- Heterofunctionalized Cavitands by Macrocyclization of Sequence-Defined Foldamers
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Macrocyclic hosts have long been the workhorses of molecular recognition. Despite the widespread use of container-shaped molecules as synthetic receptors, an efficient preparation of cavitands bearing multiple functional groups has not been realized. This Letter describes a new cavitand derived from a sequence-defined oligoamide foldamer scaffold. A solid-phase synthesis approach is reported, which enables the display of multiple chemically diverse functional groups on the cavitand rim.
- Meisel, Joseph W.,Hu, Chunhua T.,Hamilton, Andrew D.
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Read Online
- ISOINDOLINE DERIVATIVES WHICH BIND TO AN ATP BINDING SITE
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The present invention relates to novel probe compounds of formulae I and II defined herein. The present invention also relates to methods of synthesising these novel probe compounds and to their use in assays and screens for determining the binding of a test molecule to the ATP-binding site of a target protein, such as, for example, the Mismatch Repair (MMR) component proteins PMS2 and MLH1, or for determining the location and/or quantity of such target proteins in a biological sample.
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Paragraph 00195-00196
(2021/07/31)
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- Optimization of pyrazolo[1,5-a]pyrimidines lead to the identification of a highly selective casein kinase 2 inhibitor
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Casein kinase 2 (CK2) is a constitutively expressed serine/threonine kinase that has a large diversity of cellular substrates. Thus, CK2 has been associated with a plethora of regulatory functions and dysregulation of CK2 has been linked to disease development in particular to cancer. The broad implications in disease pathology makes CK2 an attractive target. To date, the most advanced CK2 inhibitor is silmitasertib, which has been investigated in clinical trials for treatment of various cancers, albeit several off-targets for silmitasertib have been described. To ascertain the role of CK2 inhibition in cancer, other disease and normal physiology the development of a selective CK2 inhibitor would be highly desirable. In this study we explored the pyrazolo [1,5-a]pyrimidine hinge-binding moiety for the development of selective CK2 inhibitors. Optimization of this scaffold, which included macrocyclization, led to IC20 (31) a compound that displayed high in vitro potency for CK2 (KD = 12 nM) and exclusive selectivity for CK2. X-ray analysis revealed a canonical type-I binding mode for IC20 (31). However, the polar carboxylic acid moiety that is shared by many CK2 inhibitors including silmitasertib was required for potency but limits the cellular activity of IC20 (31) and the cellular IC50 dropped to the low micromolar range. In summary, IC20 (31) represents a highly selective and potent inhibitor of CK2, which can be used as a tool compound to study CK2 biology and potential new applications for the treatment of diseases.
- Berger, Benedict-Tilman,Celik, Ibrahim Ethem,Greco, Francesco Aleksy,Hanke, Thomas,Knapp, Stefan,Kr?mer, Andreas,Kurz, Christian Georg,Tjaden, Amelie
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- Design, synthesis, and in vitro evaluation of novel 1,3,4-oxadiazolecarbamothioate derivatives of Rivastigmine as selective inhibitors of BuChE
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Rivastigmine has been prescribed for the therapy of Alzheimer’s disease (AD) symptoms. This drug is classified in the carbamate derivative group that has dual activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). According to the structure of Rivastigmine and its performance, a new series of 5-aryl-1,3,4-oxadiazole-2-carbamothioate compounds I–XI was synthesized using structure-based drug discovery approaches. For this purpose a set of these compounds were designed with computational docking method and their interactions with amino acid residues in the active sites of AChE and BuChE checked out. The structures of synthesized compounds were established by physicochemical and spectroscopic methods. The carbamoyl moiety of Rivastigmine structure was modified to carbamothioate and the effects of 1,3,4-oxadiazole heterocycle as a pharmacophoric nucleus were investigated. The potential of the synthesized compounds I–XI was evaluated against two most known agents of AD (AChE and BuChE) to determine their IC50 values. The results of the docking showed the range of binding affinity for the best poses of ten individual conformers for any compounds (I–XI) was between ?7.81 (VI) and ?6.75 (II) kcal/mol. The results of biological experiments displayed that most synthetic compounds (I–VIII) showed moderate to excellent selective activity range against BuChE (0.51–69.44 μM). In vitro cytotoxicity evaluation of these compounds (I–XI) by MTT assay on human dermal fibroblast (HDF) cell line exhibited no activity against HDF. The compound VI [S-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl) ethyl(methyl)carbamothioate] showed the most stable binding affinity (?7.81 kcal/mol) and the lowest IC50 value (0.51 μM) in comparison with Rivastigmine with 7.72 μM and Donepezil with 5.20 μM against BuChE.
- Fallah, Akram,Mohanazadeh, Farajollah,Safavi, Maliheh
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p. 341 - 355
(2019/12/30)
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- NOVEL COMPOUND HAVING HSP90 INHIBITORY ACTIVITY OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND MEDICAL USE THEREOF
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The present invention relates to a novel compound having HSP90 inhibitory activity or a pharmaceutically acceptable salt thereof, and a medicinal use thereof, and composition comprising a dihydroxyphenyl compound or a benzamide compound, which is a novel compound having the HSP90 inhibitory activity of the present invention can effectively inhibit HSP90, and thus can be usefully used as a pharmaceutical composition for preventing or treating HSP90-mediated diseases or a health functional food for preventing or improving HSP90-mediated diseases, which selected from the group consisting of cancer diseases, degenerative neurological diseases and viral infections.
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Paragraph 0114; 0115; 0127; 0128; 0129; 0252; 0253; 0254
(2019/02/13)
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- SOLID FOAM COMPRISING MESOGENIC LIGAND-FUNCTIONALIZED NANOPARTICLES AND METHODS OF MAKING AND USING THE SAME
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Solid foam structures having multiple compartments comprising mesogenic ligand-functionalized nanoparticles are provided. Compositions that include these structures, as well as methods of making the structures are also provided. The structures, compositions and methods find use in a variety of applications, such as, photonics, luminescent coatings and multi-compartment encapsulation technologies.
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Page/Page column 56-57
(2019/05/10)
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- NIRF turn-on nanoparticles based on the tumor microenvironment for monitoring intracellular protein delivery
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A dual responsive NIRF turn-on protein delivery system incorporating an NIRF turn-on probe and protein into one single nanoparticle has been constructed. It can be taken up efficiently by A549 cells, where protein release and NIRF recovery happen simultaneously in response to low pH and excessive H2O2. This work provides a novel system for monitoring intracellular protein delivery.
- Xu, Huaibao,Wang, Yi,Pei, Zhichao,Ji, Wei,Pei, Yuxin
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supporting information
p. 14930 - 14933
(2019/12/24)
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- Design, synthesis, and biological evaluation of a series of resorcinol-based N-benzyl benzamide derivatives as potent Hsp90 inhibitors
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Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90α inhibitory activity with IC50 value of 5.3 nM and an excellent growth inhibition with GI50 value of 0.42 μM against non-small cell lung cancer cells, H1975. Compound 30f effectively reduces the expression levels of Hsp90 client proteins including Her2, EGFR, Met, Akt, and c-Raf. Consequently, compound 30f promotes substantial cleavages of PARP, Caspase 3, and Caspase 8, indicating that 30f induces cancer cell death via apoptotic pathway. Moreover, cytochrome P450 assay indicates that compound 30f has weak inhibitory effect on the activities of five major P450 isoforms (IC50 > 5 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between 30f and the substrate drugs of the five major P450 isoforms are not expected. Compound 30f also inhibits the tumor growth in a mouse xenograft model bearing subcutaneous H1975 without noticeable abnormal behavior and body weight changes. The immunostaining and western immunoblot analysis of EGFR, Met, Akt in xenograft tissue sections of tumor further demonstrate a good agreement with the in vitro results.
- Park, Sun You,Oh, Yong Jin,Lho, Yunmee,Jeong, Ju Hui,Liu, Kwang-Hyeon,Song, Jaeyoung,Kim, Soong-Hyun,Ha, Eunyoung,Seo, Young Ho
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p. 390 - 401
(2017/12/07)
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- Identification of N-Hydroxycinnamamide analogues and their bio-evaluation against breast cancer cell lines
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The present study demonstrates the identification of N-hydroxycinnamamide derivatives and their anticancer potential against human triple-negative breast cancer cell line MDA-MB?231, MCF-7 and non-malignant origin cell line, HEK-293 (human embryonic kidney). MTT assay was studied with HEK-293 cell line. Anticancer potential of the N-hydroxycinnamamide derivatives were compared with marked drug Tamoxifen through in vitro study. The compound numbers 3b and 3h exhibit most potent activity against antagonistic breast cancer cells (MDA-MB-231) with IC50 13μM and 5μM respectively. Compound 3h promotes DNA fragmentation and induction of apoptosis. Furthermore, loss of mitochondrial membrane potential induced by compound 3h. The major mechanism of compound 3h for anti-breast cancer activity was probably initiation of reactive oxygen species (ROS) in cancer cells thereby persuading apoptotic cell deaths in cancer cells.
- Shukla, Akhilesh Kumar,Hamidullah,Shrivash, Manoj Kumar,Tripathi, Vishwa Deepak,Konwar, Rituraj,Pandey, Jyoti
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p. 475 - 483
(2018/08/21)
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- Synergistic Photo-Copper-Catalyzed Hydroxylation of (Hetero)aryl Halides with Molecular Oxygen
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Photoredox-mediated copper-catalyzed hydroxylation of (hetero)aryl halides (including chlorides, bromides, and iodides) with O2 at room temperature has been developed. Preliminary mechanistic studies indicate no arylcopper intermediate and that aryl radicals are involved in this procedure. 18O-labeling experiments confirm the hydroxyl oxygen atom originated from molecular oxygen.
- Zhang, Xin,Wu, Ge,Gao, Wenxia,Ding, Jinchang,Huang, Xiaobo,Liu, Miaochang,Wu, Huayue
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supporting information
p. 708 - 711
(2018/02/09)
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- Study of new synthesized ferrocenyl ionic liquids in oxidative esterification reaction
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In this work, novel ferrocene-based ionic liquids, 1-(ferrocenylbutyl)-4-(3-methylimidazolium) Azide and 1-(ferrocenylbutyl)-4-(3-methylimidazolium) Tetrafluoroborate, were synthesized and utilized in the oxidation esterification reaction of aldehydes in the present of different reagents such as NaN3, (K2CO3 and NCS), (KI and KCN), (I2 and K2CO3), (KMnO4). The results were compared with that of [BMIM][X] (X?Cl, BF4) under the same conditions. As expected, ferrocene-based ionic liquids showed better results; It seems, iron nuclear may play a similar role such as iron catalysts in these novel ionic liquids and can facilitated the oxidation esterification reaction with improve the yield and decrease the reaction time.
- Teimuri-Mofrad, Reza,Rahimpour, Keshvar,Rezaei, Hannaneh,Valizadeh, Hassan,Aghaiepour, Alireza
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p. 1425 - 1435
(2018/04/05)
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- Novel Compound and Anti-viral Composition Comprising the Same
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The present invention relates to a pharmaceutical composition and a feed additive, comprising a compound represented by chemical formula 2, a compound represented by chemical formula 1 or chemical formula 2, or a pharmaceutically acceptable salt thereof as an effective component. Specifically, compositions comprising the compound of the present invention as an effective component are safe to normal cells due to having no cytotoxicity, while effectively suppressing proliferation and transmission of disease-causing virus including porcine respiratory reproductive syndrome virus, and thus may be used as an agent for preventing or treating viral diseases.COPYRIGHT KIPO 2017
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Paragraph 0046; 0048; 0050-0052
(2018/02/21)
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- Natural product-inspired rational design, synthesis and biological evaluation of 2,3-dihydropyrano[2,3-f]chromen-4(8H)-one based hybrids as potential mitochondrial apoptosis inducers
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Synthesis of novel pyranochromanone amide hybrids, by combining pyranochromanone pharmacophore and privileged scaffolds such as 2-amino-1,3,4-thiadiaole/2-aminothiazole/aminopyridine/aminonaphthalene and anti-cancer evaluation of a series led us to discover a series of new chemical entities (NCEs) showing broad spectrum of anti-cancer activity against three different human cancer cell lines (MCF-7, A549 and HeLa), at IC50values ranging from 14.3 to 97.8?μM. Among them, some compounds such as 15b, 15d, 20a and 20b displayed excellent activity against breast cancer cell line MCF-7. Detailed biological studies such as AO/EB dual staining, Hoechst 33342 staining, FACS analysis of mitochondrial membrane potential (Δψm) using JC-1 dye and DNA fragmentation confirmed the apoptosis induced by the hybrids. Gene expression studies by Real time RT-PCR has shown that these compounds are efficient regulator of anti-apoptotic gene Bcl-2. Western blot analysis also revealed that these compounds persuade apoptosis through intrinsic pathway by up-regulating the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl-2. Molecular docking studies reveal that compounds 15b and 20b binds efficiently with Bcl-2 promoter G-quadruplex.
- Sakthivel, Palaniappan,Ilangovan, Andivelu,Kaushik, Mahabir Prasad
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p. 302 - 318
(2016/07/11)
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- Targeting the entry region of Hsp90's ATP binding pocket with a novel 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl amide
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The molecular chaperone Hsp90 plays an important role in cancer cell survival and proliferation by regulating the maturation and stabilization of numerous oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 has emerged as an attractive therapeutic target for cancer treatment. In this study, the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors are described. Among the synthetic compounds, 6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl amide 19 exhibits a remarkable binding affinity to the N-terminus of Hsp90 in a fluorescence polarization (FP) binding assay (IC50= 50.3 nM). Furthermore, it effectively inhibits the proliferation of H1975 non-small cell lung cancer (NSCLC) and Skbr3 breast cancer cell lines with GI50values of 0.31 μM and 0.11 μM, respectively. Compound 19 induces the degradation of the Hsp90 client proteins including EGFR, Her2, Met, c-Raf, and Akt, and consequently promotes apoptotic cancer cell death. Compound 19 also inhibits the growth of H1975 xenografts in NOD-scid IL2R gammanullmice without any apparent body-weight loss. The immunohistologic evaluation indicates that compound 19 decreases the expression of Akt in xenograft tumor tissue via an inhibition of the Hsp90 chaperon function. Additionally, the cytochrome P450 assay indicates that compound 19 has no effect on the activities of five major P450 isoforms (IC50> 50 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between compound 19 and the substrate drugs of the five major P450 isoforms are not expected. Overall, compound 19 represents a new class of Hsp90 inhibitor with its 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl-amide structure, and it has the therapeutic potential to overcome drug resistance in cancer chemotherapy.
- Jeong, Ju Hui,Oh, Yong Jin,Lho, Yunmee,Park, Sun You,Liu, Kwang-Hyeon,Ha, Eunyoung,Seo, Young Ho
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p. 1069 - 1080
(2016/11/09)
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- New thienopyridine compound having inhibitory activity on Hsp90 and medical use thereof
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The present invention relates to a novel thienopyridine compound having Hsp90 inhibitory activities, and relates to medical uses thereof. According to the present invention, the thienopyridine compound has excellent inhibitory effects of Hsp90, and induces the degradation of Hsp90 client protein, which generates cancer diseases or neurodegenerative diseases through the inhibition of Hsp90, thereby being efficiently used as a health food or a drug for treating or preventing Hsp90-mediated diseases such as cancer diseases or neurodegenerative diseases.COPYRIGHT KIPO 2016
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Paragraph 0043-0049
(2017/04/12)
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- THREE-DIMENSIONAL STRUCTURES OF MESOGENIC LIGAND-FUNCTIONALIZED NANOPARTICLES AND METHODS OF MAKING AND USING THE SAME
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Three-dimensional structures of stably associated mesogenic ligand-functionalized nanoparticles are provided. Compositions that include these structures, as well as methods of making the structures are also provided. The structures, compositions and methods find use in a variety of applications, such as light emitting devices (e.g., video displays, lights, etc.), inks, photonics and encapsulation technologies.
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Page/Page column 40-41
(2016/07/27)
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- An efficient one-pot oxidative esterification of aldehydes to carboxylic esters using B(C6F5)3-TBHP
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A simple and efficient protocol for oxidative esterification of diverse aldehydes with alcohols was accomplished with tert-butyl hydroperoxide and 1 mol % of tris(pentafluorophenyl)borane [B(C6F5)3] to generate the corresponding esters in good to excellent yields. The present protocol represents compatibility with wide range of functional groups as well as exceptional tolerance toward acid labile protecting groups such as TBDPS, TBDMS, acetonide, and Boc.
- Guggilapu, Sravanthi Devi,Prajapti, Santosh Kumar,Babu, Bathini Nagendra
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supporting information
p. 889 - 892
(2015/02/05)
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- Synthesis and evaluation of salicylanilide derivatives as potential epidermal growth factor receptor inhibitors
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Two series of novel salicylanilide were synthesized as potential epidermal growth factor receptor (EGFR) inhibitors. The enzyme inhibitory activity against EGFR of all compounds was carried out, and their antiproliferative activities against the A549 and A431 cell lines were also evaluated. Of the compounds studied, majority of them exhibited high antiproliferative activities compared with gefitinib; especially, 12a and 12b exhibited stronger inhibitory activity against EGFR with IC50 values of 10.4 ± 2.25 and 15.4 ± 2.33 nM, respectively, which were comparable to the positive control of gefitinib (IC50 = 12.1 ± 2.21 nM). Compound 12b also showed outstanding inhibitory activity against A431 and A549 cell lines with the IC50 values of 0.42 ± 0.43 μM and 0.57 ± 0.43 μM, which was better than the positive controls. In the molecular modeling study, compound 12b was bound into the active pocket of EGFR with two hydrogen bond and with minimum binding free energy ΔGb = -25.1125 kcal/mol. The result also suggested that compound 12b could bind the EGFR kinase well.
- Hu, Minhua,Ye, Wenfeng,Li, Jiaming,Zhong, Guochen,He, Guangwei,Xu, Qinlong,Zhang, Yanchun
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p. 280 - 289
(2015/03/04)
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- Synthesis of the 2-methylene analogue of the HRV 3C protease inhibitor thysanone (2-carbathysanone)
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The Human Rhinovirus (HRV) is the major aetiological agent for the common cold, for which only symptomatic treatment is available. HRV maturation and replication is entirely dependent on the activity of a virally encoded 3C protease that represents an attractive target for the development of therapeutics to treat the common cold. Herein we report the synthesis and biological evaluation of the 2-methylene analogue of the HRV 3C protease inhibitor (-)-thysanone (1) namely 2-carbathysanone (2), in an attempt to decipher the structural features in the natural product that are responsible for the 3C protease activity. 2-Carbathysanone (2) (and related analogues (±)-cis-23, (±)-cis-30, (±)-31) did not inhibit HRV 3C protease, indicating that the lactol functionality present in (-)-thysanone (1) is a critical structural feature required for inhibition.
- Schuenemann, Katrin,Furkert, Daniel P.,Choi, Eun Cho,Connelly, Stephen,Fraser, John D.,Sperry, Jonathan,Brimble, Margaret A.
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supporting information
p. 905 - 912
(2014/02/14)
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- Physiological activity of Chinese Lichen (Gyrophora esculenta) component, methyl 2,4-dihydroxy-6-methylbenzoate and the related compounds
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It was confirmed that there was a higher expression of antioxidant potential in methyl 2,4-dihydroxy-6-methylbenzoate (orsellinic acid methyl ester) (2), which was isolated from methanol extract oil of Chinese lichen Gyrophora esculenta rather than from commercialized ascorbic acid. Taking this into account, 4 types of compounds-(4-7) which are known to be related to compound (2)-have been synthesized by using 2,4-dihydroxy benzoic acid (3) as starting material. After that, some physiological activity tests on these compounds have been conducted in the following aspects: antioxidant potential, cytotoxicity, cytokine suppressant effect and histamine liberation inhibition and the effects have been evaluated, respectively. The result shows that (2) and methyl 2,4-dihydroxybenzoate (4) showed high radical expression in both antioxidant potential and histamine liberation inhibition. It was also found that none of these compounds expresses cytotoxicity.
- Wu, Shuhsien,Zhao, Zhendong,Okada, Yoshiharu,Watanabe, Yoshiyuki,Takahata, Toshiyuki,Inoue, Toshio,Otsubo, Eiji,Wang, Jing,Lu, Yanju,Nomura, Masato
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p. 702 - 708
(2014/06/09)
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- MACROCYCLIC FLT3 KINASE INHIBITORS
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The present invention relates to macrocylic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of FLT3 (FMS-Related Tyrosine kinase 3). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the treatment of cell proliferative disorders, such as cancer.
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Paragraph 0724-0726
(2014/10/16)
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- Zearalenone mimics: Synthesis of (E)-6-(1-Alkenyl)-substituted β-resorcylic acid esters
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Two versatile strategies for the synthesis of mimics of the Fusarium mycotoxin zearalenone (1) have been developed. Optimized preparation of (E)-6-(1-alkenyl) substituted β-resorcylic acid esters was realized via ortho-directed lithiation of variable substrates combined with allylation/isomerization or via formylation/Schlosser-Wittig olefination using different protective group patterns. Spontaneous decarboxylation of (E)-6-(1-alkenyl) substituted β-resorcylic acids indicated the influence of this substituent on the chemical behavior of these compounds. These mimics were already used for the development of optimized standard protocols for the synthesis of phase II metabolites of ZEN (glucosides, glucuronides), and further applications (i.e., sulfate conjugates) are still under investigation. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
- Mikula, Hannes,Hametner, Christian,Froehlich, Johannes
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p. 1939 - 1946
(2013/05/22)
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- Mono-/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV
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Using hydroxy-/dihydroxybenzoic acids as leads, a series of methyl, ethyl and iso-propyl esters of 4-hydroxy-benzoic acid, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-dihydroxybenzoic acids and of coumaric acid, were obtained and investigated for the inhibition of six mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, the cytosolic CA I, II and VII, and the transmembrane CA IX, XII and XIV, many of which are established drug targets. Other compounds incorporating phenol/catechol moieties were obtained from dopamine by reaction with fluorescein isothiocyanate or with 2,4,6-trisubstituted pyrylium salts. Some aminophenols were also derivatized in a similar manner, by using pyrylium salts. Many of these compounds showed increased inhibitory action compared to the lead compounds from which they were obtained, with efficacy in the submicromolar range against most investigated CA isoforms. As phenols are a class of less investigated CA inhibitors (CAIs) compared to the sulfonamides, and their mechanism of inhibition is less well understood, compounds of the type designed here may be helpful in gaining more insights into these phenomena.
- Carta, Fabrizio,Vullo, Daniela,Maresca, Alfonso,Scozzafava, Andrea,Supuran, Claudiu T.
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supporting information
p. 1564 - 1569
(2013/04/10)
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- MACROCYCLIC FLT3 KINASE INHIBITORS
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The present invention relates to macrocylic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of FLT3 (FMS-Related Tyrosine kinase 3). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the treatment of cell proliferative disorders, such as cancer.
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Page/Page column 55
(2013/04/13)
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- Factors affecting orthogonality in the deprotection of 2,4-di-protected aromatic ethers employing solid-supported acids
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Selective deprotection of aromatic ethers bearing two protecting groups on the same aromatic ring by solid-supported acids (Amberlyst-15 and PTS-Si) was systematically investigated. ortho-Directing protonation by the carbonyl group as well as carbocation stability and quenching are the important determining factors for the orthogonal deprotection process. Stablilized carbocations (e.g., those from the MOM and PMB groups) could be removed with high selectivity.
- Tangdenpaisal, Kassrin,Sualek, Supannee,Ruchirawat, Somsak,Ploypradith, Poonsakdi
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experimental part
p. 4316 - 4325
(2009/10/17)
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- Liquid crystalline and nonlinear optical properties of bent-shaped compounds derived from 3,4′-biphenylene
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The synthesis of different bent-core molecules derived from 3,4′-biphenylene bearing azo, azoxy, imine or ester linkages in their lateral structures is reported. Structure-activity relationships for their liquid crystalline behaviour are discussed. SmCP, USmCP and Colob mesophases are found depending on the type and number of these connecting units. The sequence ester ≈ azoxy > imine > azo can be proposed for the mesophase range, with significant differences observed in terms of mesopahase stabilization. SHG studies on these compounds give nonlinear coefficients in the range of 1-8 pm V-1. The molecular origin for these values is analyzed semi-quantitatively. It was concluded that the SHG performance of bent-core mesogens in general can still be increased substantially. An approach to improve the properties of these materials is briefly outlined. The Royal Society of Chemistry 2007.
- Pintre, Inmaculada C.,Gimeno, Nelida,Serrano, Jose Luis,Ros, M. Blanca,Alonso, Ibon,Folcia, Cesar L.,Ortega, Josu,Etxebarria, Jesus
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p. 2219 - 2227
(2008/02/11)
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- Solid-supported acids as mild and versatile reagents for the deprotection of aromatic ethers
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Equation Presented p-Toluene sulfonic acid (p-TsOH) immobilized either on polystyrene (PS) or silica (Si) was found to be effective in cleaving aromatic ethers containing isopropyl, tert-butyl, allyl, and benzyl groups, as well as mono-, di-, and trimethoxylated benzyl groups, in moderate to excellent yields (54-95%). These protecting groups could be selectively deprotected when they were simultaneously present on the same or different aromatic rings in a substrate.
- Ploypradith, Poonsakdi,Cheryklin, Pannarin,Niyomtham, Nattisa,Bertoni, Daniel R.,Ruchirawat, Somsak
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p. 2637 - 2640
(2008/02/08)
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- A mild and selective method for the hydrolysis of esters with trimethyltin hydroxide
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Mild, selective, and efficient: A new method that involves the use of trimethyltin hydroxide for the hydrolysis of specific ester groups allows chemists to steer clear of unwanted elimination reactions and epimerizations. For example, the conversion of ester 1 into carboxylic acid 2 takes place under mild conditions, with nearly complete retention of stereochemical integrity. 1,2-DCE = 1,2-dichloroethane.
- Nicolaou,Estrada, Anthony A.,Zak, Mark,Lee, Sang Hyup,Safina, Brian S.
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p. 1378 - 1382
(2007/10/03)
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- A simple and effective method for chemoselective esterification of phenolic acids
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A new method for efficient and chemoselective esterification of phenolic acids in KHCO3/alkyl halide/DMF reaction system is described, by which a series of phenoic acid esters were obtained in excellent yields.
- Guo, Wei,Li, Junfei,Fan, Ningjuan,Wu, Weiwei,Zhou, Peiwen,Xia, Chizhong
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p. 145 - 152
(2007/10/03)
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- Hydroxy-methoxybenzoic methyl esters: Synthesis and antifeedant activity on the pine weevil, Hylobius abietis
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The pine weevil Hylobius abietis (L.) (Coleoptera: Curculionidae) feeds on the bark of coniferous seedlings and is the economically most important forestry restocking pest in large parts of Europe. Substances with an antifeedant effect may offer an environmentally friendly alternative to insecticides for the protection of planted seedlings. Bioassays were performed on commercial and synthetic methyl hydroxy-methoxybenzoates in order to determine their possible antifeedant activity. Two methyl hydroxy-methoxybenzoates were synthesized by esterification and mono-O-methylation of two dihydroxybenzoic acids. A regioselective protection-deprotection strategy was used in the synthetic pathway of the other non-commercial esters, esterification and selective pivaloylation of the less-hindered hydroxyl group of other commercial dihydroxybenzoic acids gave diester intermediates, which then were O-methylated before methanolysis of the pivaloyl group which yielded the desired non-commercial methyl hydroxy-methoxybenzoates. The five synthesized methyl hydroxy-methoxybenzoic esters were complemented with commercial samples of the five other isomers of methyl hydroxy-methoxybenzoate and spectrometric data were collected for the complete set of isomers. All ten isomers were tested for their antifeedant effect on the pine weevil. The effect varied considerably among the hydroxy-methoxybenzoic esters. Methyl 2-hydroxy-3-methoxybenzoate showed the highest effect and may thus be a candidate for practical use in pine weevil pest management.
- Legrand, Sacha,Nordlander, G?ran,Nordenhem, Henrik,Borg-Karlson, Anna-Karin,Unelius, C. Rikard
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p. 829 - 835
(2007/10/03)
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- Hydrolysis of acetals in water under hydrothermal conditions
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A simple method for the hydrolysis of acetals and ketals was accomplished in neutral water or aqueous media by hydrothermal treatment without using acidic reagents. The deacetalization reaction was effectively accelerated in the presence of calcium chloride. Because no acidic catalysts were employed, neutralization of the reaction mixture was not necessary after the reaction. This sequence was successfully applied to the hydrolysis of chitosan, a biodegradable polyaminosaccharide.
- Sato, Kimihiko,Kishimoto, Tsutomu,Morimoto, Minoru,Saimoto, Hiroyuki,Shigemasa, Yoshihiro
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p. 8623 - 8625
(2007/10/03)
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- Studies on synthesis of 3(2H)-benzofuranone derivatives
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Two known methods were used for synthesis of 2,6-disubstituted-3(2H)-benzofuranone derivatives. It was found that depending on the reaction conditions, degradation products or the products of oxidation were isolated. This latter reaction became the main process when the ring closure was performed starting from methoxy- or 2-propoxy-desoxybenzoin and diethyl bromo-(or chloro-)-malonate to give D,L- and meso-dimers of the substituted 3(2H)-benzofuranones.
- Bokotey, Sandor,Koevari-Radkai, Maria,Podanyi, Benjamin,Ritz, Imola,Hanusz, Miklos,Batori, Sandor
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p. 2325 - 2343
(2007/10/03)
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- The first total synthesis of (±)-napyradiomycin A1
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(±)-Napyradiomycin A1 has been stereoselectively synthesized through a tandem Michael-Dieckmann type reaction and the introduction of a side chain and two chlorine atoms onto the pyranonaphthoquinone core.
- Tatsuta, Kuniaki,Tanaka, Yoshiki,Kojima, Masazumi,Ikegami, Hiroshi
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- Inhibitors of protein isoprenyl transferases
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Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2—, and (i) heterocyclic-L2—; R2 is selected from (a) (b) —C(O)NH—CH(R14)—C(O)OR15, (c) (d) —C(O)NH—CH(R14)—C(O)NHSO2R16 (e) —C(O)NH—CH(R14)-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R14)—C(O)NR17R18; R3 is heterocyclic, aryl, substituted or unsubstituted cycloalkyl; R4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1 is absent or is selected from (a) —L4—N(R5)—L5—, (b) —L4—O—L5—, (c) —L4—S(O)n—L5— (d) —L4-L6—C(W)—N(R5)—L5—, (e) —L4-L6—S(O)m—N(R5)—L5—, (f) —L4—N(R5)—C(W)—L7-L5—, (g) —L4—N(R5)—S(O)p—L7—L5—, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, and (j) optionally substituted alkynylene are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.
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- Novel chemoselective de-esterification of esters of polyacetoxy aromatic acids by lipases
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Candida cylindracea lipase (CCL) and porcine pancreatic lipase (PPL) have been used for deacetylation of peracetates of methyl and ethyl esters of six different polyphenolic acids in organic solvents. Exclusive de-esterification of the ester groups derived from the phenolic hydroxy and aliphatic acid over the ester group of the aromatic acid and aliphatic alcohol has been achieved affording the corresponding esters of phenolic acids in as high yields as 90-97%. The results have been corroborated with the mechanism of lipase action.
- Parmar, Virinder S.,Kumar, Ajay,Bicht, Kirpal S.,Mukherjee, Shubhasish,Prasad, Ashok K.,Sharma, Sunil K.,Wengel, Jesper,Olsen, Carl E.
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p. 2163 - 2176
(2007/10/03)
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- Structure-based design of parasitic protease inhibitors
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To streamline the preclinical phase of pharmaceutical development, we have explored the utility of structural data on the molecular target and synergy between computational and medicinal chemistry. We have concentrated on parasitic infectious diseases with a particular emphasis on the development of specific noncovalent inhibitors of proteases that play a key role in the parasites' life cycles. Frequently, the structure of the enzyme target of pharmaceutical interest is not available. In this setting we have modeled the structure of the relevant enzyme by virtue of its sequence similarity with proteins of known structure. For example, we have constructed a homology-based model of falcipain, the trophozoite cysteine protease, and used the computational ligand identification algorithm DOCK to identify in compound enzyme inhibitors including oxalic bis(2-hydroxy-1-naphthylmethylene)hydrazide (1) [Ring, C.S.; Sun, E.; McKerow, J.K.; Lee, G.; Rosenthal, P.J., Kuntz, I.D.; Cohen, F.E., Proc. Natl Acad. Sci. U.S.A. 1993, 90, 3583]. Compound 1 inhibits falcipain (IC50 6 μM) and the organism in vitro as judged by hypoxanthine. uptake (IC50 7 μM). Following this lead, to date, we have identified potent bis arylacylhydrazides (IC50 150 nM) and chalcones (IC50 200 nM) that are active against both chloroquine-sensitive and chloroquine-resistant strains of malaria. In a second example, cruzain, the crystallographically determined structure of a papain-like cysteine protease, resolved to 2.35 A, was available. Aided by DOCK, we have identified a family of bis-arylacylhydrazides that are potent inhibitors of cruzain (IC50 600 μM). These compounds represent useful leads for pharmaceutical development over strict enzyme inhibition criteria in a structure-based design program.
- Li, Rongshi,Chen, Xiaowu,Gong, Baoqing,Selzer, Paul M.,Li, Zhe,Davidson, Eugene,Kurzban, Gary,Miller, Robert E.,Nuzum, Edwin O.,McKerrow, James H.,Fletterick, Robert J.,Gillmor, Sarah A.,Craik, Charles S.,Kuntz, Irwin D.,Cohen, Fred E.,Kenyon, George L.
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p. 1421 - 1427
(2007/10/03)
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- Influence of lateral alkoxy substitution on mesomorphic properties of copper complexes
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Coordination complexes between copper and some lateral alkoxy chain-substituted N-(4-(4'-alkoxybenzoyloxy)salicylidene)-4-n-butylaniline have been synthesized.The lateral chain was introduced on the outer ring bearing the ester function.In the case of a 3,4-disubstitution, the mesomorphic behavior is related to the number of carbons in the terminal chain.If this is too small, the mesomorphic properties of the complexes disappear.In contrast, copper complexes are liquid crystalline and show more ordered phases by comparison with the free ligand.In case of a 2,4-disubstitution, the phases are nematic and the clearing temperatures are near room temperature, but the observed phases are essentially monotropic for the ligands, as well as for the complexes.Keywords: nematic / copper complex / lateral substitution / Schiff base
- Berdague, Philippe,Perez, Felix,Courtieu, Jacques,Bayle, Jean-Pierre
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p. 335 - 343
(2007/10/02)
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- PRODUCTION, PROPERTIES, AND MASS-SPECTROMETRIC INVESTIGATION OF THE DABSYLATES OF PHENOLS
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The reaction of monohydric and dihydric phenols and phloroglucinol with 4'-(dimethylamino)azobenzene-4-sulfonyl chloride (dabsyl chloride) leads to the respective mono-, di-, and triabsylates of the phenols.Their structures were confirmed by IR, PMR, and mass spectrometry.A scheme is proposed for the dissociation of the phenol dabsylates under electron impact.The transformation of the phenols into the derivatives by reaction with dabsyl chloride is recommended for highly sensitive and selective determination of the individual phenols by high-performance liquid chromat ography with spectrophotometric detection and for spectrophotometric determination of total phenol content.
- Dem'yanov, P. I.,Khimenes, M. P.,Bogdashkina, V. I.,Petrosyan, V. S.
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p. 767 - 777
(2007/10/02)
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- Nematocidal principles in 'oakmoss absolute' and nematocidal activity of 2,4-dihydroxybenzoates
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Nematocidal principles obtained from oakmoss absolute were identified as methyl 2,4-dihydroxy-3,6-dimethylbenzoate (2), ethyl 3-formyl-2,4-dihydroxy-6-methylbenzoate (4), and ethyl 5-chloro-3-formyl-2,4-dihydroxy-6-methylbenzoate (7). In relation to their structures, the nematocidal activity of 2,4-dihydroxybenzoates of methyl to tetradecyl was tested and the strongest activity was found in the octyl ester (minimal lethal concentration=13 μM).
- Ahad,Goto,Kiuchi,Tsuda,Kondo,Sato
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p. 1043 - 1046
(2007/10/02)
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- Safety-catch anchoring linkage for synthesis of peptide amides by Boc/Fmoc strategy
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2-Methoxy-4,4'-bis(methylthio)benhydrylamine (10) and the corresponding disulfoxide were prepared and tested as a model amide protecting groups for their stability toward acidic conditions. Subsequently, the novel 4-[4,4'-bis(methylsulfinyl)-2-oxy-(9-fluorenylmethyloxycarbonyl) benzhydrylamino]butanoic acid (SCAL) handle (9) has been prepared and applied to solid-phase peptide synthesis of C-terminal peptide amide using both 9-fluorenylmethyloxycarbonyl (Fmoc) and tert-butyloxycarbonyl (Boc) groups for N(α)-amino protection.
- Patek,Lebl
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p. 3891 - 3894
(2007/10/02)
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- STRUCTURE OF MULBERROFURAN M, A NOVEL ARYLBENZOFURAN DERIVATIVE FROM THE CULTIVATED MULBERRY TREE (MORUS ALBA L.)
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A novel arylbenzofuran derivative named mulberrofuran M (1) was isolated from an acetone extract of the reddish violet powder obtained from the surface of the root bark of cultivated mulberry tree (Ichinose, a cultivated variety of Morus Alba L.).The structure was shown to be 1 on the basis of spectral evidence.
- Hano, Yoshio,Hirakura, Kazuhiro,Someya, Takehisa,Nomura, Taro
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p. 1251 - 1255
(2007/10/02)
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- Chemistry of 1,3,5-Tris(trimethylsiloxy)-1-methoxyhexa-1,3,5-triene, a β-Tricarbonyl Trianion Equivalent
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The title compound has been synthesized and its chemistry studied.Condensation with orthoesters, acid chlorides, or imidazolides gave aromatic compounds in a 5C + 1C condensation.A formal synthesis of lasiodiplodin has been completed.
- Chan, T. H.,Stoessel, D.
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p. 2423 - 2428
(2007/10/02)
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- Chemoselective Methylation of Caboxylic Acids using DBU and Iodomethane
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Chemoselective methylation of carboxylic acid groups in presence of alcoholic or phenolic hydroxy groups or another carboxylic acid group can be accomplished in high yields using DBU and iodomethane.
- Mal, Dipakranjan
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p. 331 - 336
(2007/10/02)
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- An Investigation into the Regioselectivity of the Acid Catalysed Claisen Rearrangement of Methyl 4- and 5-Allyloxy-2-hydroxybenzoate and Derivatives
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The observed products from the acid catalysed Claisen rearrangement of the methyl esters (1c-g) indicate that, unlike the thermal reaction, regiochemical control is independent of internal hydrogen bonding.
- Harwood, Laurence M.
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p. 530 - 532
(2007/10/02)
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