- Preparation method of 2-fluoro-5-formyl chloropyridine
-
The invention relates to a preparation method of 2-fluoro-5-formyl chloropyridine, and belongs to the technical field of organic chemistry. The method comprises the following steps: 1) taking 2-fluoro-5-methylpyridine as a raw material, and reacting in the presence of potassium permanganate or sodium permanganate to obtain 2-fluoro-5-formic acid pyridine; and 2) carrying out reflux reaction on the2-fluoro-5-formic acid pyridine and thionyl chloride or oxalyl chloride in a chlorinated solvent, after the reaction is finished, carrying out reduced pressure distillation on the solvent, adding analkane solvent, freezing, filtering to obtain a 2-fluoro-5-formyl chloropyridine solution, and carrying out reduced pressure distillation to obtain the 2-fluoro-5-formyl chloropyridine. According to the invention, the method has the advantages that the conversion rate is high, the purity of the obtained product reaches 99.0% or above, the single impurity content is smaller than 0.5%, the production cost is low, and the method is suitable for industrial production.
- -
-
Page/Page column 4; 5
(2021/02/13)
-
- Crystal structure-guided design of berberine-based novel chitinase inhibitors
-
Glycoside hydrolase family 18 (GH18) chitinases play an important role in various organisms ranging from bacteria to mammals. Chitinase inhibitors have potential applications as pesticides, fungicides, and anti-asthmatics. Berberine, a plant-derived isoquinoline alkaloid, was previously reported to inhibit against various GH18 chitinases with only moderate K i values ranging between 20 and 70 μM. In this report, we present for the first time the berberine-complexed crystal structure of SmChiB, a model GH18 chitinase from the bacterium Serratia marcescens. Based on the berberine-binding mode, a hydrophobic cavity-based optimisation strategy was developed to increase their inhibitory activity. A series of berberine derivatives were designed and synthesised, and their inhibitory activities against GH18 chitinases were evaluated. The compound 4c showed 80-fold-elevated inhibitory activity against SmChiB and the human chitinase hAMCase with K i values at the sub-micromolar level. The mechanism of improved inhibitory activities was proposed. This work provides a new strategy for developing novel chitinase inhibitors.
- Chen, Lei,Zhu, Ling,Chen, Jinli,Chen, Wei,Qian, Xuhong,Yang, Qing
-
p. 1937 - 1943
(2020/11/12)
-
- NOVEL NUCLEOSIDE OR NUCLEOTIDE DERIVATIVES, AND USES THEREOF
-
The present disclosure relates to a novel nucleoside or nucleotide derivative, a racemate thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition for preventing or treating viral infection-associated diseases, containing the same as an active ingredient.
- -
-
Paragraph 0091
(2020/12/10)
-
- PROLONGED ECTOPARASITE-CONTROLLING AGENT FOR ANIMAL
-
A compound represented by Formula (1) can be used as a prolonged ectoparasite-controlling agent for an animal. A preparation for systemic application for use in prolonged control of an ectoparasite in an animal include the compound. A method for prolonged
- -
-
Paragraph 0180
(2019/04/16)
-
- The flocculated acryloyldimethyltauric molecule ligand
-
Provided are certain benzothiazole, imidazothiazole, imidazopyrimidine and imidazopyridine compounds, including, for example: formula (I) and pharmaceutically and physiologically acceptable salts, hydrates, and solvates thereof. Such compounds can be used as diagnostic ligands or labels of tau protein and PHF.
- -
-
Paragraph 0574; 0717
(2016/10/08)
-
- HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt
-
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
- -
-
Paragraph 0318; 0319
(2014/05/07)
-
- Design, synthesis and insecticidal activity of novel anthranilic diamides with benzyl sulfide scaffold
-
A series of novel anthranilic diamides with benzyl sulfide scaffold were synthesized, in which N-pyridylpyrazole moiety generally regarded as key pharmacophore was abandoned. The target compounds were characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The preliminary bioassays indicated that half of the title compounds were endowed with good insecticidal activities against armyworm (Mythimna sepatara) at the concentration of 500 mg/L. Exhilaratingly, the synthesized compound 3a was also active against Tetranychus cinnabarinus at 100 mg/L. The difference in activities between the target compounds was influenced by the substituents, which provided some hints for further investigation on structure modifications.
- Chen, Yin-Bo,Li, Ji-Ling,Shao, Xu-Sheng,Xu, Xiao-Yong,Li, Zhong
-
p. 673 - 676
(2013/07/26)
-
- Labeling of benzodioxin piperazines with fluorine-18 as prospective radioligands for selective imaging of dopamine D4 receptors
-
The D4 receptor is of high interest for research and clinical application but puts high demands on appropriate radioligands to be useful tools for investigation. Search for adequate radioligands suitable for in vivo imaging is therefore still in progress. The potential neuroleptic drug 6-(4-[4-fluorobenzyl]piperazin-1-yl)benzodioxin shows high affinity and selectivity to the D4 receptor. Derivatization of this lead structure by adding hydrophilic moieties was carried out in order to lower its lipophilicity what led to three new putative dopamine receptor D4 ligands. A comprehensive description of the syntheses of standard compounds and corresponding labeling precursors is given which were obtained in satisfactory yields. Furthermore, the radiosyntheses by direct 18F-labeling and build-up synthesis were compared. All derivatives of 6-(4-[4-fluorobenzyl]- piperazin-1-yl)benzodioxin were successfully synthesized in 18F- labeled form with radiochemical yields of 9-35% and molar activities of 30-60 GBq/μmol using one-pot procedures. 2013 John Wiley & Sons, Ltd. Derivatives of the lead structure 6-(4-[4-fluorobenzyl]-piperazine-1-yl) benzodioxin were successfully synthesized, labeled via direct 18F-substitution or build-up synthesis leading to new putative radioligands for imaging of the dopamine D4 receptor. Reductive amination proved as the method of choice for preparation of substituted benzyl-derivatives of piperazine as precursors and standards, and also superior for build-up radiofluorination (RCY = 9 - 35;%) in comparison to direct 18F- labeling (RCY = 1 - 5;%).
- Kuegler, Fabian,Ermert, Johannes,Coenen, Heinz H.
-
p. 609 - 618
(2013/12/04)
-
- Rapid and efficient synthesis of [18F]fluoronicotinamides, [18F]fluoroisonicotinamides and [18F]fluorobenzamides as potential pet radiopharmaceuticals for melanoma imaging
-
In an attempt to simplify nucleophilic radiofluorination reactions to be amenable for automation, a series of [18F]fluoronicotinamides, [ 18F]fluoroisonicotinamides and [18F]fluorobenzamides were synthesized using one-step
- Al Jammaz,Al-Otaibi,Okarvi,Amartey
-
experimental part
p. 312 - 317
(2012/06/04)
-
- METHODS AND COMPOUNDS FOR INHIBITING MRP1
-
The present invention further relates to a method of inhibiting MRP1 in a mammal which comprises administering to a mammal in need thereof an effective amount of a compound of formula (I).
- -
-
-
- Pyrrolidine-modified and 6-substituted analogs of nicotine: a structure-affinity investigation
-
Because the structural requirements for the binding of nicotine to central nicotine receptors remain largely uninvestigated, we undertook a systematic investigation of pyrrolidine ring-opened analogs.This led to a subsequent investigation of related conformationally restricted derivatives of these analogs.The results are reported relative to the binding of several well-known and widely used nicotine receptor ligands.Although none of the ring-opened analogs binds with higher affinity than (-)-nicotine (Ki = 2.3 nM), 3-(N-methyl-N-ethylaminomethyl)pyridine (12a; Ki = 28 nM) binds with significant affinity.A conformationally restricted analog of 12a, N-methyl naphthyridine 30b (Ki = 18 nM), binds with similar affinity. 6-Substitution of 12a and racemic nicotine seems to be tolerated when the substituent is halogen or methyl.In functional studies (hypolocomotion and antinociception in mice; stimulus generalization in nicotine-trained rats) 30b retains nicotine-like properties.Several of the 6-substituted compounds were 2 to 20 times more potent than (+/-)nicotine.Although the intact pyrrolidine ring of nicotine appears important for optimal affinity, its presence is not an absolute requirement for activity, and 6-position substitution of the pyridine nucleus can influence both binding and functional activity. - Keywords: nicotine; nicotine receptor; drug discrimination; antinociception.
- Dukat, M.,Fiedler, W.,Dumas, D.,Damaj, I.,Martin, B. R.,et al.
-
p. 875 - 888
(2007/10/03)
-
- Bis-acyloxymethyl derivatives
-
This invention relates to new pyridyl, quinoline and acridine bis-acyloxymethyl compounds; to compositions comprising these compounds; and to processes for their utility as fungicides, bactericides and as inhibitors of the growth of cancer in warm-blooded animals. In accordance with this invention, new bis-acyloxymethyl derivatives are provided of the formula: STR1 wherein B is selected from substituted and unsubstituted alkyl, cycloalkyl, aryl, alkenyl, cycloalkenyl and alkynyl; A is selected from hydrogen and B; or, A and B together comprise a pyrrolizine; L is selected from STR2 wherein Y is selected from hydrogen or STR3 each R and Z is independently selected from hydrogen or substituted and unsubstituted alkyl, cycloalkyl, aryl, alkenyl, cycloalkenyl, alkynyl, amine group, each Z' is independently selected from hydrogen and substituted or unsubstituted alkyl; M is Z or is selected from halogen, nitro, hydroxyl, nitrile and substituted or unsubstituted, carboxylic acid group, carboxylic acid ester group, carboxylic acid amide group, sulfonic acid group and sulfonic acid amide group; ether group, thioether group, acylated hydroxyl, sulfonylamide, sulfonylurea, sulfoxide group, sulfone group and mixtures thereof; each n is the same and is 0 or 1; q is from 0-4; and, X is the anion of an acid.
- -
-
-
- Synthesis, Chemistry, and Antineoplastic Activity of α-Halopyridinium Salts: Potential Pyridone Prodrugs of Acylated Vinylogous Carbinolamine Tumor Inhibitors
-
A series of 4- and 5-methyl>-1H-pyrrolizin-5-yl>-2-halopyridinium iodides were synthesized.The rates of hydrolysis of the α-halopyridinium salts to the corresponding pyridones, and the reactivities of the carbamate moieties were studied as a function of pH, buffer composition, and ionic strength.The 4- and 5-pyrrolizinyl-2-halopyridinium iodides and the corresponding pyridones were evaluated against P388 lymphocytic leukemia in vivo.The α-fluoropyridinium compounds were active but the α-chloro compounds were not.This activity was correlated with the rates of hydrolysis of the α-halopyridinium compounds to the active pyridone.Compounds that were active in the P388 screen were evaluated in L1210 leukemia, M5076 carcinoma, and MX-1 mammary xenograft assays in mice.
- Anderson, Wayne K.,Dean, Dennis C.,Endo, Toshiyasu
-
p. 1667 - 1675
(2007/10/02)
-
