- Exploration of phenylpropanoic acids as agonists of the free fatty acid receptor 4 (FFA4): Identification of an orally efficacious FFA4 agonist
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The long chain free fatty acid receptor 4 (FFA4/GPR120) has recently been recognized as lipid sensor playing important roles in nutrient sensing and inflammation and thus holds potential as a therapeutic target for type 2 diabetes and metabolic syndrome. To explore the effects of stimulating this receptor in animal models of metabolic disease, we initiated work to identify agonists with appropriate pharmacokinetic properties to support progression into in vivo studies. Extensive SAR studies of a series of phenylpropanoic acids led to the identification of compound 29, a FFA4 agonist which lowers plasma glucose in two preclinical models of type 2 diabetes.
- Sparks, Steven M.,Aquino, Christopher,Banker, Pierette,Collins, Jon L.,Cowan, David,Diaz, Caroline,Dock, Steven T.,Hertzog, Donald L.,Liang, Xi,Swiger, Erin D.,Yuen, Josephine,Chen, Grace,Jayawickreme, Channa,Moncol, David,Nystrom, Christopher,Rash, Vincent,Rimele, Thomas,Roller, Shane,Ross, Sean
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p. 1278 - 1283
(2017/06/19)
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- Catalytic wet air oxidation of m-cresol over a surface-modified sewage sludge-derived carbonaceous catalyst
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Sewage sludge-derived carbonaceous materials (SW) treated with different kinds of acids were used as catalysts for catalytic wet air oxidation (CWAO) of m-cresol. The SW catalysts were characterized by XRF, XRD, FTIR, XPS and TPD-MS. The results showed that SW treated with HNO3 (HNO3-SW) exhibited the best catalytic activity. When the initial concentration of m-cresol was 5000 mg L-1, the conversion of m-cresol reached 99.0% with HNO3-SW after 90 min at 160 °C and 0.66 MPa oxygen. Continuous experiments were carried out for 8 d to investigate the durability and catalytic performance of HNO3-SW in CWAO reaction. Some correlation was observed between the conversion of m-cresol and the content of carboxyl groups, indicating that the carboxyl group might play a key role in determining the catalytic activity of SW catalysts in CWAO reaction. Based on the intermediate products identified by GC-MS, HPLC-MS, IC and HRMS analyses, the oxidation pathways of m-cresol in CWAO were proposed.
- Yu, Yang,Wei, Huangzhao,Yu, Li,Gu, Bin,Li, Xianru,Rong, Xin,Zhao, Ying,Chen, Lili,Sun, Chenglin
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p. 1085 - 1093
(2016/02/27)
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- Formylation of electron-rich aromatic rings mediated by dichloromethyl methyl ether and TiCl4: Scope and limitations
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Here the aromatic formylation mediated by TiCl4 and dichloromethyl methyl ether previously described by our group has been explored for a wide range of aromatic rings, including phenols, methoxy- and methylbenzenes, as an excellent way to produce aromatic aldehydes. Here we determine that the regioselectivity of this process is highly promoted by the coordination between the atoms present in the aromatic moiety and those in the metal core.
- Ramos-Tomillero, Iván,Paradís-Bas, Marta,De Pinho Ribeiro Moreira, Ibério,Bofill, Josep María,Nicolás, Ernesto,Albericio, Fernando
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supporting information
p. 5409 - 5422
(2015/05/13)
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- Abnormal Ito-Saegusa oxidation of TIPS enol ether assisted by a hydroxy group on a side chain
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Although Ito-Saegusa oxidation gives defined α,β-unsaturated ketones from silyl enol ether of ketones controlled by the position of the sp2 carbon of the silyl enol ether, the formation of a regioisomeric product that was oxidized abnormally wa
- Hiraoka, Shiharu,Harada, Shinji,Nishida, Atsushi
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experimental part
p. 3079 - 3082
(2011/06/26)
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- PYRAZOLE DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, MEDICINAL USE THEREOF, AND INTERMEDIATE FOR PRODUCTION THEREOF
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The present invention provides pyrazole derivatives represented by the general formula: wherein R1 represents H, an optionally substituted C1-6 alkyl group etc.; one of Q and T represents a group represented by the general formula: or a group represented by the general formula: while the other represents an optionally substituted C1-6 alkyl group etc.; R2 represents H, a halogen atom, OH, an optionally substituted C1-6 alkyl group etc.; X represents a single bond, O or S; Y represents a single bond, a C1-6 alkylene group etc. ; Z represents CO or SO2; R4 and R5 represent H, an optionally substituted C1-6 alkyl group etc.; and R3, R6 and R7 represent H, a halogen atom etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT1 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.
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Page/Page column 59-60
(2008/06/13)
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- Photochemical synthesis, conformational analysis, and transformation of [60]fullerene-o-quinodimethane adducts bearing a hydroxy group
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The photochemical reactions of [60]fullerene with various aromatic aldehydes or ketones 1a-n carrying an alkyl group at the ortho position were examined. Some of them afforded stable o-quinodimethane adducts 2 with a hydroxy group attached to the cyclohexene ring. The adducts 2 were found to adopt one or both of two conformers A and E, which possess pseudoaxial and pseudoequatorial hydroxy groups, respectively. The conformer ratios depended remarkably on the substituents attached to the aromatic nucleus and the cyclohexene ring. The dynamic behavior of 2 was also investigated by the VT-NMR technique.
- Nakamura, Yosuke,O-kawa, Kyoji,Minami, Satoshi,Ogawa, Toshio,Tobita, Seiji,Nishimura, Jun
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p. 1247 - 1252
(2007/10/03)
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- NOVEL COMPOUNDS USEFUL AS NEURO-PROTECTIVE AGENTS
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This invention relates to novel phenyl oxazoles, thiazoles, oxazolines, oxadiazoles and benzoxazoles useful as neuro-protective agents.
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- Compounds useful as neuro-protective agents
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This invention relates to novel phenyl oxazoles, thiazoles, oxazolines, oxadiazoles and benzoxazoles useful as neuro-protective agents.
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- Method for treating pain
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The present invention provides a method for treating pain using a composition comprising certain phenyl oxazoles or phenyl thiazoles in combination with a Drug Useful in the Treatment of Pain.
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- Method for treating neuropathic pain
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The present invention provides a method for treating neuropathic pain comprising administering an analgesic dosage of a compound of formula I to an animal in need of such treatment certain phenyl oxazoles or phenyl thiazoles.
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- Use of phenyl oxazole or phenyl thiazole derivatives for treating neuropathic pain
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The present invention provides a method for treating neuropathic pain comprising administering an analgesic dosage of a compound of formula I to an animal in need of such treatment certain phenyl oxazoles or phenyl thiazoles.
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- Use of phenyl oxazole or phenyl thiazole derivatives for treating pain
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The present invention provides a method for treating pain comprising administering to an animal in need of such treatment, an analgesic dosage of certain phenyl oxazoles or phenyl thiazoles.
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- Method for treating pain
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The present invention provides a method for treating pain using a composition comprising certain phenyl oxazoles or phenyl thiazoles in combination with a Drug Useful in the Treatment of Pain.
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- SUBSTITUENT EFFECTS ON THE PHOTOCHEMISTRY OF o-TOLUALDEHYDES
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The effect of 4-oxy and 4,5-dioxy substituents on the photochemical conversion of 2-methylbenzaldehydes to o-quinodimethanes (o-QDMs) has been studied.The presence of a 4-methoxy, or a 4 and 5-methoxy substituent prevented the photochemical formation of the o-QDM whereas 4-acetoxy and 4,5-diacetoxy-2-methylbenzaldehyde and the corresponding mesylates and tosylates were successfully converted to the o-QDMs.
- Charlton, James L.,Koh, Kevin
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p. 5595 - 5598
(2007/10/02)
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- Selective Syntheses Using Cyclodextrin as Catalyst. 1. Control of Orientation in the Attack of Dichlorocarbene at Phenolates
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4-Hydroxybenzaldehydes, 2,4-dihydroxybenzaldehyde, and 4-(dichloromethyl)-2,5-cyclohexadienones were synthesized in virtually 100percent selectivities and high yields from the corresponding phenols and chloroform in alkaline aqueous solutions by using α- or β-cyclodextrin (α- or β-CD) as catalyst.The regulation of the molar ratio of chloroform to CD below unity throughout the reaction time, by controlling the rate of addition of chloroform, was definitely required to attain high selectivity.Under these conditions, dichlorocarbene, prepared in situ from chloroform and sodium hydroxide, attacked overwhelmingly at the para carbon of phenols with almost perfect suppression of the reaction at the ortho carbon.The structure of the ternary molecular complex composed of β-CD, chloroform, and phenol, formed in the reaction mixture for the selective synthesis of 4-hydroxybenzaldehyde, was determined by NMR spectroscopy.The selective catalysis by CDs was attributed to the regulation of molecular conformation of phenols with respect to chloroform, and thus to dichlorocarbene, in the ternary complex.
- Komiyama, Makoto,Hirai, Hidefumi
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p. 2018 - 2021
(2007/10/02)
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- The Formylation of an Aromatic Nucleus by the Use of 2-Ethoxy-1,3-dithiolane
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The reaction of various phenols with 2-ethoxy-1,3-dithiolane proceeded smoothly in the presence of BF3*Et2O to afford 1,3-dithiolan-2-ylated phenols, which were readily hydrolyzed to the corresponding aldehydes.This process was also extended to N,N-dimethylaniline and indole.
- Jo, Shigeo,Tanimoto, Shigeo,Sugimoto, Toyonari,Okano, Masaya
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p. 2120 - 2123
(2007/10/02)
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