- Rational design of a new class of toll-like receptor 4 (tlr4) tryptamine related agonists by means of the structure- and ligand-based virtual screening for vaccine adjuvant discovery
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In order to identify novel lead structures for human toll-like receptor 4 (hTLR4) modulation virtual high throughput screening by a peta-flops-scale supercomputer has been performed. Based on the in silico studies, a series of 12 compounds related to tryptamine was rationally designed to retain suitable molecular geometry for interaction with the hTLR4 binding site as well as to satisfy general principles of drug-likeness. The proposed compounds were synthesized, and tested by in vitro and ex vivo experiments, which revealed that several of them are capable to stimulate hTLR4 in vitro up to 25% activity of Monophosphoryl lipid A. The specific affinity of the in vitro most potent substance was confirmed by surface plasmon resonance direct-binding experiments. Moreover, two compounds from the series show also significant ability to elicit production of interleukin 6.
- Honegr, Jan,Dolezal, Rafael,Malinak, David,Benkova, Marketa,Soukup, Ondrej,De Almeida, Joyce S. F. D.,Franca, Tanos C. C.,Kuca, Kamil,Prymula, Roman
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- Synthesis of 3,3-disubstituted oxindoles by palladium-catalyzed asymmetric intramolecular α-arylation of amides: Reaction development and mechanistic studies
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Palladium complexes incorporating chiral N-heterocyclic carbene (NHC) ligands catalyze the asymmetric intramolecular α-arylation of amides producing 3,3-disubstituted oxindoles. Comprehensive DFT studies have been performed to gain insight into the mechanism of this transformation. Oxidative addition is shown to be rate-determining and reductive elimination to be enantioselectivity-determining. The synthesis of seven new NHC ligands is detailed and their performance is compared. One of them, L8, containing a tBu and a 1-naphthyl group at the stereogenic centre, proved superior and was very efficient in the asymmetric synthesis of fifteen new spiro-oxindoles and three azaspiro-oxindoles often in high yields (up to 99 %) and enantioselectivities (up to 97 % ee; ee=enantiomeric excess). Three palladacycle intermediates resulting from the oxidative addition of [Pd(NHC)] into the aryl halide bond were isolated and structurally characterized (X-ray). Using these intermediates as catalysts showed alkene additives to play an important role in increasing turnover number and frequency. Copyright
- Katayev, Dmitry,Jia, Yi-Xia,Sharma, Akhilesh K.,Banerjee, Dipshikha,Besnard, Celine,Sunoj, Raghavan B.,Kuendig, E. Peter
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supporting information
p. 11916 - 11927
(2013/09/23)
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- BICYCLOANILINE DERIVATIVE
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The invention relates to a compound of a general formula (I): wherein A1 and A2 each mean a nitrogen atom or an optionally-substituted methine group; Ring B means a 5-membered to 7-membered aliphatic ring, or a spiro or bicyclo ring formed from the aliphatic ring and any other 3-membered to 7-membered aliphatic ring; R1 means a hydrogen atom, or an optionally-substituted C1-C6 alkyl group, or an optionally-substituted aryl, aralkyl or heteroaryl group; R2 means an optionally-substituted aryl, aralkyl or heteroaryl group; and X means a group of =NH or =O, etc. Based on its excellent Wee1 kinase-inhibitory effect, the compound of the invention has cell growth-inhibitory effect and has an additive/synergistic effect with any other anticancer agent, and is therefore useful in the field of medicine.
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Page/Page column 67
(2010/04/25)
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- MEDICAMENTS
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A compound of formula (I) is described: wherein R1 and R2 are as defined in the text and wherein the compounds are intended for use in treating medical conditions characterized by an imbalance in dopamine receptor activity.
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Page/Page column 72
(2009/06/27)
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- NOVEL 2 AMINO-PYRIMIDINE DERIVATIVES, PROCESSES FOR PREPARING THEM, PHARMACEUTICAL COMPOSITIONS THEREOF
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The present invention concerns novel 2 amino pyrimidine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals.
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Page/Page column 164-165
(2008/06/13)
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- Norcaradienes from the intramolecular cyclopropanation reactions of diazomethyl ketones. Valuable intermediates for the synthesis of polycyclic diterpenes
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The intramolecular cyclopropanation reactions of the aromatic ring in tetrahydronaphthyl diazomethyl ketones initiated by rhodium(II) and copper(II) derived transition metal catalysts afford stable norcaradiene products. Further elaboration has led to pentacyclic structures that have considerable potential for the expeditious synthesis of complex polycyclic diterpenes.
- Morris, Jonathan C.,Mander, Lewis N.,Hockless, David C. R.
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p. 455 - 467
(2007/10/03)
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- Aromatic amine derivatives
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This invention relates to novel aromatic amine compounds having the structure: STR1 where each W, Z1 and Z2 is independently H, C1 -C6 alkyl, C1 -C6 alkoxy, OH, F, Cl, Br, I, NO2, CN, SO2 NHR3, NR42, CONR32, COR5 ; where each R1 and R2 is independently H, C1 -C6 straight or branched chain alkyl or phenyl; where each X and Y is independently CH2, NR4, S, S=O, SO2 ; where n is 0, 1 or 2; where each p and q is independently 1 or 2; where R3 is H, C1 -C6 straight or branched chain alkyl or phenyl; where R4 is H, C1 -C6 straight or branched chain alkyl or COR3 ; and where R5 is H, C1 -C6 straight or branched chain alkyl or phenyl, C1 -C6 straight or branched chain alkoxy or OH. In addition the invention includes using such compounds for the treatment of benign prostatic hyperplasia, lowering intraocular pressure and inhibiting cholesterol synthesis.
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