155975-19-2Relevant articles and documents
COMPOUNDS, COMPOSITIONS AND METHODS FOR SYNTHESIS
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Paragraph 001626; 001427; 001628; 001629, (2019/01/10)
The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.
Exploiting Chromophore-Protein Interactions through Linker Engineering to Tune Photoinduced Dynamics in a Biomimetic Light-Harvesting Platform
Delor, Milan,Dai, Jing,Roberts, Trevor D.,Rogers, Julia R.,Hamed, Samia M.,Neaton, Jeffrey B.,Geissler, Phillip L.,Francis, Matthew B.,Ginsberg, Naomi S.
supporting information, p. 6278 - 6287 (2018/06/01)
Creating artificial systems that mimic and surpass those found in nature is one of the great challenges of modern science. In the context of photosynthetic light harvesting, the difficulty lies in attaining utmost control over the energetics, positions and relative orientations of chromophores in densely packed arrays to transfer electronic excitation energy to desired locations with high efficiency. Toward achieving this goal, we use a highly versatile biomimetic protein scaffold from the tobacco mosaic virus coat protein on which chromophores can be attached at precise locations via linkers of differing lengths and rigidities. We show that minor linker modifications, including switching chiral configurations and alkyl chain shortening, lead to significant lengthening of the ultrafast excited state dynamics of the system as the linkers are shortened and rigidified. Molecular dynamics simulations provide molecular-level detail over how the chromophore attachment orientations, positions, and distances from the protein surface lead to the observed trends in system dynamics. In particular, we find that short and rigid linkers are able to sandwich water molecules between chromophore and protein, leading to chromophore-water-protein supracomplexes with intricately coupled dynamics that are highly dependent on their local protein environment. In addition, cyclohexyl-based linkers are identified as ideal candidates to retain rotational correlations over several nanoseconds and thus lock relative chromophore orientations throughout the lifetime of an exciton. Combining linker engineering with judicious placement of chromophores on the hydrated protein scaffold to exploit different chromophore-bath couplings provides a clear and effective path to producing highly controllable artificial light-harvesting systems that can increasingly mimic their natural counterparts, thus aiding to elucidate natural photosynthetic mechanisms.
NOVEL NICOTINAMIDE DERIVATIVE OR SALT THEREOF
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Paragraph 1432; 1433, (2014/10/29)
The object of the present invention is to provide a compound and a pharmaceutical composition having excellent Syk inhibitory activity. According to the present invention, a nicotinamide derivative represented by the following formula (I) or a salt thereof is provided, wherein R1 is a substituent represented by the following formula (II-1), (III-1), or (IV-1) (wherein R3, R4, R5, n, and X1 have the same definitions as those described in the specification), and R2 is a pyridyl, indazolyl, phenyl, pyrazolopyridyl, benzisoxazolyl, pyrimidinyl, or quinolyl group, each of which optionally has at least one substituent.
Activation of carboxylic acids in asymmetric organocatalysis
Monaco, Mattia Riccardo,Poladura, Belen,Diaz De Los Bernardos, Miriam,Leutzsch, Markus,Goddard, Richard,List, Benjamin
supporting information, p. 7063 - 7067 (2014/07/08)
Organocatalysis, catalysis using small organic molecules, has recently evolved into a general approach for asymmetric synthesis, complementing both metal catalysis and biocatalysis.1 Its success relies to a large extent upon the introduction of novel and generic activation modes.2 Remarkably though, while carboxylic acids have been used as catalyst directing groups in supramolecular transition-metal catalysis,3 a general and well-defined activation mode for this useful and abundant substance class is still lacking. Herein we propose the heterodimeric association of carboxylic acids with chiral phosphoric acid catalysts as a new activation principle for organocatalysis. This self-assembly increases both the acidity of the phosphoric acid catalyst and the reactivity of the carboxylic acid. To illustrate this principle, we apply our concept in a general and highly enantioselective catalytic aziridine-opening reaction with carboxylic acids as nucleophiles. Activation by dimerization: There is still no general activation mode for carboxylic acids in organocatalysis. The formation of heterodimers between chiral phosphoric acid diesters and carboxylic acids can be used to activate and direct reactivity of the latter in asymmetric reactions. This novel principle has been applied to the ring-opening desymmetrization and kinetic resolution of aziridines leading to valuable amino alcohols.
Helix-forming propensity of aliphatic urea oligomers incorporating noncanonical residue substitution patterns
Pendem, Nagendar,Douat, Celine,Claudon, Paul,Laguerre, Michel,Castano, Sabine,Desbat, Bernard,Cavagnat, Dominique,Ennifar, Eric,Kauffmann, Brice,Guichard, Gilles
supporting information, p. 4884 - 4892 (2013/05/09)
Aliphatic N,N′-linked oligoureas are peptidomimetic foldamers that adopt a well-defined helical secondary structure stabilized by a collection of remote three-center H-bonds closing 12- and 14-membered pseudorings. Delineating the rules that govern helix formation depending on the nature of constituent units is of practical utility if one aims to utilize this helical fold to place side chains in a given arrangement and elaborate functional helices. In this work, we tested whether the helix geometry is compatible with alternative substitution patterns. The central -NH-CH(R)-CH2-NH-CO- residue in a model oligourea pentamer sequence was replaced by guest units bearing various substitution patterns [e.g., -NH-CH2-CH2-NH-CO-, -NH-CH2-CH(R)-NH-CO-, and -NH-CH(R1)-CH(R 2)-NH-CO-], levels of preorganization (cyclic vs acyclic residues), and stereochemistries, and the helix formation was systematically assessed. The extent of helix perturbation or stabilization was primarily monitored in solution by Fourier transform IR, NMR, and electronic circular dichroism spectroscopies. Our results indicate that although three new substitution patterns were accommodated in the 2.5-helix, the helical urea backbone in short oligomers is particularly sensitive to variations in the residue substitution pattern (position and stereochemistry). For example, the trans-1,2- diaminocyclohexane unit was experimentally found to break the helix nucleation, but the corresponding cis unit did not. Theoretical calculations helped to rationalize these results. The conformational preferences in this series of oligoureas were also studied at high resolution by X-ray structure analyses of a representative set of modified oligomers.
Discovery and structure-activity relationships of 4-aminoquinazoline derivatives, a novel class of opioid receptor like-1 (ORL1) antagonists
Okano, Masahiko,Mito, Jun,Maruyama, Yasufumi,Masuda, Hirofumi,Niwa, Tomoko,Nakagawa, Shin-ichiro,Nakamura, Yoshitaka,Matsuura, Akira
experimental part, p. 119 - 132 (2011/02/25)
Synthesis and structure-activity relationship studies of a series of 4-aminoquinazoline derivatives led to the identification of (1R,2S)-17, N-[(1R,2S)-2-({2-[(4-chlorophenyl)carbonyl]amino-6-methylquinazolin-4-yl}amino)cyclohexyl]guanidine dihydrochloride, as a highly potent ORL1 antagonist with up to 3000-fold selectivity over the μ, δ, and κ opioid receptors. Molecular modeling clarified the structural factors contributing to the high affinity and selectivity of (1R,2S)-17.
Novel Compounds
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Page/Page column 14; 55, (2008/06/13)
Compounds of Formulae I, or pharmaceutically acceptable salts thereof: wherein A1, A2, G1, G2 G3, R1, R2, X, Y, Z, m, n and p are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.
Resolution of racemic 2-aminocyclohexanol derivatives and their application as ligands in asymmetric catalysis
Schiffers, Ingo,Rantanen, Toni,Schmidt, Frank,Bergmans, Werner,Zani, Lorenzo,Bolm, Carsten
, p. 2320 - 2331 (2007/10/03)
A preparatively easy and efficient protocol for the resolution of racemic 2-aminocyclohexanol derivatives is described, delivering both enantiomers with >99% enantiomeric excess (ee) by sequential use of (R)- and (S)-mandelic acid. A simple aqueous workup procedure permits the isolation of the amino alcohols in analytically pure form and the almost quantitative recovery of mandelic acid. Debenzylation of enantiopure trans-2-(N-benzyl)amino-1- cyclohexanol by hydrogenation and subsequent derivatization give access to a broad variety of diversely substituted derivatives. Furthermore, the corresponding cis isomers are readily available. Applications of these optically active aminocyclohexanols in catalyzed asymmetric phenyl transfer reactions to benzaldehydes and transfer hydrogenations of aryl ketones lead to products with up to 96% ee.
Synthesis and Evaluation of (1S,2R/1R,2S)-Aminocyclohexylglycyl PNAs As Conformationally Preorganized PNA Analogues for DNA/RNA Recognition
Govindaraju,Kumar, Vaijayanti A.,Ganesh, Krishna N.
, p. 1858 - 1865 (2007/10/03)
Conformationally constrained cis-aminocyclohexylglycyl PNAs have been designed on the basis of stereospecific imposition of 1,2-cis-cyclohexyl moieties on the aminoethyl segment of aminoethylglycyl PNA (aegPNA). The introduction of the cis-cyclohexyl ring
Heterocycle derivatives and drugs
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, (2008/06/13)
There is provided an excellent novel analgesic having an analgesic effect which is effective widely against a pain including a chronic pain or an allodynia accompanied with herpes zoster by acting on a nociceptin receptor. The present invention relates to a compound represented by the following formula: or a salt thereof. In the formula, X and Y are same or different and each represents a nitrogen atom or CH; R1 represents a hydrogen atom or alkyl and the like; A1 and A2 are same or different and each represents a single bond or a divalent aliphatic hydrocarbon group; Q represents a single bond, cycloalkylene group, phenylene group or divalent heterocyclic group; R2A, R2B, R2C and R2D are same or different and each represents a hydrogen atom, alkyl or phenyl; E represents a ethenylene group or —NRCO— (in which R is hydrogen or alkyl) and the like; R3 represents a phenyl group or a heterocyclic group; R4 and R5 are same or different and each represents a hydrogen atom, alkyl, alkoxy, aralkyloxy, halogen, nitro, hydroxy, alkoxycarbonyl, —NR6R7 (in which R6 and R7 are same or different and each represents a hydrogen atom or alkyl) and the like.
