53874-66-1Relevant articles and documents
Some examples of phase-transfer catalysis application in organochlorine chemistry
Sirovski, Felix S.
, p. 437 - 441 (1999)
Kinetics of phase-transfer catalysed (PTC'd) dehydrochlorination of the α-isomer of hexachlorocyclohexane in the presence of proton donors was investigated. Carboxylic acids and picric acid act as inhibitors. Benzyl alcohol strongly promotes the reaction. The plots of observed rate constants vs phenol and pentachlorophenol concentration have a bell-shaped form that was not observed before. An example of long-chain quats application in the synthesis of the ketamine anaesthetic intermediate by dehydrochlorination in dilute alkali is shown. Another application of phase-transfer catalysis (PTC) in organochlorine chemistry is the aqueous (sodium hypochlorite) chlorination of alkyl aromatic compounds. The results of m-phenoxytoluene chlorination and reaction kinetics in the presence of the polymeric crown are described.
Preparation method of m-phenoxy benzaldehyde
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, (2021/04/28)
The invention provides a preparation method of m-phenoxy benzaldehyde, and belongs to the technical field of organic synthesis. The preparation method provided by the invention comprises the following steps: condensing m-cresol serving as a raw material with halogenated benzene to obtain m-phenoxytoluene, reacting the m-phenoxytoluene with chlorine to chloridize methyl to obtain a m-phenoxytoluene chloro product, oxidizing the m-phenoxytoluene chloro product through Komblum to obtain an oxide of the m-phenoxytoluene chloro product, and directly hydrolyzing the m-phenoxytoluene chloro product without separation to obtain the product m-phenoxy benzaldehyde. The preparation method provided by the invention has the advantages that the raw materials are cheap and easily available, the yield is high, the product quality meets the market demand, the problems of high raw material price, many side reactions, many impurities, low yield, large wastewater amount and serious environmental pollution in the traditional process are solved, and the production cost of m-phenoxybenzaldehyde is greatly reduced. Data of the embodiment shows that the total yield of m-phenoxybenzaldehyde obtained by the preparation method provided by the invention is 83.5%, and the gas phase content is 99.3%.
Palladium-catalyzed carbonylative cyclization of benzyl chlorides with anthranils for the synthesis of 3-arylquinolin-2(1: H)-ones
Liu, Jian-Li,Xu, Ren-Rui,Wang, Wei,Qi, Xinxin,Wu, Xiao-Feng
supporting information, p. 3584 - 3588 (2021/05/04)
An efficient carbonylative procedure for the synthesis of 3-arylquinoin-2(1H)-ones has been established. Through a palladium-catalyzed aminocarbonylation of benzyl chlorides with anthranils, a variety of 3-arylquinoin-2(1H)-one products were obtained in moderate to excellent yields with good functional group tolerance. This journal is
Discovery of HWL-088: A highly potent FFA1/GPR40 agonist bearing a phenoxyacetic acid scaffold
Li, Zheng,Ren, Qiang,Wang, Xuekun,Zhou, Zongtao,Hu, Lijun,Deng, Liming,Guan, Li,Qiu, Qianqian
, (2019/09/06)
Based on a previously reported phenoxyacetic acid scaffold, compound 7 (HWL-088) has been identified as a superior free fatty acid receptor 1 (FFA1) agonist by comprehensive structure-activity relationship study. Our results indicated that the introduction of ortho-fluoro greatly increased the activity of phenoxyacetic acid series, and the unique structure-activity relationship in biphenyl moiety is different from previously reported FFA1 agonists. Moreover, the modeling study was also performed to better understand the binding mode of present series. Compound 7 significantly improved glucose tolerance both in normal and diabetic models, and even exerted greater potential on glucose control than that of TAK-875. These findings provided a novel candidate HWL-088, which is currently in preclinical study to evaluate its potential for the treatment of diabetes.
Improving metabolic stability with deuterium: The discovery of HWL-066, a potent and long-acting free fatty acid receptor 1 agonists
Liu, Chunxia,Li, Zheng,Shi, Wei,Li, Huilan,Wang, Nasi,Dai, Yuxuan,Liao, Chen,Huang, Wenlong,Qian, Hai
, p. 1547 - 1554 (2018/07/31)
The free fatty acid receptor 1 (FFA1) is a potential target due to its function in enhancing of glucose-stimulated insulin secretion. The FFA1 agonist GW9508 has great potential for the treatment of type 2 diabetes mellitus, but it has been suffering from high plasma clearance probably because the phenylpropanoic acid is vulnerable to β-oxidation. To identify orally available analog without influence on the unique pharmacological mechanism of GW9508, we tried to interdict the metabolically labile group by incorporating two deuterium atoms at the α-position of phenylpropionic acid affording compound 4 (HWL-066). As expected, HWL-066 revealed a lower clearance (CL?=?0.23?L?1?hr?1?kg?1), higher maximum concentration (Cmax?=?5907.47?μg/L), and longer half-life (T1/2?=?3.50?hr), resulting in a 2.8-fold higher exposure than GW9508. Moreover, the glucose-lowering effect of HWL-066 was far better than that of GW9508 and comparable with TAK-875. Different from glibenclamide, no side-effect of hypoglycemia was observed in mice after oral administrating HWL-066 (80?mg/kg).
Novel deuterated phenylpropionic acid derivative, preparation method thereof, and use of derivative as medicine
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, (2017/10/07)
The invention relates to a novel deuterated phenylpropionic acid derivative represented by general formula (I), a preparation method thereof, and a use of a medicinal composition containing the derivative as a medicine for treating diabetes and metabolic syndrome. The deuterated phenylpropionic acid derivative has excellent in vivo blood sugar lowering activity, and can be used for preparing medicines for preventing or treating diabetes.
Discovery of phenylsulfonyl acetic acid derivatives with improved efficacy and safety as potent free fatty acid receptor 1 agonists for the treatment of type 2 diabetes
Li, Zheng,Liu, Chunxia,Xu, Xue,Qiu, Qianqian,Su, Xin,Dai, Yuxuan,Yang, Jianyong,Li, Huilan,Shi, Wei,Liao, Chen,Pan, Miaobo,Huang, Wenlong,Qian, Hai
, p. 458 - 479 (2017/07/10)
The free fatty acid receptor 1 (FFA1) has emerged as an attractive anti-diabetic target that mediates glucose-stimulated insulin secretion. Several FFA1 agonists have been reported, but many of them possessed somewhat high lipophilicity and/or molecular weight. Herein, we describe the identification of sulfone-carboxylic acid moiety with the multiple advantages of reducing lipophilicity, cytotoxicity and β-oxidation associated with compound 2. Further structure-activity relationship study based on the previleged scaffolds led to the discovery of 2-{(4-[(2’-chloro-[1,1’-biphenyl]-3-yl)methoxy]phenyl)sulfonyl}acetic acid (compound 20), which showed a better balance than compound 2 in terms of physicochemical properties, cytotoxicity profiles and pharmacokinetic properties. Subsequent in vivo studies demonstrated that compound 20 robustly improves the glucose tolerance both in normal and type 2 diabetic models without the risk of hypoglycemia. Compared to the high risk of TAK-875 induced liver toxicity, there was no significant adverse effects such as hepatic and renal toxicity were observed in the chronic toxicity studies of compound 20 even at the higher dose.
HETEROCYCLIC COMPOUNDS AS NAV CHANNEL INHIBITORS AND USES THEREOF
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, (2015/09/28)
The present invention relates to heterocyclic compounds of formula (I) wherein: Z1 is C(R)(R), C(O), C(S), or C(NR); 2 Z is C(R)(R), 0, S, SO, S02, or NR; X is -O-, -S-, -S02-, -SO-, -C(O)-, -C02-, -C(O)N(R)-, -NRC(O)-, -NRC(O) N(R)-, -NRSO2-, or -N(R)-; or X is absent; A is an optionally substituted C1_6 aliphatic, C5-10 aryl, 3-8 membered saturated or partially unsaturated carbocyclic ring, 3-7 membered heterocylic ring, or a 5-6 membered heteroaryl ring; Y is -CH2-, -O-, -S-, -S02-, -SO-, -C(O)-, -C02-, -C(O)N(R)-, -NRC(O)-, - NRC(O)N(R)-, -NRS02-, or -N(R)-; B is an optionally substituted C5-10 aryl or 5-6 membered heteroaryl ring; m is 0, 1, 2, or 3; n is 0, 1, 2, or 3; q is 0, 1, 2, or 3; and r is 1 or 2; and pharmaceutically acceptable compositions thereof, useful as Navl.6 inhibitors.
PYRIDINE DERIVATIVES SUBSTITUTED BY HETEROCYCLIC RING AND PHOSPHONOAMINO GROUP, AND ANTI-FUNGAL AGENT CONTAINING SAME
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Page/Page column 84, (2009/04/24)
Anti-fungal agent having excellent anti-fungal action physicochemical properties including safety and water solubility. Compound represented by formula (I), or salt thereof: wherein R1 represents hydrogen, halogen, amino, R11-NH- wherein R11 represents C1-6 alkyl, hydroxy C1-6 alkyl, C1-6 alkoxy C1-6 alkyl, or C1-6alkoxycarbonyl C1-6 alkyl, R12-(CO)-NH- wherein R12 represents C1-6 alkyl group or C1-6 alkoxy C1-6 alkyl, C1-6 alkyl, hydroxy C1-6 alkyl, cyano C1-6 alkyl, C1-6 alkoxy, or C1-6 alkoxy C1-6 alkyl or a phosphonoamino group; R2 represents hydrogen, C1-6 alkyl, amino, or a di C1-6 alkylamino group or a phosphonoamino group; one of X and Y is nitrogen while the other is nitrogen or oxygen; ring A represents a 5- or 6-member heteroaryl ring or a benzene ring which may have a halogen atom or 1 or 2 C1-6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, oxygen, sulfur, -CH2O-, -OCH2-, -NH-, -CH2NH-, -NHCH2-, -CH2S-, or -SCH2-; R3 represents hydrogen or halogen or C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, a 5- or 6-member heteroaryl group or a 5- or 6-member nonaromatic heterocyclic group which may have 1 or 2 substituents; and R4 represents hydrogen or halogen; provided that either R1 or R2 represents a phosphonoamino group.
PYRIDINE DERIVATIVE SUBSTITUTED BY HETEROARYL RING, AND ANTIFUNGAL AGENT COMPRISING THE SAME
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Page/Page column 90, (2009/06/27)
The present invention provides an antifungal agent that has excellent antifungal action, and is also excellent in terms of its properties, safety, and metabolic stability. The present invention discloses a compound represented by the following formula I or a salt thereof, and an antifungal agent comprising the compound or the salt: wherein R1 represents a hydrogen atom, a halogen atom, an amino group, a C1-6 alkyl group, a C1-6 alkoxy group, or a C1-6-alkoxy-C1-6-alkyl group; R2 represents a hydrogen atom or an amino group; X, Y, Z, and W independently represent a nitrogen atom, an oxygen atom, a sulfur atom, or -CH-, provided that at least two among X, Y, and W are nitrogen atoms; the ring A represents a 5- or 6-membered heteroaryl ring or a benzene ring; Q represents a methylene group, an oxygen atom, -CH2O-, -OCH2-, -NH-, -NHCH2-, or -CH2NH-; and R3 represents a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, or a 5- or 6-membered heteroaryl group, each of which may have one or two substituents.
