- 3-(5-METHOXY-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE DERIVATIVES AND USES THEREOF
-
The present disclosure relates to compounds of formula (I') and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.
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Page/Page column 317
(2021/06/26)
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- Highly selective reductive catalytic fractionation at atmospheric pressure without hydrogen
-
Reductive catalytic fractionation (RCF) is an efficient and selective way to produce phenolic monomers from lignin. However, this strategy is difficult to scale up due to its high operating pressure. In this work, we investigated RCF reaction at or near atmospheric pressure and without the use of hydrogen. The atmospheric RCF (ARCF) was conducted in acidified ethylene glycol in glass vessels at 185-195 °C catalyzed by 5% Ru/C. The products mainly include propylguaiacol and propylsyringyl (up to 95.6% among the lignin monomers) and do not contain propanolguaiacol, propanolsyringyl, or H monomers. Although the total yield of lignin monomers in ARCF is about one-quarter less than that of RCF, the operation of ARCF is much easier, milder, safer, and cheaper due to the atmospheric condition and the feasibility of the semi-continuous operation.
- Ren, Tianyu,You, Shengping,Zhang, Zhaofeng,Wang, Yuefei,Qi, Wei,Su, Rongxin,He, Zhimin
-
supporting information
p. 1648 - 1657
(2021/03/09)
-
- 4-Acyl Pyrrole Capped HDAC Inhibitors: A New Scaffold for Hybrid Inhibitors of BET Proteins and Histone Deacetylases as Antileukemia Drug Leads
-
Multitarget drugs are an emerging alternative to combination therapies. In three iterative cycles of design, synthesis, and biological evaluation, we developed a novel type of potent hybrid inhibitors of bromodomain, and extra-terminal (BET) proteins and histone deacetylases (HDACs) based on the BET inhibitor XD14 and well-established HDAC inhibitors. The most promising new hybrids, 49 and 61, displayed submicromolar inhibitory activity against HDAC1-3 and 6, and BRD4(1), and possess potent antileukemia activity. 49 induced apoptosis more effectively than the combination of ricolinostat and birabresib (1:1). The most balanced dual inhibitor, 61, induced significantly more apoptosis than the related control compounds 62 (no BRD4(1) affinity) and 63 (no HDAC inhibition) as well as the 1:1 combination of both. Additionally, 61 was well tolerated in an in vivo zebrafish toxicity model. Overall, our data suggest an advantage of dual HDAC/BET inhibitors over the combination of two single targeted compounds.
- Ahlert, Heinz,Bhatia, Sanil,Borkhardt, Arndt,Breit, Bernhard,Gunther, Stefan,Hansen, Finn K.,Hugle, Martin,Kraft, Fabian B.,Mishra, Pankaj,Schaker-Hubner, Linda,Schliehe-Diecks, Julian,Scholer, Andrea,Warstat, Robin
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p. 14620 - 14646
(2021/10/20)
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- Nematicidal activity of benzyloxyalkanols against pine wood nematode
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Pine wilt disease (PWD) is caused by the pine wood nematode (PWN; Bursaphelenchus xylophilus) and causes severe environmental damage to global pine forest ecosystems. The current strategies used to control PWN are mainly chemical treatments. However, the continuous use of these reagents could result in the development of pesticide-resistant nematodes. Therefore, the present study was undertaken to find potential alternatives to the currently used PWN control agents abamectin and emamectin. Benzyloxyalkanols (BzOROH; R = C2–C9 ) were synthesized and the nematicidal activity of the synthetic compounds was investigated. Enzymatic inhibitory assays (acetylcholinesterase (AChE) and glutathione S-transferase (GST)) were performed with BzOC8OH and BzOC9OH to understand their mode of action. The benzyloxyalkanols showed higher nematicidal activity than did benzyl alcohol. Among the tested BzOROHs, BzC8OH and BzC9OH showed the strongest nematicidal activity. The LD50 values of BzC8OH and BzC9OH were 246.1 and 158.0 ppm, respectively. No enzyme inhibitory activity was observed for BzC8OH and BzC9OH. The results suggested that benzyloxyalcohols could be an alternative nematicidal agent.
- Kim, Junheon,Lee, Su Jin,Park, Joon Oh,Yoon, Kyungjae Andrew
-
-
- Composition for controlling pine wood nematode containing benzyloxyalcohol
-
The present invention relates to a composition for controlling pine nematode comprising a benzyloxyalcohol compound and a method for controlling pine nematode using the same.
- -
-
Paragraph 0055-0056
(2021/06/15)
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- Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma
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Traditional EZH2 inhibitors are developed to suppress the enzymatic methylation activity, and they may have therapeutic limitations due to the nonenzymatic functions of EZH2 in cancer development. Here, we report proteolysis-target chimera (PROTAC)-based EZH2 degraders to target the whole EZH2 in lymphoma. Two series of EZH2 degraders were designed and synthesized to hijack E3 ligase systems containing either von Hippel-Lindau (VHL) or cereblon (CRBN), and some VHL-based compounds were able to mediate EZH2 degradation. Two best degraders, YM181 and YM281, induced robust cell viability inhibition in diffuse large B-cell lymphoma (DLBCL) and other subtypes of lymphomas, outperforming a clinically used EZH2 inhibitor EPZ6438 (tazemetostat) that was only effective against DLBCL. The EZH2 degraders displayed promising antitumor activities in lymphoma xenografts and patient-derived primary lymphoma cells. Our study demonstrates that EZH2 degraders have better therapeutic activity than EZH2 inhibitors, which may provide a potential anticancer strategy to treat lymphoma.
- Tu, Yalin,Sun, Yameng,Qiao, Shuang,Luo, Yao,Liu, Panpan,Jiang, Zhong-Xing,Hu, Yumin,Wang, Zifeng,Huang, Peng,Wen, Shijun
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p. 10167 - 10184
(2021/07/26)
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- Protein degradation targeting chimera for degrading androgen receptor
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The invention relates to a novel difunctional molecule compound based on VHL ligand induction and application of the difunctional molecule compound in synthesis of the compounds and pharmaceutical compositions thereof. The compound is shown as a formula I. The compound can selectively induce AR protein degradation and can be used for treating cancers such as prostatic cancer and breast cancer.
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-
Paragraph 0218-0223
(2021/07/24)
-
- IDEBENONE COMPOUNDS
-
The present application provides idebenone derivatives or analogues useful for treating a disease or disorder in a subject in need thereof. Pharmaceutical compositions comprising the compounds and methods of treating the disease or disorder are also provided.
- -
-
Page/Page column 60; 61
(2021/10/22)
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- CONDENSED PYRROLES AS NOVEL BROMODOMAIN INHIBITORS
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Compounds of formula (1) or (2) and their use in the treatment of diseases or conditions for which a bromodomain inhibitor is indicated.
- -
-
Paragraph 0098-00102
(2020/07/14)
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- Regio/site-selective alkylation of substrates containing a: Cis -, 1,2- or 1,3-diol with ferric chloride and dipivaloylmethane as the catalytic system
-
In this study, we reported the regio/site-selective alkylation of substrates containing a cis-, 1,2- or 1,3-diol with FeCl3 as a key catalyst. A catalytic system consisting of FeCl3 (0.01-0.1 equiv.) and dipivaloylmethane (FeCl3/dipivaloylmethane = 1/2) was used to catalyze the alkylation in the presence of a base. The produced selectivities and isolated yields were similar to those obtained by methods using the same amount of FeL3 (L = acylacetone ligand) as the catalyst in most cases. The previously reported FeL3 catalysts for alkylation are not commercially available and have to be synthesized prior to use. In contrast, FeCl3 and dipivaloylmethane (Hdipm) are very common and inexpensive nontoxic reagents in the lab, thereby making the method much greener and easier to handle. Mechanism studies confirmed for the first time that FeCl3 initially reacts with two equivalents of Hdipm to form [Fe(dipm)3] in the presence of a base in acetonitrile, followed by the formation of a five or six-membered ring intermediate between [Fe(dipm)3] and two hydroxyl groups of the substrate. A subsequent reaction between the cyclic intermediate and the alkylating agent results in selective alkylation of the substrate.
- Lv, Jian,Liu, Yu,Zhu, Jia-Jia,Zou, Dapeng,Dong, Hai
-
supporting information
p. 1139 - 1144
(2020/03/11)
-
- 4-Acyl Pyrroles as Dual BET-BRD7/9 Bromodomain Inhibitors Address BETi Insensitive Human Cancer Cell Lines
-
Various malignant human diseases show disturbed signaling pathways due to increased activity of proteins within the epigenetic machinery. Recently, various novel inhibitors for epigenetic regulation have been introduced which promise a great therapeutic benefit. Inhibitors for the bromo- and extra-terminal domain (BET) family were of particular interest after inhibitors had shown a strong antiproliferative effect. More recently, the focus has increasingly shifted to bromodomains (BDs) outside the BET family. Based on previously developed inhibitors, we have optimized a small series of 4-acyl pyrroles, which we further analyzed by ITC, X-ray crystallography, selectivity studies, the NCI60 cell-panel, and GI50 determinations for several cancer cell lines. The inhibitors address both, BET and BRD7/9 BDs, with very high affinity and show a strong antiproliferative effect on various cancer cell lines that could not be observed for BD family selective inhibitors. Furthermore, a synergistic effect on breast cancer (MCF-7) and melanoma (SK-MEL-5) was proven.
- Hügle, Martin,Regenass, Pierre,Warstat, Robin,Hau, Mirjam,Schmidtkunz, Karin,Lucas, Xavier,Wohlwend, Daniel,Einsle, Oliver,Jung, Manfred,Breit, Bernhard,Günther, Stefan
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p. 15603 - 15620
(2020/12/23)
-
- ANANDAMIDE COMPOUNDS
-
The present application provides anandamide and 2-arachidonyl glycerol compounds useful for treating a disease or disorder in a subject in need thereof. Pharmaceutical compositions comprising the compounds and methods of treating diseases or disorders are also provided.
- -
-
Page/Page column 38
(2020/07/25)
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- General and Phosphine-Free Cobalt-Catalyzed Hydrogenation of Esters to Alcohols
-
Catalytic hydrogenation of esters is essential for the sustainable production of alcohols in organic synthesis and chemical industry. Herein, we describe the first non-noble metal catalytic system that enables an efficient hydrogenation of non-activated esters to alcohols in the absence of phosphine ligands (with a maximum turnover number of 2391). The general applicability of this protocol was demonstrated by the high-yielding hydrogenation of 39 ester substrates including aromatic/aliphatic esters, lactones, polyesters and various pharmaceutical molecules.
- Shao, Zhihui,Zhong, Rui,Ferraccioli, Raffaella,Li, Yibiao,Liu, Qiang
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supporting information
p. 1125 - 1130
(2019/10/22)
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- Catalytic Transfer Hydrogenation Using Biomass as Hydrogen Source
-
We developed an operationally simple method for the direct use of biomass-derived chemical entities in a fundamentally important process, such as hydrogenation. Various carbohydrates, starch, and lignin were used for stereoselective hydrogenation. Employing a transition metal catalyst and a novel catalytic system, the reduction of alkynes, alkenes, and carbonyl groups with high yields was demonstrated. The regioselective hydrogenation to access different stereoisomers was established by simple variations in the reaction conditions. This work is based on an unprecedented catalytic system and represents a straightforward application of biomass as a reducing reagent in chemical reactions.
- Antonchick, Andrey P.,Manna, Srimanta
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p. 3094 - 3098
(2018/09/14)
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- Antibody drug conjugate, intermediate, preparation method, pharmaceutical composition and uses thereof
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Disclosed are an antibody drug conjugate IB, which uses ether linkages for connection, and improves the water solubility, stability and cytotoxicity in vivo and in intro, and an intermediate, a pharmaceutical composition, and uses of the antibody drug conjugate. The antibody drug conjugate has simple synthetic steps and a high yield.
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Page/Page column 127; 128
(2019/11/11)
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- Novel compound 6,6-dimethyl tetrahydropyran-2-methanol and preparing method thereof
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The invention discloses a novel compound that is 6,6-dimethyl tetrahydropyran-2-methanol and a preparing method thereof. The method includes preparing benzyloxy ethanol by utilizing a sodium alkoxideprocess; then oxidizing the benzyloxy ethanol into benzyloxy acetaldehyde by utilizing a swern oxidation process; reacting the benzyloxy acetaldehyde and allyltributyltin prepared by utilizing a Grignard reaction to obtain 1-(benzyloxy)-4-penten-2-ol; subjecting the 1-(benzyloxy)-4-penten-2-ol and acetone to cyclization under catalysis of trimethylchlorosilane and potassium iodide to obtain 4-iodo-6,6-dimethyl tetrahydropyran-2-methanol; and subjecting the 4-iodo-6,6-dimethyl tetrahydropyran-2-methanol to hydrogenation to remove iodine to obtain the target product that is the 6,6-dimethyl tetrahydropyran-2-methanol. According to the method, reactions are relatively mild, products can be easily treated and purified, and the method is suitable for batch preparation, and therefore the methodhas important application value.
- -
-
Paragraph 0014; 0015-0016; 0024; 0030
(2018/04/03)
-
- Benzoxazine compound and its preparation methods and application
-
The invention relates to a benzoxazine compound represented in the following formula 1. The benzoxazine compound can serve as a beta 2 receptor agonist. The formula can be seen from the description.
- -
-
Paragraph 0093; 0094; 0095
(2017/10/07)
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- Chitosan grafted with a heteropolyanion-based ionic liquid as an effective and reusable catalyst for acetalization
-
Chitosan immobilized with an acidic ionic liquid (CS-VImPS-PW) was fabricated via a radical addition reaction of N-vinylimidazoliumpropane sulfonate and chitosan, followed by acidification with a heteropolyacid. It was characterized by a Fourier transform infrared spectrometer, solid-state 13C nuclear magnetic resonance spectrometer, thermogravimetric analyzer, elemental analyzer, and Hammett indicator. Some acetalization reactions were investigated to evaluate the catalytic activity of CS-VImPS-PW. The results show that CS-VImPS-PW is highly active for the acetalization reactions in high acetal yields ranging from 83.2 to 96.2% and can be reused 8 times without noticeable loss of activity.
- Zhang, Wei-Hong,Liu, Shan-Shan,Liu, Ping,Xu, Jie,Xue, Bing,Wei, Xian-Yong,Li, Yong-Xin
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p. 41404 - 41409
(2016/05/19)
-
- An Iron(III) Catalyst with Unusually Broad Substrate Scope in Regioselective Alkylation of Diols and Polyols
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In this study, [Fe(dibm)3] (dibm=diisobutyrylmethane) is shown to have unusually broad scope as a catalyst for the selective monoalkylation of a diverse set of 1,2- and 1,3-diol-containing structures. The mechanism is proposed to proceed via a cyclic dioxolane-type intermediate, formed between the iron(III) species and two adjacent hydroxyl groups. This approach represents the first transition-metal catalysts that are able to replace stoichiometric amounts of organotin reagents in regioselective alkylation. The reactions generally lead to very high regioselectivities and high yields, on par with, or better than, previous methods used for regioselective alkylation.
- Ren, Bo,Ramstr?m, Olof,Zhang, Qiang,Ge, Jiantao,Dong, Hai
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p. 2481 - 2486
(2016/02/12)
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- Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl α-GalCer Analogues
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Replacement of the amide moiety in the structure of α-GalCer with a 1,2,3-triazole linker is known to elicit a response skewed toward Th2 immunity, and glycolipids containing an aromatic ring in the terminus of their acyl or phytosphingosine structural component exhibit an enhanced Th1 immune response. In the current study, synthesis and immunological screening of a focused library of benzyloxyalkyl-substituted 1,2,3-triazolyl α-GalCer analogues are reported. The novel α-GalCer analogues activate invariant natural killer T (iNKT) cells via CD1d mediated presentation, which was confirmed by in vitro tests performed on iNKT hybridomas incubated with CD1d proteins. When tested on isolated murine splenocytes, the T1204B and T1206B compounds stimulated higher levels of both IFN-γ and IL-4 cytokine expression in vitro compared to that of α-GalCer.
- Verma, Yogesh Kumar,Reddy, Bonam Srinivasa,Pawar, Mithun S.,Bhunia, Debabrata,Sampath Kumar, Halmuthur M.
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supporting information
p. 172 - 176
(2016/03/01)
-
- Influence of the side-chain structure and molecular weight on the re-entrant behaviors of mesogen-jacketed liquid crystalline polymers
-
Three series of mesogen-jacketed liquid crystalline polymers (MJLCPs) containing different terminal groups (phenmethyl, diphenylmethyl and triphenylmethyl) in the side chains, abbreviated as Pv-m-Bn, Pv-m-DPM, Pv-m-Tr (m = 2, 4, 6, 8, 10, and 12, which are the number of methylene units between the terephthalate core and terminal groups in the side chains), were designed and successfully synthesized via free-radical polymerization. Molecular characterization of the polymers was performed by 1H NMR, GPC and TG analysis. The phase structures and transitions of the polymers were investigated by a combination of techniques including DSC, POM and 1D/2D WAXD. The experimental results revealed that all the polymers exhibited excellent thermal stabilities and the re-entrant behaviors of the MJLCPs were found to be strongly dependent on the structure of the side-chain, i.e., the spacer length increased with the volume of the terminal groups when the polymers exhibited the re-entrant isotropic phase. On the other hand, a series of MJLCPs, poly{2,5-bis[(diphenylmethoxy-ethyl)oxycarbonyl]-styrenes} (Pv-2-DPMs), with different molecular weights (Mn) and narrow Mn distributions have been successfully synthesized via ATRP. The results indicated that when the Mn was below 1.73 × 104 g mol-1, only the isotropic phase was observed. When Mn was between 3.40 × 104 g mol-1 and 8.48 × 104 g mol-1, a re-entrant isotropic phase was formed at low temperatures and a columnar nematic phase at high temperatures. By further increasing the Mn to exceed 9.71 × 104 g mol-1, a stable columnar nematic phase was developed. This work provides two effective ways to design and synthesize MJLCPs with re-entrant behaviors; moreover, it is meaningful to deeply understand the structure-property relationships of MJLCPs.
- Xiang, Zheng,Chen, Sheng,Luo, Yongbing,Li, Ping,Zhang, Hailiang
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p. 78516 - 78527
(2016/09/09)
-
- (Z)-Selective enol triflation of α-alkoxyacetoaldehydes: Application to synthesis of (Z)-allylic alcohols via cross-coupling reaction and [1,2]-wittig rearrangement
-
The stereoselective transformation of α-alkoxyacetoaldehydes to the corresponding (Z)-vinyl triflates was achieved by treatment with phenyl triflimide and DBU. The stereochemistry was explained by the "syn-effect," which was attributed primarily to an σ → π interaction. The β-alkoxy vinyl triflates obtained were applied to the stereoselective synthesis of structurally diverse (Z)-allylic alcohols via transition metal-catalyzed cross-coupling reaction and [1,2]-Wittig rearrangement.
- Kurosawa, Fumiya,Nakano, Takeo,Soeta, Takahiro,Endo, Kohei,Ukaji, Yutaka
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p. 5696 - 5703
(2015/06/16)
-
- SILICON PARTICLES TARGETING TUMOR CELLS
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A silicon particle comprising a silicon body, a functionalized silica surface surrounding the silicon body, and a targeting moiety specifically targeting tumor cells, and, optionally, an enzymatically metabolizable compound,is useful in the treatment of cancer by producing cell death after particle internalization.
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Page/Page column 53; 54
(2015/12/08)
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- Development of a sensitive bioluminogenic probe for imaging highly reactive oxygen species in living rats
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A sensitive bioluminogenic probe for highly reactive oxygen species (hROS), SO3H-APL, was developed based on the concept of dual control of bioluminescence emission by means of bioluminescent enzyme-induced electron transfer (BioLeT) and modulation of cell-membrane permeability. This probe enables non-invasive visualization of physiologically relevant amounts of hROS generated deep inside the body of living rats for the first time. It is expected to serve as a practical analytical tool for investigating a wide range of biological functions of hROS in vivo. The design concept should be applicable to other in vivo bioluminogenic probes. You light up my life: A sensitive bioluminogenic probe for highly reactive oxygen species (hROS) was developed based on the concept of dual control of bioluminescence emission by means of bioluminescent enzyme-induced electron transfer (BioLeT) and modulation of cell-membrane permeability. This probe enables non-invasive visualization of physiologically relevant amounts of hROS generated deep inside the body of living rats.
- Kojima, Ryosuke,Takakura, Hideo,Kamiya, Mako,Kobayashi, Eiji,Komatsu, Toru,Ueno, Tasuku,Terai, Takuya,Hanaoka, Kenjiro,Nagano, Tetsuo,Urano, Yasuteru
-
supporting information
p. 14768 - 14771
(2016/02/05)
-
- Synthesis of some acyclic quaternary ammonium compounds. Alkylation of secondary and tertiary amines in a two-phase system
-
A series of acyclic symmetrical and asymmetrical quaternary ammonium chlorides of the general formula R1R2R3N+AR4Cl- (R1 = Me, Bu; R2 = n-C12H25, PhCH2, C n H2n+1(OCH2CH2) m, n = 9 and 12, m = 1 and 2; R3 = n-C12H25, PhCH2, HOCH2CH2,-OOCCH2; R4 = n-C12H25, PhCH2; A = (CH2CH2O)1,2, CH2C(O)O) was synthesized by the alkylation of tertiary amines in a two-phase system containing water. A convenient method for the synthesis of the initial symmetrical and asymmetrical tertiary amines of the general formula MeNR1R2 (R1 = Me, Bu; R2 = n-C12H25, PhCH2, CnH2n+1(OCH2CH2) m, n = 9 and 12, m = 1 and 2) in an organic phase-aqueous phase heterogeneous system, which allows the use of aqueous solutions of alkali and amines, was developed. The improved method for the preparation of intermediate ethylene glycol and diethylene glycol monoethers is monoalkylation of glycols in dioxane using solid KOH in a two-phase system.
- Kharlamov,Artyushin,Bondarenko
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p. 2445 - 2454
(2015/08/03)
-
- Biological evaluation of new mimetics of annonaceous acetogenins: Alteration of right scaffold by click linkage with aromatic functionalities
-
A small library of analogues of annonaceous acetogenins through click linkage with aromatic moieties is established using a convergent modular fragment-assembly approach. These analogues exhibited low micromolar inhibitory activities against the proliferation of several human cancer cell lines. Structure-activity relationship (SAR) of these analogues indicates that replacement of the methoxy groups of ubiquinone ring with methyl groups is proved to be a useful strategy for improving the anticancer activity of quinone-acetogenin hybrids.
- Liu, Yanghan,Xiao, Qicai,Liu, Yongqiang,Li, Zheng,Qiu, Yatao,Zhou, Guang-Biao,Yao, Zhu-Jun,Jiang, Sheng
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p. 248 - 258
(2014/04/17)
-
- Is macrocycle a synonym for kinetic inertness in Gd(III) complexes? Effect of coordinating and noncoordinating substituents on inertness and relaxivity of Gd(III) chelates with DO3A-like ligands
-
Gadolinium chelates with octadentate ligands are widely used as contrast agents for magnetic resonance imaging (MRI), with macrocyclic ligands based on DO3A being preferred for the high kinetic inertness of their Gd chelates. A major challenge in the design of new bifunctional MRI probes is the need to control the rotational motion of the chelate, which greatly affects its relaxivity. In this work we explored facile alkylation of a secondary amine in macrocyclic DO3A-like ligands to create a short, achiral linkage to limit the undesired internal motion of chelates within larger molecular constructs. The acetate moiety on the trans nitrogen was also replaced with either a bidentate (ethoxyacetate, L1 or methyl picolinate, L2) or bulky monodentate (methyl phosphonate, L3) donor arm to give octa- or heptadentate ligands, respectively. The resultant Gd(III) complexes were all monohydrated (q = 1) and exhibited water residency times that spanned 2 orders of magnitude (τM = 2190 ± 170, 3500 ± 90, and 12.7 ± 3.8 ns at 37 C for GdL1, GdL2, and GdL3, respectively). Alkylation of the secondary amine with a noncoordinating biphenyl moiety resulted in coordinatively saturated q = 0 complexes of octadentate ligands L1 and L2. Relaxivities were limited by slow water exchange and/or lack of water coligand. All complexes showed decreased inertness compared to [Gd(DO3A)] despite higher ligand denticity, and inertness was further decreased upon N-alkylation. These results demonstrate that high kinetic inertness and in vivo safety of Gd chelates with macrocyclic ligands should not be generalized.
- Polasek, Miloslav,Caravan, Peter
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p. 4084 - 4096
(2013/05/09)
-
- Use of triazole-ring formation to attach a Ru/TsDPEN complex for asymmetric transfer hydrogenation to a soluble polymer
-
The cycloaddition of a chiral ligand containing a terminal alkyne to a soluble polymer containing an azide provides a convenient means for the attachment of an asymmetric transfer hydrogenation catalyst to a soluble polymer support. Using these ligands in complexes with Ru(II), gave good results in terms of conversion and enantioselectivity (up to 95% ee) in ketone reduction reactions.
- Zammit, Charlotte M.,Wills, Martin
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p. 844 - 852
(2013/08/23)
-
- SUBSTITUTED PYRAZOLYL-BASED CARBOXAMIDE AND UREA DERIVATIVES BEARING A PHENYL MOIETY SUBSTITUTED WITH AN O-CONTAINING GROUP AS VANILLOID RECEPTOR LIGANDS
-
The invention relates to substituted pyrazolyl-based carboxamide and urea derivatives of formula (Q) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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-
Page/Page column 118
(2013/05/23)
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- COMPOSITIONS, SYNTHESIS, AND METHODS OF USING PHENYLCYCLOALKYLMETHYLAMINE DERIVATIVES
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The present invention provides novel phenylcycloalkylmethylamme derivatives, and methods of preparing phenylcycloalkylmethylamme derivatives. The present invention also provides methods of using phenylcycloalkylmethylamme derivatives and compositions of phenylcycloalkylmethylamme derivatives. The pharmaceutical compositions of the compounds of the present invention can be used for treating and/or preventing obesity and obesity related co- morbid indications and depression and depression related co-morbid indications.
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Page/Page column 53-54
(2013/07/19)
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- Catalytic hydrogenation of esters. Development of an efficient catalyst and processes for synthesising (R)-1,2-propanediol and 2-(l-Menthoxy)ethanol
-
A ruthenium catalyst for the reduction of esters by hydrogenation has been developed. Processes for the hydrogenation of esters have also been developed for (R)-1,2-propanediol and 2-(l-menthoxy)ethanol. The catalyst shows good catalytic activity for the hydrogenation of esters in methanol. Methyl lactate was reduced at 30 °C and gave turnover numbers (TON) up to 4000. The optical purity of the (R)-1,2-propanediol made by the hydrogenation of methyl (R)-lactate was higher than that via the asymmetric hydrogenation of hydroxyacetone. A hydrogenation process to replace the lithium aluminum hydride (LAH) reduction used in the production of 2-(l-menthoxy)ethanol was developed.
- Kuriyama, Wataru,Matsumoto, Takaji,Ogata, Osamu,Ino, Yasunori,Aoki, Kunimori,Tanaka, Shigeru,Ishida, Kenya,Kobayashi, Tohru,Sayo, Noboru,Saito, Takao
-
experimental part
p. 166 - 171
(2012/05/20)
-
- RESIST COMPOSITION, METHOD OF FORMING RESIST PATTERN, COMPOUND AND ACID GENERATOR
-
A resist composition including: a base component (A) which exhibits changed solubility in an alkali developing solution under action of acid; and an acid-generator component (B) which generates acid upon exposure, wherein said acid-generator component (B) comprises an acid generator (B1) including a compound represented by general formula (b1-11) shown below: wherein R7″ to R9″ each independently represent an aryl group or an alkyl group, wherein two of R7″ to R9″ may be bonded to each other to form a ring with the sulfur atom, and at least one of R7″ to R9″ represents a substituted aryl group having a group represented by general formula (I) shown below as a substituent; X? represents an anion; and Rf represents a fluorinated alkyl group.
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-
-
- A concise and diastereoselective synthesis of piperidine and indolizidine alkaloids via aza-Prins cyclization
-
The synthesis of 2-substituted and 2,4-disubstituted piperidine alkaloids such as (±)-coniine, (±)-hydroxypipecolic acid, (±)-pipecolic acid, (±)-coniceine, and (±)-4-hydroxy-2- hydroxy-methyl piperidine have been accomplished in a highly diastereo-selective manner by employing aza-Prins cyclization as a key step to construct the piperidine core of these alkaloids. Georg Thieme Verlag Stuttgart · New York.
- Reddy, Basi V. Subba,Chaya, Dudhmal N.,Yadav, Jhillu S.,Gree, Rene
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experimental part
p. 297 - 303
(2012/03/26)
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- New insight on 2-naphthylmethyl (NAP) ether as a protecting group in carbohydrate synthesis: A divergent approach towards a high-mannose type oligosaccharide library
-
A new method for selective cleavage of 2-naphthylmethyl (NAP) ether utilizing 10-20 molar excess of HF/pyridine in toluene was revealed and strategically applied to a divergent approach towards generation of a high-mannose type oligosaccharide library.
- Li, Yao,Roy, Bimalendu,Liu, Xinyu
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supporting information; experimental part
p. 8952 - 8954
(2011/10/02)
-
- Potent antitumor mimetics of annonaceous acetogenins embedded with an aromatic moiety in the left hydrocarbon chain part
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Annonaceous acetogenins are a large family of naturally occurring polyketides exhibiting remarkable anticancer activities. The first generation of annonaceous acetogenin mimetic (1, AA005) exhibits comparable activity as that of natural products and presents much higher selectivity between cancer and normal cells. In this work, we report the design, synthesis, and evaluation of a new series of compound 1 analogues in which a variety of conformation- constrained fragments were embedded in the left hydrocarbon chain part. Compound 7 bearing a biphenyl moiety was identified to exhibit more potent antiproliferative activity and preferentially target cancer cells over normal cells and thus represents a new lead for further optimization.
- Xiao, Qicai,Liu, Yongqiang,Qiu, Yatao,Zhou, Guangbiao,Mao, Chan,Li, Zheng,Yao, Zhu-Jun,Jiang, Sheng
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supporting information; experimental part
p. 525 - 533
(2011/03/19)
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- Resist composition, method of forming resist pattern, novel compound, and acid generator
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A resist composition including a base component (A) which exhibits changed solubility in an alkali developing solution under action of acid and an acid-generator component (B) including a compound represented by (b1-1), a compound represented by (b1-1′) and/or a compound represented by (b1-1″) (R1″-R3″ represents an aryl group or an alkyl group, provided that at least one of R1″-R3″ represents a substituted aryl group being substituted with a group represented by (b1-1-0), and two of R1″-R3″ may be mutually bonded to form a ring with the sulfur atom; X represents a C3-C30 hydrocarbon group; Q1 represents a carbonyl group-containing divalent linking group; X10 represents a C1-C30 hydrocarbon group; Q3 represents a single bond or a divalent linking group; Y10 represents —C(═O)— or —SO2—; represents a C1-C10 alkyl group or a fluorinated alkyl group: Q2 represents a single bond or an alkylene group; and W represents a C2-C10 alkylene group).
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- RESIST COMPOSITION, METHOD OF FORMING RESIST PATTERN, POLYMERIC COMPOUND, AND COMPOUND
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A resist composition including a base component (A) which exhibits changed solubility in an alkali developing solution under action of an acid, and an acid generator component (B), wherein the base component (A) includes a polymeric compound (A0) containing a structural unit (a0) represented by the general formula (a0-1) shown below: (wherein, R1 represents a hydrogen atom, an alkyl group or a halogenated alkyl group; R2 represents a bivalent linking group containing at least one kind of polar groups selected from the group consisting of —O—, —C(═O)—, —C(═O)—O—, a carbonate linkage (—O—C(═O)—O—), —S—, —S(═O)2—, —S(═O)2—O—, —NH—, —NR04— (wherein, R04 represents an alkyl group or an acyl group), and —NH—C(═O)—; and R3 represents a cyclic group containing a sulfonyl group within the ring skeleton).
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- Synthesis and use of a stable aminal derived from TsDPEN in asymmetric organocatalysis
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A stable aminal formed stereoselectively from (R,R)-N-tosyl-1,2-diphenyl-1, 2-ethylenediamine (TsDPEN) is capable of asymmetric organocatalysis of Diels-Alder and α-amination reactions of aldehydes.
- Gosiewska, Silvia,Soni, Rina,Clarkson, Guy J.,Wills, Martin
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supporting information; experimental part
p. 4214 - 4217
(2010/09/12)
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- Synthesis of N-heterocycles, beta-amino acids, and allyl amines via aza-payne mediated reaction of ylides and hydroxy aziridines
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An ylide-based aza-Payne rearrangement of 2,3-aziridin-1-ols leads to an efficient process for the preparation of pyrrolidines. The aza-Payne rearrangement under the basic reaction conditions favors the formation of epoxy amines. Subsequent nucleophilic attack of the epoxide by the ylide yields a bis-anion, which upon a 5-exo-tet ring closure yields the desired pyrrolidine, thus completing the relay of the 3-membered the 5-membered nitrogen containing ring system. This process takes place with complete transfer of stereochemical fidelity, and can be applied to sterically hindered aziridinols.
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Page/Page column 23
(2009/01/23)
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- NOVEL COMPOUND AND METHOD OF PRODUCING THE SAME, ACID GENERATOR, RESIST COMPOSITION AND METHOD OF FORMING RESIST PATTERN
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A resist composition including a base component (A) which exhibits changed solubility in an alkali developing solution under action of acid and an acid-generator component (B) which generates acid upon exposure, the acid-generator component (B) including an acid generator (B1) consisting of a compound represented by general formula (b1-1) shown below: wherein RX represents a hydrocarbon group which may have a substituent exclusive of a nitrogen atom; each of Q2 and Q3 independently represents a single bond or a divalent linkage group; Y1 represents an alkylene group or fluorinated alkyl group of 1 to 4 carbon atoms; and Z+ represents an organic cation exclusive of an ion represented by general formula (w-1).
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- Ferric perchlorate as an efficient and useful catalyst for the selective benzylation and methylation of alcohols with benzyl chloride and methyl iodide
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A mild and efficient method was developed for selective benzylation and methylation of hydroxyl compounds in the presence of a catalytic amount of ferric perchlorate. We showed that ferric perchlorate was very effective in selectively promoting the benzylation and methylation of primary aliphatic and benzylic alcohols versus secondary aliphatic alcohols and phenolic hydroxy groups. Graphical abstract: [Figure not available: see fulltext.]
- Behbahani, Farahnaz K.,Heravi, Majid M.,Oskooie, Hossien A.
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experimental part
p. 181 - 184
(2010/03/26)
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- Electrochemically induced intermolecular anion transfer
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Two macrocyclic anion receptors with the proper signaling units were designed to control intermolecular anion transfer using an electrochemical stimulus. The solubility of both receptors drastically improved when one equivalent of benzoate was added to the suspension in the NMR tube. Macrocycles 1 and 2 were prepared via multistep synthetic pathways. An important enhancement of the MLCT emission intensity was initially seen when benzoate was added to a solution of macrocycles 1. Spectroelectrochemical experiments were conducted for a mixture which contained receptors 1,2 and benzoate in equimolar concentration in acetone. The reversibility of the anion transfer could be shown and hence, electrochemical reduction of ferrocenium to ferrocene at -0.2 V was simultaneously accompanied by an enhancement of the emission intensity.
- Curiel, David,Beer, Paul D.,Tarraga, Alberto,Molina, Pedro
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supporting information; experimental part
p. 7534 - 7538
(2010/03/02)
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- Targeting ketone drugs towards transport by the intestinal peptide transporter, PepT1
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Thiodipeptide prodrugs of the ketone nabumetone are shown to have affinity for, and be transported by, PepT1 in vitro. The Royal Society of Chemistry 2009.
- Foley, David,Bailey, Patrick,Pieri, Myrtani,Meredith, David
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supporting information; scheme or table
p. 1064 - 1067
(2009/05/30)
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- The in vitro transport of model thiodipeptide prodrugs designed to target the intestinal oligopeptide transporter, PepT1
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A thiodipeptide carrier system is shown to be effective at enabling a range of covalently bound molecules, including benzyl, benzoyl and ibuprofen conjugates, to be transported via the intestinal peptide transporter PepT1, demonstrating its potential as a rational drug delivery target.
- Foley, David,Pieri, Myrtani,Pettecrew, Rachel,Price, Richard,Miles, Stephen,Lam, Ho Kam,Bailey, Patrick,Meredith, David
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supporting information; experimental part
p. 3652 - 3656
(2009/10/23)
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- Synthesis of 3'-O-phosphonoethyl nucleosides with an adenine and a thymine base moiety
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The synthesis and antiviral evaluation of new 3'-O-phosphonoethyl modified phosphonate nucleosides related to PMDTA and PMDTT is described. The reaction scheme starts from protected L-threose and the phosphonate group is introduced by the Arbuzov reaction. The 2'-OH as well as the 2'-deoxygenated nucleosides have been obtained. Unfortunately, none of these synthesized compounds shows activity against HIV and HCV.
- Huang, Qiuya,Herdewijn, Piet
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scheme or table
p. 337 - 351
(2010/10/02)
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- Discovery of novel 1-azoniabicyclo[2.2.2]octane muscarinic acetylcholine receptor antagonists
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A novel 4-hydroxyl(diphenyl)methyl substituted quinuclidine series was discovered as a very promising class of muscarinic antagonists. The structure-activity relationships of the connectivity of the diphenyl moiety to the quinuclidine core and around the ring nitrogen side chain are described. Computational docking studies using an homology model of the M3 receptor readily explained the observed structure-activity relationship of the various compounds. Compound 14o was identified as a very potent, slowly reversible M3 antagonist with a very long in vivo duration of bronchoprotection.
- Lainé, Dramane I.,McCleland, Brent,Thomas, Sonia,Neipp, Christopher,Underwood, Brian,Dufour, Jeremy,Widdowson, Katherine L.,Palovich, Michael R.,Blaney, Frank E.,Foley, James J.,Webb, Edward F.,Luttmann, Mark A.,Burman, Miriam,Belmonte, Kristen,Salmon, Michael
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supporting information; experimental part
p. 2493 - 2505
(2010/03/04)
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- Design, synthesis, and photophysical characterization of water-soluble chlorins
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(Chemical Equation Presented) The use of chlorins as photosensitizers or fluorophores in a range of biological applications requires facile provisions for imparting high water solubility. Two free base chlorins have been prepared wherein each chlorin bears a geminal dimethyl group in the reduced ring and a water-solubilizing unit at the chlorin 10-position. In one design (FbC1-PO 3H2), the water-solubilizing unit is a 1,5-diphosphonopent-3-yl ("swallowtail") unit, which has previously been used to good effect with porphyrins. In the other design (FbC2-PO 3H2), the water-solubilizing unit is a 2,6-bis(phosphonomethoxy)phenyl unit. Two complementary routes were developed for preparing FbC2-PO3H2 that entail introduction of the protected phosphonate moieties either in the Eastern-half precursor to the chlorin or by derivatization of an intact chlorin. Water-solubilization is achieved in the last step of each synthesis upon removal of the phosphonate protecting groups. The chlorins FbC1-PO3H2 and FbC2-PO3H2 are highly water-soluble (>10 mM) as shown by 1H NMR spectroscopy (D2O) and UV-vis absorption spectroscopy. The photophysical properties of the water-soluble chlorins in phosphate-buffered saline solution (pH 7.4) at room temperature were investigated using static and time-resolved absorption and fluorescence spectroscopic techniques. Each chlorin exhibits dominant absorption bands in the blue and the red region (λ = 398, 626 nm), a modest fluorescence yield (Φf ≈ 0.11), a long singlet excited-state lifetime (τ = 7.5 ns), and a high yield of intersystem crossing to give the triplet state (Φisc = 0.9). The properties of the water-soluble chlorins in aqueous media are comparable to those of hydrophobic chlorins in toluene. The high aqueous solubility combined with the attractive photophysical properties make these compounds suitable for a wide range of biomedical applications.
- Borbas, K. Eszter,Chandrashaker, Vanampally,Muthiah, Chinnasamy,Hooi, Ling Kee,Holten, Dewey,Lindsey, Jonathan S.
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p. 3145 - 3158
(2008/09/19)
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- Diastereomerically and enantiomerically pure 2,3-disubstituted pyrrolidines from 2,3-aziridin-1-ols using a sulfoxonium ylide: A one-carbon homologative relay ring expansion
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An ylide-based aza-Payne rearrangement of 2,3-aziridin-1-ols leads to an efficient process for the preparation of pyrrolidines. The aza-Payne rearrangement under basic reaction conditions favors the formation of epoxy amines. Subsequent nucleophilic attack of the epoxide by the ylide yields a bis-anion, which upon a 5-exo-tet ring-closure yields the desired pyrrolidine, thus completing the relay of the three-membered to the five-membered nitrogen-containing ring system. This process takes place with complete transfer of stereochemical fidelity and can be applied to sterically hindered aziridinols.
- Schomaker, Jennifer M.,Bhattacharjee, Somnath,Yan, Jun,Borhan, Babak
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p. 1996 - 2003
(2007/10/03)
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- Regioselectivity in arene-catalyzed reductive lithiation of acetals of chlorobenzaldehydes
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The regioselectivity of arene-catalyzed reductive lithiation of acetals of chlorobenzaldehydes strongly depends on the form of lithium metal employed as a reducing agent. According to previous findings, naphthalene catalyzed reductions run in the presence of lithium powder (high Na content) led to competitive metalations of both aromatic carbon-chlorine and benzylic carbon-oxygen bonds. At variance with these results, naphthalene catalyzed reductions run in the presence of lithium wire (either high or low Na content) led to highly regioselective metalation of aromatic carbon-chlorine bonds. These results disclose new possibilities of selective applications of arene-catalyzed reductive lithiation reactions.
- Azzena, Ugo,Dettori, Giovanna,Sforazzini, Giuseppe,Yus, Miguel,Foubelo, Francisco
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p. 1557 - 1563
(2007/10/03)
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