145166-06-9Relevant academic research and scientific papers
COMPOUNDS, COMPOSITIONS AND METHODS FOR SYNTHESIS
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Paragraph 001588; 001589; 001590; 001591; 00756; 00757; 0076, (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.
Hybrid Organo- and Biocatalytic Process for the Asymmetric Transformation of Alcohols into Amines in Aqueous Medium
Liardo, Elisa,Ríos-Lombardía, Nicolás,Morís, Francisco,Rebolledo, Francisca,González-Sabín, Javier
, p. 4768 - 4774 (2017/07/24)
A hybrid organo- and biocatalytic system for the asymmetric conversion of racemic alcohols into amines was developed. Combining an organocatalyst, AZADO, an oxidant, NaOCl, and an enzyme, ω-transaminase, we implemented a one-pot oxidation-transamination sequential process in aqueous medium. The method showed broad substrate scope and was successfully applied to conventional secondary alcohols and sterically hindered β-substituted cycloalkanols, where a highly stereoselective dynamic asymmetric bioamination enabled us to set up both contiguous stereocenters with very high enantio- and diastereomeric ratio (>90% yield, >99% ee, and up to 49:1 dr).
CYCLOHEXANEDIAMINE COMPOUNDS AND METHODS FOR THEIR PREPARATION
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Paragraph 0112; 0113; 0114, (2014/10/04)
The present invention provides processes for the preparation of cyclohexanediamine compounds of formula Ia and intermediates thereof. The compounds are useful as Syk kinase inhibitors and in various pharmaceutical compositions, and particularly useful for treating conditions mediated at least in part by Syk kinase activity.
Chemoenzymatic preparation of optically active trans- and cis-cyclohex-4-ene-1,2-diamine and trans-6-aminocyclohex-3-enol derivatives
Quijada, F. Javier,Rebolledo, Francisca,Gotor, Vicente
, p. 7670 - 7674 (2012/09/21)
Lipase from Burkholderia cepacia (PSL-C) effectively catalyzed the kinetic resolution of both racemic trans-N,N-diallylcyclohex-4-ene-1,2-diamine (±)-6 and its precursor trans-6-(diallylamino)cyclohex-3-enol (±)-5. The resulting optically active vicinal diamine and β-amino alcohol were converted into a precursor of oseltamivir and a cis-cyclohex-4-ene-1,2-diamine derivative, respectively.
4 - [CYCLOALKYLOXY (HETERO) ARYLAMINO] THIENO [2, 3 - D] PYRIMIDINES HAVING MNKL/ MNK2 INHIBITING ACTIVITY FOR PHARMACEUTICAL COMPOSITIONS
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Page/Page column 63-64, (2011/09/30)
The present invention relates to novel thienopyrimidine compounds of general formula (I), pharmaceutical compositions comprising these compounds and their therapeutic use for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2a or Mnk2b) and/or variants thereof.
SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS mTOR INHIBITORS
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Page/Page column 130; 131, (2011/04/14)
Compounds of Formula I: and salts thereof in which R1, R2, R2a, R3, n, X and ring B have the meanings given in the specification, are inhibitors of mTOR and are useful in the treatment of diseases which are sensitive to inhibition of mTOR, such as cancers.
Synthesis of annulated 1,4-dioxanes and perhydro-1,4-oxazines by domino-wacker-carbonylation and domino-wacker-mizoroki-heck reactions
Tietze, Lutz F.,Heins, Arne,Soleiman-Beigi, Mohammad,Raith, Christian
experimental part, p. 1123 - 1146 (2010/10/20)
Palladium(II) -catalyzed domino reactions for the formation of 1,4-dioxanes and perhydro-1,4-oxazines starting from hydroxy alkenes are described. The domino-Wacker-carbonylation comprises a Wacker oxidation, subsequent CO-insertion and a nucleophilic substitution of the intermediately formed Pd-species. The domino-Wacker-Mizoroki-Heck reaction proceeds via a Wacker oxidation, subsequent insertion into the olefinic π-bond of α,β-unsatura-ted carbonyl compounds and β-hydride elimination.
Intramolecular azide-alkyne [3 + 2] cycloaddition: Versatile route to new heterocyclic structural scaffolds
Li, Rongti,Jansen, Daniel J.,Datta, Apurba
experimental part, p. 1921 - 1930 (2009/06/28)
Investigating the relatively unexplored intramolecular version of the azide-alkyne [3 + 2] cycloaddition, the present studies demonstrate the utility of the above reaction in the synthesis of a variety of as yet unreported heterocyclic structural scaffolds. The approach involved initial installation of strategic azide and alkyne moieties on a common structural framework, followed by their intramolecular cycloaddition studies. The pivotal azidoalkyne intermediates were efficiently accessed from a variety of easily available starting materials such as olefins, epoxides, amino acids, amino alcohols, ketones etc. The key reactions for incorporation of the azide functionality into the desired framework involved azidolysis of epoxides, displacement of hydroxy groups with azide nucleophiles, and diazo transfer on amine. Attachment of the desired alkyne functionalities was accomplished by either N-, or, O-alkylation with appropriate propargylic halides. The azidoalkynes thus prepared underwent smooth intramolecular cycloaddition, resulting in a variety of novel triazolooxazine and triazolopyrazine derivatives. Interestingly, unlike in the intermolecular version, metal catalysis was not necessary for the performance of the above cycloadditions. It is expected that the results from the present studies and its further extension will provide a potentially fertile pathway to a variety of unique chemical entities of structural and biological significance.
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.
