- Preparation method of (R)-1-alkanoyl-2-substituted pyrrolidine-2-formamide and medicinal application of (R)-1-alkanoyl-2-substituted pyrrolidine-2-formamide
-
The invention discloses (R)-1-alkanoyl-2-substituted pyrrolidine-2-formamide as shown in a general formula (I), a preparation method of a compound, a new application of the compound and a pharmaceutical composition containing the compound in the aspect of inhibiting neuroglial cell inflammation.
- -
-
Paragraph 0048-0049
(2021/01/12)
-
- Computational discovery, structural optimization and biological evaluation of novel inhibitors targeting transient receptor potential vanilloid type 3 (TRPV3)
-
Transient receptor potential vanilloid type 3 (TRPV3) is a Ca2+ permeable nonselective cation channel and expressed abundantly in skin keratinocytes. TRPV3 emerges as an attractive target for treatment of pruritic, inflammatory, pain and skin-related diseases. However, only a few reports of TRPV3 inhibitors exist at present besides some patents. Therefore, TRPV3 research has always been fraught with challenges. Through a combination of virtual screening and biological evaluation, compound P1 (10 μM) was identified as a top hit with 34.5% inhibitory effect on 2-APB (1 mM)-evoked currents of mTRPV3-WT. Further structural optimization provided the inhibitor PC5 with the best activity (IC50 = 2.63 ± 0.28 μM), and point mutation assays indicated that amino acids V629 and F633 are crucial for the binding of PC5 and TRPV3. In summary, these newly discovered inhibitors could serve as promising lead compounds for the development of TRPV3 inhibitors in the future.
- Zhang, Fang,Lin, Yiyu,Min, Wenjian,Hou, Yi,Yuan, Kai,Wang, Jin,Yang, Peng
-
-
- Catalyst for synthesizing acyl chloride compounds and application thereof
-
The invention relates to a catalyst for synthesizing an acyl chloride compound and application of the catalyst. The structural formula is as shown in the specification, and in the formula, R is alkali of which the carbon atom number is 1-12. The catalyst is capable of effectively increasing the product yield, improving the production efficiency and lowering the production cost of acyl chloride, and has wide application prospects. The invention further provides a method for synthesizing acyl chloride with the catalyst.
- -
-
Paragraph 0017-0022
(2020/10/20)
-
- Nickel-Catalyzed Cross-Coupling of Alkyl Carboxylic Acid Derivatives with Pyridinium Salts via C-N Bond Cleavage
-
The electrophile-electrophile cross-coupling of carboxylic acid derivatives and alkylpyridinium salts via C-N bond cleavage is developed. The method is distinguished by its simplicity and steers us through a variety of functionalized ketones in good to excellent yields. Besides acid chlorides, carboxylic acids were also employed as acylating agents, which enabled us to incorporate acid-sensitive functional groups such as MOM, BOC, and acetal. Control experiments with TEMPO revealed a radical pathway.
- Pulikottil, Feba Thomas,Pilli, Ramadevi,Suku, Rohith Valavil,Rasappan, Ramesh
-
supporting information
p. 2902 - 2907
(2020/04/09)
-
- Substituted pyrazole compound, preparation method, pharmaceutical composition and applications thereof
-
The invention discloses a substituted pyrazole compound represented by a formula I, and a preparation method, a pharmaceutical composition and applications thereof, wherein the compound has characteristics of good stability, excellent solubility, low cytotoxicity and remarkable neuroprotective effect, can effectively prevent and treat nerve cell injury, and is an ideal medicinal compound for preventing or treating cerebral stroke, cerebral embolism, cerebral stroke sequelae, cerebral stroke dyskinesia, mitochondrial encephalomyopathy and amyotrophic lateral sclerosis of spinal cord.
- -
-
Paragraph 0118; 0122; 0123
(2020/03/12)
-
- Visible-Light-Assisted Gold-Catalyzed Fluoroarylation of Allenoates
-
A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.
- Feng, Chao,Tang, Hai-Jun,Zhang, Xinggui,Zhang, Yu-Feng
-
supporting information
p. 5242 - 5247
(2020/02/28)
-
- Base-promoted Lewis acid catalyzed synthesis of quinazoline derivatives
-
A one-pot protocol has been developed for the synthesis of quinazolinones from amide-oxazolines with TsCl via a cyclic 1,3-azaoxonium intermediate and 6π electron cyclization in the presence of a Lewis acid and base. The process is operationally simple and has a broad substrate scope. This method provides a unique strategy for the construction of quinazolinones.
- Cui, Xin-Feng,Hu, Fang-Peng,Huang, Guo-Sheng,Lu, Guo-Qiang
-
supporting information
p. 4376 - 4380
(2020/10/20)
-
- Preparation method of 2,4,6-trimethylbenzoyl chloride and acyl chloride co-production technology
-
The invention relates to the field of new materials of fine chemicals, in particular to 2,4,6-trimethylbenzoyl chloride (also known as trimesoyl chloride) and an environment-friendly and economical novel preparation process technology for co-producing series acyl chloride products.
- -
-
Paragraph 0036-0038
(2020/11/25)
-
- Preparation method of acid chloride
-
The invention belongs to the technical field of compound preparation methods, and particularly discloses a preparation method of acid chloride. The problems that a chlorinating agent adopted in an existing preparation method of the acid chloride has high irritation, high toxicity and high corrosion are solved, carboxylic acid RCOOH is subjected to acylating chlorination by using triphenylphosphineand the chlorinating agent; and then a reaction is carried out at a room temperature, and violent stirring is performed in the reaction process. The preparation method has simple operation and a short reaction time for preparing the acid chloride, a high product recovery rate and high working efficiency, can be realized at the normal temperature, and reduces energy consumption, hydrogen chlorideis not escaped, a large amount of acid gas is not generated, fewer three wastes is generated, side reactions to acid-sensitive groups when acid-sensitive compounds are synthesized are avoided, and thepreparation method is more environmentally friendly and can be better realized.
- -
-
Paragraph 0021-0026
(2019/03/28)
-
- Preparing method of photoinitiator 2-methyl-2-hydroxy-1-phenylacetone
-
The invention discloses a preparing method of a photoinitiator 2-methyl-2-hydroxy-1-phenylacetone. The preparing method comprises the steps of conducting acylation reaction on isobutyric acid and phosphorus trichloride, after the reaction is completed, introducing hydrogen chloride gas to make the intermediate state reaction complete, obtaining 2-chloride-2-methyl propionylchloride through chlorination reaction, conducting Friedel-Crafts reaction with benzene in the presence of a catalyst to obtain 2-chloride-2-methyl-1-phenylpropane-1-ketone, and finally after alkaline hydrolysis, washing anddistillation, obtaining the photoinitiator 1173. According to the preparing method, hydrogen chloride is introduced into the acylation step, so that the reaction yield is increased, and byproduct odors are reduced; meanwhile, chlorination reaction of a conventional technology is conducted one step in advance, the production cost of the conventional technology is reduced, and thus the product hasmarket competitiveness.
- -
-
Page/Page column 4-6
(2019/04/30)
-
- Isoalantolactone derivative, pharmaceutical composition and application thereof
-
The invention relates to an isoalantolactone derivative, a pharmaceutical composition and application thereof, especially use of the isoalantolactone derivative shown as formula (I) or a salt pharmaceutical compound thereof in preparation of adjuvant drugs treating cancer, a pharmaceutical composition containing a therapeutically effective amount of isoalantolactone derivative (I) or its salt anda pharmaceutically acceptable carrier or a composition with other anticancer drugs.
- -
-
Paragraph 0014
(2019/02/02)
-
- Pd/Cu-Catalyzed Cascade C(sp3)-H Arylation and Intramolecular C-N Coupling: A One-Pot Synthesis of 3,4-2 H-Quinolinone Skeletons
-
In this letter, we successfully explored a cascade Pd/Cu-catalyzed intermolecular C(sp3)-H arylation of amides and intramolecular C-N coupling reaction. This method provides a one-pot strategy to synthesize 3,4-2H-quinolinone with good regioselectivity of C-H arylation and C-N coupling from C-I and C-X bonds from readily available starting materials.
- Xiao, Han-Zhi,Wang, Wen-Shu,Sun, Yu-Song,Luo, Hao,Li, Bo-Wen,Wang, Xiao-Dong,Lin, Wei-Li,Luo, Fei-Xian
-
supporting information
p. 1668 - 1671
(2019/03/11)
-
- Electrochemical [4+2] Annulation-Rearrangement-Aromatization of Styrenes: Synthesis of Naphthalene Derivatives
-
We report the first electrochemical strategy to synthesize functionalized naphthalene derivatives through [4+2] annulation—rearrangement–aromatization from styrenes under mild conditions. The electrolysis does not require metals, oxidants and high valence substrates, indicating the atom and step-economy ideals. The dehydrodimer produced through [4+2] cycloaddition of 4-methoxy α-methyl styrene is isolated and proved to be the key intermediate for the following oxydehydrogenation to form carbon cation, which undergoes rearrangement–aromatization to afford the final products. This reaction represents a powerful access to construct multi-substituted naphthalene blocks in a single step.
- Ma, Yueyue,Lv, Jufeng,Liu, Chengyu,Yao, Xiantong,Yan, Guoming,Yu, Wei,Ye, Jinxing
-
supporting information
p. 6756 - 6760
(2019/04/17)
-
- Synthesis and bioactivities of diamide derivatives containing a phenazine-1-carboxamide scaffold
-
Taking natural product phenazine-1-carboxamide (PCN) as a lead compound, a series of novel phenazine-1-carboxylic acid diamide derivatives were designed and synthesised. Their structures were confirmed by 1H-NMR and HRMS. The bioassays showed that some of the target compounds exhibited promising in vitro fungicidal activities, and exhibited excellent and selective herbicidal activities. Particularly, compounds c, h, o and s displayed root length inhibition activities against barnyard grass with the rate of more than 80%. Compound c exhibited the best activity among all the target compounds against barnyard grass stalk length with the IC50 value of 0.158?mmol/L, and compound o exhibited the best and wide spectrum inhibition against barnyard grass root length and rape in both root length and stalk length herbicidal activities with its IC50 values of 0.067, 0.048 and 0.059?mmol/L respectively. The analysis of preliminary Structure-Activity Relationships provides the theoretical basis for further design of phenazine-1-carboxylic acid.
- Zhu, Xiang,Zhang, Min,Yu, Linhua,Xu, Zhihong,Yang, Dan,Du, Xiaoying,Wu, Qinglai,Li, Junkai
-
supporting information
p. 2453 - 2460
(2018/03/29)
-
- 2-Amino-5,6-difluorophenyl-1 H-pyrazole-Directed PdII Catalysis: Arylation of Unactivated β-C(sp3)-H Bonds
-
Palladium-catalyzed arylation of unactivated β-C(sp3)-H bonds in carboxylic acid derivatives with aryl iodides is described for the first time using 2-amino-5,6-difluorophenyl-1H-pyrazole as an efficient and readily removable directing group. Two fluoro groups are installed at the 5- and 6-position of the anilino moiety in 2-aminophenyl-1H-pyrazole, clearly enhancing the directing ability of the auxiliary. In addition, the protocol employs Cu(OAc)2/Ag3PO4 (1.2/0.3) as additives, evidently reducing the stoichiometric amount of expensive silver salts. Furthermore, this process exhibits high β-site selectivity, compatibility with diverse substrates containing α-hydrogen atoms, and excellent functional group tolerance.
- Yang, Jinyue,Fu, Xiaopan,Tang, Shibiao,Deng, Kezuan,Zhang, Lili,Yang, Xianjin,Ji, Yafei
-
p. 10221 - 10236
(2019/08/20)
-
- Synthesis of 1,3-Diketones and β-Keto Thioesters via Soft Enolization
-
Ketones and thioesters undergo soft enolization and acylation using crude acid chlorides on treatment with MgBr2·OEt2 and i-Pr2NEt to give 1,3-diketones and β-keto thioesters, respectively. The use of crude acid chlorides adds efficiency and cost reduction by avoiding the need to purify and/or purchase them. The process is conducted in a direct fashion that does not require prior enolate formation, further enhancing its efficiency and making it very easy to carry out. The method is suitable for large scale applications. ?
- Aderibigbe, Sabrina O.,Coltart, Don M.
-
p. 9770 - 9777
(2019/08/27)
-
- Benzoxazin-4-ones as novel, easily accessible inhibitors for rhomboid proteases
-
Rhomboid proteases form one of the most widespread intramembrane protease families. They have been implicated in variety of human diseases. The currently reported rhomboid inhibitors display some selectivity, but their construction involves multistep synthesis protocols. Here, we report benzoxazin-4-ones as novel inhibitors of rhomboid proteases with a covalent, but slow reversible inhibition mechanism. Benzoxazin-4-ones can be synthesized from anthranilic acid derivatives in a one-step synthesis, making them easily accessible. We demonstrate that an alkoxy substituent at the 2-position is crucial for potency and results in low micromolar inhibitors of rhomboid proteases. Hence, we expect that these compounds will allow rapid synthesis and optimization of inhibitors of rhomboids from different organisms.
- Yang, Jian,Barniol-Xicota, Marta,Nguyen, Minh T.N.,Ticha, Anezka,Strisovsky, Kvido,Verhelst, Steven H.L.
-
supporting information
p. 1423 - 1427
(2018/03/06)
-
- Phenazine-1-carboxylic acid bisamide compounds and application thereof
-
The invention provides phenazine-1-carboxylic acid bishydrazide compounds and an application thereof, and belongs to the technical field of preparation of pesticide compounds; the general formula of the compounds has the following structure defined in the specification, wherein R is saturated C2-C6 straight-chain or branched-chain alkyl, unsaturated C2-C6 alkyl, halogen substituted C2-C6 hydrocarbonyl, C3-C8 cycloalkyl, and substituted phenyl containing one or more saturated or unsaturated hydrocarbonyl, alkoxy, halogen, fluorine-containing methyl, nitryl, cyano group, ester group, ketone group and formyl group, substituted pyridyl, substituted furyl, substituted pyrimidyl, substituted pyrazolyl, substituted thiazolyl, substituted thienyl, substituted imidazolyl or substituted triazolyl. The phenazine-1-dihydrazine carboxylic acid compounds have novel structure, can be used for prevention and treatment of diseases on crops and weeds and have market application prospects.
- -
-
Paragraph 0059; 0060; 0061; 0062
(2018/03/28)
-
- Preparation method for 2-isopropyl-4-(methyl aminomethyl) thiazole hydrochloride
-
The invention belongs to the field of medical intermediate synthesis, relates to a preparation method for ritonavir intermediate synthesis and particularly relates to a preparation method for 2-isopropyl-4-(methyl aminomethyl) thiazole hydrochloride. Isobutyric acid firstly reacts with thionyl chloride, and then ammonium sulfide and ammonium hydroxide are subjected to sulfo-reaction and aminating reaction, the existing process of using phosphorus pentasulfide for performing sulfo-reaction after acylation is replaced, the heavy smell is prevented from generating in the preparation process to avoid the environmental pollution. According to the invention, 1,3-dihydroxy acetone is adopted for replacing 1,3-dichloroacetone with high price, heavy smell and high pollution, the cost is saved and the preparation is environmentally friendly. According to the preparation method provided by the invention, the process is simple, the yield higher than that of the prior art and the preparation method is suitable for industrial production.
- -
-
Paragraph 0033-0035
(2018/04/01)
-
- Pd(II)-Catalyzed Enantioselective C(sp3)-H Borylation
-
Pd(II)-catalyzed enantioselective borylation of C(sp3)-H bonds has been realized for the first time using chiral acetyl-protected aminomethyl oxazoline ligands. This reaction is compatible with carbocyclic amides containing α-tertiary as well as α-quaternary carbon centers. The chiral β-borylated amides are useful synthons for the synthesis of chiral β-hydroxylated, β-fluorinated, and β-arylated carboxylic acids.
- He, Jian,Shao, Qian,Wu, Qingfeng,Yu, Jin-Quan
-
supporting information
p. 3344 - 3347
(2017/03/15)
-
- Palladium-Catalyzed β-Mesylation of Simple Amide via Primary sp3 C-H Activation
-
A β-mesylation of primary sp3 C-H bonds from simple amides with methanesulfonic anhydride (Ms2O) has been established successfully at 80 °C in a Pd(OAc)2 (catalyst)/K2S2O8 (oxidant)/CF3CH2OH (solvent) system. These amide substrates involve N-monosubstituted linear, branch, or cyclic alkanes, and electron-deficient benzyl compounds. The β-mesylated amide products can be converted easily to β-fluoroamides or β-lactams through inter- or intramolecular SN2 processes.
- Zhao, Ren,Lu, Wenjun
-
supporting information
p. 1768 - 1771
(2017/04/11)
-
- Synthetic method for 2,4,6-trimethylbenzene-1,3,5-triamine and N,N,N-triacylated product
-
The invention provides a synthetic method for 2,4,6-trimethylbenzene-1,3,5-triamine and an N,N,N-triacylated product. The method comprises the following steps: S1, performing a nitration reaction on mesitylene with structural formula IV as a reaction raw material in the presence of a mixed acid of fuming nitric acid and concentrated sulfuric acid, and after the nitration reaction, performing filtration and drying to obtain 1,3,5-trimethyl-2,4,6-trinitryl benzene with structural formula III; S2, performing a hydrogenation reaction on 1,3,5-trimethyl-2,4,6-trinitryl benzene and a reducer hydrazine hydrate to reduce nitryl to amino, and performing purification to obtain 2,4,6-trimethylbenzene-1,3,5-triamine with structure formula II; and S3, performing an acylation reaction on 2,4,6-trimethylbenzene-1,3,5-triamine and an acylation reagent to obtain N,N,N-triacyl-2,4,6-trimethylbenzene-1,3,5-triamine with structural formula I.
- -
-
Paragraph 0088; 0089; 0090; 0101
(2017/12/27)
-
- Anhydrides from aldehydes or alcohols via oxidative cross-coupling
-
A novel type of metal-free oxidative cross-coupling for the synthesis of symmetrical and mixed anhydrides from aldehydes or benzylic alcohols has been developed. The aldehydes or alcohols were converted in situ into their corresponding acyl chlorides, which were then reacted with an array of carboxylic acids. The methodology has a general applicability, and was successfully employed to prepare either aromatic or aliphatic symmetrical anhydrides and mixed anhydrides, which are very unstable compounds.
- Gaspa, Silvia,Amura, Ida,Porcheddu, Andrea,De Luca, Lidia
-
supporting information
p. 931 - 939
(2017/02/10)
-
- Metal-free oxidative self-coupling of aldehydes or alcohols to symmetric carboxylic anhydrides
-
A metal-free synthesis of symmetrical anhydrides has been developed starting from aldehydes, both aliphatic and aromatic or primary benzylic alcohols. The reaction occurs at room temperature and makes use of trichloroisocyanuric acid (TCCA) as an oxidant providing the desired carboxylic anhydrides in satisfactory yields.
- Gaspa, Silvia,Porcheddu, Andrea,De Luca, Lidia
-
supporting information
p. 2533 - 2536
(2017/06/13)
-
- 1 - (biphenyl-4-yl) - 2-methyl-2-morpholino-propane-1-one synthesis method
-
The invention discloses a synthetic method of 1-(biphenyl-4-yl)-2-methyl-2-morpholinopropan-1-one which is efficient free radical photoinitiator. The synthetic method of the 1-(biphenyl-4-yl)-2-methyl-2-morpholinopropan-1-one specifically comprises the steps that biphenyl serves as a raw material, an acylation reaction and a chlorination reaction are carried out on the biphenyl, and finally the biphenyl reacts with morpholine. According to the three reactions, intermediates do not need to be processed through purification, solvent dose not need to be replaced, continuous reactions can be carried out, the total yield is high, and the technology is friendly to the environment. The synthetic method of the 1-(biphenyl-4-yl)-2-methyl-2-morpholinopropan-1-one is low in cost, friendly to the environment, easy to operate and applicable to industrialization.
- -
-
Paragraph 0036; 0037
(2017/03/14)
-
- Copper(II)/Silver(I)-Catalyzed Sequential Alkynylation and Annulation of Aliphatic Amides with Alkynyl Carboxylic Acids: Efficient Synthesis of Pyrrolidones
-
A highly efficient protocol for the synthesis of pyrrolidones by the copper-catalyzed alkynylation/annulation of aliphatic amides with alkynyl carboxylic acids is discussed in this paper. A broad range of easily accessible alkynyl carboxylic acids were introduced at the β-methyl group of aliphatic amides with the assistance of an 8-aminoquinolyl auxiliary group via decarboxylation to achieve the subsequent cyclic C-N bond formation within one hour. High selectivity of β-methyl groups over methylene groups was observed, and the extension of this catalytic system to the activation of methylene C-H bonds failed. The substrates with two different groups at the α-position of the aliphatic amides lead to the formation of diastereoisomers which is determined by 1H NMR spectroscopy. The initially produced products with Z-configurations can be easily transformed to the corresponding products with E-configurations by the treatment with dilute p-toluenesulfonic acid after the reaction. This catalytic tandem decarboxylative cyclization provides a new opportunity for the direct functionalization of sp3 C-H bonds.
- Zhang, Jitan,Li, Danyang,Chen, Hui,Wang, Binjie,Liu, Zhanxiang,Zhang, Yuhong
-
supporting information
p. 792 - 807
(2016/03/09)
-
- 2-hydroxy-2-methyl-1-phenyl-1-propyl ketone synthesis process
-
The present invention discloses a 2-hydroxy-2-methyl-1-phenyl-1-propyl ketone synthesis process, which is characterized in that isobutyric acid is adopted as a raw material, an acylation reaction, a Friedel-Crafts reaction, and an alkaline hydrolysis reaction are performed to obtain a 2-hydroxy-2-methyl-1-phenyl-1-propyl ketone crude product, and fine steaming is performed to obtain the 2-hydroxy-2-methyl-1-phenyl-1-propyl ketone finished product. According to the present invention, the process is reasonable, no sulfur dioxide gas emits during the production process, the environmental pollution caused by the produced sodium chloride is low, and the product yield is high.
- -
-
Paragraph 0010
(2017/06/21)
-
- COMPOUNDS FOR REGULATING FAK AND/OR SRC PATHWAYS
-
The present application provides novel optionally substituted fused pyridine and pyrimidine bicyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating FAK and/or Src activity by administering a therapeutically effective amount of one or more of the compounds to a subject. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the FAK and/or Src pathway. Advantageously, these compounds perform as dual FAK and/or Src inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.
- -
-
Page/Page column 125; 126
(2015/03/28)
-
- Nickel-catalyzed direct thiolation of C(sp3)-H bonds in aliphatic amides
-
Nickel-catalyzed thiolation of the inactivated methyl C(sp3)-H bonds of aliphatic amides with disulfide is described. It is a novel strategy for the synthesis of thioethers with the ultimate goal of generating thioether carboxylic acids with various functional groups.
- Wang, Xie,Qiu, Renhua,Yan, Chunyang,Reddy, Vutukuri Prakash,Zhu, Longzhi,Xu, Xinhua,Yin, Shuang-Feng
-
supporting information
p. 1970 - 1973
(2015/04/27)
-
- An LC-MS/MS method to quantify acylcarnitine species including isomeric and odd-numbered forms in plasma and tissues
-
Acylcarnitines are intermediates of fatty acid and amino acid oxidation found in tissues and body fluids. They are important diagnostic markers for inherited diseases of peroxisomal and mitochondrial oxidation processes and were recently described as biomarkers of complex diseases like the metabolic syndrome. Quantification of acylcarnitine species can become challenging because various species occur as isomers and/or have very low concentrations. Here we describe a new LC-MS/MS method for quantification of 56 acylcarnitine species with acyl-chain lengths from C2 to C18. Our method includes amino acid-derived positional isomers, like methacrylyl-carnitine (2-M-C3:1-CN) and crotonyl-carnitine (C4:1-CN), and odd-numbered carbon species, like pentadecanoyl-carnitine (C15:0-CN) and heptadecanoyl-carnitine (C17:0-CN), occurring at very low concentrations in plasma and tissues. Method validation in plasma and liver samples showed high sensitivity and excellent accuracy and precision. In an application to samples from streptozotocin-treated diabetic mice, we identified significantly increased concentrations of acylcarnitines derived from branched-chain amino acid degradation and of odd-numbered straight-chain species, recently proposed as potential biomarkers for the metabolic syndrome. In conclusion, the LC-MS/MS method presented here allows robust quantification of isomeric acylcarnitine species and extends the palette of acylcarnitines with diagnostic potential derived from fatty acid and amino acid metabolism.
- Giesbertz, Pieter,Ecker, Josef,Haag, Alexander,Spanier, Britta,Daniel, Hannelore
-
p. 2029 - 2039
(2015/11/17)
-
- Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): Pharmacological characterization and assessment in a rat model of cocaine dependence
-
As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu 3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.
- Dhanya, Raveendra-Panickar,Sheffler, Douglas J.,Dahl, Russell,Davis, Melinda,Lee, Pooi San,Yang, Li,Nickols, Hilary Highfield,Cho, Hyekyung P.,Smith, Layton H.,D'Souza, Manoranjan S.,Conn, P. Jeffrey,Der-Avakian, Andre,Markou, Athina,Cosford, Nicholas D.P.
-
p. 4154 - 4172
(2014/06/09)
-
- Bromination of enamines from tertiary amides using the petasis reagent: A convenient one-pot regioselective route to bromomethyl ketones
-
An original one-pot synthesis of bromomethyl ketones is achived using the Petasis reagent (dimethyltitanocene) as a key for enamine generation. Several amides were used to test the limits of the procedure by changing either the alkyl chain R or the amino portion of the starting materials. The enamines generated in situ were allowed to react with bromine at low temperature followed by hydrolysis to yield bromomethyl ketones in excellent yields (85 to 95%). Mechanistic details and optimum conditions for the reaction are briefly discussed. The present approach offers several advantages such as regioselectivity in enamine formation, good yields, mild reaction conditions, and ease of experimentation.
- Kobeissi, Marwan,Cherry, Khalil,Jomaa, Wissam
-
supporting information
p. 2955 - 2965
(2013/09/02)
-
- Anti-HIV and NO production inhibition activities of epi-aleuritolic acid derivatives
-
Fifteen epi-aleuritolic acid derivatives were synthesized and evaluated for anti-HIV activity in 293 T cells and NO production inhibition activity. Of the derivatives, 1, 2, 3, 4, 11, and 13 showed relatively potent anti-HIV activity with EC50 values ranging from 5.80 to 13.30 μM. The most potent compound, 3α-2′,2′-dimethylsuccinic acyl epialeuritolic acid (11), displayed significant anti-HIV activity with an EC50 value of 5.80 μM. Compounds 1, 3, 4, and 11 showed NO inhibition activity, with IC50 values ranging from 3.40 to 7.10 μM and compound 1 inhibited NO production with an IC50 value of 3.40 μM.
- Liu, Jia-Bao,Zhang, Ying,Cui, Bao-Song,Cao, Ying-Li,Yuan, Shao-Peng,Guo, Ying,Hou, Qi,Li, Shuai
-
p. 515 - 524
(2013/09/02)
-
- Synthesis and evaluation of novel monosubstituted sulfonylurea derivatives as antituberculosis agents
-
A series of novel monosubstituted sulfonylurea derivatives 10a-y were synthesized and characterized by 1H NMR, 13C NMR and HRMS. These compounds were evaluated against Mycobacterium tuberculosis H37Rv in vitro. The results showed compounds 10f, 10k and 10s exhibited moderate antituberculosis activities with MIC values in the range of 20-100 mg/L. Compounds 10b and 10o displayed good antituberculosis activities (MIC 10 mg/L), which were comparable with that of the sulfometuron methyl. Both of the two compounds showed little cytotoxicities, with an IC50 against THP-1 cells greater than 100 mg/L.
- Pan, Li,Jiang, Ying,Liu, Zhen,Liu, Xing-Hai,Liu, Zhuo,Wang, Gang,Li, Zheng-Ming,Wang, Di
-
scheme or table
p. 18 - 26
(2012/07/01)
-
- Non-hydrolysable analogues of inorganic pyrophosphate as inhibitors of hepatitis C virus RNA-dependent RNA-polymerase
-
Inorganic pyrophosphate (PPi) is the product of the polymerization reaction catalyzed by DNA-and RNA-polymerases. A number of novel non-hydrolsable PPi analogues was synthesized; some of them inhibited the polymerization reaction catalyzed by hepatitis C virus RNA-dependent RNA-polymerase (NS5B). A new pharmacophore based on a non-hydrolysable methylenediphosphonate backbone has been developed. The structure-activity relationship analysis of 12 bisphosphonates is presented and the structural features crucial for NS5B polymerase activity inhibition are stated. Pleiades Publishing, Ltd., 2012.
- Yanvarev,Korovina,Usanov,Kochetkov
-
experimental part
p. 224 - 229
(2012/08/27)
-
- Pd(ll)-Catalyzed olefination of sp3 C-H bonds
-
"Chemical equation presented" The first Pd(II)-catalyzed sp3 C-H olefination reaction has been developed using N-arylamide directing groups. Following olefination, the resulting intermediates were found to undergo rapid 1,4-addition to give the corresponding &-lactams. Notably, this method was effective with substrates containing (-hydrogen atoms and could be applied to effect methylene C-H olefination of cyclopropane substrates.
- Wasa, Masayuki,Engle, Keary M.,Yu, Jin-Quan
-
supporting information; experimental part
p. 3680 - 3681
(2010/05/15)
-
- Amide-directed arylation of sp3 C-H bonds using Pd(II) and Pd(0) catalysts
-
Protocols to effect β-arylation of sp3 C-H bonds via Pd(II)/(IV) and Pd(0)/(II) catalytic cycles have been achieved using a newly developed monodentate CONHC6F5 directing group. These reactions provide an unprecedented means to functionalize sp3 C-H bonds in aliphatic carboxylic acid-derived substrates.
- Wasa, Masayuki,Yu, Jin-Quan
-
experimental part
p. 4811 - 4815
(2010/08/06)
-
- Nucleophilic acyl substitution via aromatic cation activation of carboxylic acids: Rapid generation of acid chlorides under mild conditions
-
The first example of aromatic cation-activated nucleophilic acyl substitution has been achieved. The conversion of carboxylic acids to their corresponding acid chlorides occurs rapidly in the presence of 3,3-dichlorocyclopropenes via the intermediacy of cyclopropenium carboxylate complexes. The effect of cyclopropene substituents on the rate of conversion is examined. The addition of tertiary amine base is found to dramatically accelerate reaction, and conditions were developed for the preparation of acid sensitive acid chlorides. Preparative scale peptide couplings of two N-Boc amino acids were achieved with this method.
- Hardee, David J.,Kovalchuke, Lyudmila,Lambert, Tristan H.
-
supporting information; experimental part
p. 5002 - 5003
(2010/06/13)
-
- Chemical composition of Inula cuspidata C.B. Clarke
-
Thymyl isobutyrate, thymol, thymyl isovalerate, 8α-hydroxy presilphiperfolene and intermedeol have been isolated from steam volatile extract of Inula cuspidata and identified from their spectral data, synthesis and chemical modification of major constituents. Sharp qualitative and quantitative variations among the constituents of leaf, flower and roots of Inula cuspidata are noticed.
- Mathela,Tiwari,Padalia,Chanotiya
-
p. 1249 - 1253
(2008/12/23)
-
- Synthesis of carnitine benzyl esters as prodrugs
-
The introduction of C-2 acyl groups and a benzyl ester onto L-carnitine generated a series of carnitine benzyl esters as prodrug with improved liposolubility, stability and bioavailability.
- Gong, Xiao-Wei,Li, Jin-Pei,Wu, Ji-Feng,Li, Xun,Zhai, Hai-Min,Feng, Bo,Xu, Wen-Fang,Tang, Wei
-
experimental part
p. 327 - 330
(2009/05/30)
-
- Synthesis of esters of D, L-, D(+)-, and L(-)-camphor oximes: Structure-odor correlation
-
Esters of D,L-, D(+)-, and L(-)-camphor oximes were synthesized, and the correlation between their structure and odor was examined.
- Dikusar,Zhukovskaya,Vyglazov
-
p. 1982 - 1985
(2008/02/08)
-
- Vanillin esters in reactions with indan-1,3-dione
-
2-Methoxy-4-(12-oxo-12H-benzo[f]indeno[1,2-b]quinolin-13-yl)phenyl esters of carboxylic acids were synthesized by the three component condensation of indan-1,3-dione, 2-naphthylamine, and O-acylvanillin. 2-Arylidenindan-1,3-diones formed during the reaction were isolated. Springer Science+Business Media, Inc. 2006.
- Kozlov,Basalaeva
-
p. 1223 - 1228
(2008/09/21)
-
- Vanilline alkanoates in the synthesis of hexahydrobenzacridine and octahydroxanthene derivatives
-
Cascade heterocyclization of 1,3-cyclohexanedione and dimedone with 2-naphthylamine and vanilline esters gave derivatives of 2-methoxy-4-(alkyl-11- oxo-7,8,9,10,11,12-hexahydrobenz[a]acridin-12-yl)- and 2-methoxy-4-(alkyl-1,8- dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl esters of aliphatic (C1- C4 ) carboxylic acids. 2005 Pleiades Publishing, Inc.
- Kozlov,Basalaeva
-
p. 617 - 621
(2007/10/03)
-
- Preparative synthesis of vanillin and vanillal alkanoates
-
Procedures for preparing vanillin and vanillal alkanoates were developed.
- Dikusar,Vyglazov,Moiseichuk,Zhukovskaya,Kozlov
-
p. 120 - 124
(2007/10/03)
-
- MAYTANSINOID ANALOGS AS ANTITUMOR AGENTS
-
Ansamycin analogs, including maytansinoid analogs, and their use in treating cell proliferative diseases and conditions, and in particular, for use as antitumor agents.
- -
-
Page/Page column 9
(2008/06/13)
-
- Vanillin esters of aliphatic acids in the synthesis of 4,7-phenanthroline derivatives
-
Condensation of vanillin esters of aliphatic acids with 6-aminoquinoline and cyclic c-diketones (1,3-cyclohexanedione and dimedone) afforded new 2-methoxy-4-(11-oxo-7,8,9,10,11,12-hexahydrobenzo[b][4,7]phenanthrolin-12-yl) phenyl esters of carboxylic acids.
- Kozlov,Gusak,Tereshko,Dikusar
-
p. 705 - 710
(2007/10/03)
-
- Method for preparing a benzylic-type ether
-
The invention concerns a method for preparing a benzylic-type ether from an aromatic compound. The inventive method for preparing a benzylic-type ether from an aromatic compound is characterised in that it consists in: in a first step, acylating an aromatic compound by reacting said aromatic compound with an acylating agent, in the presence of an efficient amount of zeolite or a Friedel-Crafts catalyst leading to a ketonic compound; in a second step, reducing the carbonyl group into carbinol leading to a benzylic alcohol; in a third step, etherifying the hydroxyl group, by reacting the benzylic alcohol with another alcohol, in the presence of an efficient amount of zeolite.
- -
-
-
- Process for functionalising a phenolic compound carrying an electron-donating group
-
The invention concerns a method for functionalizing a phenolic compound bearing an electron-donor group, in said group para position, inter alia a method for the amidoalkylation of a phenolic compound bearing an electron-donor group, and more particularly, a phenolic compound bearing an electron-donor group preferably, in the hydroxyl group ortho position. The method for functionalizing in para position with respect to an electron-donor group carried by a phenolic compound is characterised in that the phenolic compound bearing an electron-donor group is subjected to the following steps: a first step which consists of protecting the hydroxyl group in the form of a sulphonic ester function; a second step which consists in reacting the protected phenolic compound with an electrophilic reagent; optionally, a third step deprotecting the hydroxyl group.
- -
-
-
- Benzothiazole derivatives with activity as adenosine receptor ligands
-
The present invention relates to substituted benzothiazole derivitives and to their pharmaceutically acceptable salts useful for the treatment of diseases related to the adenosine receptor.
- -
-
-
- Process facilitating the regeneration of a catalyst based on a zeolite used in an acylation reaction, catalyst and use
-
The present invention relates to a process facilitating the regeneration of a catalyst based on a zeolite, employed in an acylation reaction. Another subject of the invention is a process for acylation of an aromatic ether, comprising, in a preferred alternative form, an additional stage of regeneration of the catalyst. The process of the invention, which makes it possible to regenerate more easily a catalyst based on a zeolite, employed in an acylation reaction, is characterized in that the zeolite is modified by addition of an effective quantity of at least one metallic element M chosen from the elements of group 8 of the Periodic Classification of the elements.
- -
-
-