- Generation of Alkoxyl Radicals by Photoredox Catalysis Enables Selective C(sp3)-H Functionalization under Mild Reaction Conditions
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Reported herein is the first visible-light-induced formation of alkoxyl radicals from N-alkoxyphthalimides, and the Hantzsch ester as the reductant is crucial for the reaction. The selective hydrogen atom abstraction by the alkoxyl radical enables C(sp3)-H allylation and alkenylation reactions under mild reaction conditions at room temperature. Broad substrate variations, including a structurally complexed steroid, undergo the C(sp3)-H functionalization reaction effectively with high regio- and chemoselectivity.
- Zhang, Jing,Li, Yang,Zhang, Fuyuan,Hu, Chenchen,Chen, Yiyun
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supporting information
p. 1872 - 1875
(2016/02/03)
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- Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
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The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.
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- Synthesis and structure-activity relationship (SAR) of 2-methyl-4-oxo-3- oxetanylcarbamic acid esters, a class of potent N-acylethanolamine acid amidase (NAAA) inhibitors
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N-Acylethanolamine acid amidase (NAAA) is a lysosomal cysteine hydrolase involved in the degradation of saturated and monounsaturated fatty acid ethanolamides (FAEs), a family of endogenous lipid agonists of peroxisome proliferator-activated receptor-α, which include oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). The β-lactone derivatives (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide (2) and (S)-N-(2-oxo-3-oxetanyl)- biphenyl-4-carboxamide (3) inhibit NAAA, prevent FAE hydrolysis in activated inflammatory cells, and reduce tissue reactions to pro-inflammatory stimuli. Recently, our group disclosed ARN077 (4), a potent NAAA inhibitor that is active in vivo by topical administration in rodent models of hyperalgesia and allodynia. In the present study, we investigated the structure-activity relationship (SAR) of threonine-derived β-lactone analogues of compound 4. The main results of this work were an enhancement of the inhibitory potency of β-lactone carbamate derivatives for NAAA and the identification of (4-phenylphenyl)-methyl-N-[(2S,3R)-2-methyl-4-oxo-oxetan-3-yl]carbamate (14q) as the first single-digit nanomolar inhibitor of intracellular NAAA activity (IC50 = 7 nM on both rat NAAA and human NAAA).
- Ponzano, Stefano,Bertozzi, Fabio,Mengatto, Luisa,Dionisi, Mauro,Armirotti, Andrea,Romeo, Elisa,Berteotti, Anna,Fiorelli, Claudio,Tarozzo, Glauco,Reggiani, Angelo,Duranti, Andrea,Tarzia, Giorgio,Mor, Marco,Cavalli, Andrea,Piomelli, Daniele,Bandiera, Tiziano
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p. 6917 - 6934
(2013/10/01)
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- DISUBSTITUTED BETA-LACTONES AS INHIBITORS OF N-ACYLETHANOLAMINE ACID AMIDASE (NAAA)
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The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.
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- OXAZOLE AND THIAZOLE DERIVATIVES AND THEIR USES
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A quaternary ammonium compound of formula (I) having M3 receptor antagonist activity; a composition comprising such a compound; the use of such a compound in therapy (such as asthma or COPD); and a method of treating a patient with such a compound.
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Page/Page column 34
(2008/12/08)
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- AGONISTS OF THE SPHINGOSINE- 1- PHOSPHATE RECEPTOR (SLP)
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The invention provides compounds of formula I and formula II, their preparation, a their use as pharmaceutically active immunosuppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, as well as other disorders modulated by lymphopenia or SlP receptors.
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Page/Page column 79-80
(2008/06/13)
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- PHENETHANOLAMINE DERIVATIVES AS BETA2 ADRENORECEPTOR AGONISTS
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The present invention relates to compounds according to formula (I), a process for preparing them, the intermediate compounds of the process and the use of the compounds in the manufacture of a medicament for use in treating diseases such as ARDS, pulmonary emphysema, bronchitis, bronchiectasis, COPD, asthma and rhinitis. The compounds are beta2 adrenoreceptor agonists.
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Page/Page column 102
(2008/06/13)
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- Reductive cleavage of the C-O bond of acetals and orthoesters: Reduction by silane in the presence of a Rh-PPh3 complex
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Reductions of acetals to ethers and of orthoester to acetal by hydrosilane using rhodium catalyst are described.
- Ohta, Tetsuo,Michibata, Tsugumi,Yamada, Kazuyuki,Omori, Ryohei,Furukawa, Isao
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p. 1192 - 1193
(2007/10/03)
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- Stamping of monomeric SAMs as a route to structured crystallization templates: Patterned titania films
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Gold-coated glass slides have be patterned by using self-assembled monolayers (SAM) of alkane thiols. Through the use of a special thiol terminated with a styrene monomer, microstructures of 5 to 10 μm width and 70 A height have been formed on the surface
- Bartz, Marcus,Terfort, Andreas,Knoll, Wolfgang,Tremel, Wolfgang
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p. 4149 - 4153
(2007/10/03)
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- Ethoxylation of aralkyl alcohols
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An important reaction, the oligoaddition of ethylene oxide to the alcoholic hydroxyl group was investigated.The aralkyl alcohols were chosen as base material: benzyl-, β-phenylethyl- and γ-phenylpropyl alcohols.The first members of their homologue ethoxylated series were prepared and used as standards for the determination of the average degree of ethoxylation (IR, UV, refractive indices) and of the molar mass distribution (HPLC).
- Huszar, Klara Parlagh,Klug, Otto,Parlagh, Gyula,Rusznak, Istvan,Sallay, Peter,et al.
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p. 241 - 252
(2007/10/03)
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- Homogeneous hydroxyethylation of phenyl-substituted alcohols
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Homogeneous glycol ether derivatives of phenyl group substituted alcohols (benzyl-, β-phenyl ethyl- and γ-phenyl propyl-) were synthesised by repeated Williamson synthesis starting in two cases from the halogen derivatives of the corresponding alcohols. In the case of β-phenylethanol the first homologue was prepared in the reaction of benzyl group protected ethylene chlorohydrine and β-phenyl-ethyl alcohol. The reaction product was hydrogenolysed (removing the benzyl group by hydrogenolyzis), halogenated and used to the synthesis of higher homologues as starting material.
- Sallay, Peter,Ahmed, Mohamed H. M.,Rusznak, Istvan,Farkas, Laszlo,Tungler, Antal
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- β1-Selective Adrenoceptor Antagonists. 2. 4-Ether-Linked Phenoxypropanolamines
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A series of 4-substituted phenoxypropanolamines was prepared and examined for β-adrenoceptor activity.Some of the compounds, especially the oxy>ethoxy>phenoxy>propanolamines (14, 15, and 24), showed potent β1-blo
- Machin, Peter J.,Hurst, David N.,Bradshaw, Rachel M.,Blaber, Leslie C.,Burden, David T.,et al.
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p. 1570 - 1576
(2007/10/02)
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