- On the Necessity of Nucleobase Protection for 2-Thiouracil for Fmoc-Based Pseudo-Complementary Peptide Nucleic Acid Oligomer Synthesis
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A selection of benzyl-based protecting groups for thiouracil (SU) for the synthesis of pseudo-complementary peptide nucleic acid (PNA) has been evaluated. The 4-methoxybenzyl-protecting group that has found use for SU during Boc-based oligomerization is also suitable for Fmoc-based oligomerization. Furthermore, it is demonstrated that SU protection is unnecessary for the successful synthesis of thiouracil-containing PNA. The new 2-thiothymine (ST) PNA monomer has also been prepared and incorporated into an oligomer and its binding to complementary PNA evaluated.
- Hudson, Robert H.E.,Heidari, Ali,Martin-Chan, Timothy,Park, Gyeongsu,Wisner, James A.
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Read Online
- Design, synthesis, and structure–activity relationship study of potent mapk11 inhibitors
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Huntington’s disease (HD) is a rare single-gene neurodegenerative disease, which can only be treated symptomatically. Currently, there are no approved drugs for HD on the market. Studies have found that MAPK11 can serve as a potential therapeutic target f
- Gong, Mengdie,Li, Honglin,Li, Lu,Li, Shiliang,Sun, Hongxia,Tu, Mingyan,Zhao, Zhenjiang,Zhu, Lili
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supporting information
(2022/01/04)
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- Incorporation of Pseudo-complementary Bases 2,6-Diaminopurine and 2-Thiouracil into Serinol Nucleic Acid (SNA) to Promote SNA/RNA Hybridization
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Serinol nucleic acid (SNA) is a promising candidate for nucleic acid-based molecular probes and drugs due to its high affinity for RNA. Our previous work revealed that incorporation of 2,6-diaminpurine (D), which can form three hydrogen bonds with uracil, into SNA increases the melting temperature of SNA-RNA duplexes. However, D incorporation into short self-complementary regions of SNA promoted self-dimerization and hindered hybridization with RNA. Here we synthesized a SNA monomer of 2-thiouracil (sU), which was expected to inhibit base pairing with D by steric hindrance between sulfur and the amino group. To prepare the SNA containing D and sU in high yield, we customized the protecting groups on D and sU monomers that can be readily deprotected under acidic conditions. Incorporation of D and sU into SNA facilitated stable duplex formation with target RNA by suppressing the self-hybridization of SNA and increasing the stability of the heteroduplex of SNA and its complementary RNA. Our results have important implications for the development of SNA-based probes and nucleic acid drugs.
- Kamiya, Yukiko,Sato, Fuminori,Murayama, Keiji,Kodama, Atsuji,Uchiyama, Susumu,Asanuma, Hiroyuki
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supporting information
p. 1266 - 1271
(2020/02/25)
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- COMPOUNDS FOR MODULATING DDAH AND ADMA LEVELS, AS WELL AS METHODS OF USING THEREOF TO TREAT DISEASE
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Disclosed are compounds that can modulate DDAH and the amount of asymmetric dimethylarginine (ADMA) in a subject. Also provided are pharmaceutical compositions comprising these compounds, as well as methods of using these compositions to treat and/or prevent diseases associated with elevated or low levels of DDAH and ADMA.
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Page/Page column 47; 49; 55; 63-64; 74; 76; 79; 81; 82; 90; 91
(2019/11/19)
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- PNA monomers fully compatible with standard Fmoc-based solid-phase synthesis of pseudocomplementary PNA
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Here we report the synthesis of new PNA monomers for pseudocomplementary PNA (pcPNA) that are fully compatible with standard Fmoc chemistry. The thiocarbonyl group of the 2-thiouracil (sU) monomer was protected with the 4-methoxy-2-methybenzyl group (MMPM), while the exocyclic amino groups of diaminopurine (D) were protected with Boc groups. The newly synthesized monomers were incorporated into a 10-mer PNA oligomer using standard Fmoc chemistry for solid-phase synthesis. Oligomerization proceeded smoothly and the HPLC and MALDI-TOF MS analyses indicated that there was no remaining MMPM on the sU nucleobase. The new PNA monomers reported here would facilitate a wide range of applications, such as antigene PNAs and DNA nanotechnologies.
- Sugiyama, Toru,Hasegawa, Genki,Niikura, Chie,Kuwata, Keiko,Imamura, Yasutada,Demizu, Yosuke,Kurihara, Masaaki,Kittaka, Atsushi
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supporting information
p. 3337 - 3341
(2017/07/07)
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- NOVEL SOLUBLE GUANYLATE CYCLASE ACTIVATORS AND THEIR USE
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The invention relates to activators of soluble guanylate cyclase of formula (I) and their use in pharmaceutical compositions, primarily topically administered ophthalmic compositions. The pharmaceutical compositions are useful for reducing intraocular pre
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Page/Page column 42; 42
(2015/03/28)
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- Oxidative hydroxylation mediated by alkoxysulfonium ions
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Oxidative hydroxylation of toluene derivatives via alkoxysulfonium ion intermediates was achieved by integration of anodic oxidation and hydrolysis to give benzyl alcohols which are also susceptible to oxidation. Alkenes were also oxidized to give 1,2-diols without overoxidation. The integration of electrochemical oxidative cyclization and hydrolysis was achieved using alkenes bearing a nitrogen atom in an appropriate position to give cyclic β-amino-substituted alcohols.
- Ashikari, Yosuke,Nokami, Toshiki,Yoshida, Jun-Ichi
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supporting information; experimental part
p. 938 - 941
(2012/05/05)
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- ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
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Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.
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- TETRAHYDROISOQUINOLINE COMPOUND
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The present invention relates a specific tetrahydroisoquinoline compound which is useful as a chemokine receptor type 3 (CCR3) antagonist, and a pharmaceutical composition comprising the same as an active ingredient. The tetrahydroisoquinoline compound of the present invention is useful for the treatment or prevention of a disease in which CCR3 participates.
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Page/Page column 77
(2010/01/29)
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- Regioselective reductive opening of substituted phthalans: synthetic applications
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The reductive opening of substituted phthalans 6, 11, 12, 20, 21 and 28 with lithium and a catalytic amount of DTBB leads to the formation of corresponding functionalised organolithium intermediates 8, 15, 16, 23, 25 and 29+30 in a regioselective manner. The further reaction of these dianions with different electrophiles, mainly carbonyl compounds, gives the expected functionalised benzylic alcohols 9, 17, 18, 24, 26 and 31+32. The observed stereochemistry can be easily explained taking into account the values of the electron densities deduced by semiempirical PM3 calculations.
- García, Daniel,Foubelo, Francisco,Yus, Miguel
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p. 4275 - 4286
(2008/09/20)
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- BICYCLIC DERIVATIVES AS PPAR MODULATORS
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The present invention is directed to compounds represented by the following structural formula, Formula (I), and stereoisomers, pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: (a) R2 is selected from the group consisting of C0-C8 alkyl and C1-4- heteroalkyl; (b) X is selected from the group consisting of a single bond, O, S, S(O)2 and N; (c) U is an aliphatic linker wherein one carbon atom of the aliphatic linker is optionally replaced with O, NH or S, and wherein such aliphatic linker is optionally substituted with from one to four substituents each independently selected from R30; (d) Y is selected from the group consisting of C, O, S, NH and a single bond; and (e) E is C(R3)(R4)A or A.
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Page/Page column 60
(2008/06/13)
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- FUSED HETEROCYCLIC DERIVATIVES AS PPAR MODULATORS
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The present invention is directed to compounds represented by the following structural formula, Formula I: wherein (a) X is selected from the group consisting of a single bond, O, S. S(O)2 and N; (b) U is an aliphatic linker; (c) Y is selected from the group consisting of C, O, S, NH and a single bond; (d) E is C(R3) (R4)A or A and wherein (i) A is selected from the group consisting of carboxyl, tetrazole, C1-C6 alkylnitrile, carboxamidek, sulfonamide and acylsulfonamide; (e) B is selected from the group consisting of S, O, C, and N; (f) Z is selected from the group consisting of N and C; with the proviso that when B is C then Z is N.
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- Estrogen receptor-β potency-selective ligands: Structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues
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Through an effort to develop novel ligands that have subtype selectivity for the estrogen receptors alpha (ERα) and beta (ERβ), we have found that 2,3-bis(hydroxyphenyl)propionitrile (DPN) acts as an agonist on both ER subtypes, but has a 70-fold higher relative binding affinity and 170-fold higher relative potency in transcription assays with ERβ than with ERα. To investigate the ERβ affinity- and potency-selective character of this DPN further, we prepared a series of DPN analogues in which both the ligand core and the aromatic rings were modified by the repositioning of phenolic hydroxy groups and by the addition of alkyl substituents and nitrile groups. We also prepared other series of DPN analogues in which the nitrile functionality was replaced with acetylene groups or polar functions, to mimic the linear geometry or polarity of the nitrile, respectively. To varying degrees, all of the analogues show preferential binding affinity for ERβ (i.e., they are ERβ affinity-selective), and many, but not all of them, are also more potent in activating transcription through ERβ than through ERα (i.e., they are ERβ potency-selective). meso-2,3-Bis(4-hydroxyphenyl)succinonitrile and dl-2,3-bis(4-hydroxyphenyl)succinonitrile are among the highest ERβ affinity-selective ligands, and they have an ERβ potency selectivity that is equivalent to that of DPN. The acetylene analogues have higher binding affinities but somewhat lower selectivities than their nitrile counterparts. The polar analogues have lower affinities, and only the fluorinated polar analogues have substantial affinity selectivities. This study suggests that, in this series of ligands, the nitrile functionality is critical to ERβ selectivity because it provides the optimal combination of linear geometry and polarity. Furthermore, the addition of a second nitrile group β to the nitrile in DPN or the addition of a methyl substitutent at an ortho position on the β-aromatic ring increases the affinity and selectivity of these compounds for ERβ. These ERβ-selective compounds may prove to be valuable tools in understanding the differences in structure and biological function of ERα and ERβ.
- Meyers,Sun,Carlson,Marriner,Katzenellenbogen,Katzenellenbogen
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p. 4230 - 4251
(2007/10/03)
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- Some evidence in favour of an electron transfer mechanism in the TiO2 photosensitized oxidation of benzyl derivatives in aqueous media
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The structure and/or distribution of products from the TiO2-sensitized photooxidation of some benzyl derivatives in aerated and/or deaerated aqueous media and in the presence of Ag2SO4 are reported. The results suggest that the single electron transfer process from the substrate to the photogenerated hole, previously proposed in CH3CN, should also be operative on gradually going from aqueous CH3CN to pure water.
- Ranchella, Michele,Rol, Cesare,Sebastiani, Giovanni V.
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p. 311 - 315
(2007/10/03)
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