- Self-assembly of an amphiphilic iron(III) chelator: Mimicking iron acquisition in marine bacteria
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(Figure Presented) Iron rations: Amphiphilic catechol-based chelators and their iron complexes self-assemble in solution at physiological pH values to form spherical particles (see cryo-TEM image). In terms of iron nutrition properties these abiotic chela
- Apostol, Mariana,Baret, Paul,Serratrice, Guy,Desbrieres, Jacques,Putaux, Jean-Luc,Stebe, Marie-Jose,Expert, Dominique,Pierre, Jean-Louis
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Read Online
- The total synthesis of berberine and selected analogues, and their evaluation as amyloid beta aggregation inhibitors
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The total synthesis of berberine and selected analogues. And their evaluation as amyloid β (Aβ) aggregation inhibitors is described. The key step in the synthesis, the assembly of the berberine framework, was accomplished using an intermolecular Heck reaction. Berberine analog 17 incorporating a tertiary amine moiety showed good anti Aβ aggregation activity, water solubility, and almost no toxicity to nerve cells.
- Tajiri, Misato,Yamada, Ryo,Hotsumi, Mayumi,Makabe, Koki,Konno, Hiroyuki
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- Computational discovery, structural optimization and biological evaluation of novel inhibitors targeting transient receptor potential vanilloid type 3 (TRPV3)
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Transient receptor potential vanilloid type 3 (TRPV3) is a Ca2+ permeable nonselective cation channel and expressed abundantly in skin keratinocytes. TRPV3 emerges as an attractive target for treatment of pruritic, inflammatory, pain and skin-related diseases. However, only a few reports of TRPV3 inhibitors exist at present besides some patents. Therefore, TRPV3 research has always been fraught with challenges. Through a combination of virtual screening and biological evaluation, compound P1 (10 μM) was identified as a top hit with 34.5% inhibitory effect on 2-APB (1 mM)-evoked currents of mTRPV3-WT. Further structural optimization provided the inhibitor PC5 with the best activity (IC50 = 2.63 ± 0.28 μM), and point mutation assays indicated that amino acids V629 and F633 are crucial for the binding of PC5 and TRPV3. In summary, these newly discovered inhibitors could serve as promising lead compounds for the development of TRPV3 inhibitors in the future.
- Zhang, Fang,Lin, Yiyu,Min, Wenjian,Hou, Yi,Yuan, Kai,Wang, Jin,Yang, Peng
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- Design, synthesis and apoptosis inducing activity of nonsteroidal flavone-methanesulfonate derivatives on MCF-7 cell line as potential sulfatase inhibitor
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In recent years, focusing on new potent anticancer agents with selective activity is one of the greatest challenges in cancer therapy. Breast cancer is the most common cancer and the main cause of cancer deaths in women. The sulfatase enzyme plays an important role in converting the sulfated steroids into non-sulfate steroid hormones, which increases the growth and development of many hormone-dependent cancers, such as breast cancer. In this regard, structure-based optimization was conducted to design novel flavone-sulfonates pharmacophore as a new steroid sulfatase inhibitor. In the present work, the conventional methods for the synthesis of 4-oxo-2-phenyl-4H-chromen-7-yl methanesulfonate derivatives were reported. Their cytotoxicity was evaluated with MTT assay against a breast cancer cell line (MCF-7). The apoptosis inducing activity of the most cytotoxic compound 3c with an IC50 value of 0.615 μM was evaluated in comparison to docetaxel in the presence of estradiol which is a crucial growth factor to survive the cancerous cells. The results of double staining Annexin V-FITC/PI analysis suggested that the cytotoxic activity of this compound 3c in MCF-7 cells occurs via apoptosis. Molecular docking studies were conducted to clarify the inhibition mode of the most promising compound (3c) over the sulfatase (1P49) binding site. The analysis revealed the role of hydrogen bond interaction with Gly181 and hydrophobic interactions through the 1P49 active site in the ligand-receptor complex as significant descriptors to rationalize the potential inhibition activity. [Figure not available: see fulltext.]
- Javadi, Mahdiyeh H. S.,Iraji, Aida,Safavi, Maliheh,Montazeri, Hamed,Tarighi, Parastoo,Eftekhari, Samane,Navidpour, Latifeh,Mirfazli, Seyedeh Sara
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p. 1677 - 1687
(2021/07/26)
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- TYK2 Inhibitor compounds containing alkoxy and amide groups
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The invention belongs to the field of pharmaceutical chemistry, and provides TYK2 inhibitor compounds containing alkoxy and amide groups and a preparation method thereof, and relates to application of the compound in preparation of medicines for treating
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Paragraph 0101-0102; 0107-0108
(2021/11/21)
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- IRON(III) AND GALLIUM(III) METAL ORGANIC POLYHEDRA, METHODS OF MAKING SAME, AND USES THEREOF
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Compounds may have at least two structural units, which may be referred to as ligands. Each structural unit includes at least one spacer group and two or more donor groups. Compounds may have two or more iron(III) cations, one or more of which may be a hi
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Paragraph 0107; 0108
(2021/01/23)
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- Synthesis, characterization, antioxidant, and antibacterial activities of new 2,3-dimethoxy and 3-acetoxy-2-methyl benzamides
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Abstract: We performed a series of novel benzamide compounds which were synthesized starting from 2,3-dimethoxybenzoic acid or 3-acetoxy-2-methylbenzoic acid and amine derivatives. All the obtained products were purified, and the analysis of these product
- Yakan, Hasan,Cakmak, Sukriye,Kutuk, Halil,Yenigun, Semiha,Ozen, Tevfik
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p. 2767 - 2787
(2020/03/23)
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- Design and synthesis of 3-benzylaminocoumarin-7-O-sulfamate derivatives as steroid sulfatase inhibitors
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Steroid sulfatase (STS) is a sulfatase enzyme that catalyzes the conversion of sulfated steroid precursors to free steroid. The inhibition of STS could abate estrogenic steroids that stimulate the proliferation and development of breast cancer, and therefore STS is a potential target for adjuvant endocrine therapy. In this study, a series of 3-benzylaminocoumarin-7-O-sulfamate derivatives targeting STS were designed and synthesized. Structure-relationship activities (SAR) analysis revealed that attachment of a benzylamino group at the 3-position of coumarin improved inhibitory activity. Compound 3j was found to have the highest inhibition activity against human placenta isolated STS (IC50 0.13 μM) and MCF-7 cell lines (IC50 1.35 μM). Kinetic studies found compound 3j to be an irreversible inhibitor of STS, with KI and kinact value of 86.9 nM and 158.7 min?1, respectively.
- Chang, Chiao-Nien,Chen, Mei-Jou,Chiu, Pei-Fang,Hng, Yue,Liang, Pi-Hui,Lin, I-Chun,Lin, Mei-Hsiang,Lin, Tzung-Sheng,Liu, I-Chen,Lu, Yeh-Lin,Tsai, Keng-Chang
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- 6,7-Dimethoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinoline amides and corresponding ester isosteres as multidrug resistance reversers
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Aiming to deepen the structure–activity relationships of the two P-glycoprotein (P-gp) modulators elacridar and tariquidar, a new series of amide and ester derivatives carrying a 6,7-dimethoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinoline scaffold linked to different methoxy-substituted aryl moieties were synthesised. The obtained compounds were evaluated for their P-gp interaction profile and selectivity towards the two other ABC transporters, multidrug-resistance-associated protein-1 and breast cancer resistance protein, showing to be very active and selective versus P-gp. Two amide derivatives, displaying the best P-gp activity, were tested in co-administration with the antineoplastic drug doxorubicin in different cancer cell lines, showing a significant sensitising activity towards doxorubicin. The investigation on the chemical stability of the derivatives towards spontaneous or enzymatic hydrolysis, showed that amides are stable in both models while some ester compounds were hydrolysed in human plasma. This study allowed us to identify two chemosensitizers that behave as non-transported substrates and are characterised by different selectivity profiles.
- Bartolucci, Gianluca,Braconi, Laura,Colabufo, Nicola Antonio,Contino, Marialessandra,Dei, Silvia,Giampietro, Roberta,Manetti, Dina,Perrone, Maria Grazia,Riganti, Chiara,Romanelli, Maria Novella,Teodori, Elisabetta,Chiaramonte, Niccolò
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p. 974 - 992
(2020/04/24)
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- A two-qubit molecular architecture for electron-mediated nuclear quantum simulation
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A switchable interaction between pairs of highly coherent qubits is a crucial ingredient for the physical realization of quantum information processing. One promising route to enable quantum logic operations involves the use of nuclear spins as protected
- Atzori, Matteo,Chiesa, Alessandro,Morra, Elena,Chiesa, Mario,Sorace, Lorenzo,Carretta, Stefano,Sessoli, Roberta
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p. 6183 - 6192
(2018/08/07)
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- Preparation method of 2,3-dimethoxybenzoyl chloride
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The invention relates to a preparation method of 2,3-dimethoxybenzoyl chloride, which belongs to the technical field of medicine technology. The invention solves the technical problem of a more advanced preparation method of 2,3-dimethoxybenzoyl chloride.
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Paragraph 0007-0010
(2019/01/14)
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- A Helicate-Based Three-State Molecular Switch
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The control of structural transformations triggered by external signals is important for the development of novel functional devices. In the present study, it is demonstrated that helicates can be designed to structurally respond to the presence of differ
- Chen, Xiaofei,Gerger, Thomas M.,R?uber, Christoph,Raabe, Gerhard,G?b, Christian,Oppel, Iris M.,Albrecht, Markus
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supporting information
p. 11817 - 11820
(2018/09/09)
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- Amide Effects in C?H Activation: Noncovalent Interactions with L-Shaped Ligand for meta Borylation of Aromatic Amides
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A new concept for the meta-selective borylation of aromatic amides is described. It has been demonstrated that while esters gave para borylations, amides lead to meta borylations. For achieving high meta selectivity, an L-shaped bifunctional ligand has been employed and engages in an O???K noncovalent interaction with the oxygen atom of the moderately distorted amide carbonyl group. This interaction provides exceptional control for meta C?H activation/borylation.
- Bisht, Ranjana,Hoque, Md Emdadul,Chattopadhyay, Buddhadeb
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supporting information
p. 15762 - 15766
(2018/11/10)
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- Synthetic method for 2,5-diaryloxazole compounds and anti-inflammatory pharmaceutical compounds containing the 2,5-diaryloxazole compounds
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The present inventors have invented an effective synthesis method for a 2,5-diaryloxazole compound from a commercially available starting material. The synthesis method uses the Delepine reaction and the Robinson-Gabriel reaction as main steps. For oxazole compounds synthesized in the present invention, the present inventors have evaluated the inhibitory effect of LPS-induced NO production in RAW 264.7 cells, and have found that the oxazole compounds of the present invention significantly inhibit NO production in a concentration-dependent manner. Therefore, the oxazole compounds of the present invention may be potential compounds which can be used as anti-inflammatory agents.COPYRIGHT KIPO 2018
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Paragraph 0060; 0077; 0078
(2019/02/02)
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- Anti-inflammatory pharmaceutical compounds containing 2,5-diaryloxazole compounds
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The present invention efficiently diaryloxazole compounds inside the victims of the commercial starting material from 2, 5 - configurated. The synthesis [...] (Delepine) [pu [pu] l - the adventures reaction a hole of major steps reaction. In the present invention synthesized oxazole compounds the present invention with respect to the victims of the RAW 264. 7 NO generation have caused LPS - in assessing, oxazole compounds of the present invention depending on the concentration of the present invention were found to significantly NO billion number generation number may be likely oxazole compounds are anti-inflammatory compound as a lever with each other. (by machine translation)
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Paragraph 0023; 0040; 0041
(2019/02/21)
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- Selective mono-alkylation of N-methoxybenzamides
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We report our latest discovery of norbornene derivative modulated highly mono-selective ortho-C-H activation alkylation reactions on arenes bearing simple mono-dentate coordinating groups. The reaction features the use of readily available benzamides and alkyl halides. During the study, we prepared 30 mono-alkylated aryl amides in good yields with good mono-selectivity. We have also demonstrated that structurally rigid alkenes such as norbornene and its derivatives are a good class of ligand and could be used for future direct C-H functionalizations. The utilization of norbornene type ligands for assistance in C-H activation processes has opened a new window for future molecular design using direct C-H functionalization strategies.
- Chen, Zenghua,Hu, Le'an,Zeng, Fanyun,Zhu, Ranran,Zheng, Shasha,Yu, Qingzhen,Huang, Jianhui
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supporting information
p. 4258 - 4261
(2017/04/21)
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- Conformational Selection as the Mechanism of Guest Binding in a Flexible Supramolecular Host
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This study offers a detailed mechanistic investigation of host-guest encapsulation behavior in a new enzyme-mimetic metal-ligand host and provides the first observation of a conformational selection mechanism (as opposed to induced fit) in a supramolecula
- Hong, Cynthia M.,Kaphan, David M.,Bergman, Robert G.,Raymond, Kenneth N.,Toste, F. Dean
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supporting information
p. 8013 - 8021
(2017/06/21)
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- Efficient Synthesis and In Vitro Biological Evaluation of 2,5-Diaryloxazoles as Potential Nitric Oxide Production Inhibitors
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An efficient first synthesis of 2,5-diaryloxazoles 1–5 was accomplished from commercially inexpensive precursors and in overall yields of 38–48%. The synthesis proceeds via α-aminoketones and cyclodehydration (Robinson–Gabriel reaction) as key step. Next, these oxazoles were examined for their inhibitory effect against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells and were found to display concentration-dependent inhibition of NO production without cytotoxicity. Of note, compound 3 (70.7%; IC50 = 2.33 μM) was identified as a potent inhibitor in view of its comparable inhibitory effect with the positive control, NG-monomethyl-L-arginine acetate (L-NMMA) (79.3%; IC50 = 4.51 μM) followed by compounds 5 (68.3%; IC50 = 2.30 μM) and 2 (53.9%; IC50 = 6.31 μM). As a whole, compound 3 may hold great promise for further development of NO production targeted anti-inflammatory agent.
- Jang, Ha Young,Damodar, Kongara,Kim, Jin-Kyung,Jun, Jong-Gab
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p. 1481 - 1485
(2017/12/04)
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- Targeting telomerase with radiolabeled inhibitors
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The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells,123I-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An123I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC50of 1.58?μM (MST-312 IC50: 0.23?μM). Clonogenic assays showed a dose dependant effect of123I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435.
- Waghorn, Philip A.,Jackson, Mark R.,Gouverneur, Veronique,Vallis, Katherine A.
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p. 117 - 129
(2016/09/23)
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- Spectroscopic properties and preparation of some 2,3-dimethoxybenzamide derivatives
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In this study, a series of substituted secondary amide compounds were synthesized starting from 2,3-dimethoxybenzoic acid and aniline derivatives. The structures of these synthesized compounds were determined using IR, 1H NMR and 13C
- Cakmak, Sukriye,Kutuk, Halil,Odabasoglu, Mustafa,Yakan, Hasan,Buyukgungor, Orhan
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p. 181 - 194
(2016/02/27)
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- Searching for indole derivatives as potential mushroom tyrosinase inhibitors
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Tyrosinase is a copper-containing enzyme widely distributed in nature, involved in the biosynthesis of melanin whose role is to protect the skin from ultraviolet damage. A great interest has been shown on the melanin involvement in malignant melanoma and
- Ferro, Stefania,Certo, Giovanna,De Luca, Laura,Germanò, Maria Paola,Rapisarda, Antonio,Gitto, Rosaria
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p. 398 - 403
(2016/03/26)
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- Structural interrogation of benzosuberene-based inhibitors of tubulin polymerization
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The discovery of 3-methoxy-9-(3′,4′,5′-trimethoxyphenyl)-6,7-dihydro-5H-benzo[7]annulen-4-ol (a benzosuberene-based analogue referred to as KGP18) was originally inspired by the natural products colchicine and combretastatin A-4 (CA4). The relative struct
- Herdman, Christine A.,Devkota, Laxman,Lin, Chen-Ming,Niu, Haichan,Strecker, Tracy E.,Lopez, Ramona,Liu, Li,George, Clinton S.,Tanpure, Rajendra P.,Hamel, Ernest,Chaplin, David J.,Mason, Ralph P.,Trawick, Mary Lynn,Pinney, Kevin G.
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p. 7497 - 7520
(2015/12/18)
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- IMPROVED PROCESS FOR PREPARATION OF 2,3-DIHYDROXY BENZONITRILE
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Disclosed is one pot process of the preparation of 2,3-dihydroxy benzonitrile from 2,3-dialkoxy benzoic acid without prior isolation of the intermediates. Further disclosed is the preparation of 2,3-dihydroxy benzonitrile by dealkylation of 2,3-dialkoxy benzonitrile using suitable aluminum salt-amine complex.
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Page/Page column 10-12
(2014/02/15)
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- Beyond directed ortho metalation: Ru-catalyzed CAr-O activation/cross-coupling reaction by amide chelation
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Disclosed is a new, catalytic, and general methodology for the chemical synthesis of biaryl, heterobiaryl, and polyaryl molecules by the cross-coupling of o-methoxybenzamides with aryl boroneopentylates. The reaction is based on the activation of the unreactive C-OMe bond by the proximate amide directing group using catalytic RuH2(CO)(PPh3)3 conditions. A one-step, base-free coupling process is thereby established that has the potential to supersede the useful two-step directed ortho metalation/cross- coupling reaction involving cryogenic temperature and strong base conditions. High regioselectivity, orthogonality with the Suzuki-Miyaura reaction, operational simplicity, minimum waste, and convenient scale-up make these reactions suitable for industrial applications.
- Zhao, Yigang,Snieckus, Victor
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supporting information
p. 11224 - 11227
(2014/09/29)
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- A versatile total synthesis of 8-oxyberberine and oxohomoberberines
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The total syntheses of 8-oxyberberine and oxohomoberberines were accomplished starting from commercially available 5-bromobenzo[d][1,3]dioxole, piperonal and sesamol in high total yield. The key steps involved a modified Pomeranz-Fritsch reaction and the intramolecular Heck cyclization. This approach is short, convenient and suitable for the preparation of homoberberine analogues.
- He, Yun,Zheng, Yang,Hai, Li,Wu, Yong
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p. 1121 - 1127
(2015/01/16)
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- Efficient synthesis of hydroxyl isoindolones by a Pd-mediated C-H activation/annulation reaction
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Radical reaction: A convenient synthesis of hydroxyl isoindolones by a Pd-catalyzed C-H activation/annulation reaction with near "click chemistry" efficiency is presented (see scheme; TBHP=tert-butyl hydrogen peroxide). This methodology features short reaction times (10-30 min), high atom economy, wide substrate scope (22 examples), and good reaction yields (up to 93 %). Copyright
- Yu, Qingzhen,Zhang, Nana,Huang, Jianhui,Lu, Shaonan,Zhu, Yi,Yu, Xiaoxiao,Zhao, Kang
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supporting information
p. 11184 - 11188
(2013/09/02)
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- LEUKOTRIENE B4 ANTAGONIST COMPOUND
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The present invention provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof. Also, the present invention provides a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof a
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Page/Page column 11
(2013/07/25)
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- A tetrameric hetero-octanuclear cyclic helicate formed from a bridging ligand with two inequivalent binding sites
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A bis-bidentate bridging ligand H2L with inequivalent hard and soft binding sites (catecholate and pyrazolyl-pyridine, respectively) reacts with a mixture of Ti(iv) and Zn(ii) ions to afford an octanuclear heterometallic Ti4Zn4
- Metherell,Ward
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p. 14281 - 14285
(2013/09/02)
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- Synthesis and biological activities of new halophenols
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A series of new halophenols were synthesized, and their structures were established on the basis of 1H, 13C NMR and mass spectral data. All of the prepared compounds were screened for their in vitro protein tyrosine kinase (PTK) and vascular smooth muscle cell (VSMC) proliferation inhibitory activity. Twelve halophenols showed significant PTK inhibitory activity, most of them exhibited stronger activities than that of genistein, a positive reference compound. Several halophenols also displayed moderate VSMC proliferation inhibitory activity, compound 8c showed higher activity than that of tetrandrine, a positive reference compound. The preliminary structure-activity relationships of these compounds were investigated and discussed. The results provided a foundation for the action mechanism study and further structure optimization of the halophenols.
- Zheng, Fei Lang,Ban, Shu Rong,Feng, Xiu E.,Zhao, Cheng Xiao,Du, Guan Hua,Li, Qing Shan
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p. 303 - 311
(2013/07/28)
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- Synthesis and anti-tumor evaluation of B-ring modified caged xanthone analogues of gambogic acid
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Gambogic acid (GA, 1), the most prominent member of Garcinia natural products, has been reported to be a promising anti-tumor agent. Previous studies have suggested that the planar B ring and the unique 4-oxa-tricyclo[4.3.1. 03,7]dec-2-one cage
- Li, Xiang,Zhang, Xiaojin,Wang, Xiaojian,Li, Nianguang,Lin, Changjun,Gao, Yuan,Yu, Zhuoqin,Guo, Qinglong,You, Qidong
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experimental part
p. 35 - 42
(2012/03/26)
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- Studies on chemical modification and biology of a natural product, gambogic acid (III): Determination of the essential pharmacophore for biological activity
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Caged 4-oxa-tricyclo[4.3.1.03,7]dec-2-one structural motifs are found in Garcinia natural products that demonstrate anti-tumor activity. Gambogic acid (GA, 1), the most abundant caged Garcinia xanthones, has been reported to be a promising anti-cancer agent. To identify the essential pharmacophore for its anti-tumor activity, a series of GA analogues that address potential key structural features for biological activity were synthesized, among which compound 11a displayed comparable in vitro anti-tumor activity as GA. Mechanistic studies on 11a determined that the compound induces apoptosis as well as arrests the G2/M phase of the cell cycle in HepG2 cells. The determination of the essential part of the scaffold found in GA to maintain anti-tumor effects, and the SAR based on the caged pharmacophore are reported and will provide key information for future anti-cancer drug development studies.
- Wang, Xiaojian,Lu, Na,Yang, Qian,Gong, Dandan,Lin, Changjun,Zhang, Shenglie,Xi, Meiyang,Gao, Yuan,Wei, Libing,Guo, Qinglong,You, Qidong
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experimental part
p. 1280 - 1290
(2011/04/22)
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- Synthesis and antimicrobial evaluation of new benzofuran derivatives
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Thirteen compounds, based on benzofuran skeleton bearing aryl substituents at its C-3 position through methanone linker, were synthesized and screened for their antibacterial and antifungal activities against four bacteria Escherichia coli, Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus subtilis, and a fungus Candida albicans. Four hydrophobic benzofuran analogs were found to exhibit favorable antibacterial activities (MIC80 = 0.39-3.12 μg/mL), which were better than the control drugs.
- Jiang, Xizhen,Liu, Wenlu,Zhang, Wei,Jiang, Faqin,Gao, Zhe,Zhuang, Hao,Fu, Lei
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experimental part
p. 3526 - 3530
(2011/07/31)
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- Synthesis and in vitro protein tyrosine kinase inhibitory activity of furan-2-yl(phenyl)methanone derivatives
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A series of novel furan-2-yl(phenyl)methanone derivatives were synthesized, and their structures were established on the basis of 1H-NMR, 13C-NMR and mass spectral data. All the prepared compounds were screened for their in vitro protein tyrosine kinase inhibitory activity and several new derivatives exhibited promising activity, which, in some cases, was identical to, or even better than that of genistein, a positive reference compound. The preliminary structure-activity relationships of these compounds were investigated and are discussed.
- Zheng, Fei Lang,Ban, Shu Rong,Feng, Xiu E,Zhao, Cheng Xiao,Lin, Wenhan,Li, Qing Shan
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experimental part
p. 4897 - 4911
(2011/08/10)
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- Anti-tumoral activities of dioncoquinones B and C and related naphthoquinones gained from total synthesis or isolation from plants
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Dioncoquinones belong to a family of natural naphthoquinone products of interest due to their promising anti-tumoral and anti-infective activities. In particular, dioncoquinones A (5) and B (6) have been shown to be highly active against Leishmania major and multiple myeloma cells without any significant toxicity toward normal blood cells. Their effective concentrations against multiple myeloma cell lines were similar to those of melphalan, a well known DNA-alkylating agent used in a standard therapy against B cell lymphoma and multiple myeloma. We report on the first total synthesis of the highly oxygenated anti-tumoral agent dioncoquinone B (6) and the isolation of its new, even higher-oxygenated analogs, dioncoquinones C (7), D (8), and E (9), from cell cultures of Triphyophyllum peltatum. In addition, several derivatives of these compounds were synthesized, including dioncoquinone C (7), and a small library of naphthoquinones was created. Furthermore, the first structure-activity relationship (SAR) study on this class of compounds was conducted, showing that each of the three hydroxy groups, at C-3, C-5, and C-6, is required for improved anti-tumoral activities and decreased cytotoxicities.
- Bringmann, Gerhard,Zhang, Guoliang,Hager, Anastasia,Moos, Michael,Irmer, Andreas,Bargou, Ralf,Chatterjee, Manik
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experimental part
p. 5778 - 5789
(2012/02/01)
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- Structural modification of diketo acid portion in 1H-benzylindole derivatives HIV-1 integrase inhibitors
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Our previous studies led to discovery of a very potent benzylindoldiketo acid (CHI-1043) acting as HIV-1 integrase strand transfer inhibitor. We herein report the synthesis of new structurally different compounds in which the 1,3-diketo acid moiety has been substituted with other functionalities. The synthesized derivatives were evaluated for their activity on the IN enzyme and in MT-4 cells but only 4-[l-(4-fluorobenzyl)-4-methoxy-1H-indol-3-yl)-3-hydroxyfuran-2(5H)-one (12) was able to strongly inhibit HIV-1 probably by biotransformation into CHI-1043.
- Ferro, Stefania,De Grazia, Sara,De Luca, Laura,Barreca, Maria Letizia,Debyser, Zeger,Chimirri, Alba
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experimental part
p. 947 - 959
(2009/09/30)
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- Synthesis and investigation of a chiral enterobactin analogue based on a macrocyclic peptide scaffold
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A chiral C3-symmetric enterobactin analogue (1) has been synthesized by attachment of three 2,3-dihydroxybenzoyl units to a chiral oxazole-containing macrocyclic peptide scaffold. Complex formation kinetics and stoichiometry with various metal ions were investigated by spectrophotometric methods. In the cases of AlIII, InIII and FeIII complexes, UV absorption and CD kinetics showed nonlinearity, which results from slow conformational changes of the octahedral complexes. Virtual binding constants were determined from UV absorption data and showed selective binding of GaIII in preference to FeIII, by two orders of magnitude. CD spectroscopy revealed highly diastereoselective binding of Al III, GaIII, InIII, FeIII and Ge IV ions at room temperature, corresponding to the helical chirality opposite to that of the analogous enterobactin complexes. Ab initio calculations confirmed the energetic stabilization of the A isomers relative to the A isomers.
- Pinter, Aron,Haberhauer, Gebhard
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scheme or table
p. 11061 - 11068
(2009/11/30)
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- Concise enantioselective total syntheses of (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine and (+)-norchelidonine by a PdII-catalyzed ring-opening strategy
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New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine, and (+)-norchelidonine are described. Our rapid and convergent route to this class of natural products involved the development and application of a Pd II-catalyzed asymmetric ring-opening reaction of a mesoazabicyclic alkene with an aryl boronic acid as the key step. By screening a variety of functionalized ortho-substituted aryl boronic acids, chiral ligands and reaction conditions we were able to prepare the requisite cis-1-amino-2- aryldihydronaphthalenes in high yield and in up to 90% ee. Early attempts to complete the synthesis of (+)-homochelidonine using an N-Boc azabicyclic alkene are described in full. The successful route required a protecting group alteration followed by B ring for-mation and then stereoselective installation of the C-11 syn-hydroxy group by regioselective epoxide ring-opening using a hydride source. Ring-opening of the same epoxide intermediate with water ultimately led to the synthesis of (+)-chelamidine. The same strategy was then used to synthesize the other structurally similar B/C hexahydrobenzo[c] phenanthridine alkaloids, (+)-chelidonine, (+)-chelamidine, and (+)norchelidonine.
- Fleming, Matthew J.,McManus, Helen A.,Rudolph, Alena,Chan, Walter H.,Ruiz, Jeremy,Dockendorff, Chris,Lautens, Mark
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experimental part
p. 2112 - 2124
(2009/04/06)
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- Ortho-substituted catechol derivatives: The effect of intramolecular hydrogen-bonding pathways on chloride anion recognition
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(Chemical Equation Presented) This paper reports a series of chloride anion receptors containing two catechol head groups connected through their ortho-positions via a spacer chain. The linking group chosen to attach the spacer chain to the catechol units has a major impact on the anion-binding potential of the receptor. Linking groups that are capable of forming stable six-membered intramolecular hydrogen-bonded rings with the catechol O-H groups significantly inhibit the ability of the catechol units to hydrogen bond to chloride anions. However, where the linking groups are only capable of forming five- or seven-membered intramolecular hydrogen-bonded rings, then anion binding via hydrogen bonding through the catechol O-H groups becomes a possibility. This process is solvent dependent; the presence of competitive solvent (e.g., DMSO-d6) disrupts the intramolecular hydrogen-bonding pattern and enhances anion binding relative to simple unfunctionalized catechol. The most effective receptor is that in which the hydrogen-bonding linker (-CH 2CONH-) is most distant from the catechol units and can only form a seven-membered intramolecular hydrogen-bonded ring. In this case, the receptor, which contains two catechol units, is a more effective chloride anion binder than simple unfunctionalized catechol, demonstrating that the two head groups, in combination with the N-H groups in the linker, act cooperatively and enhance the degree of anion binding. In summary, this paper provides insight into the hydrogen-bonding patterns in orthofunctionalized catechols and the impact these have on the potential of the catechol O-H groups to hydrogen bond to a chloride anion.
- Winstanley, Keith J.,Smith, David K.
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p. 2803 - 2815
(2008/02/01)
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- Metallosupramolecular chemistry with bis(benzene-o-dithiolato) ligands
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The bis(benzene-o-dithiol) ligands H4-1, H4-2, and H4-3 react with [Ti(OC2H5)4] to give dinuclear triple-stranded helicates [Ti2L3]4- (L = 14, 2
- Kreickmann, Thorsten,Diedrich, Christian,Pape, Tania,Huynh, Han Vinh,Grimme, Stefan,Hahn, F. Ekkehardt
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p. 11808 - 11819
(2007/10/03)
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- Synthesis and biological evaluation of novel bisphosphonates with dual activities on bone in vitro
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In an effort to generate novel anti-osteoporosis agents, new bisphosphonates with various benzoyl groups on side chains have been synthesized and evaluated for activities on both bone resorption and bone formation in vitro. Several candidates showed distinct dual activities: promoting bone formation and inhibiting bone resorption.
- Xie, Yuli,Ding, Huasheng,Qian, Lihui,Yan, Xueming,Yang, Chunhao,Xie, Yuyuan
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p. 3267 - 3270
(2007/10/03)
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- An efficient acid- and metal-free one-pot synthesis of benzothiazoles from carboxylic acids
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Carboxylic acids are converted to benzothiazoles in a one-pot reaction with thionyl chloride followed by treatment with 2-aminothiophenol under acid- and catalyst-free conditions. Georg Thieme Verlag Stuttgart.
- Rudrawar, Santosh,Kondaskar, Atul,Chakraborti, Asit K.
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p. 2521 - 2526
(2007/10/03)
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- HIGHLY SELECTIVE NOVEL AMIDATION METHOD
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The present invention provides an industrial production method with a short process having a high yield of an aliphatic cyclic carboxamide having carboxyl group, which comprises reacting functional group-selectively using an inexpensive condensing agen
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Page/Page column 29-30
(2010/02/15)
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- A convenient synthesis of 4-alkoxylated isoindolin-1-ones
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A short synthesis of 4-alkoxylated isoindolin-1-ones based upon the S NAr reaction applied to phosphorylated 2-methoxybenzamides followed by alkaline cleavage of the phosphoryl auxiliary is reported.
- Moreau, Anne,Couture, Axel,Deniau, Eric,Grandclaudon, Pierre
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p. 1664 - 1670
(2007/10/03)
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- Chiral oxazoline route to enantiomerically pure biphenyls: Magnesio and copper mediated asymmetric hetero- and homo-coupling reactions
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A series of chiral biphenyls were prepared via asymmetric reactions involving chiral oxazolines. One series of chiral biphenyls was reached by the magnesium mediated coupling of aryl bromides (via their Grignard reagents) with o-methoxyaryl oxazolines. In
- Meyers,Nelson, Todd D.,Moorlag, Henk,Rawson, David J.,Meier, Anton
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p. 4459 - 4473
(2007/10/03)
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- Synthesis of 2-hydroxy-3-methylbut-3-enyl substituted coumarins and xanthones as natural products. Application of the Schenck ene reaction of singlet oxygen with ortho-prenylphenol precursors
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Application of our original photooxidation-reduction methodology to prenylated dihydroxycoumarin and trihydroxyxanthone compounds led to the corresponding ortho-(2-hydroxy-3-methylbut-3-enyl)phenol derivatives with yields ranging from 8 to 65%. In most of the reported experiments, the oxidation products distribution, after the photooxygenation step, was controlled by the competition between the large group effect and the stabilising phenolic assistance effect. We also showed that ortho-(3-hydroxy-3- methylbut-1-enyl)phenol derivatives could be considered as biogenetic precursors of 2,2-dimethylbenzopyranic structures.
- Helesbeux, Jean-Jacques,Duval, Olivier,Dartiguelongue, Caroline,Séraphin, Denis,Oger, Jean-Michel,Richomme, Pascal
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p. 2293 - 2300
(2007/10/03)
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- Synthesis of the α,β-unsaturated δ-lactones (+)-anhydrocalopin and (+)-dehydrocalopin
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During our investigations on the calopin group of mushroom metabolites, a synthesis of 3,4-disubstituted α,β-unsaturated δ-lactones has been developed. It was applied to the synthesis of optically active dehydrocalopin (2) and anhydrocalopin (3).
- Ebel, Heiner,Zeitler, Kirsten,Steglich, Wolfgang
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p. 101 - 106
(2007/10/03)
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- Synthesis of 2-(5-Bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues and their binding affinities for dopamine D2, D3, and D4 receptors
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A series of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues was prepared and their affinity for dopamine D2, D3, and D4 receptors was measured using in vitro binding assays. The results of receptor bin
- Mach, Robert H.,Huang, Yunsheng,Freeman, Rebekah A.,Wu, Li,Blair, Suwanna,Luedtke, Robert R.
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p. 225 - 233
(2007/10/03)
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- Photochromic properties of new benzoindene-fused 2H-chromenes
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The synthesis and the photochromic properties of new photochromic 6,7- and 7,8-benzoindene annellated benzopyrans are described. When compared to parent indeno-fused 2H-chromenes (2H-[1]benzopyrans), compounds 10 and 12 exhibit a significant bathochromic shift of maximum-absorption wavelength, an increase in the colorability, and similar fading rates.
- Martins, Cristina I.,Coelho, Paulo J.,Carvalho, Luis M.,Oliveira-Campos, Ana M.F.,Samat, Andre,Guglielmetti, Robert
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p. 570 - 578
(2007/10/03)
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- Iron(III) chelation: Tuning of the pH dependence by mixed ligands
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The iron(III) chelating properties of two heteropodands with 8-hydroxyquinoline and catechol binding groups were examined and compared to those of the corresponding homopodal analogues, O-TRENSOX and TRENCAMS. Like the parent homopodands, the two heteropo
- Albrecht-Gary, Anne-Marie,Blanc, Sylvie,Biaso, Frederic,Thomas, Fabrice,Baret, Paul,Gellon, Gisele,Pierre, Jean-Louis,Serratrice, Guy
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p. 2596 - 2605
(2007/10/03)
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- Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells
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Naphthyridine 7 inhibits the strand transfer of the integration process catalyzed by integrase with an IC50 of 10 nM and inhibits 95% of the spread of HIV-1 infection in cell culture at 0.39 μM. It does not exhibit cytotoxicity in cell culture
- Zhuang, Linghang,Wai, John S.,Embrey, Mark W.,Fisher, Thorsten E.,Egbertson, Melissa S.,Payne, Linda S.,Guare Jr., James P.,Vacca, Joseph P.,Hazuda, Daria J.,Felock, Peter J.,Wolfe, Abigail L.,Stillmock, Kara A.,Witmer, Marc V.,Moyer, Gregory,Schleif, William A.,Gabryelski, Lori J.,Leonard, Yvonne M.,Lynch Jr., Joseph J.,Michelson, Stuart R.,Young, Steven D.
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p. 453 - 456
(2007/10/03)
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