- Small Molecule Analogs of the Nemo Binding Peptide
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The invention is directed to a method of inhibiting, within a living cell, the interaction between NF-κB essential modulator (“NEMO”) with IκB kinase-β (IKK-β) at the NEMO binding domain (NBD), comprising exposing the cell to an effective amount or concentration of a compound of the invention, a NEMO-binding domain analog (NBDA). The invention is further directed to a method of treating a condition in a patient, wherein inhibiting the interaction between NF-κB essential modulator (“NEMO”) with IκB kinase-β (IKK-β) at the NEMO binding domain (NBD) is medically indicated, comprising administering to the patient an effective dose of a compound of the invention. Conditions that can be treated by a method of the invention includes muscular dystrophy, asthma, inflammatory bowel disease, multiple sclerosis, Parkinson's Disease, arthritis, diabetes, graft versus host disease, accelerated aging, heart ischemia, cancer, UV-induced skin damage, or an age-related pathology.
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- Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates
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The structure-activity relationship of a series of dihydroisoquinoline BACE-1 inhibitors is described. Application of structure-based design to screening hit 1 yielded sub-micromolar inhibitors. Replacement of the carboxylic acid of 1 was guided by X-ray
- Bowers, Simeon,Xu, Ying-Zi,Yuan, Shendong,Probst, Gary D.,Hom, Roy K.,Chan, Wayman,Konradi, Andrei W.,Sham, Hing L.,Zhu, Yong L.,Beroza, Paul,Pan, Hu,Brecht, Eric,Yao, Nanhua,Lougheed, Julie,Tam, Danny,Ren, Zhao,Ruslim, Lany,Bova, Michael P.,Artis, Dean R.
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p. 2181 - 2186
(2013/04/23)
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- NOVEL COMPOUNDS
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The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R1, R2, R3 and R4 are defined as mentioned in the description, the tautomers thereof, the isomers thereof, the diastereomers thereof, the enantiomers thereof, the hydrates thereof, the mixtures thereof and the salts thereof as well as the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, the use thereof and processes for the preparation thereof.
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Page/Page column 88
(2011/08/22)
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- Pd(II)-catalyzed hydroxyl-directed C-H olefination enabled by monoprotected amino acid ligands
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A novel Pd(II)-catalyzed ortho-C-H olefination protocol has been developed using spatially remote, unprotected tertiary, secondary, and primary alcohols as the directing groups. Mono-N-protected amino acid ligands were found to promote the reaction, and an array of olefin coupling partners could be used. When electron-deficient alkenes were used, the resulting olefinated intermediates underwent subsequent Pd(II)-catalyzed oxidative intramolecular cyclization to give the corresponding pyran products, which could be converted into ortho-alkylated alcohols under hydrogenolysis conditions. The mechanistic details of the oxidative cyclization step are discussed and situated in the context of the overall catalytic cycle.
- Lu, Yi,Wang, Dong-Hui,Engle, Keary M.,Yu, Jin-Quan
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supporting information; experimental part
p. 5916 - 5921
(2010/07/05)
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- Use of 5-hydroxy-4H-benzo[1,4]oxazin-3-ones as β2-adrenoceptor agonists
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Novel β2-agonists with a 5-hydroxy-4H-benzo[1,4]oxazin-3-one moiety as head group are described. Systematic chemical variations at the phenethylamine residue of these compounds lead to the discovery of compound 6m as potent, full agonist of the β2-adrenoceptor with a high β1/β2-selectivity. Molecular modeling revealed an interaction between the carboxylic acid group of 6m and a lysine residue (K305) of the β2-receptor as putative explanation for the high observed selectivity. Further, compound 6m displayed in a guinea pig in vivo model a complete reversal of acetylcholine induced bronchoconstriction which lasted over the complete study time of 5 h.
- Hoenke, Christoph,Bouyssou, Thierry,Tautermann, Christofer S.,Rudolf, Klaus,Schnapp, Andreas,Konetzki, Ingo
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scheme or table
p. 6640 - 6644
(2010/06/12)
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- Aldehydes, acetals, alcohols and ethers having 3-methyl- or 3,5-dimethyl-benzyl groups, their manufacture and perfume materials containing same
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Compounds of the general formula (I) STR1 and compounds of the general formula (II) STR2 in which R1 represents --OH, --CH2 OH, --CH2 --OCH3, --CHOH--CH3, --CHO or --CH(OCH3)2, R
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