943-45-3Relevant articles and documents
Exploration of a 14-3-3 PPI Pocket by Covalent Fragments as Stabilizers
Sijbesma, Eline,Hallenbeck, Kenneth K.,Andrei, Sebastian A.,Rust, Reanne R.,Adriaans, Joris M. C.,Brunsveld, Luc,Arkin, Michelle R.,Ottmann, Christian
, p. 976 - 982 (2021/05/27)
The systematic discovery of functional fragments binding to the composite interface of protein complexes is a first critical step for the development of orthosteric stabilizers of protein-protein interactions (PPIs). We have previously shown that disulfide trapping successfully yielded covalent stabilizers for the PPI of 14-3-3 with the estrogen receptor ERα. Here we provide an assessment of the composite PPI target pocket and the molecular characteristics of various fragments binding to a specific subpocket. Evaluating structure-activity relationships highlights the basic principles for PPI stabilization by these covalent fragments that engage a relatively large and exposed binding pocket at the protein/peptide interface with a "molecular glue"mode of action.
The formation of benzoxacin-3-ones: Via intramolecular Nicholas reactions and synthesis of 8-membered heliannuols
Green, James R.,St. Onge, Brent
supporting information, p. 7152 - 7155 (2021/08/30)
The γ-carbonyl cations generated from propargyl ether-Co2(CO)6 complexes undergo intramolecular Nicholas reactions to give dehydrobenzoxacin-3-one-Co2(CO)6 complexes in good yields. Reductive decomplexation and subsequent manipulation allows the synthesis of (±)-heliannuol K methyl ether and the formal syntheses of (±)-heliannuol K, (±)-heliannuol A, and (-)-heliannuol L.
PRMT5 INHIBITORS AND USES THEREOF
-
, (2019/04/05)
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
Thiazole-5-carboxamide compounds, and its preparation, and pharmaceutical composition and use thereof (by machine translation)
-
Paragraph 0215-0218, (2016/10/20)
The invention relates to a novel 2-phenylthiazole-5-methanamide compound shown as a general formula I, a precursor, a stereo isomer and physiologically-acceptable salt thereof, a medicinal composition containing the compound, and an application of the compound as the aspect of medicine.
PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF
-
, (2014/07/08)
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.
Pd(II)-catalyzed ortho - Or meta-C-H olefination of phenol derivatives
Dai, Hui-Xiong,Li, Gang,Zhang, Xing-Guo,Stepan, Antonia F.,Yu, Jin-Quan
supporting information, p. 7567 - 7571 (2013/06/27)
A combination of weakly coordinating auxiliaries and ligand acceleration allows for the development of both ortho- and meta-selective C-H olefination of phenol derivatives. These reactions demonstrate the feasibility of directing C-H functionalizations when functional groups are distal to target C-H bonds. The meta-C-H functionalization of electron-rich phenol derivatives is unprecedented and orthogonal to previous electrophilic substitution of phenols in terms of regioselectivity. These methods are also applied to functionalize α-phenoxyacetic acids, a fibrate class of drug scaffolds.
Synthesis and preliminary antihyperlipidaemic activities evaluation of andrographolide derivatives
Wang, Bin,Tang, Chunlei,Han, Yaodan,Guo, Ruzhou,Qian, Hai,Huang, Wenlong
experimental part, p. 293 - 298 (2012/07/30)
Recent studies indicated that andrographolide was a potential antihyperlipidaemic therapeutic agent. In the paper, the synthesis of a series of andrographolide derivatives was described and their antihyperlipidaemic activities were evaluated in vivo. As compared with TG, TC, HDL-C and LDL-C concentrations, some of the derivatives exhibited better antihyperlipidaemic effects than positive control atromide. Therein, compound 6i, which was the most potent compound, could serve as a new lead for further development of antihyperlipidaemic agents.
Reactions of triflate esters and triflamides with an organic neutral super-electron-donor
Jolly, Phillip I.,Fleary-Roberts, Nadia,O'Sullivan, Steven,Doni, Eswararao,Zhou, Shengze,Murphy, John A.
supporting information; scheme or table, p. 5807 - 5810 (2012/08/28)
The bis-pyridinylidene 13 converts aliphatic and aryl triflate esters to the corresponding alcohols and phenols respectively, using DMF as solvent, generally in excellent yields. While the deprotection of aryl triflates has been seen with other reagents and by more than one mechanism, the deprotection of alkyl triflates is a new reaction. Studies with 18O labelled DMF indicate that the C-O bond stays intact and hence it is the S-O bond that cleaves, underlining that the cleavage results from the extraordinary electron donor capability of 13. Trifluoromethanesulfonamides are converted to the parent amines in like manner, representing the first cleavage of such substrates by a ground-state organic reducing reagent.
NOVEL AMIDE AND AMIDINE DERIVATIVES AND USES THEREOF
-
Page/Page column 35, (2010/11/03)
The present invention relates to inhibitors of 11-β-hydroxysteroid dehydrogenase type 1 enzyme and their use in treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, central nervous system disorders, and diseases and conditions that are related to excessive glucocorticoids.
One-pot reduction of aryl iodides using 4-DMAP methiodide salt
Garnier, Jean,Murphy, John A.,Zhou, Sheng-Ze,Turner, Andrew T.
scheme or table, p. 2127 - 2131 (2009/05/07)
An efficient one-pot procedure is described for the reduction of aryl iodides to aryl anions using a structurally simple bis-pyridinylidene electron donor, prepared in situ by treating 4-DMAP methiodide salt with base. The results show (i) that pyridinylidene carbenes can be easily used for intermolecular C-C bond formation, (ii) that bis-pyridinylidenes demonstrate superior robustness compared to electron-donor systems based on bis-imidazolylidenes, and (iii) that electron-donor strength is enhanced in the simplified DMAP-based donor. Deuterated analogues of this donor also provide mechanistic information on the source of protons when the aryl anions are quenched in situ. Georg Thieme Verlag Stuttgart.
