF-α production inhibition potential. The most active compound in the series showed an in vivo anti-inflammatory efficacy of 83.1?% when compared to diclofenac sodium (81.6?%). Evaluation of ulcer index and biochemical estimation for oxidative stress also revealed that this compound was safe on gastric mucosa and did not induce oxidative stress in tissues. When further tested for LPS induced TNF-α production inhibition in mice, it showed a better inhibition (ID50?=?6.23?mg/kg) when compared to standard inhibitor, SB 203580 (ID50?=?28.40?mg/kg). The p38α MAP kinase docking score of this active compound was also found to be better than that of SB 203580. Graphical abstract: [Figure not available: see fulltext.]
- Somakala, Kanagasabai,Amir, Mohammad,Sharma, Vidushi,Wakode, Sharad
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- Decatungstate Catalyzed Synthesis of Trifluoromethylthioesters from Aldehydes via a Radical Process
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Here we report a mild and general method for the trifluoromethylthiolation of aldehydes using N-trifluoromethylthiosaccharin as the CF3S radical source and sodium decatungstate (NaDT) as the photocatalyst. This reaction proceeds via hydrogen at
- Ye, Zhegao,Lei, Ziran,Ye, Xiaodong,Zhou, Liejin,Wang, Yanan,Yuan, Zheliang,Gao, Feng,Britton, Robert
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supporting information
p. 765 - 775
(2021/12/17)
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- Chemoselective and ligand-free aerobic oxidation of benzylic alcohols to carbonyl compounds using alumina-supported mesoporous nickel nanoparticle as an efficient recyclable heterogeneous catalyst
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An economically efficient and operationally simple ligand-free protocol for the chemoselective oxidation of benzylic alcohols to carbonyl compounds has been developed using alumina-supported nickel nanoparticles as a stable recyclable heterogeneous catalyst along with potassium tert-butoxide in the presence of aerial oxygen as an eco-friendly oxidant. The aliphatic alcohols remained unaffected under the present condition. Excellent chemoselectivity has also been demonstrated through intermolecular and intramolecular competition experiments. This protocol accommodates a diverse range of substituents with the tolerance of various sensitive moieties during the reaction. The catalyst could be recovered by filtration and reused consecutively without any significant loss in the catalytic activity. Moreover, the heterogeneity of the catalyst has also been established by the “hot filtration method (Sheldon's test)”.
- Das, Asit Kumar,Nandy, Sneha,Bhar, Sanjay
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- Catalytic study of the copper-based magnetic nanocatalyst on the aerobic oxidation of alcohols in water
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A copper-based magnetic nanocatalyst has been prepared by co-precipitation method and characterized by FESEM, EDS, TEM, XRD, XRF, ICP–OES, FTIR, and BET analysis. This new nanocatalyst displays a good activity toward the aerobic oxidation of a wide range of alcohols in water. Moreover, it is recyclable up to five following runs by simple filtration without any significant loss of its catalytic activity.
- Dehkordi, S. Saeid Saei,Albadi, Jalal,Jafari, Abbas Ali,Samimi, Heshmat Allah
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p. 2527 - 2538
(2021/03/24)
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- Ruthenium-on-Carbon-Catalyzed Facile Solvent-Free Oxidation of Alcohols: Efficient Progress under Solid-Solid (Liquid)-Gas Conditions
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A protocol for the ruthenium-on-carbon (Ru/C)-catalyzed solvent-free oxidation of alcohols, which proceeds efficiently under solid-solid (liquid)-gas conditions, was developed. Various primary and secondary alcohols were transformed to corresponding aldehydes and ketones in moderate to excellent isolated yields by simply stirring in the presence of 10% Ru/C under air or oxygen conditions. The solvent-free oxidation reactions proceeded efficiently regardless of the solid or liquid state of the substrates and reagents and could be applied to gram-scale synthesis without loss of the reaction efficiency. Furthermore, the catalytic activity of Ru/C was maintained after five reuse cycles.
- Park, Kwihwan,Jiang, Jing,Yamada, Tsuyoshi,Sajiki, Hironao
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p. 1200 - 1205
(2021/12/29)
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- Discovery of 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids as novel PPARα agonists with anti-hyperlipidemic and antioxidant activities: Design, synthesis and in vitro/in vivo biological evaluation
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In the current work, a series of novel 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids (10a-o) and (11a-e) were synthesized and evaluated as new PPARα agonists in order to find new agents with higher activity and fewer side effects. The 2-propanoic acid derivative 10a and the 2-butanoic acid congener 10i showed the best overall PPARα agonistic activity showing Emax% values of 50.80 and 90.55%, respectively, and EC50 values of 8.9 and 25.0 μM, respectively, compared to fenofibric acid with Emax = 100% and EC50 = 23.22 μM, respectively. These two compounds also stimulated carnitine palmitoyltransferase 1A gene transcription in HepG2 cells and PPARα protein expression. Molecular docking simulations were performed for the newly synthesized compounds to study their predicted binding pattern and energies in PPARα active site to rationalize their promising activity. In vivo, compounds 10a and 10i elicited a significant hypolipidemic activity improving the lipid profile in triton WR-1339-induced hyperlipidemic rats, including serum triglycerides, total cholesterol, LDL, HDL and VLDL levels. Compound 10i possessed better anti-hyperlipidemic activity than 10a. At a dose of 200 mg/kg, it demonstrated significantly lower TC, TG, LDL and VLDL levels than that of fenofibrate at the same dose with similar HDL levels. Compounds 10i and 10a possessed atherogenic indices (CRR, AC, AI, CRI-II) like that of fenofibrate. Additionally, a promising antioxidant activity indicated by the increased tissue reduced glutathione and plasma total antioxidant capacity with decreased plasma malondialdehyde levels was demonstrated by compounds 10a and 10i. No histopathological alterations were recorded in the hepatic tissue of compound 10i (200 mg/kg).
- Hassan, Rasha M.,Aboutabl, Mona E.,Bozzi, Manuela,El-Behairy, Mohammed F.,El Kerdawy, Ahmed M.,Sampaolese, Beatrice,Desiderio, Claudia,Vincenzoni, Federica,Sciandra, Francesca,Ghannam, Iman A.Y.
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- Dibenzazepine-linked isoxazoles: New and potent class of α-glucosidase inhibitors
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α-Glucosidase inhibition is a valid approach for controlling hyperglycemia in diabetes. In the current study, new molecules as a hybrid of isoxazole and dibenzazepine scaffolds were designed, based on their literature as antidiabetic agents. For this, a series of dibenzazepine-linked isoxazoles (33–54) was prepared using Nitrile oxide-Alkyne cycloaddition (NOAC) reaction, and evaluated for their α-glucosidase inhibitory activities to explore new hits for treatment of diabetes. Most of the compounds showed potent inhibitory potency against α-glucosidase (EC 3.2.1.20) enzyme (IC50 = 35.62 ± 1.48 to 333.30 ± 1.67 μM) using acarbose as a reference drug (IC50 = 875.75 ± 2.08 μM). Structure-activity relationship, kinetics and molecular docking studies of active isoxazoles were also determined to study enzyme-inhibitor interactions. Compounds 33, 40, 41, 46, 48–50, and 54 showed binding interactions with critical amino acid residues of α-glucosidase enzyme, such as Lys156, Ser157, Asp242, and Gln353.
- Umm-E-Farwa,Ullah, Saeed,Khan, Maria Aqeel,Zafar, Humaira,Atia-tul-Wahab,Younus, Munisaa,Choudhary, M. Iqbal,Basha, Fatima Z.
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supporting information
(2021/05/10)
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- NaI-mediated oxidative amidation of benzyl alcohols/aromatic aldehydes to benzamides via electrochemical reaction
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In this research, we have developed a mild electrochemical process for oxidative amidation of benzyl alcohols/aromatic aldehydes with cyclic amines into the corresponding benzamides. This electroorganic synthetic method proceeds using NaI as a redox mediator under ambient temperature in undivided cell, providing more than 25 examples of amide products in moderate to good yields. The benefits of this reaction include one-pot synthesis, open air condition, proceed in aqueous media and no requirement of external conducting salt, base and oxidant.
- Rerkrachaneekorn, Tanawat,Tankam, Theeranon,Sukwattanasinitt, Mongkol,Wacharasindhu, Sumrit
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supporting information
(2021/04/15)
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- Total synthesis and biological evaluation of 7-hydroxyneolamellarin A as hypoxia-inducible factor-1α inhibitor for cancer therapy
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7-Hydroxyneolamellarin A (7-OH-Neo A, 1), a natural marine product derived from sponge Dendrilla nigra, was first synthesized with 10% overall yield under the instruction of convergent synthetic strategy. We found that 7-OH-Neo A could attenuate the accum
- Li, Guangzhe,Shao, Yujie,Pan, Yue,Li, Yueqing,Wang, Yang,Wang, Liu,Wang, Xu,Shao, Kun,Wang, Shisheng,Liu, Naixuan,Zhang, Jingdong,Zhao, Weijie,Nakamura, Hiroyuki
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supporting information
(2021/09/04)
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- Catalytic δ-hydroxyalkynone rearrangement in the stereoselective total synthesis of centrolobine, engelheptanoxides A and C and analogues
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A catalytic stereoselective total synthesis of centrolobine and engelheptanoxides A and C has been completed via a metal-free catalytic δ-hydroxyalkynone rearrangement to 2,3-dihydro-4H-pyran-4-one and diastereoselective hydrogenation to the all syn-2,4,6-trisubstituted pyran strategy. The onliest required chirality was introduced by Jacobsen kinetic resolution, which further directed the diastereoselective hydrogenation. A first stereoselective synthesis of engelheptanoxide A is also accomplished. The analogues and derivatives of centrolobine and engelheptanoxides prepared were evaluated for antitubercular activity against M. tuberculosis H37Rv ATCC 27294.
- Ahmad, Mohammad N.,Chopra, Sidharth,Fernandes, Rodney A.,Kumar, Praveen
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- Method for preparing novel crystalline forms of 1-(4-benzyloxy-benzyl)-3-methyl-thiourea
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The present disclosure relates to a method for preparing 1-(4-benzyloxy-benzyl)-3-methyl-thiourea and a method for preparing a novel stable crystalline form A of 1-(4-benzyloxy-benzyl)-3-methyl-thiourea.
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Page/Page column 6
(2021/05/05)
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- Stereostructure Clarifying Total Synthesis of the (Polyenoyl)tetramic Acid Militarinone B. A Highly Acid-Labile N-Protecting Group for Amides ?
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The 5S, 8′R, and 10′R configurations of militarinone B (3), which is a natural product from Paecilomyces militaris, should equal those in its biosynthetic precursor, militarinone C. The configuration at C-1′ emerged from syntheses of the militarinone B candidates 1′′S- and 1′′R-(5S,8′R,10′R)-3 from the building blocks 9, 11, 14, and 15a while introducing TMB as a more acid-labile N-protecting group for β-ketoamides than DMB. Comparisons of 1′′S- and 1′′R-(5S,8′R,10′R)-3 with natural militarinone B (3; reisolated from Nature) revealed identity versus distinctness.
- Drescher, Christian,Brückner, Reinhard
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supporting information
p. 6194 - 6199
(2021/08/18)
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- Chromium-Salen Complex/Nitroxyl Radical Cooperative Catalysis: A Combination for Aerobic Intramolecular Dearomative Coupling of Phenols
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We describe an aerobic intramolecular dearomative coupling reaction of tethered phenols using a catalytic system consisting of a chromium-salen (Cr-salen) complex combined with a nitroxyl radical. This novel catalytic system enables formation of various spirocyclic dienone products including those unable to be accessed by previously reported methods efficiently under mild reaction conditions.
- Nagasawa, Shota,Fujiki, Shogo,Sasano, Yusuke,Iwabuchi, Yoshiharu
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p. 6952 - 6968
(2021/05/29)
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- Oxoammonium-Mediated Allylsilane–Ether Coupling Reaction
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A new C(sp3)?H functionalization reaction consisting of the oxidative α-allylation of allyl- and benzyl- methyl ethers has been developed. The C?C coupling could be carried out under mild conditions thanks to the use of cheap and green oxoammonium salts. The scope of the reaction was studied over 27 examples, considering the nature of the substituents on the two coupling partners.
- Carlet, Federica,Bertarini, Greta,Broggini, Gianluigi,Pradal, Alexandre,Poli, Giovanni
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supporting information
p. 2162 - 2168
(2021/04/02)
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- Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity
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Encouraged by our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Herein, we report the design, synthesis and biological evaluation of a series of novel oseltamivir derivatives via the structural modifications at C5–NH2 of oseltamivir targeting 150-cavity. Among them, compound 5c bearing 4-(3-methoxybenzyloxy)benzyl group exhibited the most potent activity, which was lower or modestly improved activities than oseltamivir carboxylate (OSC) against N1 (H1N1), N1 (H5N1) and N1 (H5N1–H274Y). Specifically, there was 30-fold loss of activity against the wild-type strain H1N1. However, 5c displayed 4.85-fold more potent activity than OSC against H5N1–H274Y NA. Also, 5c demonstrated low cytotoxicity in vitro and no acute toxicity in mice. Molecular docking studies provided insights into the high potency of 5c against N1 and N1–H274Y mutant NAs. Besides, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability of representative compounds were conducted to evaluate their drug-like properties.
- Jia, Ruifang,Zhang, Jian,Bertagnin, Chiara,Cherukupalli, Srinivasulu,Ai, Wei,Ding, Xiao,Li, Zhuo,Zhang, Jiwei,Ju, Han,Ma, Xiuli,Loregian, Arianna,Huang, Bing,Zhan, Peng,Liu, Xinyong
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- Nitrosoarene-Catalyzed HFIP-Assisted Transformation of Arylmethyl Halides to Aromatic Carbonyls under Aerobic Conditions
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A rare metal-free nucleophilic nitrosoarene catalysis accompanied by highly hydrogen-bond-donor (HBD) solvent, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), organocatalytically converts arylmethyl halides to aromatic carbonyls. This protocol offers an effective means to access a diverse array of aromatic carbonyls with good chemoselectivity under mild reaction conditions. The activation of arylmethyl halides by HFIP to generate stable carbocation and autoxidation of in situ generated hydroxylamine to nitrosoarene in the presence of atmospheric O2 are the keys to success.
- Pradhan, Suman,Sharma, Vishali,Chatterjee, Indranil
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supporting information
p. 6148 - 6152
(2021/08/03)
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- Visible light photoredox catalyzed deprotection of 1,3-oxathiolanes
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An efficient visible light photoredox catalyzed aerobic deprotection of 1,3-oxathiolanes using organic dye Eosin Y as a photocatalyst is disclosed. The deprotection procedure features the use of a metal-free catalyst, mild conditions, a broad range of substrate scope, and good functional group tolerance. 35 examples were tested under the standard conditions and most of them afforded the deprotected products in modest to high yields.
- Yang, Mingyang,Xing, Zhimin,Fang, Bowen,Xie, Xingang,She, Xuegong
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supporting information
p. 288 - 291
(2020/01/13)
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- Design, synthesis, biological evaluation and molecular dynamics studies of 4-thiazolinone derivatives as protein tyrosine phosphatase 1B (PTP1B) inhibitors
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Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signaling pathway, and more and more studies have shown that it is a potential target for the treatment of type 2 diabetes mellitus (T2DM). In this study, 17 new 4-thiazolinone derivatives were designed and synthesized as novel PTP1B inhibitors, and ADMET prediction confirmed that these compounds were to be drug-like. In vitro enzyme activity experiments were performed on these compounds, and it was found that a plurality of compounds had good inhibitory activity and high selectivity against PTP1B protein. Among them, compound 7p exhibited the best inhibitory activity with an IC50 of 0.92 μM. The binding mode of compound 7p and PTP1B protein was explored, revealing the reason for its high efficiency. In addition, molecular dynamics simulations for the PTP1BWT and PTP1Bcomp#7p systems revealed the effects of compound 7p on PTP1B protein at the molecular level. In summary, the study reported for the first time that 4-thiazolinone derivatives as a novel PTP1B inhibitor had good inhibitory activity and selectivity for the treatment of T2DM, providing more options for the development of PTP1B inhibitors. AbbreviationsBBB blood-brain barrierCDC25B cell division cycle 25 homolog BCYP2D6 Cytochrome P450 2D6 bindingDCCM dynamic cross-correlation mapDS Discovery StudioH bond hydrogen bondHIA human intestinal absorptionLAR leukocyte antigen-related phosphataseMD molecular dynamicsMEG-2 maternal-effect germ-cell defective 2MM-PBSA molecular mechanics Poisson Boltzmann surface area)PCA principal component analysisPDB Protein Data BankpNPP p–nitrophenyl phosphatePPB plasma protein bindingPTP1B protein tyrosine phosphotase 1BRMSD root mean square deviationRMSF root mean square fluctuationSHP-1 src homologous phosphatase-1SHP-2 src homologous phosphatase-2SPC single-point chargeTCPTP T cell protein tyrosine phosphataseT2DM Type 2 diabetes mellitusVDW van der Waals Communicated by Ramaswamy H. Sarma.
- Liu, Wen-Shan,Wang, Rui-Rui,Yue, Hai,Zheng, Zhi-Hui,Lu, Xin-Hua,Wang, Shu-Qing,Dong, Wei-Li,Wang, Run-Ling
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p. 3814 - 3824
(2019/11/03)
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- Targeting receptor tyrosine kinase VEGFR-2 in hepatocellular cancer: Rational design, synthesis and biological evaluation of 1,2-disubstituted benzimidazoles
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In this study, a novel series of 1,2-disubstituted benzo[d]imidazoles was rationally designed as VEGFR-2 inhibitors targeting hepatocellular carcinoma. Our design strategy is twofold; it aimed first at studying the effect of replacing the 5-methylfuryl moiety of the well-known antiangiogenic 2-furylbenzimidazoles with an isopropyl moiety on the VEGFR-2 inhibitory activity and the cytotoxic activity. Our second objective was to further optimize the structures of the benzimidazole derivatives through elongation of the side chains at their one-position for the design of more potent type II-like VEGFR-2 inhibitors. The designed 1,2-disubstituted benzimidazoles demonstrated potent cytotoxic activity against the HepG2 cell line, reaching IC50 = 1.98 μM in comparison to sorafenib (IC50 = 10.99 μM). In addition, the synthesized compounds revealed promising VEGFR-2 inhibitory activity in the HepG2 cell line, e.g., compounds 17a and 6 showed 82% and 80% inhibition, respectively, in comparison to sorafenib (% inhibition = 92%). Studying the effect of 17a on the HepG2 cell cycle demonstrated that 17a arrested the cell cycle at the G2/M phase and induced a dose-dependent apoptotic effect. Molecular docking studies of the synthesized 1,2-disubstituted benzimidazoles in the VEGFR-2 active site displayed their ability to accomplish the essential hydrogen bonding and hydrophobic interactions for optimum inhibitory activity.
- Abdel-Mohsen, Heba T.,Abdullaziz, Mona A.,Ali, Mamdouh M.,El Diwani, Hoda I.,El Kerdawy, Ahmed M.,Flanagan, Keith J.,Mahmoud, Abeer E. E.,Ragab, Fatma A. F.,Senge, Mathias O.
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- Design and synthesis of novel Flavone-based histone deacetylase inhibitors antagonizing activation of STAT3 in breast cancer
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Histone deacetylases (HDACs) inhibitors have demonstrated a great clinical achievement in hematological malignancies. However, the efficacy of HDACs inhibitors in treating solid tumors remains limited due to the complicated tumor microenvironment. In this study, we designed and synthesized a class of novel HDACs inhibitors based on the structure of flavones and isoflavones, followed by biological evaluation. To be specific, a lead compound 15a was discovered with strong anti-proliferative effects on a variety of solid tumor cells, especially for breast cancer cells with resistance to SAHA. Studies demonstrated that 15a could significantly inhibit the activity of HDAC 1, 2, 3 (class I) and 6 (class IIB), leading to a dose-dependent accumulation of acetylated histones and α-Tubulin, cell cycle arrest (G1/S phase) and apoptosis in breast cancer cells. Furthermore, the lead compound 15a could also antagonize the activation of STAT3 induced by HDACs inhibition in some breast cancer cells, which further reduced the level of pro-survive proteins in tumor cells and enhanced anti-tumor activity regulated by STAT3 signaling in vivo. Overall, our findings demonstrated that the novel compound 15a might be a HDACs inhibitor candidate, which could be used as promising chemotherapeutic agent for breast cancer.
- Wei, Mingming,Xie, Maodun,Zhang, Zhen,Wei, Yujiao,Zhang, Juan,Pan, Hongli,Li, Benlong,Wang, Jingjing,Song, Yang,Chong, Chuangke,Zhao, Rui,Wang, Jiefu,Yu, Li,Yang, Guang,Yang, Cheng
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- Fumarate related impurity and preparation method and application thereof (by machine translation)
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The preparation method of the related impurities comprises the following steps: No.No.No. STR8No.No. wherein the (I) preparation method, of ,R the related impurities is. shown, in the specification, and the preparation method of, the 1 present, application, further, discloses, the preparation method, and of the related impurities. (by machine translation)
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Paragraph 0089-0090
(2020/02/04)
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- N-Heterocyclic Carbene Catalyzed Deuteration of Aldehydes in D 2 O
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An N-heterocyclic carbene (NHC)-catalyzed direct deuteration of aldehydes in a mixed solvent of deuterium oxide (D 2 O) and cyclopentyl methyl ether was established. The present deuteration is possibly initiated by the formation of a Breslow intermediate from the aldehyde and the NHC, with subsequent trapping by D 2 O providing the monodeuterated aldehyde.
- Miki, Yuya,Sajiki, Hironao,Sawama, Yoshinari
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supporting information
p. 699 - 702
(2020/04/07)
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- HETEROCYCLIC COMPOUNDS AS MUTANT IDH INHIBITORS
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The present disclosure relates generally to compounds useful in treatment of conditions associated with mutant isocitrate dehydrogenase (mt-IDH), particularly mutant IDH1 enzymes. Specifically, the present invention discloses compound of formula (IA), which exhibits inhibitory activity against mutant IDH1 enzymes. Method of treating conditions associated with excessive activity of mutant IDH1 enzymes with such compound is disclosed. Uses thereof, pharmaceutical composition, and kits are also disclosed.
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Paragraph 0442-0443
(2020/07/16)
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- Exploring intermolecular contacts in multi-substituted benzaldehyde derivatives: X-ray, Hirshfeld surface and lattice energy analyses
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Crystal structures of six benzaldehyde derivatives (1-6) have been determined and their supramolecular networks were established by an X-ray crystallographic study. The study has shown that the compounds are linked by various intermolecular interactions s
- Hosten, Eric C.,Hulushe, Siya T.,Louzada, Marcel,Manyeruke, Meloddy H.,Rigin, Sergei,Watkins, Gareth M.
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p. 16861 - 16874
(2020/05/18)
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- Ancillary ligands switch the activity of Ru–NHC-based oxidation precatalysts
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Herein we demonstrate how the inner-sphere coordinating ligands switch the activity of Ru–NHC-based oxidation precatalysts in the oxidative conversion of olefins to carbonyl compounds, with the help of a series of systematically varied imidazolydene-NHC (Im-NHC) and triazolydene-NHC (Tz-NHC)-based ruthenium(II)-complexes. It is shown that the catalytic activity of the para-cymene-containing precatalysts varies in the order of [(Tz-NHC)Ru(para-cymene)Cl]+ > [(Im-NHC)Ru(para-cymene)Cl]+, while the order of activity of the MeCN-containing precatalysts is found to be reversed, i.e., [(Im-NHC)Ru(MeCN)4]2+ > [(Tz-NHC)Ru(MeCN)4]2+. Along with the electronic influence of the NHC ligands, the effect of the lability of the para-cymene and MeCN ligands, and the overall charge of the complexes might be attributed toward such a switching of catalytic activity. This finding led to develop a new precatalyst with improved activity which was further utilized in selective oxidation of a series of styrene substrates containing other oxidation-sensitive functionalities.
- Gupta, Suraj K.,Mandal, Tanmoy,Gangber, Tejaswinee,Singh, Vivek,Choudhury, Joyanta
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supporting information
(2019/10/28)
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- A Simple, Mild and General Oxidation of Alcohols to Aldehydes or Ketones by SO2F2/K2CO3 Using DMSO as Solvent and Oxidant
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A practical, general and mild oxidation of primary and secondary alcohols to carbonyl compounds proceeds in yields of up to 99% using SO2F2 as electrophile in DMSO as both the oxidant and the solvent at ambient temperature. No moisture- and oxygen-free conditions are required. Stoichiometric amount of inexpensive K2CO3, which generates easy to separate by-products, is used as the base. Thus, 5-gram scale runs proceeded in nearly quantitative yields by a simple filtration as the work-up. The use of a polar solvent such as DMSO, which usually promotes competing Pummerer rearrangement, is also noteworthy. This protocol is compatible with a variety of common N-, O-, and S-functional groups on (hetero)arene, alkene and alkyne substrates (68 examples). The protocol was applied (99% yield) to a formal synthesis of the important cholesterol-lowering drug Rosuvastatin. (Figure presented.).
- Zha, Gao-Feng,Fang, Wan-Yin,Leng, Jing,Qin, Hua-Li
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supporting information
p. 2262 - 2267
(2019/04/17)
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- A molybdenum based metallomicellar catalyst for controlled and chemoselective oxidation of activated alcohols in aqueous medium
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A surfactant based oxodiperoxo molybdenum complex, which could activate molecular oxygen, has been employed as a catalyst for controlled oxidation of benzylic alcohols to corresponding carbonyls. The oxidation reactions were carried out under aqueous environment, however, in the absence of any extraneous base or co-catalyst. Sensitive/oxidizable functional groups like cyano, sulfide, hydroxyl, aryl-hydroxyl, alkene (internal/terminal), alkyne (internal/terminal), and acetal were tolerated during the transformations. Such selectivity is attributed to the mild nature of the catalyst. The methodology could also be scaled-up for multi-gram synthesis and the protocol is likely to find practical use since it requires an inexpensive recyclable-catalyst and easily available oxidant (under green conditions). A plausible mechanism is proposed with the help of preliminary computational study.
- Thiruvengetam, Prabaharan,Chakravarthy, Rajan Deepan,Chand, Dillip Kumar
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p. 123 - 133
(2019/07/19)
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- PTP1B (protein tyrosine phosphatase 1B) inhibitor containing indolepropionic acid rhodamine structures
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The invention provides a novel PTP1B (protein tyrosine phosphatase 1B) inhibitor adopting a compound containing indolepropionic acid rhodamine structures and pharmaceutically acceptable salt of the compound. Researches show that the inhibitor can effectively inhibit the activity of PTP1B, and can serve as an insulin sensitizer for preventing and/or treating PTP1B mediated insulin resistant relateddiseases, particularly, II type diabetes and obesity. The invention also provides a preparation method of the inhibitor.
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Paragraph 0019; 0020
(2019/09/17)
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- Synthesis and biological evaluation of tryptophan-derived rhodanine derivatives as PTP1B inhibitors and anti-bacterial agents
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Several series of novel tryptophan-derived rhodanine derivatives were synthesized and identified as potential competitive PTP1B inhibitors and antibacterial agents. Among the compounds studied, 10b was found to have the best in vitro inhibition activity against PTP1B (IC50 = 0.36 ± 0.02 μM). In addition, the compounds also showed potent inhibition against other PTPs, especially CDC25B. Molecular docking analysis demonstrated that compounds 7c and 10b could occupy both the catalytic site and the adjacent pTyr binding site simultaneously. The compounds also showed higher levels of activity against gram-positive strains, the gram-negative strain Escherichia coli 1924, and multidrug-resistant gram-positive bacterial strains. Compounds 7c, 8c, 9e, 10a, and 10c had comparable or more potent antibacterial activity than the positive controls.
- Liu, Hongyan,Sun, Danwen,Du, Hang,Zheng, Changji,Li, Jingya,Piao, Huri,Li, Jia,Sun, Liangpeng
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p. 163 - 173
(2019/04/13)
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- Synthesis of cinnamic amide derivatives and their anti-melanogenic effect in α-MSH-stimulated B16F10 melanoma cells
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Of the three enzymes that regulate the biosynthesis of melanin, tyrosinase and its related proteins TYRP-1 and TYRP-2, tyrosinase is the most important because of its ability to limit the rate of melanin production in melanocytes. For treating skin pigmentation disorders caused by an excess of melanin, the inhibition of tyrosinase enzyme is by far the most established strategy. Cinnamic acid is a safe natural product with an (E)-β-phenyl-α,β-unsaturated carbonyl motif that we have previously shown to play an important role in high tyrosinase inhibition. Since cinnamic acid is relatively hydrophilic, which hinders its absorption on the skin, fifteen less hydrophilic cinnamic amide derivatives (1–15) were designed as safe and more potent tyrosinase inhibitors and were synthesized through a Horner-Wadsworth-Emmons reaction. The use of conc-HCl and acetic acid for debenzylation of the O-benzyl-protected cinnamic amides 40–54 produced the following three results. 1) Cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group, irrespective of the amine type of the amides, produced complex compounds with high polarity. 2) Cinnamic amides 40–42, 44, 50–52, and 54 with a benzylamino, or diethylamino group produced the desired debenzylated cinnamic amides 1–3, 5, 10–13, and 15. 3) Cinnamic amides 45–47, and 49 with an anilino moiety provided 3,4-dihydroquinolinones 16–19 through intramolecular Michael addition of the anilide group. Notably, the use of BBr3 as an alternative debenzylating agent for debenzylation of cinnamic amides 45–49 with the anilino moiety provided our desired cinnamic amides 6–10 without inducing the intramolecular Michael addition. Debenzylation of cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group was also successfully accomplished using BBr3 to give 4, 9, and 14. Among the nine compounds that inhibited mushroom tyrosinase more potently at 25 μM than kojic acid, four cinnamic amides 4, 5, 9, and 14 showed 3-fold greater tyrosinase inhibitory activity than kojic acid. The docking simulation using tyrosinase indicated that these four cinnamic amides (?6.2 to ?7.9 kcal/mol) bind to the active site of tyrosinase with stronger binding affinity than kojic acid (?5.7 kcal/mol). All four cinnamic amides inhibited melanogenesis and tyrosinase activity more potently than kojic acid in α-MSH-stimulated B16F10 melanoma cells in a dose-dependent manner without cytotoxicity. The strong correlation between tyrosinase activity and melanin content suggests that the anti-melanogenic effect of cinnamic amides is due to tyrosinase inhibitory activity. Considering that the cinnamic amides 4, 9, and 14, which exhibited strong inhibition on mushroom tyrosinase and potent anti-melanogenic effect in B16F10 cells, commonly have a 2,4-dihydroxyphenyl substituent, the 2,4-dihydroxyphenyl substituent appears to be essential for high anti-melanogenesis. These results support the potential of these four cinnamic amides as novel and potent tyrosinase inhibitors for use as therapeutic agents with safe skin-lightening efficiency.
- Ullah, Sultan,Kang, Dongwan,Lee, Sanggwon,Ikram, Muhammad,Park, Chaeun,Park, Yujin,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
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- Tyrosinase inhibition and anti-melanin generation effect of cinnamamide analogues
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Abnormal melanogenesis results in excessive production of melanin, leading to pigmentation disorders. As a key and rate-limiting enzyme for melanogenesis, tyrosinase has been considered an important target for developing therapeutic agents of pigment disorders. Despite having an (E)-β-phenyl-α,β-unsaturated carbonyl scaffold, which plays an important role in the potent inhibition of tyrosinase activity, cinnamic acids have not attracted attention as potential tyrosinase inhibitors, due to their low tyrosinase inhibitory activity and relatively high hydrophilicity. Given that cinnamic acids’ structure intrinsically features this (E)-scaffold and following our experience that minute changes in the chemical structure can powerfully affect tyrosinase activity, twenty less hydrophilic cinnamamide derivatives were designed as potential tyrosinase inhibitors and synthesised using a Horner-Wadsworth-Emmons reaction. Four of these cinnmamides (4, 9, 14, and 19) exhibited much stronger mushroom tyrosinase inhibition (over 90% inhibition) at 25 μM compared to kojic acid (20.57% inhibition); crucially, all four have a 2,4-dihydroxy group on the β-phenyl ring of the scaffold. A docking simulation using tyrosinase indicated that the four cinnamamides exceeded the binding affinity of kojic acid, and bound more strongly to the active site of tyrosinase. Based on the strength of their tyrosinase inhibition, these four cinnamamides were further evaluated in B16F10 melanoma cells. All four cinnamamides, without cytotoxicity, exhibited higher tyrosinase inhibitory activity (67.33 – 79.67% inhibition) at 25 μM than kojic acid (38.11% inhibition), with the following increasing inhibitory order: morpholino (9) = cyclopentylamino (14) cyclohexylamino (19) N-methylpiperazino (4) cinnamamides. Analysis of tyrosinase activity and melanin content in B16F10 cells showed that the four cinnamamides dose-dependently inhibited both cellular tyrosinase activity and melanin content and that their inhibitory activity at 25 μM was much better than that of kojic acid. The results of melanin content analysis well matched those of the cellular tyrosinase activity analysis, indicating that tyrosinase inhibition by the four cinnamamides is a major factor in the reduction of melanin production. These results imply that these four cinnamamides with a 2,4-dihydroxyphenyl group can act as excellent anti-melanogenic agents in the treatment of pigmentation disorders.
- Ullah, Sultan,Park, Chaeun,Ikram, Muhammad,Kang, Dongwan,Lee, Sanggwon,Yang, Jungho,Park, Yujin,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
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- Total synthesis and application of natural product of 7-hydroxy novel lamellarin A and analogues of natural product of 7-hydroxy novel lamellarin A
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The invention belongs to the technical field of pharmaceutical and chemical engineering, and provides total synthesis and application of a natural product of 7-hydroxy novel lamellarin A and analoguesof the natural product of the 7-hydroxy novel lamellarin A. The invention provides the 7-hydroxy novel lamellarin A natural product and the series of analogues of the 7-hydroxy novel lamellarin A natural product. Tested compounds all have medium to good HIF-1 inhibitory activity, and have no market toxicity under the effective inhibition concentration of HIF-1 of the tested compounds, and it is indicated that the compounds have the potential for treating cancers by inhibiting transcription activating of the HIF-1.
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Paragraph 0078-0080
(2019/11/12)
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- Coordination Booster-Catalyst Assembly: Remote Osmium Outperforming Ruthenium in Boosting Catalytic Activity
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Presented herein is a set of bimetallic and trimetallic “coordination booster-catalyst” assemblies in which the coordination complexes [RuII(terpy)2] and [OsII(terpy)2] acted as boosters for enhancement of the catalytic activity of [RuII(NHC)(para-cymene)]-based catalytic site. The boosters accelerated the oxidative loss of para-cymene from the catalytic site to generate the active catalyst during the oxidation of alkenes and alkynes into corresponding aldehydes, ketones and diketones. It was found that the boosting efficiency of the [OsII(terpy)2] units was considerably higher than its congener [RuII(terpy)2] unit in these assemblies. Mechanistic studies were conducted to understand this unique improvement.
- Mandal, Tanmoy,Singh, Vivek,Choudhury, Joyanta
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supporting information
p. 4774 - 4779
(2019/11/11)
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- NH3?H2O: The Simplest Nitrogen-Containing Ligand for Selective Aerobic Alcohol Oxidation to Aldehydes or Nitriles in Neat Water
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Aqueous ammonia (NH3?H2O) has been shown to serve as the simplest nitrogen-containing ligand to effectively promote copper-catalyzed selective alcohol oxidation under air in water. A series of alcohols with varying electronic and steric properties were selectively oxidized to aldehydes with up to 95 % yield. Notably, by increasing the amount of aqueous ammonia in neat water, the exclusive formation of aryl nitriles was also accomplished with good-to-excellent yields. Additionally, the catalytic system exhibits a high level of functional group tolerance with ?OH, ?NO2, esters, and heteroaryl groups all being amenable to the reaction conditions. This one-pot and green oxidation protocol provides an important synthetic route for the selective preparation of either aldehydes or nitriles from commercially available alcohols.
- Zhang, Guofu,Ma, Danting,Zhao, Yiyong,Zhang, Guihua,Mei, Guangyao,Lyu, Jinghui,Ding, Chengrong,Shan, Shang
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p. 885 - 889
(2018/12/10)
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- Umpolung of Carbonyl Groups as Alkyl Organometallic Reagent Surrogates for Palladium-Catalyzed Allylic Alkylation
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Palladium-catalyzed allylic alkylation of nonstabilized carbon nucleophiles is difficult and remains a major challenge. Reported here is a highly chemo- and regioselective direct palladium-catalyzed C-allylation of hydrazones, generated from carbonyls, as a source of umpolung unstabilized alkyl carbanions and surrogates of alkyl organometallic reagents. Contrary to classical allylation techniques, this umpolung reaction utilizes hydrazones prepared not only from aryl aldehydes but also from alkyl aldehydes and ketones as renewable feedstocks. This strategy complements the palladium-catalyzed coupling of unstabilized nucleophiles with allylic electrophiles by providing an efficient and selective catalytic alternative to the traditional use of highly reactive alkyl organometallic reagents.
- Zhu, Dianhu,Lv, Leiyang,Li, Chen-Chen,Ung, Sosthene,Gao, Jian,Li, Chao-Jun
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supporting information
p. 16520 - 16524
(2018/11/23)
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- Synthetic process of 3-(4-benzyloxy-phenyl)-2-cyanoacrylate
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The invention discloses a synthetic process of 3-(4-benzyloxy-phenyl)-2-cyanoacrylate. The synthetic process includes the following steps of 1, under an inert atmosphere, blending and stirring p-hydroxy benzaldehyde, benzyl halide, alkali, a solvent and a catalyst at the room temperature for 3-10 hours, then pouring the mixture into water, using an extraction agent for extraction, and sequentiallyconducting washing, drying and concentration on an organic phase to obtain an intermediate 4-(phenyl-methoxy) benzaldehyde; 2, under the inert atmosphere, making 4-(phenyl-methoxy) benzaldehyde, acetic acid, ethyl cyanoacetate and a catalytic amount of piperidine subjected to a reflux reaction in methylbenzene for 3-12 hours; after the reaction is finished, lowering the temperature to the room temperature, adding a quenching agent, and sequentially conducting washing, drying, concentration and purification on the organic phase to obtain 3-(4-benzyloxy-phenyl)-2-cyanoacrylate. The synthetic process is low in preparation cost, high in yield and simple in aftertreatment.
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Paragraph 0021; 0022; 0023; 0033; 0038
(2018/09/14)
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- Carbonyl–Olefin Cross-Metathesis Through a Visible-Light-Induced 1,3-Diol Formation and Fragmentation Sequence
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A visible-light-mediated approach to carbonyl–olefin cross-metathesis is described. Photoinduced hole catalysis was used to promote the formation of 1,3-diols from aldehydes and styrenes, which were then readily fragmented under acidic conditions to form the cross-metathesis products. The use of 1,3-diols as intermediates, rather than the energetically more demanding oxetanes, provides a new, orthogonal mechanistic strategy for carbonyl–olefin cross-metathesis. Furthermore, this approach does not require any metals, ligands, or additives, and provides the products with high levels of E selectivity. A mechanistic rationale is provided and supported by both theoretical calculations and experiments. Additionally, a practical synthesis of a new acridinium-based photocatalyst, including full characterization, is presented.
- Pitzer, Lena,Sandfort, Frederik,Strieth-Kalthoff, Felix,Glorius, Frank
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supporting information
p. 16219 - 16223
(2018/11/23)
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- Synthesis and evaluation of the antibacterial activities of aryl substituted dihydrotriazine derivatives
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Five series of dihydrotriazine derivatives containing chalcone (13a–i), phenoxy acetophenone (14a–b), benzyl benzene (15a–c), naphthoxyl acetophenone (16a–b) and benzyl naphthalene (17a–h) moieties were designed and synthesized. The antibacterial and antifungal activities of these compounds were evaluated against several strains of Gram-positive and Gram-negative bacteria, as well as a single fungus. Compound 17h was found to be the most potent of all of the compounds tested, with an MIC value of 0.5 μg/mL against several Gram-positive (Staphylococcus aureus 4220 and QRSA CCARM 3505) and Gram-negative (Escherichia coli 1924) strains of bacteria. However, this compound was inactive against Pseudomonas aeruginosa 2742 and Salmonella typhimurium 2421, indicating that its antibacterial spectrum is similar to those of the positive controls gatifloxacin and moxifloxacin. The cytotoxic activity of the compound 13i, 16b and 17h was assessed in Human normal liver cells.
- Zhang, Tian-Yi,Yu, Zhan-Kui,Jin, Xue-Jun,Li, Ming-Yue,Sun, Liang-Peng,Zheng, Chang-Ji,Piao, Hu-Ri
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supporting information
p. 1657 - 1662
(2018/03/29)
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- Exploring physicochemical space: Via a bioisostere of the trifluoromethyl and ethyl groups (BITE): Attenuating lipophilicity in fluorinated analogues of Gilenya for multiple sclerosis
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The direct, catalytic vicinal difluorination of terminal alkenes via an I(i)/I(iii) manifold was exploited to install a chiral, hybrid bioisostere of the CF3 and Et groups (BITE) in Gilenya; the first orally available drug for the clinical management of Multiple Sclerosis (MS). This subtle fluorination pattern allows lipophilicity (logD) to be tempered compared to the corresponding CF3 and Et derivatives (CH2CH3 > CH2CF3 > CHFCH2F).
- Erdeljac, Nathalie,Kehr, Gerald,Ahlqvist, Marie,Knerr, Laurent,Gilmour, Ryan
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supporting information
p. 12002 - 12005
(2018/11/21)
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- Design, synthesis and anti-melanogenic effect of cinnamamide derivatives
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Pigmentation disorders are attributed to excessive melanin which can be produced by tyrosinase. Therefore, tyrosinase is supposed to be a vital target for the treatment of disorders associated with overpigmentation. Based on our previous findings that an (E)-β-phenyl-α,β-unsaturated carbonyl scaffold can play a key role in the inhibition of tyrosinase activity, and the fact that cinnamic acid is a safe natural substance with a scaffolded structure, it was speculated that appropriate cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. Thus, ten cinnamamides were designed, and synthesized by using a Horner-Emmons olefination as the key step. Cinnamamides 4 (93.72% inhibition), 9 (78.97% inhibition), and 10 (59.09% inhibition) with either a 2,4-dihydroxyphenyl, or 4-hydroxy-3-methoxyphenyl substituent showed much higher mushroom tyrosinase inhibition at 25 μM than kojic acid (18.81% inhibition), used as a positive control. Especially, the two cinnamamides 4 and 9 having a 2,4-dihydroxyphenyl group showed the strongest inhibition. Docking simulation with tyrosinase revealed that these three cinnamamides, 4, 9, and 10, bind to the active site of tyrosinase more strongly than kojic acid. Cell-based experiments carried out using B16F10 murine skin melanoma cells demonstrated that all three cinnamamides effectively inhibited cellular tyrosinase activity and melanin production in the cells without cytotoxicity. There was a close correlation between cellular tyrosinase activity and melanin content, indicating that the inhibitory effect of the three cinnamamides on melanin production is mainly attributed to their capability for cellular tyrosinase inhibition. These results imply that cinnamamides having the (E)-β-phenyl-α,β-unsaturated carbonyl scaffolds are promising candidates for skin-lighting agents.
- Ullah, Sultan,Park, Yujin,Ikram, Muhammad,Lee, Sanggwon,Park, Chaeun,Kang, Dongwan,Yang, Jungho,Akter, Jinia,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
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p. 5672 - 5681
(2018/10/24)
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- Synthesis and in vitro evaluation of diverse heterocyclic diphenolic compounds as inhibitors of DYRK1A
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Dual-specificity tyrosine phosphorylation-related kinase 1A (DYRK1A) is a dual-specificity protein kinase that catalyses phosphorylation and autophosphorylation. Higher DYRK1A expression correlates with cancer, in particular glioblastoma present within the brain. We report here the synthesis and biological evaluation of new heterocyclic diphenolic derivatives designed as novel DYRK1A inhibitors. The generation of these heterocycles such as benzimidazole, imidazole, naphthyridine, pyrazole-pyridines, bipyridine, and triazolopyrazines was made based on the structural modification of the lead DANDY and tested for their ability to inhibit DYRK1A. None of these derivatives showed significant DYRK1A inhibition but provide valuable knowledge around the importance of the 7-azaindole moiety. These data will be of use for developing further structure-activity relationship studies to improve the selective inhibition of DYRK1A.
- Zhou, Qingqing,Reekie, Tristan A.,Abbassi, Ramzi H.,Indurthi Venkata, Dinesh,Font, Josep S.,Ryan, Renae M.,Munoz, Lenka,Kassiou, Michael
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p. 5852 - 5869
(2018/11/10)
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- Linear diarylheptanoids as potential anticancer therapeutics: synthesis, biological evaluation, and structure–activity relationship studies
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In efforts to develop effective anticancer therapeutics with greater selectivity toward cancerous cell and reduced side-effects, such as emetic effects due to detrimental action of the drug toward the intestinal flora, a series of linear diarylheptanoids (LDHs) were designed and synthesized in 7 steps with good-to-moderate yields. All synthesized compounds were evaluated for their antibacterial, antiproliferative, and topoisomerase-I and -IIα inhibitory activity. Overall, all compounds showed little to no activity against the bacterial strains tested. Most of the synthesized compounds showed good antiproliferative activity against human breast cancer cell lines (T47D); specifically, the IC50 values of compounds 6a, 6d, 7j, and 7e were 0.09, 0.64, 0.67, and 0.99 μM, respectively. Among the tested compounds, 7b inhibited topo-I by 9.3% (camptothecin 68.8%), 7e and 7h inhibited topo-IIα by 38.4 and 47.4% (etoposide 76.9%), respectively, at the concentration of 100 μM. These results suggest that a set of promising anticancer agents can be obtained by reducing inhibitory actions on different microbes to provide enhanced selectivity against cancerous cells.
- Motiur Rahman,Lu, Yang,Lee, Hwa-Jong,Jo, Hyunji,Yin, Wencui,Alam, Mohammad Sayed,Cha, Hyochang,Kadi, Adnan A.,Kwon, Youngjoo,Jahng, Yurngdong
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- Evaluating Gold and Selenium Chemistry for Selective Transformations of Lignin Model Compounds
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Applications of gold and selenium chemistry are reported as novel approaches to promote lignin depolymerization into more valuable chemicals via selective oxidation reactions (alcohol oxidations and Baeyer-Villiger reactions). In this study, we proposed two different oxidative methodologies using Au/SiO2 and phenylseleninic acid resin (PAR) as stable and reusable catalysts to promote selective transformations of the β-O-4 linkage of lignin model compounds. After evaluating the catalytic systems under batch conditions, they were both applied in a packed-bed reactor for continuous flow operations. By using Au/SiO2 as a catalyst under flow conditions, ketones were efficiently obtained (up to 86% conversion) from the oxidation of alcohols with a residence time (tR) of 30 min. In the case of Baeyer-Villiger oxidations catalyzed by phenylseleninic acid resin, the corresponding esters were obtained in up to 91% conversion (tR=30 min). Both systems efficiently catalyzed the conversion of the lignin model compounds. (Figure presented.).
- Santos, Wagner C. C.,Dias, Kevin A.,Santos, Leidaiany P.,Kisukuri, Camila M.,Rodrigues, Thenner S.,Geonmonond, Rafael S.,Camargo, Pedro H. C.,Andrade, Leandro H.
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supporting information
p. 1376 - 1383
(2018/02/13)
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- Novel cinnamic acid–tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study
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A novel series of cinnamic acid–tryptamine hybrids was designed, synthesized, and evaluated as cholinesterase inhibitors. Anticholinesterase assays showed that all of the synthesized compounds displayed a clearly selective inhibition of butyrylcholinesterase (BChE), but only a moderate inhibitory effect toward acetylcholinesterase (AChE) was detected. Among these cinnamic acid–tryptamine hybrids, compound 7d was found to be the most potent inhibitor of BChE with an IC50 value of 0.55 ± 0.04 μM. This compound showed a 14-fold higher inhibitory potency than the standard drug donepezil (IC50 = 7.79 ± 0.81 μM) and inhibited BChE through a mixed-type inhibition mode. Moreover, a docking study revealed that compound 7d binds to both the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of BChE. Also, compound 7d was evaluated against β-secretase, which exhibited low activity (inhibition percentage: 38%).
- Ghafary, Shahrzad,Najafi, Zahra,Mohammadi-Khanaposhtani, Maryam,Nadri, Hamid,Edraki, Najmeh,Ayashi, Neda,Larijani, Bagher,Amini, Mohsen,Mahdavi, Mohammad
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- Reduction of N,N-Dimethylcarboxamides to Aldehydes by Sodium Hydride–Iodide Composite
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A new and concise protocol for selective reduction of N,N-dimethylamides into aldehydes was established using sodium hydride (NaH) in the presence of sodium iodide (NaI) under mild reaction conditions. The present protocol with the NaH-NaI composite allows for reduction of not only aromatic and heteroaromatic but also aliphatic N,N-dimethylamides with wide substituent compatibility. Retention of α-chirality in the reduction of α-enantioriched amides was accomplished. Use of sodium deuteride (NaD) offers a new step-economical alternative to prepare deuterated aldehydes with high deuterium incorporation rate. The NaH-NaI composite exhibits unique chemoselectivity for reduction of N,N-dimethylamides over ketones.
- Chan, Guo Hao,Ong, Derek Yiren,Yen, Zhihao,Chiba, Shunsuke
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- Method for preparing aldehyde by oxidizing primary alcohol
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The invention discloses a method for preparing aldehyde by catalytic oxidation of primary alcohol. The method comprises the steps that the primary alcohol as shown in a formula (I) or (III) is taken as a raw material, copper salt is taken as a catalyst, air is taken as an oxidizing agent, TEMPO (2,2,6,6-tetramethyl-1-piperidine-N-oxyl compound) is taken as a pro-oxygenic agent, ammonium hydroxide is taken as a co-catalyst and solvent, the primary alcohol, the copper salt, the air, the TEMPO and the ammonium hydroxide are mixed uniformly and react for 9 to 24 hours at the temperature of 60 to 120 DEG C; after the reaction, reaction liquid is subjected to aftertreatment to obtain aldehyde as shown in a formula (II) or (IV). The method has the advantages of high reaction rate and yield, low cost, convenience in operation and safety in reaction. The whole process is environmental friendly and free of pollution.
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Paragraph 0026; 0027; 0028; 0029; 0030; 0071; 0072-0075
(2017/07/21)
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- New promising porphyrazine-based agents for optical theranostics of cancer
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New porphyrazine bases containing peripheral benzyloxyphenyl groups have been synthesized by the template method. The procedure includes condensation of aromatic aldehydes with malononitrile, transformation of arylmethylidenemalononitriles to arylethenetricarbonitriles, template assembly of porphyrazine macrocycle on bis(indenyl)ytterbium(II) complex, and removal of the central metal ion. Luminescence properties of the synthesized porphyrazines and their dependence on the viscosity of the medium were studied, and the light and dark toxicities of the porphyrazines have been estimated. The obtained results suggest the possibility of using these porphyrazines as optical theranostic agents of new generation.
- Lermontova,Grigor’ev,Peskova,Ladilina, E. Yu.,Balalaeva,Klapshina,Boyarskii
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p. 479 - 484
(2017/05/01)
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- Synthesis and biological evaluation of dihydrotriazine derivatives as potential antibacterial agents
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A series of 1,4-dihydro-1,3,5-triazine derivatives were designed and synthesized and their antibacterial and antifungal activities were evaluated. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains, with minimum inhibitory concentrations (MICs) in the range of 2.1–181.2?μmol/L. Compounds 7a and 7c presented the most potent inhibitory activities against Gram-positive bacteria (e.g., Staphylococcus aureus 4220), Gram-negative bacteria (e.g., Escherichia coli 1924), and the fungus Candida albicans 7535, with MICs of 2.1 or 4.1?μmol/L. Especially, compound 7a was the most potent, with an MIC of 2.1?μmol/L against four multidrug-resistant, Gram-positive bacterial strains. The cytotoxic activity of the compound 7a, 7c and 7f was assessed in HepG2 cells, and the results suggest that 1,4-dihydro-1,3,5-triazine derivatives bearing a 6-benzyloxynaphthalen moiety are interesting scaffolds for the development of novel antibacterial agents.
- Zhang, Tian-Yi,Li, Chao,Tian, Yu-Shun,Li, Jia-Jun,Sun, Liang-Peng,Zheng, Chang-Ji,Piao, Hu-Ri
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supporting information
p. 1737 - 1742
(2017/07/27)
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- Design and synthesis of neolamellarin a derivatives targeting heat shock protein 90
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In this study, we designed and synthesized a novel family of neolamellarin A derivatives that showed high inhibitory activity toward heat shock protein 90 (Hsp90), a kinase associated with cell proliferation. The 3,4-bis(catechol)pyrrole scaffold and the benzyl group with methoxy modification at N position of pyrrole are essential to the Hsp90 inhibitory activity and cytotoxicity of these compounds. Western blot analysis demonstrated that these compounds induced dramatic depletion of the examined client proteins of Hsp90, and accelerated cancer cell apoptosis. Docking simulations suggested that the binding mode of 9p was similar to that of the VER49009, a potent inhibitor of Hsp90. Further molecular dynamics simulation indicated that the hydrophobic interactions as well as the hydrogen bonds contributed to the high affinity of 9p to Hsp90.
- Jiang, Long,Yin, Ruijuan,Wang, Xueting,Dai, Jiajia,Li, Jing,Jiang, Tao,Yu, Rilei
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supporting information
p. 24 - 33
(2017/04/21)
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- Pyrrole marine alkaloid Neolamellarin A analogs and its preparation method and application
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The invention relates to pyrrole ocean alkaloids Neolamellarin A analogues as shown in the formula I and a preparation method and application thereof. Experiments show that, some of the pyrrole ocean alkaloids Neolamellarin A analogues have strong inhibitory effect on tumor cell lines; some of the pyrrole ocean alkaloids Neolamellarin A analogues have very good neuro cell protective effect; and some of the pyrrole ocean alkaloids Neolamellarin A analogues have very strong inhibitory effect on heat shock protein Hsp90.
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Paragraph 0069-0071
(2017/10/27)
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- Photophysical studies of 2,6-dibrominated BODIPY dyes substituted with 4-benzyloxystyryl substituents
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A series of novel 2,6-dibrominated BODIPY dyes with styryl groups at the 3,5-positions has been prepared, and their photophysical properties have been analyzed to assess their potential utility for use as photosensitizers in photodynamic therapy and in bi
- Ngoy, Bokolombe P.,Molupe, Nthabeleng,Harris, Jessica,Fomo, Gertrude,Mack, John,Nyokong, Tebello
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p. 431 - 438
(2017/08/02)
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