- WDR5 INHIBITORS AND MODULATORS
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Isoquinolinone compounds and derivatives inhibit WDR5 and associated protein-protein interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject, such as cancer cell proliferation.
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Paragraph 00144; 00224
(2020/06/10)
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- Tuning the adsorption behaviors of water, methanol, and ethanol in a porous material by varying the flexibility of substituted groups
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Exploring the adsorption and separation of water, methanol, and ethanol is important concerning the use of a sustainable energy source from biofuel. In this paper, the effects of the flexibility of substituted groups have been studied based on three iso-reticular metal-organic frameworks (MOFs), in which the pore surface is decorated with propargyl (-CH2-C≡CH), allyl (-CH2-CH=CH2), and propyl (-CH2-CH2-CH3) groups respectively. These substituted groups stretch into the channel, acting as gates, and the gate-opening for guests is controlled by the flexibility as well as host-guest interactions. Our study results indicate that (i) the adsorption capacity of water, methanol and ethanol enhances accordingly with the increase of the flexibility of substituted groups; (ii) the adsorptive discrimination of water, methanol, and ethanol on this porous sorbent could be tuned by varying the substituted groups.
- Sha, Yunfei,Bai, Shizhe,Lou, Jiaying,Wu, Da,Liu, Baizhan,Ling, Yun
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supporting information
p. 7235 - 7239
(2016/06/01)
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- A Modular Synthesis of Multidentate S-, N- and O-Containing Meta- and Paracyclophanes
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The development of a modular approach to macrocycle assembly has enabled the synthesis of a library of pyridine-based macrocycles possessing multiple donor sites where chirality was readily introduced from (R)- or (S)-alanine, a representative amino acid. The facile, regioselective, nucleophilic ring opening of aziridines by dithiols enabled the synthesis of thioether-based linkers which on subsequent alkylation provided access to optically pure macrocycles. A modular approach to macrocyclic assembly has enabled the synthesis of a library of macrocycles possessing multiple donor sites where chirality was readily introduced from (S)-alanine. Key to this approach was the facile, regioselective, nucleophilic ring opening of aziridines by dithiols followed by macrocylisation under conditions of high dilution.
- Rasheed, Omer K.,Bailey, Patrick D.,Lawrence, Amy,Quayle, Peter,Raftery, James
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supporting information
p. 6988 - 6993
(2015/11/16)
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- Zn2+ complexes of 3,5-Bis[(1,5,9-triazacyclododecan-3-yloxy) methyl]phenyl conjugates of oligonucleotides as artificial RNases: The effect of oligonucleotide conjugation on uridine selectivity of the cleaving agent
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2-(3,5-Bis{[1,5,9-tris(trifluoroacetyl)-1,5,9-triazacyclododecan-3-yloxy] methyl}phenoxy)ethanol was synthesized and converted to a O-(2-cyanoethyl)-N,N- diisopropylphosphoramidite building block, 12. 2′-O-Methyl oligoribonucleotides incorporating a 2-[(2S,4S,5R)-4-hydroxy-5-(hydroxymethyl) tetrahydrofuran-2-yl)ethyl 4-oxopentanoate or a 2-{2-[2-({[(2R,4S,5R)-4-hydroxy- 5-(hydroxymethyl)tetrahydrofuran-2-yl]acetyl}amino)ethoxy]ethoxy}ethyl 4-oxopentanoate non-nucleosidic unit close to the 3′-terminus were assembled on a solid support, the 4-oxopentanoyl protecting groups were removed by treatment with hydrazinium acetate on-support, and 12 was coupled to the exposed OH function. The deprotected conjugates were purified by HPLC, and their ability to cleave a complementary RNA containing either uridine or some other nucleoside at the potential cleaving site was compared. Somewhat unexpectedly, conjugation to an oligonucleotide did not enhance the catalytic activity of the Zn2+-bis(azacrown) complex and virtually abolished its selectivity towards the uridine sites. Copyright
- Niittymaeki, Teija,Burakova, Ekaterina,Laitinen, Evelina,Leisvuori, Anna,Virta, Pasi,Loennberg, Harri
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- Solid-phase synthesis and acidolytic degradation of sterically congested oligoether dendrons
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Up to third-generation sterically crowded polyether dendrons were prepared on a solid support, using a novel building block derived from dimethyl 5-hydroxyisophthalate via O-allylation/Claisen rearrangement key steps. These dendrons underwent smooth disas
- Karabline, Jeny,Portnoy, Moshe
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experimental part
p. 4788 - 4794
(2012/08/08)
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- OXADIAZOLE COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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The invention provides novel beta-secretase inhibitors and methods for their including methods of treating Alzheimer's disease.
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Page/Page column 200
(2012/05/05)
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- COMPOUNDS CONTAINING FUSED RINGS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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The invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.
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Page/Page column 89
(2011/11/01)
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- Novel photo-cross-linkable dendrimers having thermal de-cross-linking properties
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Novel poly(aryl ether) type dendrimers having photo-cross-linking and thermal de-cross-linking properties were synthesized by a convergent method. A protected A2B monomer, 1-allyloxy-3,5-bis(bromomethyl)benzene, was newly prepared for the dendrimer synthesis. Palladium-catalyzed deprotection of an allyl group proceeded in high yields. The films of dendrimers containing a photoacid generator (PAG) became insoluble in solvents on irradiation. The irradiated films became soluble in solvents after baking at 120-200°C. The insolubilization and redissolution profiles were strongly affected by irradiation and baking conditions and the generation of the dendrimers. A reaction pathway was studied by TGA and DTA analysis and FT-IR spectroscopy.
- Okamura, Haruyuki,Shirai, Masamitsu
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scheme or table
p. 5087 - 5094
(2011/11/29)
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- Macrocyclic Compounds Useful as Bace Inhibitors
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The invention relates to novel macrocyclic compounds of the formula (I), in which all of the variables are as defined in the specification, the number of ring atoms included in the macrocyclic ring being 14, 15, 16 or 17, in free base form or in acid addition salt form, to their preparation, to their use as medicaments and to medicaments comprising them.
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Page/Page column 34
(2008/12/05)
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- Inhibitors of the FEZ-1 metallo-β-lactamase
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Metallo-β-lactamases (MBLs) catalyze the hydrolysis of β-lactams including penicillins, cephalosporins and carbapenems. Starting from benzohydroxamic acid (1) structure-activity studies led to the identification of selective inhibitors of the FEZ-1 MBL, e.g., 2,5-substituted benzophenone hydroxamic acid 17 has a Ki of 6.1 ± 0.7 μM against the FEZ-1 MBL but does not significantly inhibit the IMP-1, BcII, CphA or L1 MBLs.
- Lienard, Benoit M.R.,Horsfall, Louise E.,Galleni, Moreno,Frere, Jean-Marie,Schofield, Christopher J.
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p. 964 - 968
(2008/12/23)
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- Parallel combinatorial synthesis of glycodendrimers and their hydrogelation properties
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A series of glycodendrons has been assembled using a parallel combinatorial approach, and it has been shown that subtle structural variations between dendrons give rise to significant differences in their hydrogelation behavior.
- McWatt, Martin,Boons, Geert-Jan
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p. 2535 - 2545
(2007/10/03)
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- Total synthesis of an enantiomeric pair of FR980482. 2. Syntheses of the aromatic and the optically active aliphatic segments
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The synthesis of the aromatic segment 4 was achieved starting from commercially available 5-hydroxyisophthalic acid (6) by utilizing Claisen rearrangement of 9, bromolactonization of 12, and modified Curtius rearrangement of 16 as the key steps. Furthermore, the optically active aliphatic segments 5 and ent-5 were synthesized in enantiomerically pure forms starting with natural (2R, 3R)- and unnatural (2S, 3S)-diethyl tartrate (7 and ent-7), respectively: The synthetic scheme features epoxide formation of 26, nucleophilic epoxide opening of 27 with an azide anion, reduction of the azide function in 33 to an amine, and formation of the N-protected 1,3-oxazolidine 35.
- Yoshino, Toshiharu,Nagata, Yuriko,Itoh, Etsuko,Hashimoto, Masaru,Katoh, Tadashi,Terashima, Shiro
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p. 10239 - 10252
(2007/10/03)
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- Total synthesis of natural (+)-FR900482. 2. Efficient syntheses of the aromatic and the optically active aliphatic fragments
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The synthesis of the aromatic fragment 4 was achieved starting from commercially available 5-hydroxy-isophthalic acid (6) by utilizing Claisen rearrangement of 9, bromolactonization of 12, and modified Curtius rearrangement of 16 as key steps. Furthermore, the optically active aliphatic fragment 5 was synthesized in an optically pure form starting with L-diethyl tartrate (7) by featuring epoxide formation of 26, nucleophilic epoxide opening of 27 with an azide anion, reduction of the azide function in 33 to an amine, and formation of the N-protected 1,3-oxazolidine 35.
- Yoshino, Toshiharu,Nagata, Yuriko,Itoh, Etsuko,Hashimoto, Masaru,Katoh, Tadashi,Terashima, Shiro
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p. 3475 - 3478
(2007/10/03)
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