- (4-(([1,2,4]TRIAZOLO[4,3-A]PYRIDINE-6-YL)OXY)-1,2,3,4-TETRAHYDRONAPHTHALEN-1-YL) UREIDO DERIVATIVES AS ANTI-INFLAMMATORY P38 MAPK INHIBITORS FOR TREATING DISEASES OF THE RESPIRATORY TRACT
-
This invention relates to (4-(([l,2,4]triazolo[4,3-a]pyridine-6-yl) oxy)-1,2,3,4-tetrahydronaphthalen-1-yl)ureido derivatives that are p38 MAPK (mitogen activated protein kinase) inhibitors as antiinflammatory agents for treating diseases of the respirato
- -
-
Page/Page column 159; 169
(2019/01/06)
-
- C?H Cyanation of 6-Ring N-Containing Heteroaromatics
-
Heteroaromatic nitriles are important compounds in drug discovery, both for their prevalence in the clinic and due to the diverse range of transformations they can undergo. As such, efficient and reliable methods to access them have the potential for far-reaching impact across synthetic chemistry and the biomedical sciences. Herein, we report an approach to heteroaromatic C?H cyanation through triflic anhydride activation, nucleophilic addition of cyanide, followed by elimination of trifluoromethanesulfinate to regenerate the cyanated heteroaromatic ring. This one-pot protocol is simple to perform, is applicable to a broad range of decorated 6-ring N-containing heterocycles, and has been shown to be suitable for late-stage functionalization of complex drug-like architectures.
- Elbert, Bryony L.,Farley, Alistair J. M.,Gorman, Timothy W.,Johnson, Tarn C.,Genicot, Christophe,Lallemand, Bénédicte,Pasau, Patrick,Flasz, Jakub,Castro, José L.,MacCoss, Malcolm,Paton, Robert S.,Schofield, Christopher J.,Smith, Martin D.,Willis, Michael C.,Dixon, Darren J.
-
supporting information
p. 14733 - 14737
(2017/10/07)
-
- Urea-functionalized M4L6 cage receptors: Anion-templated self-assembly and selective guest exchange in aqueous solutions
-
We present an extensive study of a novel class of de novo designed tetrahedral M4L6 (M = Ni, Zn) cage receptors, wherein internal decoration of the cage cavities with urea anion-binding groups, via functionalization of the organic components L, led to selective encapsulation of tetrahedral oxoanions EO4n- (E = S, Se, Cr, Mo, W, n = 2; E = P, n = 3) from aqueous solutions, based on shape, size, and charge recognition. External functionalization with tBu groups led to enhanced solubility of the cages in aqueous methanol solutions, thereby allowing for their thorough characterization by multinuclear (1H, 13C, 77Se) and diffusion NMR spectroscopies. Additional experimental characterization by electrospray ionization mass spectrometry, UV-vis spectroscopy, and single-crystal X-ray diffraction, as well as theoretical calculations, led to a detailed understanding of the cage structures, self-assembly, and anion encapsulation. We found that the cage self-assembly is templated by EO4n- oxoanions (n ≥ 2), and upon removal of the templating anion the tetrahedral M4L6 cages rearrange into different coordination assemblies. The exchange selectivity among EO4n- oxoanions has been investigated with 77Se NMR spectroscopy using 77SeO42- as an anionic probe, which found the following selectivity trend: PO 43- ? CrO42- > SO 42- > SeO42- > MoO 42- > WO42-. In addition to the complementarity and flexibility of the cage receptor, a combination of factors have been found to contribute to the observed anion selectivity, including the anions' charge, size, hydration, basicity, and hydrogen-bond acceptor abilities.
- Custelcean, Radu,Bonnesen, Peter V.,Duncan, Nathan C.,Zhang, Xiaohua,Watson, Lori A.,Van Berkel, Gary,Parson, Whitney B.,Hay, Benjamin P.
-
supporting information; scheme or table
p. 8525 - 8534
(2012/07/13)
-
- Methods of treatment of amyloidosis using bi-aryl aspartyl protease inhibitors
-
The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
- -
-
Page/Page column 38
(2010/02/15)
-
- METHODS OF TREATMENT OF AMYLOIDOSIS USING ASPARTYL-PROTEASE INHIBITORS
-
The invention relates to acetyl 2-hydroxy-1,3-diaminospirocyclohexanes and derivatives thereof that are useful in treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
- -
-
Page/Page column 149
(2010/02/13)
-
- Synthesis of chiral nonracemic 4-trans-substituted pipecolic acid derivatives
-
The syntheses and resolutions of enantiomerically enriched 4-phenyl, 4- tert-butyl, and 4-isopropyl pipecolic acids are described. Optically active diastereomers were prepared by diastereomeric salt formation with the chiral base, L-tyrosine hydrazide, to
- Keenan, Terence P.,Yaeger, David,Holt, Dennis A.
-
p. 4331 - 4341
(2007/10/03)
-
- Synthesis, Crystal Structure and Catalytic Activities of
-
The compound H2bbpc , which has good solubility in organic solvents, has been prepared.Reaction of with H2bbpc in ethanol and in the presence of triethylamine gave , the crystal structure of which has been determined.This complex is an active catalyst for alkene epoxidation by PhIO, cyclopropanation of styrene by ethyl diazoacetate and aziridination of styrene by PhINO2SC6H4Me-p.Its cyclic voltammogram in dichloromethane showed a reversible Ru(III)-Ru(II) couple at -0.55 V and an oxidation couple at 0.32 V.
- Ko, Po-Hung,Chen, Tai-Yuen,Zhu, Jin,Cheng, Kin-Fai,Peng, Shie-Ming,Che, Chi-Ming
-
p. 2215 - 2220
(2007/10/03)
-
- Antipruritic composition
-
An antipruritic composition for an oral medicine, injection, and external medicine, comprising an effective amount of a chelated zinc (e.g., zinc picolinate) as an antipruritic agent.
- -
-
-
- An Improved Synthesis of Homoproline and Derivatives
-
An improved, general synthesis of substituted homoprolines has been developed by using readily available substituted pyridines (1).A key step in this synthetic procedure involves the known conversion of pyridine-N-oxides to 2-cyanopyridines (3) in nearly quantitative yields.The resulting nitriles are hydrolyzed to the corresponding pyridine-2-carboxylic acids (4).Subsequent reduction of the aromatic ring with PtO2/H2 gives the homoprolines (5) in good yields as racemic cis isomers.This procedure also can be utilized for the preparation of 5,6-benzohomoprolines fromthe appropriate quinoline precursors.The N-tert-butyloxycarbonyl (Boc) derivatives of these amino acids (useful intermediates for peptide synthesis) were also prepared in good yields.
- Shuman, Robert T.,Ornstein, Paul L.,Paschal, Jonathan W.,Gesellchen, Paul D.
-
p. 738 - 741
(2007/10/02)
-
- An Electron Spin Resonance and Voltametric Investigation of Some 2-Mono- and 2,4-Di-substitued Pyridinyl Radicals
-
The chemical reduction of some 2-monosubstitued and 2,4-disubstitued pyridinium ions has been investigated by means of e.s.r. spectroscopy and the result compared with those of an electrochemical study on the same species.By combining the electrochemical and e.s.r. data, a scale of stability has been determined for the investigated pyridinyl radicals.N-Methyl-2-cyanopyridinyl, wich was found to be too unstable to be observed, eventually evolved to the 2,4-dicyano-substitued radical.E.s.r. studies have also been carried out on the structurally similar, although more persistent, N-germylpyridinyls.
- Greci, Lucedio,Alberti, Angelo,Carelli, Italo,Trazza, Antonio,Casini, Antonio
-
p. 2013 - 2018
(2007/10/02)
-