- Isatin–Coumarin Hybrids Tethered via Diethylene Glycol: Design, Synthesis, and Their In Vitro Antitumor Activities
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A series of novel isatin–coumarin hybrids was designed, synthesized, and assessed for their in vitro antitumor activities against drug-sensitive HepG2, Hela, A549, DU145 (prostatic cancer), SKOV3, and MCF-7 as well as drug-resistant MCF-7/DOX (doxorubicin
- Fan, Yi-Lei,Huang, Zhong-Ping,Liu, Min
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- Design, Synthesis, and Antimycobacterial Activities of Diethylene Glycol Tethered Moxifloxacin–Isatin Hybrids
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A new class of diethylene glycol tethered moxifloxacin–isatin hybrids 5a–l was designed, synthesized, and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis (MTB) H37Rv and multidrug-resistant tuberculosis (MDR-TB)
- Xu, Zhi,Zhao, Shi-Jia,Deng, Jia-Lun,Wang, Qin,Lv, Zao-Sheng
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Read Online
- Gatifloxacin–Isatin Hybrids and Their Antimycobacterial Activities
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We report herein the design, synthesis, and antimycobacterial activity of a series of diethylene glycol tethered gatifloxacin–isatin hybrids 5a–o in this paper. Results revealed that all hybrids showed promising activity against both drug-sensitive and mu
- Xu, Zhi,Zhao, Shi-Jia,Deng, Jia-Lun,Wang, Qin,Lv, Zao-Sheng
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Read Online
- Ciprofloxacin–Isatin Hybrids and Their Antimycobacterial Activities
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A series of diethylene glycol tethered ciprofloxacin–isatin hybrids 5a–j were designed, synthesized, and evaluated for their in vitro antimycobacterial activity against both drug-sensitive and multidrug-resistant (MDR) Mycobacterium tuberculosis strains i
- Xu, Zhi,Zhao, Shi-Jia,Deng, Jia-Lun,Wang, Qin,Lv, Zao-Sheng
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Read Online
- Visible light-activatable cyclodextrin-conjugates for the efficient delivery of nitric oxide with fluorescent reporter and their inclusion complexes with betaxolol
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This contribution reports the design, synthesis, photochemical properties and drug inclusion capability of two novel β-cyclodextrin (βCD) conjugates, βCD-NBFNO1 and βCD-NBFNO2, covalently integrating an N-nitroso amino-nitro-benzofurazan in the primary and secondary hydroxyl rims of the βCD scaffold, respectively through flexible spacers of different length. Both βCD conjugates are water-soluble and release nitric oxide (NO) under the input of either blue or green light, with quantum yields ΦNO (blue) = 0.13, 0.31 and ΦNO (green) = 0.007, 0.013 respectively, the former representing the largest values ever reported for nonmetal-containing NO donors activatable by visible light. The good contrast between the fluorescence green emission of the chromogenic moiety after and before the NO release permits the easy and in real-time quantification of the amount of NO generated, without the addition of external fluorescent agents. Despite the presence of the appendages, these βCD derivatives are also able to complex betaxolol, a β-blocker drug widely used for the reduction of the intraocular pressure, with binding constants Kb = 500 ± 50 and 1100 ± 100 M-1, respectively, without affecting the photochemical performances. In view of the well-known vasodilator properties of NO, the present βCD derivatives represent intriguing candidates for biopharmaceutical research studies addressed to combined therapeutic ocular applications.
- Seggio, Mimimorena,Payamifar, Sara,Fraix, Aurore,Kalydi, Eszter,Kasal, Petr,Catanzano, Ovidio,Conte, Claudia,Quaglia, Fabiana,Sortino, Salvatore
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supporting information
p. 8449 - 8455
(2021/05/26)
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- Catalytic Synthesis of PEGylated EGCG Conjugates that Disaggregate Alzheimer's Tau
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The naturally occurring flavonoid ( )-epigallocatechin gallate (EGCG) is a potent disaggregant of tau fibrils. Guided by the recent cryo-electron microscopy (cryoEM) structure of EGCG bound to fibrils of tau derived from an Alzheimer s brain donor, methods to site-specifically modify the EGCG D-ring with aminoPEGylated linkers are reported. The resultant molecules inhibit tau fibril seeding by Alzheimer s brain extracts. Formulations of aminoPEGylated EGCG conjugated to the (quasi)-brain-penetrant nanoparticle Ferumoxytol inhibit seeding by AD-tau with linker length affecting activity. The protecting groupfree catalytic cycloaddition of amino azides to mono-propargylated EGCG described here provides a blueprint for access to stable nanoparticulate forms of EGCG potentially useful as therapeutics to eliminate Alzheimer s-related tau tangles.
- El Khoury, Anton,Seidler, Paul M.,Eisenberg, David S.,Harran, Patrick G.
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p. 4263 - 4271
(2021/06/18)
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- AGENTS AND METHODS FOR TREATING TAUOPATHIES
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Disclosed are agents that include a flavanol (e.g., epigallocatechm-3-gailate) or a flavanol analog, a linker coupled to the flavanol or the flavanol analog, and a earner (e.g., iron oxide nanoparticle) coupled to the linker. The disclosed agents can be u
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Page/Page column 38
(2021/12/08)
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- Design and Synthesis of Oleanolic Acid Trimers to Enhance Inhibition of Influenza Virus Entry
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Influenza is a major threat to millions of people worldwide. Entry inhibitors are of particular interest for the development of novel therapeutic strategies for influenza. We have previously discovered oleanolic acid (OA) to be a mild influenza hemagglutinin (HA) inhibitor. In this work, inspired by the 3D structure of HA as a homotrimeric receptor, we designed and synthesized 15 OA trimers with different linkers and central region via the copper-catalyzed azide-alkyne cycloaddition reaction. All of the OA trimers were evaluated for their antiviral activities in vitro, and 12c, 12e, 13c, and 13d were observed to exhibit robust potency (IC50 in the submicromolar range) against influenza A/WSN/33 (H1N1) virus that was stronger than that observed with oseltamivir. In addition, these compounds also displayed strong biological activity against A/Hong Kong/4801/2014 and B/Sichuan/531/2018 (BV). The results of hemagglutination inhibition assays and surface plasmon resonance binding assays suggest that these OA trimers may interrupt the interaction between the HA protein of influenza virus and the host cell sialic acid receptor, thus blocking viral entry. These findings highlight the utility of multivalent OA conjugates to enhance the ligand-target interactions in anti-influenza virus drug design and are also helpful for studying antiviral drugs derived from natural products.
- Huang, Boxuan,Li, Weijia,Mu, Yu,Shao, Liang,Su, Yangqing,Sun, Mengsi,Xu, Huan,Yang, Fan,Yu, Fei,Zhang, Jihong,Zhang, Yuan
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p. 1759 - 1765
(2021/11/18)
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- QUINAZOLINES COMPOUND, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
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The present invention discloses a compound of anilino polyethylene glycol ether cycloquinazoline substituted with a substituted arylmethyl heteroatomic group having the structure of formula (I) below, or a pharmaceutically acceptable salt, ester or solvate thereof, and a pharmaceutical composition comprising the same. The compound and pharmaceutical composition disclosed herein can be used in tumor targeted therapy and in the regulation of tumors and related diseases.
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Paragraph 0058-0060
(2020/07/16)
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- COMPOUNDS USEFUL IN HIV THERAPY
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The invention relates to compounds of Formula (I), (Ia), (Ib), (II) or (III), salts thereof, pharmaceutical compositions thereof, as well as therapeutic methods of treatment and prevention.
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Page/Page column 221; 222
(2020/06/19)
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- Synthesis and characterization of novel biological tetracoumarin derivatives bearing ether moieties
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A series of novel tetracoumarin derivatives (3a-f) were prepared using the reaction of ether functionalized dibenzaldehyde with 4-hydroxycoumarin in the presence of sodium acetate. The structure of compounds was validated by IR, NMR, and CHN analyzes. Antimicrobial (antibacterial and antifungal) activity was studied on the basis of the minimum bactericidal concentration, minimum inhibitory concentration and inhibitory zone diameter. Favorable biological activity was found in compound 3f.
- Behzadi, Soheila Asadpour,Sheikhhosseini, Enayatollah,Ahmadi, Sayed Ali,Ghazanfari, Dadkhoda,Akhgar, Mohammadreza
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- Electrochemical CO2 Reduction-The Effect of Chalcogenide Exchange in Ni-Isocyclam Complexes
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Among the numerous homogeneous electrochemical CO2 reduction catalysts, [Ni(cyclam)]2+ is known as one of the most potent catalysts. Likewise, [Ni(isocyclam)]2+ was reported to enable electrochemical CO2 conversion but has received significantly less attention. However, for both catalysts, a purposeful substitution of a single nitrogen donor group by chalcogen atoms was never reported. In this work, we report a series of isocyclam-based Ni complexes with {ON3}, {SN3}, {SeN3}, and {N4} moieties and investigated the influence of nitrogen/chalcogen substitution on electrochemical CO2 reduction. While [Ni(isocyclam)]2+ showed the highest selectivity toward CO2 reduction within this series with a Faradaic efficiency of 86% for the generation of CO at an overpotential of-1.20 V and acts as a homogeneous catalyst, the O-and S-containing Ni complexes revealed comparable catalytic activities at ca. 0.3 V milder overpotential but tend to form deposits on the electrode, acting as precursors for a heterogeneous catalysis. Moreover, the heterogeneous species generated from the O-and S-containing complexes enable a catalytic hydride transfer to acetonitrile, resulting in the generation of acetaldehyde. The incorporation of selenium, however, resulted in loss of CO2 reduction activity, mainly leading to hydrogen generation that is also catalyzed by a heterogeneous electrodeposit.
- Apfel, Ulf-Peter,Battistella, Beatrice,Gerschel, Philipp,Ray, Kallol,Siegmund, Daniel
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p. 1497 - 1510
(2020/04/30)
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- MONOMER AND MULTIMERIC ANTI-HBV AGENTS
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The present invention is directed to compounds, compositions and methods for preventing, treating or curing hepatitis B (HBV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment, prevention or eradication of HBV infection.
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Page/Page column 143; 192-193
(2020/05/15)
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- Small-molecular probe for glaucocalyxin A (GLA), and preparation method and application thereof
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The invention relates to a small-molecular probe for GLA, and a preparation method and application thereof, belonging to the field of medicinal chemistry. The small-molecular probe structurally comprises three parts, namely GLA, a linker and a reporter (b
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Paragraph 0040-0041
(2020/06/09)
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- Glaucocalyxin A (GLA)-biotin small-molecular probe, and preparation method and application thereof
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The invention relates to a GLA small-molecular probe, and a preparation method and application thereof, belonging to the field of medicinal chemistry. The GLA small-molecular probe structurally comprises three parts, namely GLA, a linker and a reporter (b
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Paragraph 0016; 0038-0040
(2020/06/09)
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- Bivalent HIV-1 fusion inhibitors based on peptidomimetics
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Membrane fusion is a valid target for inhibition of HIV-1 replication. A 34-mer fragment peptide (C34), which is contained in the HIV-1 envelope protein gp41, has significant anti-HIV activity. Previously, a dimeric derivative of C34 linked by a disulfide bridge at its C-terminus was found to have more potent anti-HIV activity than the C34 peptide monomer. To date, several peptidomimetic small inhibitors have been reported, but most have lower potency than peptide derivatives related to C34. In the present study we applied this dimerization concept to these peptidomimetic small inhibitors and designed several bivalent peptidomimetic HIV-1 fusion inhibitors. The importance of the length of linkers crosslinking two peptidomimetic compounds was demonstrated and several potent bivalent inhibitors containing tethered peptidomimetics were produced.
- Kobayakawa, Takuya,Ebihara, Kento,Tsuji, Kohei,Kawada, Takuma,Fujino, Masayuki,Honda, Yuzuna,Ohashi, Nami,Murakami, Tsutomu,Tamamura, Hirokazu
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- DIMERIC PEPTIDE INHIBITORS OF APOPTOSIS PROTEINS
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The present technology is directed to compounds, compositions, and methods related to treatment of cancers and viral infections mediated by lAPs. In particular the present compounds and compositions may be used to treat lAP-mediated ovarian cancer and hepatitis B infection.
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Paragraph 0155
(2019/02/13)
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- Design, Synthesis, and In Vitro Anticancer Activities of Diethylene Glycol Tethered Isatin-1,2,3-triazole-coumarin Hybrids
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A series of novel diethylene glycol tethered isatin-1,2,3-triazole-coumarin hybrids 9a–l were designed, synthesized, and evaluated for their in vitro anticancer activities against HepG2 (liver carcinoma), Hela (cervical cancer), A549 (lung adenocarcinoma)
- Diao, Quan-Ping,Guo, Hua,Wang, Gang-Qiang
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p. 1667 - 1671
(2019/04/01)
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- Diastereoselective synthesis, structure and reactivity studies of ferrocenyloxazoline gold(i) and gold(II) complexes
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In the last few decades, gold complexes have demonstrated huge potential for soft Lewis acid catalysis. Despite the intensive research on Au complexes and planar chiral metallacycles, enantiopure ferrocenylgold complexes have-surprisingly-not been reported until the studies presented in this article. Herein, we report the asymmetric synthesis of planar chiral ferrocenyl Au(i) complexes. These dinuclear species form helically chiral ten-membered (NCCCAu)2 rings stabilized by aurophilic interactions. In supramolecular solid state structures, linear, zigzag or helical Au(i) wires with regular Au?Au separations were observed. The dissolved dinuclear entities could be oxidized by Au(i) to unique ferrocenyl Au(ii) complexes featuring short Au(ii)-Au(ii) bonds, while the ferrocene core remained intact. However, our initial studies revealed the issue of configurational lability of the ferrocenyl Au(ii) complexes in terms of the element of planar chirality in the presence of the gold source, (Me2S)AuCl. This was successfully addressed by a systematic study implementing permanent σ-donor ortho-protecting groups such as methyl and trimethylsilyl, which impede an epimerization event. Oxidation of the dinuclear Au(i) complexes was also accomplished by oxidative addition reactions with halogenated solvents, preferably CHCl3. Additional reactivity studies revealed that dinuclear Au(ii) dihalide complexes are also formed with reactive alkylhalides such as iodomethane, benzylbromide and benzyliodide. Interestingly, the whole spectral range of colors (violet, blue, green, yellow, and red) is covered by the title complexes depending on the Au oxidation state and the anionic ligands in the Au(ii) complexes. This appears to be quite unusual for ferrocenes, which typically adopt orange to red colors in a non-oxidized state.
- Holz, Julia,Ayerbe García, Marta,Frey, Wolfgang,Krupp, Felix,Peters, René
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p. 3880 - 3905
(2018/03/21)
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- Crown ether functionalized magnetic hydroxyapatite as eco-friendly microvessel inorganic-organic hybrid nanocatalyst in nucleophilic substitution reactions: an approach to benzyl thiocyanate, cyanide, azide and acetate derivatives
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In this paper, high catalytic activity of 4′,4″-diformyl dibenzo-18-crown-6 anchored onto the functionalized magnetite hydroxyapatite (γ-Fe2O3@HAp–Crown) as a new, versatile and magnetically recoverable catalyst, was prepared. It evaluated as phase-transfer catalyst and molecular host system for nucleophilic substitution reactions of benzyl halides with thiocyanate, cyanide, azide and acetate anions in water. No evidence for the formation of by-products was observed and the products obtained in pure form without further purification. The nanocomposite was easily removed from solution via application of a magnetic field, allowing straightforward recovery and reuse. The synthesized nanocomposite was characterized by several techniques such as FT-IR, TGA-DTG, EDX, XRD, BET, FE-SEM, TEM and VSM.
- Azaroon, Maedeh,Kiasat, Ali Reza
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- Polyether urea bridged chiral molecular tweezers and preparation and application thereof
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The invention discloses polyether urea bridged chiral molecular tweezers and preparation and application thereof. The polyether urea bridged chiral molecular tweezers are structurally shown as formula(I) or formula (II) shown in the description. The invention also provides application of the polyether urea bridged chiral molecular tweezers in the recognition of a chiral molecular guest; the chiral molecular guest is D/L-amino acid ester hydrochloride. The polyether urea bridged chiral molecular tweezers synthesized herein have certain property of chirally recognizing D/L-amino acid ester hydrochloride and are applicable to chiral recognition and separation of enantiomers.
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Paragraph 0036; 0037
(2018/11/22)
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- Thiourea polyether bridged chiral molecular tweezer and preparation and application thereof
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The invention discloses a thiourea polyether bridged chiral molecular tweezer and a preparation and an application thereof. The thiourea polyether bridged chiral molecular tweezer takes a thiourea polyether chain as a linking group, and the ent-beyerane skeleton is taken as a chiral arm, and a structure is as shown in a formula (I) or a formula (II). The present invention provides the applicationof the thiourea polyether bridged chiral molecular tweezer for identifying a chiral molecular object, wherein the chiral molecular object is D/L-amino acid ester hydrochloride. The synthesized molecular tweezer has certain chiral recognition performance for D/L-amino-acid ester hydrochloride, and can be used for chiral recognition and separation of enantiomers.
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Paragraph 0041-0042
(2019/01/08)
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- A compound for PET imaging and use thereof
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The present invention provides a precursor compound for the production of a radioactive compound for efficient contrast of the heart, a radioactive compound prepared using the precursor compound, and uses as a contrast medium for a PET contrast medium.br
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Paragraph 0057-0058
(2018/04/21)
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- Design, Synthesis and Antitumor Activities of 1,2,3-triazole-diethylene Glycol Tethered Isatin Dimers
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A series of novel 1,2,3-triazole-diethylene glycol tethered isatin dimers were designed, synthesized, and screened for their in vitro antitumor activities in this paper. All dimers showed promising activities against the tested HepG2, Hela, A549, DU145, S
- Fan, Yi-Lei,Huang, Zhong-Ping,Liu, Min
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p. 2990 - 2995
(2018/11/10)
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- A PET contrast compound for early diagnosis of cardiovascular diseases and use thereof
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The present invention provides: a precursor compound for the production of a radioactive compound for efficient imaging of heart; a radioactive compound produced using the precursor compound; and uses thereof as a contrast medium for PET imaging. According to the present invention, it is an object of the present invention to provide an improved novel PET imaging compound having a low water absorption rate and an improved removal rate in the liver.COPYRIGHT KIPO 2019
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Page/Page column 23-28
(2019/01/30)
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- An efficient and new protocol for the Heck reaction using palladium nanoparticle-engineered dibenzo-18-crown-6-ether/MCM-41 nanocomposite in water
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Palladium nanoparticle-incorporated mesoporous organosilica (MCM-41-Crown.Pd) was synthesized via the grafting of dibenzo-18-crown-6-ether moieties on the MCM-41 surface, followed by reaction of the nanocomposite with palladium acetate and then its reduction in ethanol. The cavity of the immobilized dibenzo-18-crown-6 as host material can stabilize the palladium nanoparticles effectively and prevent their aggregation and separation from the surface. The structure of the nanocomposite was characterized using various techniques. The catalytic properties of the nanocomposite in the Heck coupling reaction, one of the most useful transformations in organic synthesis, between aryl halides and olefins in water were also explored. The main advantages of the method are low cost, high yields, easy work-up and short reaction time. The nanocatalyst can be easily separated from a reaction mixture and was successfully examined for seven runs, with a slight loss of catalytic activity.
- Azaroon, Maedeh,Kiasat, Ali Reza
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- Clickable prodrugs bearing potent and hydrolytically cleavable nicotinamide phosphoribosyltransferase inhibitors
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Purpose: Our previous study indicated that carborane containing small-molecule 1-(hydroxymethyl)-7-(4′-(trans-3″-(3′″-pyridyl)acrylamido)butyl)-1,7-dicarbadodecaborane (hm-MC4-PPEA), was a potent inhibitor of nicotinamide phosphoribosyltransferase (Nampt)
- Sadrerafi, Keivan,Mason, Emilia O.,Lee, Mark W.
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p. 987 - 995
(2018/05/07)
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- ALKYNYL INDAZOLE DERIVATIVE AND USE THEREOF
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The main object of the present invention is to provide a novel compound which has a VEGF receptor tyrosine kinase inhibitory activity and is useful as an active ingredient for the treatment of diseases accompanying angiogenesis or edema, for example, age-related macular degeneration or the like. The present invention includes, for example, an alkynyl indazole derivative represented by the following general formula (I), a pharmaceutical acceptable salt thereof, and a medicine containing thereof.
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Paragraph 0276; 0277
(2017/02/24)
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- Novel 18F-Labeled 1-Hydroxyanthraquinone Derivatives for Necrotic Myocardium Imaging
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Rapid detection and precise evaluation of myocardial viability is necessary to aid in clinical decision making whether to recommend revascularization for patients with myocardial infarction (MI). Three novel18F-labeled 1-hydroxyanthraquinone derivatives were synthesized, characterized, and evaluated as potential necrosis avid imaging agents for assessment of myocardial viability. Among these tracers, [18F]FA3OP emerged as the most promising compound with best stability and highest targetability. Clear PET images of [18F]FA3OP were obtained in rat model of myocardial infarction and reperfusion at 1 h after injection. In addition, the possible mechanisms of [18F]FA3OP for necrotic myocardium were discussed. The results showed [19F]FA3OP may bind DNA to achieve targetability to necrotic myocardium by intercalation. In summary, [18F]FA3OP was a more promising “hot spot imaging” tracer for rapid visualization of necrotic myocardium.
- Ji, Ai-Yan,Jin, Qiao-Mei,Zhang, Dong-Jian,Zhu, Hua,Su, Chang,Duan, Xing-Hua,Bian, Li,Sun, Zi-Ping,Ni, Yi-Cheng,Zhang, Jian,Yang, Zhi,Yin, Zhi-Qi
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supporting information
p. 191 - 195
(2017/03/08)
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- Specific fluorescence labeling of target proteins by using a ligand-4-azidophthalimide conjugate
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We herein propose a simple affinity-labeling method using a ligand-4-azidophthalimide (AzPI) conjugate. As a proof of concept, we show that two different ligand-AzPI conjugates enabled highly specific fluorescence labeling of their individual target proteins even in crude cell lysates. This method was also applied to label endogenous target proteins inside living cells.
- Chiba, Kosuke,Asanuma, Miwako,Ishikawa, Minoru,Hashimoto, Yuichi,Dodo, Kosuke,Sodeoka, Mikiko,Yamaguchi, Takao
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supporting information
p. 8751 - 8754
(2017/08/10)
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- Synthesis and spectral properties of new ethylene glycol bridged oxazol-5-ones: High Stokes’ shift fluorophores sensitive to solvent polarity
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A set of new oxazol-5-one fluorophores incorporating ethylene glycol chains terminated with an aldehyde unit has been synthesized and characterized structurally. Two pairs of compounds can be distinguished according to the substitution on the oxazol-5-one moiety: one pair bears a tolyl unit and the other a nitrophenyl unit. The difference within the pairs is the length of the ethylene glycol chain. The evaluation of absorption and emission properties of the new oxazol-5-one derivatives was carried out in seven different solvents of varying polarity, which showed intense absorption maxima at 384–418 nm and emission maxima at 430–607 nm, respectively. The solvatofluorism study of 3a and 3c revealed that their emission wavelengths are very sensitive to solvent polarity and are red shifted in polar solvents. 3a and 3c fluorophores exhibited high Stokes shift values between 4158 and 7921 cm? 1.
- Ozturk Urut, Gulsiye,Bayramin, Dilek,Alp, Serap
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p. 109 - 115
(2017/10/05)
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- Optimized methods for preparation of 6I-(ω-sulfanyl-alkylenesulfanyl)-β-cyclodextrin derivatives
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A general high-yielding method for the preparation of monosubstituted β-cyclodextrin derivatives which have attached a thiol group in position 6 is described. The thiol group is attached through linkers of different lengths and repeating units (ethylene glycol or methylene). The target compounds were characterized by IR, MS and NMR spectra. A simple method for their complete conversion to the corresponding disulfides as well as a method for the reduction of the disulfides back to the thiols is presented. Both, thiols and disulfides are derivatives usable for well-defined covalent attachment of cyclodextrin to gold or polydopamine-coated solid surfaces.
- Bedná?ová, Eva,Hybelbauerová, Simona,Jind?ich, Jind?ich
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supporting information
p. 349 - 352
(2016/04/05)
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- Crown ether cyclic quinazoline compound, preparation method therefor and application thereof in preparing tumor therapy and imaging drug
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The invention relates to a crown ether cyclic quinazoline derivative and medicinal salts thereof using in tumor therapy and imaging. The crown ether cyclic quinazoline compound is characterized in that a 2-, 3-, 4- substituted aniline is disposed at one end; a 6-, 7- substituted crown ether cyclic quinazoline structure is disposed at the other end; the substituent group R1 is located on the fourth-position aniline of a quinazoline mother ring and is 2-, 3-, 4- substituted alkoxy; and the crown ether cycle is located at the 6, 7 position of the mother ring, and is a 9-crown-3, 12-crown-4 and 15-crown-5, and the structural formula is formula I. The experimental result of antitumor activity in vitro of nonradioactive isotope labeling compounds shows that the compounds are good in inhibitory effect for four kind of cancer cells namely HepG2, A549, sy5y and DU145, and have the potential as cancer treatment medicine; and the body distribution experiment of 18F or 125I labeling compounds show that the compounds are higher in ingestion and certain detention in tumors and faster in blood clearance and have potential applied to tumor imaging.
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Paragraph 0030; 0031; 0032
(2016/10/09)
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- DIHYDROPYRIDAZINE-3,5-DIONE DERIVATIVE AND PHARMACEUTICALS CONTAINING THE SAME
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The present invention provides a dihydropyridazine-3,5-dione derivative or a salt thereof, or a solvate of the compound or the salt, a pharmaceutical drug, a pharmaceutical composition, a sodium-dependent phosphate transporter inhibitor, and a preventive and/or therapeutic agent for hyperphosphatemia, secondary hyperparathyroidism, chronic renal failure, chronic kidney disease, and arteriosclerosis associated with vascular calcification comprising the compound as an active ingredient, and a method for prevention and/or treatment.
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Paragraph 2215-2217
(2016/01/30)
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- A Fluorescent and Switchable Rotaxane Dual Organocatalyst
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Rotaxane organocatalysis presents a new direction toward controlled one-pot catalytic reactions. By combining molecular switches and catalysts, fluorescence and pH-responsive switching along with the exclusive selectivity of dual catalytic reactions are d
- Kwan, Chak-Shing,Chan, Albert S. C.,Leung, Ken Cham-Fai
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supporting information
p. 976 - 979
(2016/03/15)
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- α-Glucosidase inhibition and antihyperglycemic activity of flavonoids from Ampelopsis grossedentata and the flavonoid derivatives
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The dried leaves and stems of Ampelopsis grossedentata have been used as a health tea and herbal medicine for hundreds of years in China. The study was aimed at searching for novel α-glucosidase inhibitors among the richest components of A. grossedentata and their derivatives. Three known major components (1-3) were isolated by recrystallization process and six new derivatives (4-9) were obtained by etherification of the bioactive flavonoid. All compounds were evaluated for their inhibitory activities against α-glucosidase (from Saccharomyces cerevisiae). As a result, compound 9 showed a significant α-glucosidase inhibitory activity with IC50 value of 9.3 μM and acted as a competitive inhibitor with the value of the inhibition constant (Ki) being 10.3 μM. The oral administration of compound 9 at a dose of 50 mg/kg significantly reduced the post prandial blood glucose levels of normal and streptozotocin (STZ)-induced diabetic mice. Furthermore, compound 9 significantly decreased the fasting blood glucose levels in STZ-induced diabetic mice.
- Chen, Jia,Wu, Yuechan,Zou, Jianwei,Gao, Kun
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p. 1488 - 1494
(2016/03/16)
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- Candidate PET Radioligand Development for Neurofibrillary Tangles: Two Distinct Radioligand Binding Sites Identified in Postmortem Alzheimer's Disease Brain
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[18F]THK-523 and [18F]807 are promising radioligands for imaging neurofibrillary tangles (NFTs) with positron emission tomography (PET) in neurodegenerative diseases, such as Alzheimer's disease (AD) and traumatic brain injury. Although [18F]THK-523 and [18F]T807 are considered high-affinity selective radioligands for NFTs, uncertainty has existed as to whether PET radioligands for imaging NFTs bind to the same molecular site because in vitro assays for ligands binding to NFTs have been lacking. We labeled THK-523 and T807 with tritium to serve as reference radioligands for in vitro binding assays with AD brain homogenates for newly synthesized ligands. With these radioligands, we identified two distinct binding sites for small molecules, one site with high affinity for THK-523 and the other with high affinity for T807. Moreover, binding assays with [3H]PIB confirmed that the two newly identified binding sites are also distinct from the thioflavin-T binding site where all current clinically useful PET radioligands for imaging β-amyloid plaque bind with high affinity. The two newly identified binding sites are considered to reside on NFTs rather than on β-amyloid plaques. Furthermore, we applied all three binding assays to a set of newly prepared compounds, based on chain modifications to THK-523. Some compounds with high affinity and selectivity for the THK-523 binding site emerged from this set, including one with amenability to labeling with fluorine-18, namely, ligand 10b.
- Cai, Lisheng,Qu, Baoxi,Hurtle, Bryan T.,Dadiboyena, Sureshbabu,Diaz-Arrastia, Ramon,Pike, Victor W.
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p. 897 - 911
(2016/08/02)
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- DERIVATIVES OF DOLASTATIN 10 AND USES THEREOF
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Derivatives of dolastatin 10 and uses thereof, the structures of which are shown as formula I, II, III and IV are provided.
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Page/Page column 30
(2016/12/22)
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- A photosensitive chiral large ring molecule and its preparation method and use
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The invention discloses a photosensitive chiral macrocyclic molecule and a preparation method and application thereof, belonging to the field of preparation of photoresponsive materials. The preparation method for the photosensitive chiral macrocyclic mol
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Paragraph 0038-0040
(2017/03/08)
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- Highly efficient synthesis of tetra benzo spiro bis-crown ether
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Novel spiro bis-crown ethers derivatives with four benzo units connected via one carbon bridges have been prepared. These compounds represent well preorganized cavities with interesting complexation abilities towards cations. These macrocyclic were prepared by a four-step via template method by utilizing simple precursors catechol, oliethylen glycol and penta erythritol tetra bromide in good yield. Additionally, cesium carbonate could be used as an excellent base for these reactions.
- Moradgholi, Fatemeh,Vahedi, Hooshang,Lari, Jalil
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- Preparation of 7-methoxy tacrine dimer analogs and their in vitro/in silico evaluation as potential cholinesterase inhibitors
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Novel types of symmetric bis-7-methoxytacrines connected by oligoethyleneoxy chains 3-5 and nonsymmetric monomeric 7-methoxytacrines containing hydroxyl-terminated oligoethyleneoxy chains 6-8 were prepared, and their in vitro/in silico effects on human recombinant AChE (hAChE) and human plasmatic butyrylcholinesterase (hBChE) were compared, with 7-MEOTA (2) as the standard compound. The symmetric bis-7-MEOTA derivatives 3-5 showed hAChE inhibition similar to that of 2. On the other hand, their effects on hBChE revealed an increasing inhibition trend when the oligoethyleneoxy units between the two 7-MEOTA moieties became longer. Accordingly, compounds 4 and 5 showed better selectivity towards hBChE. The most effective in the inhibition hAChE and hBChE was compound 8 with the longest oligoethyleneglycol chain, whereas compounds 6 and 7 resulted in similar IC50 values. A molecular modeling study using substrates 5 and 8 showed a possible binding conformation and protein-ligand interaction between the substrates and AChE/BChE.
- Lee, Sang Kwang,Park, Min Kyun,Jhang, Ho Eun,Yi, Jinju,Nahm, Keepyong,Cho, Dae Won,Ra, Choon Sup,Musilek, Kamil,Horova, Anna,Korabecny, Jan,Dolezal, Rafael,Jun, Daniel,Kuca, Kamil Kuca
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p. 1654 - 1660
(2015/07/15)
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- A novel 2-cyanobenzothiazole-based 18F prosthetic group for conjugation to 1,2-aminothiol-bearing targeting vectors
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In a bid to find an efficient means to radiolabel biomolecules under mild conditions for PET imaging, a bifunctional 18F prosthetic molecule has been developed. The compound, dubbed [18F]FPyPEGCBT, consists of a 2-substituted pyridine moiety for [18F]F- incorporation and a 2-cyanobenzothiazole moiety for coupling to terminal cysteine residues. The two functionalities are separated by a mini-PEG chain. [18F]FPyPEGCBT could be prepared from its corresponding 2-trimethylammonium triflate precursor (100 °C, 15 min, MeCN) in preparative yields of 11% ± 2 (decay corrected, n = 3) after HPLC purification. However, because the primary radiochemical impurity of the fluorination reaction will not interact with 1,2-aminothiol functionalities, the 18F prosthetic could be prepared for bioconjugation reactions by way of partial purification on a molecularly imprinted polymer solid-phase extraction cartridge. [18F]FPyPEGCBT was used to 18F-label a cyclo-(RGDfK) analogue which was modified with a terminal cysteine residue (TCEP·HCl, DIPEA, 30 min, 43°C, DMF). Final decay-corrected yields of 18F peptide were 7% ± 1 (n = 9) from end-of-bombardment. This novel integrin-imaging agent is currently being studied in murine models of cancer. We argue that [18F]FPyPEGCBT holds significant promise owing to its straightforward preparation, 'click'-like ease of use, and hydrophilic character. Indeed, the water-tolerant radio-bioconjugation protocol reported herein requires only one HPLC step for 18F peptide purification and can be carried out remotely using a single automated synthesis unit over 124-132 min.
- Inkster, James A.H.,Colin, Didier J.,Seimbille, Yann
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supporting information
p. 3667 - 3676
(2015/03/30)
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- Synthesis and cavity size effect of pd-containing macrocycle catalyst for efficient intramolecular hydroamination of allylurethane
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Palladium-containing macrocycle catalysts (PdMCs) with different ring sizes ranging from 24 to 30 members were synthesized. The intramolecular hydroamination of an allylurethane (AU) catalyzed by PdMCs proceeded efficiently to afford the corresponding oxazolidinone (OZ) in 95% isolated yield. The dependence of the hydroamination of AU to OZ on the cavity size indicated that the reaction rate was clearly controlled by both substrate uptake and product release steps.
- Ogawa, Masahiro,Nagashima, Masaki,Sogawa, Hiromitsu,Kuwata, Shigeki,Takata, Toshikazu
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supporting information
p. 1664 - 1667
(2015/04/14)
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- Tetranuclear ruthenium(ii) complexes with oligo-oxyethylene linkers as one- and two-photon luminescent tracking non-viral gene vectors
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To prolong the observation time, increase the penetration depth and decrease self-absorption and phototoxicity, two-photon luminescent vectors have emerged as promising tools for tracking gene delivery in living cells. Herein, we report four new tetranuclear Ru(ii) complexes based on oligo-oxyethylene and polybenzimidazole as one- and two- photon luminescent tracking non-viral gene vectors. In such a molecular design, the oligo-oxyethylene, polybenzimidazole and Ru(ii) polypyridyl complexes were expected to render the vectors with increased cell permeability, biocompatibility, proton buffering capacity and one- and two-photon luminescence. Corresponding DNA interaction studies showed that the ability of the complexes to condense DNA decreased with increasing oligo-oxyethylene lengths. Additionally, all complexes protected DNA. The complexes were investigated as one- and two-photon tracking non-viral gene vectors in living cells and showed proper cellular uptake, good luciferase expression and low cytotoxicity. This journal is
- Qiu, Kangqiang,Yu, Bole,Huang, Huaiyi,Zhang, Pingyu,Ji, Liangnian,Chao, Hui
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supporting information
p. 7058 - 7065
(2015/04/14)
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- Powerful Bipodal Anion Transporters Based on Scaffolds That Contain Different Chalcogens
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A new family of bipodal anion transporters based on chalcogen-containing scaffolds has been designed and synthesized. Though structurally related to the well-studied tripodal anionophores, these molecules are simpler with only two anion-binding sites. However, the activities remain high. Anion transport could be facilitated by the new transporter at an exceptionally low loading of transporter/lipid ratio of 1:500000. This impressive efficiency is comparable with the most active one from the tren-based tripodal series. To investigate influences from different scaffolds and substituent groups, lipophilicity, anion-binding property, and transport activity of each molecule were studied. It was found that the bridge atom has a major impact on transport activities mainly as a result of anion-binding differences. The results also suggest that chalcogen can act as a key structural modulator to develop highly effective anion transporters and optimize their activities. Anion transporters based on chalcogen-containing scaffolds have been designed and synthesized. Their lipophilicities, anion binding properties, and transport activities were investigated in detail. The results suggest that chalcogen can act as a key structural modulator to develop highly effective anion transporters and optimize their activities.
- Lang, Chao,Zhang, Xin,Luo, Quan,Dong, Zeyuan,Xu, Jiayun,Liu, Junqiu
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p. 6458 - 6465
(2015/10/19)
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- Selective binding to monoamine oxidase A: In vitro and in vivo evaluation of 18F-labeled β-carboline derivatives
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In this study we synthesized four different 18F-labeling precursors for the visualization of the monoamino oxidase A using harmol derivatives. Whereas two are for prosthetic group labeling using [18F]fluoro-d2-methyl tosylate and 2-[18F]fluoroethyl-tosylate, the other three precursors are for direct nucleophilic 18F-labeling. Additionally the corresponding reference compounds were synthesized. The syntheses of [18F]fluoro-d2-methyl-harmol and 2-[18F]fluoroethyl-harmol were carried out using harmol as starting material. For direct nucleophilic 18F-labeling of the tracers carrying oligoethyled spacers (PEG), a toluenesulfonyl leaving group was employed. The radiolabeling, purification and formulation for each tracer was optimized and evaluated in vitro and in vivo. Stability tests in human serum showed that all tracers were stable over the observation period of 60 min. μPET studies using of the synthesized tracers revealed that the tracers carrying PEG spacers showed no sufficient brain uptake. Consequently, the 18F-fuoro alkylated tracers [18F]fluoro-d2-methyl-harmol and 2-[18F]fluoroethyl-harmol were further evaluated showing SUVs in the brain of 1.0 ± 0.2 g/mL and 3.4 ± 0.5 g/mL after 45 min, respectively. In blockade studies the selectivity and specificity of both tracers were demonstrated. However, for [18F]fluoro-d2-methyl-harmol a rapid washout from the brain was also observed. In vitro binding assays revealed that 2-[18F]fluoroethyl-harmol (IC50 = 0.54 ± 0.06 nM) has a higher affinity than the 18F-fluoro-d2-methylated ligand (IC50 = 12.2 ± 0.6 nM), making 2-[18F]fluoroethyl-harmol superior to the other evaluated compounds and a promising tracer for PET imaging of the MAO A.
- Schieferstein, Hanno,Piel, Markus,Beyerlein, Friderike,Lüddens, Hartmut,Bausbacher, Nicole,Buchholz, Hans-Georg,Ross, Tobias L.,R?sch, Frank
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p. 612 - 623
(2015/01/30)
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- Efficient synthesis of novel benzylidene barbituric and thiobarbituric acid derivatives containing ethyleneglycol spacers
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Knoevenagel condensation reaction of ethylene glycol-based aromatic aldehyde with barbituric acid derivatives in ethanol produced novel benzylidene barbituric and thiobarbituric acid derivatives which contain good yields of ethylene glycol spacers. Structures of the products were deduced from their IR, 1H-NMR, and 13C-NMR spectroscopy and mass spectra.
- Faryabi, Malihe,Sheikhhosseini, Enayatollah
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p. 427 - 432
(2015/02/05)
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- MCM-41 bound dibenzo-18-crown-6 ether: a recoverable phase-transfer nano catalyst for smooth and regioselective conversion of oxiranes to β-azidohydrins and β-cyanohydrins in water
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A new organic-inorganic hybrid nanocomposite was prepared by immobilizing dibenzo-18-crown-6 onto covalently linked amine functionalized mesoporous MCM-41 via a simple post-synthesis method. The heterogeneous hybrid nanocomposite was characterized by TEM,
- Yousefi, Sarah,Kiasat, Ali Reza
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p. 92387 - 92393
(2015/11/16)
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- Method for composing Ionic Liqudis for a coal dissolution
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Coal for melting a disclosure synthesis on the ionic liquid. According to one embodiment of the present invention disclosure for melting coal is contacted with 1 synthesizing the ionic liquid chloride methylene precursor difference nitride, which in turn are dissolved proper ratios to the process cooling a (S100); maltosyl chloride solution to said potassium hydroxide input process (S200); device after a lapse of time constant, members at room temperature, then being changed suspension brightened, distilled water and the water is dropped by gravitation in filtering process and, after washing the multiple times to, organic layer after the water by, concentrating it under reduced pressure process (S300); plurality of column chromatography by white solid (S400) a first precursor difference 2 ; said 2 difference by implanting methyl imidazoles precursor reagent solvent and mixing process (S500); a procedure (S600) lipid in, at a suitable temperature; cleaning turn on the order of several tens of zirconium as anhydride oil foaming vermiculite, and the plurality of end ionic liquid to obtain a process includes (S700).
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Paragraph 0023-0032
(2016/12/26)
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- CARBAZOLE AND CARBOLINE COMPOUNDS FOR USE IN THE DIAGNOSIS, TREATMENT, ALLEVIATION OR PREVENTION OF DISORDERS ASSOCIATED WITH AMYLOID OR AMYOLID-LIKE PROTEINS
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The present invention relates to novel compounds that can be employed in the diagnosis, treatment, alleviation or prevention of a group of disorders and abnormalities associated with amyloid proteins and amyloid-like proteins, such as Alzheimer's disease. Precursors for the preparation of the compounds according to the present invention are also provided.
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Page/Page column 239; 240
(2015/08/06)
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