- 1,2,4-Triazine-Modified 2′-Deoxyuridine Triphosphate for Efficient Bioorthogonal Fluorescent Labeling of DNA
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In order to establish the Diels–Alder reaction with inverse electron demand for postsynthetic DNA modification, a 1,2,4-triazine-modified 2′-deoxyuridine triphosphate was synthesized. The bioorthogonally reactive 1,2,4-triazine group was attached at the 5-position of 2′-deoxyuridine by a flexible alkyl linker to facilitate its acceptance by DNA polymerases. The screening of four DNA polymerases showed successful primer extensions, using a mixture of dATP, dGTP, dCTP, and the modified 2′-deoxyuridine triphosphate, by using KOD XL or Vent polymerase. The triazine moiety was stable under the conditions of primer extension, which was evidenced by labeling with a BCN-modified rhodamine at room temperature in yields of up to 82 %. Two or three modified bases could be incorporated in quantitative yields when the modification sites were separated by three base pairs. These results establish the 1,2,4-triazene group as a bioorthogonally reactive moiety in DNA, thereby replacing the problematic 1,2,4,5-tetrazine for postsynthetic labeling by the Diels–Alder reaction with inverse electron demand.
- Peewasan, Krisana,Wagenknecht, Hans-Achim
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- The crystal structure and vibrational spectra of potassium oxathioamidate
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The crystal and molecular structure determination of the title compound, K-SO2NC2H2, Mr = 143.21, (1) is part of a series of determinations of N-substituted oxathioamidates.The structure has been refined using single-crystal X-ray diffraction data measured at 295 K .The crystals are orthorhombic, space group Pn21a, Z = 8, with cell dimensions: a = 11.399(2) Angstroem, b = 22.131(2) Angstroem, c = 4.021(1) Angstroem, V = 1014.5(7) Angstroem3.Dcalc. = 1.875 mg m-3, Dobs = 1.600 mg m-3, F(000) = 576, μ = 13.14 cm-1.The final agreement factors for 1979 observed reflections 3?(I)> were: R = 0.062 and Rw = 0.067.The vibrational spectra confirm the geometrical differences between the two thiooxamidate molecules.KEY WORDS: Potassium oxathioamidate.
- Hereygers, Marleen L.B.F.,Desseyn, Herman O.,Perlepes, Spyros P.,Verhulst, Koen A.F.,Lenstra, Albert T.H.
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- METHODS AND COMPOSITIONS FOR INHIBITING CNKSR1
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Embodiments include compositions and methods of inhibiting CNKSR1 and methods of identifying inhibitors of CNKSR1.
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Paragraph 0154
(2014/07/07)
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- PAR4 AGONIST PEPTIDES
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The present invention provides PAR4 agonist peptides. These peptides are useful for developing robust PAR4 receptor assays.
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(2013/11/06)
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- IMIDAZOTHIADIAZOLE AND IMIDAZOPYRAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION
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The present invention provides thiazole compounds of Formula I wherein W, Y, R0, R2, R4, R5, R6, R7, X1, X2, X3 and X4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.
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Paragraph 00147
(2013/11/18)
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- Discovery of novel urea-based hepatitis C protease inhibitors with high potency against protease-inhibitor-resistant mutants
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The macrocyclic urea 2, a byproduct in the synthesis of benzoxaborole 1, was identified to be a novel and potent HCV protease inhibitor. We further explored this motif by synthesizing additional urea-based inhibitors and by characterizing them in replicase HCV protease-resistant mutants assay. Several compounds, exemplified by 12, were found to be more potent in HCV replicon assays than leading second generation inhibitors such as danoprevir and TMC-435350. Additionally, following oral administration, inhibitor 12 was found in rat liver in significantly higher concentrations than those reported for both danoprevir and TMC-435350, suggesting that inhibitor 12 has the combination of anti-HCV and pharmacokinetic properties that warrants further development of this series.
- Kazmierski, Wieslaw M.,Hamatake, Robert,Duan, Maosheng,Wright, Lois L.,Smith, Gary K.,Jarvest, Richard L.,Ji, Jing-Jing,Cooper, Joel P.,Tallant, Matthew D.,Crosby, Renae M.,Creech, Katrina,Wang, Amy,Li, Xianfeng,Zhang, Suoming,Zhang, Yong-Kang,Liu, Yang,Ding, Charles Z.,Zhou, Yasheen,Plattner, Jacob J.,Baker, Stephen J.,Bu, Wei,Liu, Liang
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supporting information; experimental part
p. 3021 - 3026
(2012/06/01)
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- ARYLCYCLOPROPYLAMINE BASED DEMETHYLASE INHIBITORS OF LSD1 AND THEIR MEDICAL USE
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The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection. Thus, in one specific aspect the invention relates to formulas (II), (III), (IV), (V), (VI), (VII), (VIII), (IX).
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Page/Page column 107; 108
(2012/02/13)
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- COMPOUNDS
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The present invention features compounds of Formula (I) and (Ia), pharmaceutical compositions and use in the treatment of viral disease:
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Page/Page column 19
(2010/08/08)
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- SUBSTITUTED SULFONAMIDE DERIVATIVES
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The invention relates to substituted sulfonamide derivatives, processes for the preparation thereof, medicaments containing these compounds and the use of substituted sulfonamide derivatives for the preparation of medicaments.
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Page/Page column 144
(2009/11/29)
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- AMINOTRIAZOLE DERIVATIVES AS ALX AGONISTS
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The invention relates to aminotriazole derivatives of formula (I), wherein A, E, R1 and R2 are as defined in the description, their preparation and their use as pharmaceutically active compounds. The compounds are useful for the prevention or treatment of diseases, which respond to the modulation of the ALX receptor such as inflammatory diseases.
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Page/Page column 80-81
(2009/07/18)
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- THIAZOLE-2-CARBOXAMIDE DERIVATIVES FOR USE AS HPPAR AGONISTS IN THE TREATMENT OF I.A. DYSLIPIDEMIA
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A compound of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof is claimed for use as a selective dual agonist of PPAR alpha and gamma.
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Page/Page column 10
(2010/02/11)
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- Substituted 1,3-thiazole compounds, their production and use
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(1) A 1,3-thiazole compound of which the 5-position is substituted with a 4-pyridyl group having a substituent including no aromatic group or (2) a 1,3-thiazole compound of which the 5-position is substituted with a pyridyl group having at the position adjacent to a nitrogen atom of the pyridyl group a substituent including no aromatic group has an excellent p38 MAP kinase inhibitory activity.
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- MEDICINAL COMPOSITIONS
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The present invention relates to an agent for the prophylaxis or treatment of pain, an agent for suppressing activation of osteoclast, and an inhibitor of osteoclast formation, which contains a p38 MAP kinase inhibitor and/or a TNF-α production inhibitor.
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- Theoretical, structural, vibrational, NMR, and thermal evidence of the inter- versus intramolecular hydrogen bonding in oxamides and thiooxamides
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This contribution describes the study of hydrogen bonding in secondary oxamides, monothiooxamides, and dithiooxamides by ab initio calculations, X-ray diffractions, NMR spectra, thermal analysis, and variable-temperature infrared and Raman spectroscopy. The results can all be interpreted as a function of the change in the strength and the nature of the hydrogen bonding by substituting oxygen for sulfur in the series CH3-HNCOCONHCH3, CH 3HNCSCONHCH3, CH3HNCSCSNHCH3 and by changing the steric influence of the alkyl group in a series of oxamides (RHNCOCNHR; R = CH3, C2H5, iC3H 7, tC49).
- Desseyn,Perlepes,Clou,Blaton,Van Der Veken,Dommisse,Hansen
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p. 5175 - 5182
(2007/10/03)
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- JNK INHIBITOR
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The present invention relates to a c-Jun N-terminal kinase inhibitor containing an azole compound (I) substituted by a nitrogen-containing aromatic group having substituent(s)(except a compound represented by the formula: ) or a salt thereof or a prodrug thereof.
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Page/Page column 91
(2010/02/07)
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- Synthesis and properties of some novel anti-calmodulin drugs
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The preparation and properties of some novel inhibitors of calmodulin function are described. The compounds are cationic derivatives of phenyl-substituted thiazoles which inhibit the calmodulin stimulation of cyclic-AMP phosphodiesterase and are active against animal tumor cells in culture. These derivatives form the basis for the preparation of new, more potent inhibitors of calmodulin function which could take advantage of the reported elevated levels of calcium-bound calmodulin in tumor cells and show preferential anti-tumor activity. Copyright (C) 1999 Elsevier Science Ltd.
- Sakai, Ted T.,Krishna, N. Rama
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p. 1559 - 1565
(2007/10/03)
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- Molecular Structure, Vibrational Spectra and Conformation of the Thiooxalic Acid Derivatives CH3S-CO-CONH2, CH3S-CS-CONH2, C2H5O-CO-CSNH2 and K
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The crystal structures of CH3S-CO-CONH2 (1), CH3S-CS-CONH2 (2), C2H5O-CO-CSNH2 (3) and KOSC-CONH2) (4) have been determined by single crystal X-ray diffraction.The molecules 1, 2 and 3 are nearly planar and form centrosymmetric dimers by N-H...O or N-H...S hydrogen bonds with the amidic oxygen or sulfur atom as acceptor atoms.The anion of 4 is not quite planar.The torsional angle around the C-C bond is 18.4 deg.The conformations of the title compounds are E,Z' (1 and 2), Z,Z' (3) and Z (4).According to the vibrational spectra, which are discussed briefly, 1 and 3 retain their conformation also in solution. - Key words: Molecular Structure, Conformation, Vibrational Spectra, Thiooxalic Acid Derivatives
- Mattes, Rainer,Waldmann, Franz
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p. 335 - 340
(2007/10/02)
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- Compounds, compositions and methods of use
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Compounds, compositions and methods of using the compounds of the formula as anti-allergics STR1 wherein X' is the same as X, X' is at the 3 or 4 position and is STR2
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