10242-36-1Relevant articles and documents
A Biocatalytic Synthesis of Heteroaromatic N-Oxides by Whole Cells of Escherichia coli Expressing the Multicomponent, Soluble Di-Iron Monooxygenase (SDIMO) PmlABCDEF
Petkevi?ius, Vytautas,Vaitekūnas, Justas,Taurait?, Daiva,Stankevi?iūt?, Jonita,?arlauskas, Jonas,??nas, Narimantas,Me?kys, Rolandas
, p. 2456 - 2465 (2019)
Aromatic N-oxides (ArN?OX) are desirable biologically active compounds with a potential for application in pharmacy and agriculture industries. As biocatalysis is making a great impact in organic synthesis, there is still a lack of efficient and convenient enzyme-based techniques for the production of aromatic N-oxides. In this study, a recombinant soluble di-iron monooxygenase (SDIMO) PmlABCDEF overexpressed in Escherichia coli was showed to produce various aromatic N-oxides. Out of 98 tested N-heterocycles, seventy were converted to the corresponding N-oxides without any side oxidation products. This whole-cell biocatalyst showed a high activity towards pyridines, pyrazines, and pyrimidines. It was also capable of oxidizing bulky N-heterocycles with two or even three aromatic rings. Being entirely biocatalytic, our approach provides an environmentally friendly and mild method for the production of aromatic N-oxides avoiding the use of strong oxidants, organometallic catalysts, undesirable solvents, or other environment unfriendly reagents. (Figure presented.).
Insights into the mechanistic and synthetic aspects of the Mo/P-catalyzed oxidation of N-heterocycles
Larionov, Oleg V.,Stephens, David,Mfuh, Adelphe M.,Arman, Hadi D.,Naumova, Anastasia S.,Chavez, Gabriel,Skenderi, Behije
, p. 3026 - 3036 (2014)
A Mo/P catalytic system for an efficient gram-scale oxidation of a variety of nitrogen heterocycles to N-oxides with hydrogen peroxide as terminal oxidant has been investigated. Combined spectroscopic and crystallographic studies point to the tetranuclear Mo4P peroxo complex as one of the active catalytic species present in the solution. Based on this finding an optimized catalytic system has been developed. The utility and chemoselectivity of the catalytic system has been demonstrated by the synthesis of over 20 heterocyclic N-oxides.
METAL CHELATING COMPOUNDS FOR USE IN TREATING DISEASES
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Page/Page column 25 ; 26, (2016/06/20)
The present invention relates to heterocyclic compounds for use in the treatment of diseases. In particular, the invention relates to heterocyclic compounds for use in the treatment of neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, and methods of making and using the same. The heterocycle compounds contain at least one electronegative atom and comprise a hydroxyl group or substituted hydroxyl group at the 1-position and the carbon at the 2-position being a carbonyl group.
2,2,2-Trifluoroacetophenone as an organocatalyst for the oxidation of tertiary amines and azines to N-oxides
Limnios, Dimitris,Kokotos, Christoforos G.
supporting information, p. 559 - 563 (2014/04/03)
A cheap, mild and environmentally friendly oxidation of tertiary amines and azines to the corresponding Noxides is reported by using polyfluoroalkyl ketones as efficient organocatalysts. 2,2,2-Trifluoroacetophenone was identified as the optimum catalyst for the oxidation of aliphatic tertiary amines and azines. This oxidation is chemoselective and proceeds in high-to-quantitative yields utilizing 10 mol% of the catalyst and H2O2 as the oxidant.
AMINONITRILES AS KYNURENINE PATHWAY INHIBITORS
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Page/Page column 91, (2014/09/29)
The present application provides novel kynurenine pathway inhibitors and pharmaceutically acceptable salts and prodrugs thereof. Also provided are methods for preparing these compounds. These compounds are useful in regulating the kynurenine pathway and the activity of indoleamine 2,3-dioxygenase and/or tryptophan 2,3-dioxygenase by administering a therapeutically effective amount of one or more of the compounds of formula (I) to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the kynurenine pathway. A variety of conditions can be treated using these compounds and include diseases which are characterized by immunosuppression, abnormal cellular proliferation and/or inflammation. In one embodiment, the disease is cancer. In another embodiment, the disease is a viral infection. In a further embodiment, the disease is depression.
Design, synthesis, and evaluation of a lanthanide chelating protein probe: CLaNP-5 yields predictable paramagnetic effects independent of environment
Keizers, Peter H. J.,Saragliadis, Athanasios,Hiruma, Yoshitaka,Overhand, Mark,Ubbink, Marcellus
experimental part, p. 14802 - 14812 (2009/02/08)
Immobilized lanthanide ions offer the opportunity to refine structures of proteins and the complexes they form by using restraints obtained from paramagnetic NMR experiments. We report the design, synthesis, and spectroscopic evaluation of the lanthanide chelator, Caged Lanthanide NMR Probe 5 (CLaNP-5) readily attachable to a protein surface via two cysteine residues. The probe causes tunable pseudocontact shifts, alignment, paramagnetic relaxation enhancement, and luminescence, by chelating it to the appropriate lanthanide ion. The observation of single shifts and the finding that the magnetic susceptibility tensors obtained from shifts and alignment analyses are highly similar strongly indicate that the probe is rigid with respect to the protein backbone. By placing the probe at various positions on a model protein it is demonstrated that the size and orientation of the magnetic susceptibility tensor of the probe are independent of the local protein environment. Consequently, the effects of the probe are readily predictable using a protein structure only. These findings designate CLaNP-5 as a protein probe to deliver unambiguous high quality structural restraints in studies on protein-protein and protein-ligand interactions.
(N-Arylaminomethyl)pyridine-N-oxides: Synthesis and characterization of potential ligand systems and the formation of their N,O-chelate aluminum complexes
Nienkemper, Katrin,Kehr, Gerald,Kehr, Seda,Fr?hlich, Roland,Erker, Gerhard
, p. 3063 - 3073 (2008/12/22)
Pyridine-N-oxide-2-carbaldehyde (4a) was converted to the corresponding imine (5a) by treatment with 2,6-diisopropylaniline. Subsequent reduction with a sodium borohydride gave the corresponding (N-arylaminomethyl)pyridine-N-oxide derivative (6a). A series of analogous compounds was prepared starting from the respective (aldimino)quinoline-N-oxide (4b) or (ketimino)pyridine-N-oxide (10) systems. Deprotonation of the (aminomethyl)pyridine-N-oxides resulted in a series of unexpected reactions, such as coupling, internal redox reactions or fragmentation. Eventually, the N,O-chelate aluminum complexes (22, 23) derived from the (aminoethyl)pyridine-N-oxide ligand systems could be obtained by treatment of the respective iminopyridine-N-oxides with trimethylaluminum. Many products were characterized by X-ray diffraction.
Gonadotropin releasing hormone receptor antagonists
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Page/Page column 26, (2010/02/15)
The present invention relates to Gonadotropin Releasing Hormone (“GnRH”) (also known as Leutinizing Hormone Releasing Hormone) receptor antagonists.
Bis(oxazoline) lewis acid catalyzed aldol reactions of pyridine N-oxide aldehydes-synthesis of optically active 2-(1-hydroxyalkyl)pyridine derivatives: Development, scope, and total synthesis of an indolizine alkaloid
Landa, Aitor,Minkkilae, Anna,Blay, Gonzalo,Jergensen, Karl Anker
, p. 3472 - 3483 (2008/02/03)
A new. short, and simplified procedure for the synthesis of optically active pyridine derivatives from prochiral pyridine-N-oxides is presented. The catalytic and asymmetric Mukaiyama aldol reaction between ketene silyl acetals and l-oxypyridine-2-carhaldehyde derivatives catalyzed by chiral copper(ii)-bis(oxazoline) complexes gave optically active 2-(hydroxyalkyl)-and 2-(anti-1.2-dihydroxyalkyl)pyridine derivatives in good yields and diastereoselectivities, and in excellent enantioselectivities - up to 99% enantiomeric excess. As a synthetic application of the developed method, a full account for the asymmetric total synthesis of a nonnatural indolizine alkaloid is provided.
PHARMACEUTICAL COMPOUNDS
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Page/Page column 77-78, (2008/06/13)
Fused pyrimidines of formula (I); wherein A represents a thiophene or furan ring; n is 1 or 2; R1 is a group of formula (II); wherein m is 0 or 1; R30 is H or C1-C6 alkyl; R4 and R5 form, together with the N atom to which they are attached, a 5- or 6-membered saturated N-containing heterocyclic group which includes 0 or 1 additional heteroatoms selected from N, S and O, which may be fused to a benzene ring and which is unsubstituted or substituted; or one of R4 and R5 is alkyl and the other is a 5- or 6-membered saturated N-containing heterocyclic group as defined above or an alkyl group which is substituted by a 5- or 6-membered saturated N-containing heterocyclic group as defined above; R2 is selected from formula (a); wherein R6 and R7 form, together with the nitrogen atom to which they are attached, a morpholine, thiomorpholine, piperidine, piperazine, oxazepane or thiazepane group which is unsubstituted or substituted; and formula (b); wherein Y is a C2-C4 alkylene chain which contains, between constituent carbon atoms of the chain and/or at one or both ends of the chain, 1 or 2 heteroatoms selected from O, N and S, and which is unsubstituted or substituted; and R3 is an indazole group which is unsubstituted or substituted; and the pharmaceutically acceptable salt thereof have activity as inhibitors of P13K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with P13 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.
