- Synthesis and characterization of 4(R)-epimer impurities of zanamivir and laninamivir octanoate
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The synthesis and characterization of compounds 7c and 8d, the 4(R)-epimer impurities of zanamivir and laninamivir octanoate, were reported for the first time. Their structures were confirmed by NMR and MS and distinguished from their corresponding active pharmaceutical ingredient (API) by coupling constant in 1H NMR and HPLC spectra. This work is of great significance for the drug-related substances analysis in zanamivir and laninamivir octanoate.
- Bi, Siju,Chen, Liang,Duan, Chuanqi,Lin, Kuaile,Liu, Weiyuan,Pan, Jing,Zhou, Ting,Zhou, Weicheng
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- Hitting a Moving Target: Simulation and Crystallography Study of ATAD2 Bromodomain Blockers
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Small molecule ligand binding to the ATAD2 bromodomain is investigated here through the synergistic combination of molecular dynamics and protein crystallography. A previously unexplored conformation of the binding pocket upon rearrangement of the gatekeeper residue Ile1074 has been found. Further, our investigations reveal how minor structural differences in the ligands result in binding with different plasticity of the ZA loop for this difficult-to-drug bromodomain.
- Dolbois, Aymeric,Batiste, Laurent,Wiedmer, Lars,Dong, Jing,Brütsch, Manuela,Huang, Danzhi,Deerain, Nicholas M.,Spiliotopoulos, Dimitrios,Cheng-Sánchez, Iván,Laul, Eleen,Nevado, Cristina,?led?, Pawe?,Caflisch, Amedeo
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supporting information
p. 1573 - 1580
(2020/09/16)
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- RADIOIODINATED COMPOUNDS
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This disclosure relates to reagents and methods useful in the synthesis of aryl iodines, for example, in the preparation of iodine labeled radiotracers. The reagents and methods provided herein may be used to access a broad range of compounds, including aromatic compounds, heteroaromatic compounds, amino acids, nucleotides, and synthetic compounds.
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Page/Page column 39
(2015/12/08)
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- PYRROLOPYRIMIDINE AND PURINE DERIVATIVES
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The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Q, T, V, W, X, Y, Z, ring A, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 and m are defined herein. There novel pyrrolopyrimidine and purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.
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- Structure-activity relationship study on α1 adrenergic receptor antagonists from beer
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Hordatine A and aperidine have been previously isolated from beer as active ingredients, which bind to muscarinic M3 receptor. In addition, these compounds have exhibited antagonist activity against the α1A adrenoceptor. Although the relative structures of these two molecules have previously been determined, the absolute stereochemistry was unclear. Hence, to elucidate the absolute stereochemistry of natural hordatine A, we synthesized each enantiomer of hordatine A and aperidine from optically pure dehydrodi-p-coumaric acid. Several additional related compounds were also synthesized for structure-activity relationship studies. Chiral column HPLC analysis demonstrated that the absolute stereochemistry of natural hordatine A is (2S,3S), while based on the isomerization mechanism, the stereochemistry of aperidine is (2R,3S). The α1A adrenoceptor binding activity of (2R,3R)-hordatine A is the most potent among the enantiomeric pairs of hordatines and aperidines. Furthermore, the related, synthetic compound, (2R,3R)-methyl benzofurancarboxylate exhibits antagonist activity against the α1A adrenoceptor at a lower concentration than that of hordatine A.
- Wakimoto, Toshiyuki,Nitta, Makoto,Kasahara, Kana,Chiba, Taketo,Yiping, Ye,Tsuji, Kuniro,Kan, Toshiyuki,Nukaya, Haruo,Ishiguro, Masaji,Koike, Minako,Yokoo, Yoshiaki,Suwa, Yoshihide
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scheme or table
p. 5905 - 5908
(2010/06/13)
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- METHOD FOR MANUFACTURING NEURAMINIC ACID DERIVATIVES
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A method for manufacturing neuraminic acid derivatives is provided, also synthetic intermediates of the neuraminic acid derivatives and methods for their manufacture, and neuraminic acid derivatives having high purity. [Means for solution] A synthetic intermediate compound represented by the formula (7) is provided: [wherein R3 represents alkyl; R4 and R5 each represents H, alkyl, phenyl, or together represent tetramethylene, pentamethylene, oxo].
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Page/Page column 78-79
(2008/12/08)
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- Non-peptide GnRH agents, methods and intermediates for their preparation
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Non-peptide GnRH agents capable of inhibiting the effect of gonadotropin-releasing hormone are described. Such compounds and their pharmaceutically acceptable salts, multimers, prodrugs, and active metabolites are suitable for treating mammalian reproductive disorders and steroid hormone-dependent tumors as well as for regulating fertility, where suppression of gonadotropin release is indicated. Methods for synthesizing the compounds and intermediates useful in their preparation are also described.
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Page/Page column 18
(2008/06/13)
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- Optimisation of the synthesis of guanidines from amines via nitroguanidines using 3,5-dimethyl-N-nitro-1H-pyrazole-1-carboxamidine
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The synthesis of the useful reagent for the preparation of guanidines, 3,5-dimethyl-N-nitro-1-pyrazole-1-carboxamidine (DMNPC), has been optimised. A detailed protocol for using this reagent for the preparation in pure form of a range of guanidines via nitroguanidines is described. A comparison has been made regarding efficiency between DMNPC and the guanidinylating reagents N,N′-bis-Boc-1-pyrazole-1-carboxamidine (2) and N,N′-bis-Boc- N′-triflylguanidine (3).
- Castillo-Melendez, Joel A.,Golding, Bernard T.
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p. 1655 - 1663
(2007/10/03)
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- Non-peptide GnRH agents
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Non-peptide GnRH agents capable of inhibiting the effect of gonadotropin-releasing hormone are of the following general formula, where X1, X2, Y, and are defined variables: Such compounds and their pharmaceutically acceptable salts, multimers, prodrugs, and active metabolites are suitable for treating mammalian reproductive disorders and steroid hormone-dependent tumors as well as for regulating fertility, where suppression of gonadotropin release is indicated. Methods for synthesizing the compounds and intermediates useful in their preparation are also described.
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- Transfection particles
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Transfection particles for delivery of nucleic acid into higher eucaryotic cells in vitroand in vivocomprises one or more nucleic acid molecules condensed by organic cationic molecules. The discrete and stable particles are obtained by complexing the nucleic acid molecules with identical or different organic cationic precursor molecules without crosslinking nucleic acid molecules, and covalently linking the precursor molecules to each other on the nucleic acid template. For specific cellular targeting, the particles may carry targeting molecules, e.g. sugars. Preferred cationic precursor molecules are lipophilic detergents that are linked to form lipids. The particles contain preferably only one nucleic acid molecule which makes them useful for gene therapy and for delivery of large DNA molecules.
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- A convenient preparation of monosubstituted N,N'-di(Boc)-protected guanidines
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1-H-Pyrazole-1-[N,N'-bis(tert-butoxycarbonyl)]carboxamidine (1) reacts under mild conditions with a number of amines and amino acids to give the respective protected guanidines in moderate to high isolated yields.
- Drake,Patek,Lebl
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p. 579 - 582
(2007/10/02)
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- An efficient method for the preparation of ω,ω'-bis-urethane protected arginine derivatives
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Fmoc-Arg(ω,w')(Boc)2-OH and Boc-Arg(ω,w')(Cbz)2-OH were prepared in two steps: Guanylation of Cu(II)-ornithine complex at N(δ) with N,N'-bis urethane protected derivatives of 1-guanylpyrazole, followed by N(α)-protection using either 9-fluorenylmethyl succinimidylcarbonate or di-t-butyl-dicarbonate in the presence of EDTA. The overall yields of these products (2 steps) were 65% and 73%.
- Wu,Matsueda,Bernatowicz
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p. 3055 - 3060
(2007/10/02)
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- Urethane protected derivatives of 1-guanylpyrazole for the mild and efficient preparation of guanidines
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Bis-urethane protected derivatives of 1-guanylpyrazole were prepared and found to readily react with relatively amines at room temperature to produce bis-protected guanidines in good yields. Simultaneous removal of both protecting groups from these products efficiently produced monosubstituted guanadines.
- Bernatowicz, Michael S.,Wu, Youling,Matsueda, Gary R.
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p. 3389 - 3392
(2007/10/02)
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