22246-18-0Relevant articles and documents
An innovative approach for the synthesis of 7-hydroxyquinolin-2(1H)-one: A key intermediate of brexpiprazole
Reddy, T Ram,Reddy, Desireddy Neha,Reddy, Bhimireddy Krishna,Kasturaiah, Chapala,Yadagiri, Kurra
, p. 834 - 836 (2018)
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.
Preparation method of brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone
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Paragraph 0028; 0033-0034, (2021/05/05)
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.
Method for synthesizing aripiprazole
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Paragraph 0127; 0128; 0129, (2019/01/16)
The invention discloses a method for synthesizing aripiprazole. The method comprises making 4-halogenated-3-nitrophenol react with an ethylenation reagent under palladium catalysis conditions to obtain 3-nitro-4-vinylphenol; making the 3-nitro-4-vinylphenol and 1,4-dihalogenated butane reacting with alkali to obtain 4-(4-halobutoxy)-2-nitro-1-styrene; making the 4-(4-halobutoxy)-2-nitro-1-styreneand 1-(2,3-dichlorophenyl)piperazine salt reacting with the alkali to obtain 1-(2,3-dichlorophenyl)-4-(4-(3-nitro-4-vinylphenoxy)butyl)piperazine; making the 1-(2,3-dichlorophenyl)-4-(4-(3-nitro-4-vinylphenoxy)butyl)piperazine reacting with CO to form the aripiprazole. The method for synthesizing the aripiprazole has the total yield of up to 77% and is simple in post treatment.
Design, synthesis, molecular docking, and in vitro antidiabetic activity of novel PPARγ agonist
Chaturvedi, Radha Nandan,Pendem, Krishnaiah,Patel, Vipul P.,Sharma, Mukta,Malhotra, Sunita
, p. 2069 - 2084 (2018/08/22)
Abstract: The present work describes the design, synthesis, molecular docking, biological evaluation, and assessment of structure–activity relationship of new derivatives based upon the molecular skeleton of the drug pioglitazone, a compound which is currently used for the management of type 2 diabetes mellitus. Pioglitazone has several side effects such as weight gain, edema, congestive heart failure, and bladder cancer. Therefore, there is a strong demand for identification of new lead candidates in the treatment of type 2 diabetes mellitus. A series of 24 compounds were prepared and evaluated for their peroxisome proliferator-activated receptor-γ (PPARγ) binding affinity assay and the IC50 values were determined. Among these compounds, six compounds exhibited promising IC50 values as compared to standard drugs pioglitazone and rosiglitazone. Furthermore, in order to confirm the target of these molecules, molecular docking study was carried out with peroxisome proliferator-activated receptor-γ (PPARγ) protein. Molecular modeling studies suggested that these compounds appropriately interact in the active sites of receptor. Graphical abstract: [Figure not available: see fulltext.].
Design of a Chemical Probe for the Bromodomain and Plant Homeodomain Finger-Containing (BRPF) Family of Proteins
Igoe, Niall,Bayle, Elliott D.,Tallant, Cynthia,Fedorov, Oleg,Meier, Julia C.,Savitsky, Pavel,Rogers, Catherine,Morias, Yannick,Scholze, Sarah,Boyd, Helen,Cunoosamy, Danen,Andrews, David M.,Cheasty, Anne,Brennan, Paul E.,Müller, Susanne,Knapp, Stefan,Fish, Paul V.
supporting information, p. 6998 - 7011 (2017/09/07)
The bromodomain and plant homeodomain finger-containing (BRPF) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Here, we describe NI-57 (16) as new pan-BRPF chemical probe of the bromodomain (BRD) of the BRPFs. Inhibitor 16 preferentially bound the BRD of BRPF1 and BRPF2 over BRPF3, whereas binding to BRD9 was weaker. Compound 16 has excellent selectivity over nonclass IV BRD proteins. Target engagement of BRPF1B and BRPF2 with 16 was demonstrated in nanoBRET and FRAP assays. The binding of 16 to BRPF1B was rationalized through an X-ray cocrystal structure determination, which showed a flipped binding orientation when compared to previous structures. We report studies that show 16 has functional activity in cellular assays by modulation of the phenotype at low micromolar concentrations in both cancer and inflammatory models. Pharmacokinetic data for 16 was generated in mouse with single dose administration showing favorable oral bioavailability.
Method for synthesizing aripiprazole using m-amino phenol as raw material
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Paragraph 0044, (2016/10/08)
The present invention discloses a method for synthesizing aripiprazole using m-amino phenol as a raw material. The synthesis method comprises: step 1, performing a substitution reaction on the m-amino phenol and 3-methoxy propionyl chloride in an aqueous solution of a strong base; step 2, performing electrophilic substitution on the product obtained in the first step using boron trifluoride diethyl ether as a catalyst; step 3, performing a substitution reaction on the product obtained in the second step and 4-bromine-1-butyl iodide under catalysis of the strong base in solvent composed of DMSO, DMF and water; and step 4, performing a substitution reaction on the product obtained in the third step and 1-(2, 3-dichloro phenyl) piperazine under catalysis of the strong base in solvent composed of DMSO, DMF and water; Tert-butyl benzenesulfonic acid 4-chloro butyl ester and 7-hydroxy-3, 4-2 (1H) dihydroquinolinone are used for a substitution reaction. Since tert-butyl benzenesulfonyloxy and chlorine respectively in 1, 4-position carbon atoms in 4-bromine-1-butyl iodide have different substitution activity, iodine is preferably substituted by hydroxy, and in this way dimerized quinolinone by-products are reduced, thereby improving the purity of the product and ensuring the yield.
Diversified synthesis of novel quinoline and dibenzo thiazepine derivatives using known active intermediates
Sharada,Satyanarayana Reddy,Sammaiah,Sumalatha
, p. 7959 - 7966 (2013/09/23)
The novel drug development to control resisting infections in conventional drug therapy is a need of today. Few antiulcer relative derivatives developed by approaching convergent synthesis. The derivatives synthesized successfully are dibenzo thiazepine-pyridine (SLN11-SLN15) and benzimidazole-hydroquinoline based derivatives (SLN16-SLN20). It involved the coupling through microwave, sonication and conventional techniques at final step. The efficient technology identified as sonication technique basically time and yield. The reported compounds were structural characterized by elemental analysis and spectral studies such as 1H, 13C NMR and MS.
METHOD FOR PRODUCING A CROSS-COUPLING PRODUCT OF A BENZENOID DIAZONIUM SALT
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Paragraph 0056; 0057; 0058; 0059; 0060; 0061, (2013/03/26)
The invention relates to a method for producing a cross-coupling product of a benzenoid dizonium salt according to the general formula (I), wherein the groups R1, R2, R3, R4, and R5 represent hydrogen, halogen, an alkyl, alkenyl, aryl, alkoxy, aryloxy, nitro, cyano, hydroxy, acetyl, and/or diazo groups independently of each, and X represents BF4, Cl, F, SO3CH3, CO2CH3, PF6, ClO2CH3, or CIO4, comprising the following steps: (a) providing a benzenoid amide, which with the exception of the diazo function has the same substituents R1, R2, R3, R4, and R5 as the benzenoid diazonium salt of the general formula (I), and hydrolytically cleaving the amide to form an amine or providing a corresponding amine, (b) diazotizing the amine thus obtained or provided with a nitrite, and (c) subsequently reacting the benzenoid diazonium salt with a coupling partner in the presence of a catalyst to form a cross-coupling product, wherein the coupling parter is represented by the general formula (II), R6, R7, and R8 are the same or different and represent hydrogen, carboxyalkyl groups, carboxyaryl groups, alkyl groups, aryl groups, alkoxy groups, aryloxy groups, wherein the groups can each contain Si, N, S, O, and or halogen atoms, or R6 and R7 with the double bound form an aromatic ring, which can be provided with R8 and one to four further substituents, independently of each other, selected from the group comprising a straight-chain or branched (C1-C6) alkyl group, a (C3-C7) cycloalkyl group, a straight-chain or branched (C1-C6) alkenyl group, a straight-chain or branched (C1-C6) alkyoxy group, halogen, the hydroxy group, an amino, di(C1-C6) alkylamino, nitro, acetyl, cyan, benzyl, 4-methoxybenzyl, 4-nitrobenzyl, phenyl, and 4-methoxyphenyl group and represents Y=H, —B(OR)2, —SnR3, —ZnR, —SiR3, or Mg (halogen), and wherein at least the steps (b) and (c) are performed without intermediate isolation of an intermediate product. According to said method, cross-couplings can be performed more simply and with improved yield without the hydroxyl group in aromatic reactants containing hydroxyl groups having to be provided with a protective group.
Selective dual inhibitors of CYP19 and CYP11B2: Targeting cardiovascular diseases hiding in the shadow of breast cancer
Hu, Qingzhong,Yin, Lina,Hartmann, Rolf W.
supporting information, p. 7080 - 7089 (2012/11/07)
Postmenopausal women are at high risk for cardiovascular diseases because of the estrogen deficiency. As for postmenopausal breast cancer patients, this risk is even higher due to inhibition of estrogens biosyntheses in peripheral tissue by the aromatase (CYP19) inhibitors applied. Because estrogen deficiency results in significantly elevated aldosterone levels, which are a major cause of cardiovascular diseases, dual inhibition of CYP19 and CYP11B2 (aldosterone synthase) is a promising treatment for breast cancer and the coinstantaneous cardiovascular diseases. By combination of important structural features of known CYP19 and CYP11B2 inhibitors, we succeeded in obtaining compounds 3 and 5 as selective dual inhibitors with IC50 values around 50 and 20 nM toward CYP19 and CYP11B2, respectively. These compounds showed also good selectivity toward CYP11B1 (selectivity factors (IC50 CYP11B1/IC 50 CYP11B2) around 50) and CYP17 (no inhibition).
Synthesis of novel 3,4-dihydroquinolin-2(1H)-one guanidines as potential antihypertensive agents
Pai,Samel
experimental part, p. 1655 - 1660 (2012/01/06)
Hydroxy-3,4-dihydroquinolin-2(1H)-ones (4a-c) were synthesized by intramolecular Friedel Craft alkylation of N-(methoxyphenyl)-3- chloropropionamides (3a-c), obtained by acylation of anisidine with chloropropionyl chloride. The hydroxy-3,4-dihydro quinolin-2(1H)- ones (4a-c) were treated with various dibromo alkanes under phase transfer catalyst conditions at room temperature to give bromoalkyloxy- 3,4-dihydroquinolin-2(1H)- ones (5a-l) which on further reaction with guanidine hydrochloride in dimethyl formamide afforded N-{4- [(2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)oxy]alkyl} guanidines (6a-l). These compounds were synthesized as potential antihypertensive agents.
