- Preparation method of brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone
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The invention belongs to the field of chemical engineering, and particularly relates to a preparation method of a brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone. According to the novel method for preparing the 7-hydroxy-1H-quinoline-2-ketone, DDQ is replaced with palladium on carbon, the obtained product is high in yield, few in impurity and easy to operate, the catalyst can be recycled, a target compound is synthesized through direct catalytic dehydrogenation, and the method has green atom economy and is suitable for industrial production.
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- O-prenylated carbostyrils as a novel class of 15-lipoxygenase inhibitors: Synthesis, characterization, and inhibitory assessment
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Catalyzed peroxidation of unsaturated lipid in animals and plants intimately is linked to the activity of 15-Lipoxygenase enzymes. Lipoxygenases (LOXs) are well known to play an important role in many acute and chronic syndromes such as inflammation, asthma, cancer, and allergy. In this study, a series of mono prenyloxycarbostyrils were synthesized and evaluated as potential inhibitors of soybean 15-Lipoxygenase (SLO) and their inhibitory potencies were compared to mono prenyloxycoumarins which had been reported in the previous works. The synthetic compounds inhibit lipoxygenase enzyme by competitive mechanism like the prenyloxy coumarins. The results showed that position and length of the prenyl moiety play the important role in lipoxygenase inhibitory activity. Among all of the synthetic compounds (coumarin and carbostyril derivatives), 5-farnesyloxycoumarin and 8-farnesyloxycarbostyril demonstrated the best inhibitory activity by IC50?values of 1.1?μM and 0.53?μM, respectively.
- Alavi, Seyed Jamal,Zebarjadi, Amir,Bafghi, Mahdi Hosseini,Orafai, Hossein,Sadeghian, Hamid
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p. 894 - 902
(2021/09/08)
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- Design, synthesis and evaluation of quinolinone derivatives containing dithiocarbamate moiety as multifunctional AChE inhibitors for the treatment of Alzheimer’s disease
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A series of novel quinolinone derivatives bearing dithiocarbamate moiety were designed and synthesised as multifunctional AChE inhibitors for the treatment of AD. Most of these compounds exhibited strong and clearly selective inhibition to eeAChE. Among them, compound 4c was identified as the most potent inhibitor to both eeAChE and hAChE (IC50 = 0.22 μM for eeAChE; IC50 = 0.16 μM for hAChE), and it was also the best inhibitor to AChE-induced Aβ aggregation (29.02% at 100 μM) and an efficient inhibitor to self-induced Aβ aggregation (30.67% at 25 μM). Kinetic and molecular modelling studies indicated that compound 4c was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 4c had good ability to cross the BBB, showed no toxicity on SH-SY5Y neuroblastoma cells and was well tolerated in mice at doses up to 2500 mg/kg (po).
- Fu, Jie,Bao, Fengqi,Gu, Min,Liu, Jing,Zhang, Zhipeng,Ding, Jiaoli,Xie, Sai-Sai,Ding, Jinsong
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p. 118 - 128
(2019/11/16)
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- Discovery of new thieno[3,2-d]pyrimidine derivatives targeting EGFRL858R/T790M NSCLCs by the conformation constrained strategy
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Studies on the third-generation of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFRL858R/T790M mutant remain hotspots, specifically for non-small cell lung cancer (NSCLC). In the current study, a new series of EGFR-TKIs with thieno[3,2-d]pyrimidine derivatives(6a-6r) bearing quinolin-2(1H)-ones were designed and synthesized, through conformational constrained strategy from the third generation of EGFR-TKI olmutinib. In vitro structure-activity relationship (SAR) studies indicated that compounds 6a, 6l, 6m, 6n and 6o exhibited good selective inhibition to EGFRL858R/T790M (IC50 ≤ 250 nM) over wild type EGFR (IC50 > 10000 nM). The observed selectivity of compounds 6l and 6o was also proved by the computational molecular docking and the cellular thermal shift assay. These compounds had good growth inhibitory effect on the four tested cancer cell lines. Specifically, 6o could significantly inhibit the colony formation, wound healing and the expression of p-EGFR and its downstream p-ERK in EGFRL858R/T790M H1975 lung cancer cells. Our findings suggest that the thieno[3,2-d]pyrimidine compounds, especially 6l and 6o, can selectively target the mutant EGFRL858R/T790M in vitro and at cellular level and may serve as the lead compounds for generating new series of the third-generation EGFR-TKIs.
- Chen, Yang,Cheng, Zhongyu,Huang, Xin,Jiang, Yaoxuan,Qiao, Hui,Xie, Jiahao,Yang, Linlin,Yu, Bin,Zhao, Wen,Zhou, Wenjuan
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- A 7 - hydroxy -2 - quinolinone of preparation method
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The invention discloses a formula I compound represented by the preparation method, the method comprises the following steps: in a solvent, in the arrowhead class under the action of the catalyst, on the compound II are shown in the following of the dehydrogenation reaction to obtain the compound I can be. Preparation method of this invention has the following advantages: the raw materials used are cheap, product yield and high purity, the purity of 98% or more, the color white and non-heterogeneous, after treatment is simple, catalyst and solvent can be recycled, wastes very little, for environmental protection, it is suitable for industrial production.
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Paragraph 0030-0043; 0047; 0048
(2019/06/07)
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- PROCESS FOR THE PREPARATION OF BREXPIPRAZOLE AND ITS INTERMEDIATES
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The present invention discloses to a process for the preparation of brexpiprazole and its pharmaceutically acceptable salt. The present invention further discloses novel intermediates and process for the preparation of the novel intermediates of brexpiprazole. The invention also discloses a process for purification of brexpiprazole to reduce or eliminate impurities.
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Page/Page column 19
(2019/05/02)
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- Oxidative Aromatization of 3,4-Dihydroquinolin-2(1 H)-ones to Quinolin-2(1 H)-ones Using Transition-Metal-Activated Persulfate Salts
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Inorganic persulfate salts were identified as efficient reagents for the oxidative aromatization of 3,4-dihydroquinolin-2(1H)-ones through the activation of readily available transition metals, such as iron and copper. The feasible protocol conforming to the requirement of green chemistry was utilized in the preparation of the key intermediate (7-(4-chlorobutoxy)quinolin-2(1H)-one 2) of brexpiprazole in 80% isolated yield on a 100 g scale, and different quinolin-2(1H)-one derivatives with various functional groups were demonstrated in 52-89% yields.
- Chen, Weiming,Sun, Changliang,Zhang, Yan,Hu, Tianwen,Zhu, Fuqiang,Jiang, Xiangrui,Abame, Melkamu Alemu,Yang, Feipu,Suo, Jin,Shi, Jing,Shen, Jingshan,Aisa, Haji A.
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p. 8702 - 8709
(2019/07/03)
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- Preparation method and application of substituted quinoline-2(1H)-one compound
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The invention belongs to the field of pharmaceutical chemistry and chemical synthesis, and concretely relates to a preparation method of a substituted quinoline-2(1H)-one compound. The invention provides a preparation method of the substituted quinoline-2(1H)-one compound. The preparation method performs an oxidation reaction on a compound represented by a formula I and an oxidant in a solvent toobtain a compound represented by a formula II. The preparation method has the advantages of simple method, high yield and low cost and is suitable for industrial production. The substituted quinoline-2(1H)-one represented by the formula II is an important intermediate of a variety of pharmaceutical active ingredients.
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Paragraph 0069-0072
(2019/11/29)
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- An innovative approach for the synthesis of 7-hydroxyquinolin-2(1H)-one: A key intermediate of brexpiprazole
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2,3-Dichloro-5,6-dicyano-p-benzoquinone (DDQ) mediated oxidation of 7-hydroxy-1,2,3,4-tetrahydro-2-quinolinone has been prepared from 3-hydroxy aniline to obtain 7-hydroxyquinolin-2(1H)-one in aqueous media. Stoichiometric quantities of DDQ and THF provides a high out put of 7-hydroxyquinolin-2(1H)-one and reduces the consumption of organic solvents and discourages by-products. Overall advantage with this approach was reduce the time cycle and cost of the brexpiprazole intermediate.
- Reddy, T Ram,Reddy, Desireddy Neha,Reddy, Bhimireddy Krishna,Kasturaiah, Chapala,Yadagiri, Kurra
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p. 834 - 836
(2018/03/13)
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- Method for preparing hydroxyl-2(1H)-quinolinone
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The invention discloses a method for preparing hydroxyl-2(1H)-quinolinone, and belongs to the field of organic chemistry. The method comprises the following steps: enabling an aminophenylboric acid compound and trans-beta-aryl acryloyl chloride to react under the existence of triethylamine or pyridine so as to generate a trans-amide intermediate, and then carrying out temperature rising reaction in an organic solvent under the existence of aluminum chloride anhydrous and B(C6F5)3; cooling after completing the reaction, and adding hydrogen peroxide for oxidization, thus obtaining the hydroxyl-2(1H)-quinolinone. The method disclosed by the invention has the advantages that raw materials are easy to obtain, hydroxyl quinolinone products in different positions can be obtained through differentinitial raw materials, and an existing synthetic route is enriched.
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Paragraph 0059; 0060; 0065; 0066
(2018/03/28)
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- PROCESSES FOR THE PREPARATION OF 7-{4-[4-(1-BENZOTHIOPHEN-4-YL)PIPERAZIN-1-YL]BUTOXY}QUINOLIN-2(1H)-ONE
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The Present Invention relates to process for the preparation of 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one represented by the following structural formula-1.
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Page/Page column 33
(2018/05/27)
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- Containing quinolinone pyrimidine and five-membered heterocyclic compound, preparation method and application thereof (by machine translation)
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The invention discloses containing quinolinone pyrimidine and five-membered heterocyclic compound, preparation method and its application, which belongs to the field of pharmaceutical chemistry. The compounds of the invention of the formula I as shown. The compounds of a plurality of tumor cells such as H1975, A549, PC9, PC3, HGC has significant inhibition and anti-personnel effects, and in the in vitro kinase level to the human epidermal growth factor receptor EGFR - L858R/T790M mutant has good inhibition activity. Can be used as a further development of the candidate or lead compound, is applied to the anti-tumor pharmaceutical preparation. (by machine translation)
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- A process for preparing 7 - hydroxy - 2 - quinolinone of the method (by machine translation)
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The invention discloses a process for preparing 7 - hydroxy - 2 - quinolinone of the method, specific steps are as follows: in the organic solvent, 3, 4 - dihydro - 7 - hydroxy - 2 - quinolone in the catalysis of DDQ heating dehydrogenation, to get the 7 - hydroxy - 2 - quinolinone. The operation is simple, mild reaction conditions, raw materials are easy, simple and efficient, pervasive is good. (by machine translation)
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Paragraph 0022-0035
(2017/10/06)
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- PROCESS FOR THE PREPARATION OF QUINOLINE-2(1H)-ONE DERIVATIVES
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The present invention relates to quinolin-2(1H)-one derivatives polymorph and its process thereof. Formula (I).
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Page/Page column 19
(2017/07/31)
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- Structure-Based Design and Optimization of Multitarget-Directed 2 H -Chromen-2-one Derivatives as Potent Inhibitors of Monoamine Oxidase B and Cholinesterases
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The multifactorial nature of Alzheimer's disease calls for the development of multitarget agents addressing key pathogenic processes. To this end, by following a docking-assisted hybridization strategy, a number of aminocoumarins were designed, prepared, and tested as monoamine oxidases (MAOs) and acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitors. Highly flexible N-benzyl-N-alkyloxy coumarins 2-12 showed good inhibitory activities at MAO-B, AChE, and BChE but low selectivity. More rigid inhibitors, bearing meta- and para-xylyl linkers, displayed good inhibitory activities and high MAO-B selectivity. Compounds 21, 24, 37, and 39, the last two featuring an improved hydrophilic/lipophilic balance, exhibited excellent activity profiles with nanomolar inhibitory potency toward hMAO-B, high hMAO-B over hMAO-A selectivity and submicromolar potency at hAChE. Cell-based assays of BBB permeation, neurotoxicity, and neuroprotection supported the potential of compound 37 as a BBB-permeant neuroprotective agent against H2O2-induced oxidative stress with poor interaction as P-gp substrate and very low cytotoxicity.
- Farina, Roberta,Pisani, Leonardo,Catto, Marco,Nicolotti, Orazio,Gadaleta, Domenico,Denora, Nunzio,Soto-Otero, Ramon,Mendez-Alvarez, Estefania,Passos, Carolina S.,Muncipinto, Giovanni,Altomare, Cosimo D.,Nurisso, Alessandra,Carrupt, Pierre-Alain,Carotti, Angelo
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p. 5561 - 5578
(2015/08/03)
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- TRIAZOLO-PYRAZINE DERIVATIVES USEFUL IN THE TREATMENT OF DISORDERS OF THE CENTRAL NERVOUS SYSTEM
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Provided herein are heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and metabolic disorders, including, but not limited to, e.g., neurological disorders, psychosis, schizophrenia, obesity, and diabetes.
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Paragraph 00220
(2014/06/23)
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- FUNCTIONALLY SELECTIVE LIGANDS OF DOPAMINE D2 RECEPTORS
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The present invention relates to novel functionally selective ligands of dopamine D2 receptors, including agonists, antagonists, and inverse agonists. The invention further relates to the use of these compounds for treating central nervous system disorders related to D2 receptors.
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Page/Page column 50
(2012/01/15)
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- 3,4-DIHYDRO-2 (1H) - QUINOLINONE AND 2 (1H)-QUINOLINONE DERIVATIVES
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The present invention relates to novel 3,4-dihydro-2(lH)-quinolinone and 2(lH)-quinolinone derivatives, their acceptable acid addition salts, solvates, hydrates and polymorphs thereof. The invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions beneficially treated by atypical antipsychotic agents. The invention further provides methods for using a compound of this invention to determine concentrations of a corresponding 3,4-dihydro-2(lH)- quinolinone or 2(lH)-quinolinone compound, particularly in biological fluids, and to determine metabolism patterns of that 3,4-dihydro-2(lH)-quinolinone or 2(1H)-quinolinone compound.
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Page/Page column 32
(2008/06/13)
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- Synthesis, absorption spectra studies and biological activity of some novel conjugated dyes
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Novel monomethine 2a-f, dimethine 4a-f and tetramethine 6a-h cyanine dyes were prepared as conjugated dyes. Such dyes incorporating coumarin and/or quinoline derivatives 1a-d. These dyes were synthesized to study their spectral behavior, solvatochromism and biological activity. These dyes are characterized by elemental analysis, IR, 1H NMR and mass-spectra.
- Abd El-Aal,Koraierm
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p. 389 - 395
(2007/10/03)
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- Synthesis of certain quinolin-2(1H)-one α-methylene-γ-butyrolactones as potential antiplatelet agents
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Certain quinolin-2(1H)-one derivatives with various α-methylene-γ- butyrolactones substituted at C(7)-position were synthesized and evaluated for their antiplatelet activity against arachidonic acid (AA)-, and platelet- activating factor (PAF)-induced aggregation in washed rabbit platelets. 7- Hydroxyquinoline 1-oxide was treated with acetic anhydride followed by the hydrolysis of 1.0 N NaOH to afford 7-hydroxyquinolin-2(1H)-one (6). The desired 7-[(2,3,4,5-tetrahydro-4-methylene-5-oxo-2-furanyl)methoxy]-quinolin- 2(1H)-ones (8a-e) were obtained from 6 via alkylation and the Reformatsky- type condensation. These quinolin-2(1H)-ones (8a-e), exhibited approximately five to seven times more potent than their coumarin counterparts against AA- and PAF-induced aggregation and are approximately two hundred times more potent than aspirin against AA-induced aggregation.
- Chen, Yeh-Long,Wang, Tai-Chi,Fang, Kuo-Chang,Chang, Nein-Chen,Tzeng, Cherng-Chyi
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p. 453 - 462
(2007/10/03)
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- A concise regiospecific synthesis of 8,8-dimethyl-2H, 8H-pyrano [6, 5- h]quinolin-2-one and related compounds
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An efficient method for the regiospecific synthesis of 8,8-dimethyl- 2H,8H-pyrano[6,5-h]quinolin-2-one and related compounds via a Claisen rearrangement is described.
- Yang, Zheng-Yu,Xia, Yi,Xia, Peng,Brossi, Arnold,Lee, Kuo-Hsiung
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p. 4505 - 4506
(2007/10/03)
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- Lewis acid catalyzed reaction of cinnamanilides: Competition of intramolecular and intermolecular Friedel-Crafts reaction
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The first intermolecular Friedel-Crafts reaction of benzene leading to the formation of 3,3-diphenylpropionanilide 7 is described. 4-Methoxyaniline was reacted with cinnamoyl chloride to give 4-methoxycinnamanilide (5a), the treatment of which with aluminum (III) chloride in chlorobenzene at 120 °C or in benzene at 80 °C afforded exclusively 6-hydroxyquinolin-2(1H)-one (3a) or 4'-hydroxy-3,3-diphenylpropionanilide (7a), respectively. The formation of 7a rather than 3a in benzene indicated that an intermolecular Friedel-Crafts reaction occurred prior to the relatively more facile intramolecular ring cyclization. This intermolecular Friedel-Crafts reaction was observed during the attempted ring cyclization of cinnamanilide and its methoxy derivatives in aluminum (III) chloride/benzene. Preparation of 3a can also be achieved in 17% overall yield via the N-oxidation of 6-hydroxyquinoline followed by acetylation and hydrolysis.
- Wang, Tai-Chi,Chen, Yeh-Long,Lee, Kuan-Han,Tzeng, Cherng-Chyi
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- Heteroaryl quinolines as inhibitors of leukotriene biosynthesis
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Compounds having the formula I: STR1 are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection and in preventing the formation of atherosclerotic plaques.
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