- The formation of benzoxacin-3-ones: Via intramolecular Nicholas reactions and synthesis of 8-membered heliannuols
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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.
- Green, James R.,St. Onge, Brent
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supporting information
p. 7152 - 7155
(2021/08/30)
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- Exploration of a 14-3-3 PPI Pocket by Covalent Fragments as Stabilizers
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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.
- Sijbesma, Eline,Hallenbeck, Kenneth K.,Andrei, Sebastian A.,Rust, Reanne R.,Adriaans, Joris M. C.,Brunsveld, Luc,Arkin, Michelle R.,Ottmann, Christian
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supporting information
p. 976 - 982
(2021/05/27)
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- PRMT5 INHIBITORS AND USES THEREOF
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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.
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Paragraph 0300-0301
(2019/04/05)
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- Thiazole-5-carboxamide compounds, and its preparation, and pharmaceutical composition and use thereof (by machine translation)
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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.
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Paragraph 0215-0218
(2016/10/20)
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- PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF
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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.
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Paragraph 00289
(2014/07/08)
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- Pd(II)-catalyzed ortho - Or meta-C-H olefination of phenol derivatives
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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.
- Dai, Hui-Xiong,Li, Gang,Zhang, Xing-Guo,Stepan, Antonia F.,Yu, Jin-Quan
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supporting information
p. 7567 - 7571
(2013/06/27)
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- Synthesis and preliminary antihyperlipidaemic activities evaluation of andrographolide derivatives
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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.
- Wang, Bin,Tang, Chunlei,Han, Yaodan,Guo, Ruzhou,Qian, Hai,Huang, Wenlong
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experimental part
p. 293 - 298
(2012/07/30)
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- Reactions of triflate esters and triflamides with an organic neutral super-electron-donor
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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.
- Jolly, Phillip I.,Fleary-Roberts, Nadia,O'Sullivan, Steven,Doni, Eswararao,Zhou, Shengze,Murphy, John A.
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supporting information; scheme or table
p. 5807 - 5810
(2012/08/28)
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- NOVEL AMIDE AND AMIDINE DERIVATIVES AND USES THEREOF
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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.
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Page/Page column 35
(2010/11/03)
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- One-pot reduction of aryl iodides using 4-DMAP methiodide salt
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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.
- Garnier, Jean,Murphy, John A.,Zhou, Sheng-Ze,Turner, Andrew T.
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scheme or table
p. 2127 - 2131
(2009/05/07)
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- Super-electron donors: Bis-pyridinylidene formation by base treatment of pyridinium salts
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Deprotonation of bispyridinium salt 7b affords bispyridinylidene 10, a very powerful neutral organic two-electron donor [E1/2 (DMF) = -1.13 V vs Ag/AgCI/KCI (sat)], presumably via the pyridinylidene 8. Donor 10 reduces aryl iodides and bromides to aryl anions in excellent yield and also reductively cleaves selected phenylalkylsulfones very efficiently.
- Murphy, John A.,Gamier, Jean,Park, Stuart R.,Schoenebeck, Franziska,Zhou, Sheng-Ze,Turner, Andrew T.
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supporting information; experimental part
p. 1227 - 1230
(2009/04/06)
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- Liquid-phase synthesis of 2-methyl-2-aryloxypropanoic acid derivatives from poly(ethylene glycol) supported 2-bromo-2-methylpropanoate
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An efficient liquid-phase synthesis of 2-methyl-2-aryloxypropanoic acid derivatives with good yields and high purity on soluble polyethylene glycol (PEG) has been developed by treatment of PEG-bound 2-bromo-2-methylpropanoate with phenoxides in the presence of a catalytic amount of NBu4I and KI, and subsequent cleavage from the PEG.
- Huang, Bin,Huang, Pei-Gang,Sheng, Shou-Ri,Wang, Qiu-Ying,Guo, Lei,Jiang, Shao-Hua
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p. 575 - 578
(2008/02/11)
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- Amido compounds and their use as pharmaceuticals
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The present invention relates to inhibitors of 11-β hydroxyl steroid dehydrogenase type 1, antagonists of the mineralocorticoid receptor (MR), and pharmaceutical compositions thereof. The compounds of the invention can be useful in the treatment of various diseases associated with expression or activity of 11-β hydroxyl steroid dehydrogenase type 1 and/or diseases associated with aldosterone excess.
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Page/Page column 43
(2010/02/15)
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- Cyclohexylamine derivative as subtype selective nmda receptor antagonists
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Described are compounds of Formula I and Formula II and their pharmaceutically acceptable salts. The compounds of Formulas I and II are antagonists of NMDA receptor channel complexes useful for treating cerebral vascular disorders such as, for example, cerebral ischemia, cardiac arrest, stroke, and Parkinson's disease.
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- Sulfamates as antiglaucoma agents
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Sulfamate esters of the formula where A is aryloxyalkyl, p is the number of unreacted hydroxy groups present on the alkyl moiety and may be zero, z is the number of --OS(O)2 NR1 R2 groups attached to carbons of the alkyl moiety and is always at least one; R1 and R2 are selected from hydrogen, loweralkyl, carboxy, and the like are useful in treating glaucoma.
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- Compounds having one or more aminosulfaonyloxy radicals useful as pharmaceuticals
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Methods of treating chronic arthritis and osteoporosis which utilize both known and novel compounds which would fall under the general formula:(HO)p--A--[--OS(O) 2 NR 1 R 2 ] zwherein A encompasses a wide range of values including but not limited to aryl, loweralkyl, cycloalkyl, and carbohydrates including sucrose and fructose; p is equal to the number of unreacted hydroxy groups contained on the molecule and may be zero; z is the number of --OS(O) 2 NR 1 R 2 groups and is always at least one; R 1 and R 2 are selected from hydrogen, loweralkyl, carboxy and the like; a novel process for preparing the compounds is provided wherein an appropriate sulfamic acid aryl ester is reacted with a hydroxy substituted A radical which may or may not contain thereon protected carboxyl, amino or hydroxy substituents, in an aprotic solvent containing a tertiary amine base. Pharmaceutical compositions for the treatment of chronic arthritis and osteoporosis are also provided.
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- Pyridylthio-acylanilide herbicides
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Novel herbicidally active pyridylthio-acylanilides of the formula STR1 in which R1, R2 and R3, independently of one another, represent hydrogen, halogen, cyano or trifluoromethyl or alkyl, alkoxy and alkylthio having 1 to 4 carbon atoms in each case, R4 represents halogen, methyl or methoxy, n represents a number 0, 1 or 2, z represents the group (Ia) STR2 or the group (Ib) STR3 where X represents oxygen, sulphur, an N--R10 or N--O--R11 group, or X and Rg tpgether represent the STR4 radical, and the other radicals can have various meanings. Intermediates of the formulae STR5 are also new.
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- Synthesis of alpha-alkoxycarboxylic acids
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Numerous alpha-carboxylic acids are prepared in a liquid medium by the reaction of an organic compound having at least one reactive hydroxyl or thiol group, with a monoketone, and a haloform, in the presence of a phase transfer catalyst and an alkali metal hydroxide. The term "alpha-alkoxycarboxylic acids" includes alpha-phenoxycarboxylic acids, alpha-thioalkoxycarboxylic acids and alpha-thiophenoxycarboxylic acids. Specific substituents on the beta carbon atom of an alpha-alkoxycarboxylic (or "2-alkoxycarboxylic") acid reaction product formed in this novel synthesis, are introduced by appropriate choice of the ketone reactant; alkoxy and phenoxy substituents on the alpha carbon atom of a 2-alkoxycarboxylic acid are introduced by appropriate choice of the organic compound having a hydroxyl or thiol group. De-alkoxylation of the 2-alkoxycarboxylic acid yields alpha-beta monoolefinically unsaturated carboxylic acids which are necessarily alpha substituted, and may also be beta-substituted. It is now possible to produce, simply and conveniently, numerous substituted alpha-beta monolefinically unsaturated carboxylic acids with a variety of substituents on the alpha carbon atom, and, optionally on the beta carbon atom of these substituted carboxylic acids. Esters may also be conventionally derived from both the 2-alkoxycarboxylic acids, and the unsaturated carboxylic acids. During the phase transfer catalyzed synthesis of this invention, an intermediate acyl halide derivative is formed prior to the formation of the 2-alkoxycarboxylic acid reaction product. The formation of the acyl halide derivative allows the subsequent direct formation, in a modification of the same reaction, of 2-alkoxycarboxylic acid amides (or "2-alkoxycarbamides"), simply by adding a primary or secondary amine to the reaction mass. By dealkoxylation of the 2-alkoxycarbamides, specific, necessarily alpha-substituted and optionally beta-substituted acrylamides are synthesized which previously could be prepared, if at all, only with difficulty.
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