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Discovery and Optimization of 2-Amino-4-methylquinazoline Derivatives as Highly Potent Phosphatidylinositol 3-Kinase Inhibitors for Cancer Treatment

Increased phosphatidylinositol 3-kinase (PI3K) signaling is among the most common alterations in cancer, spurring intensive efforts to develop new cancer therapeutics that target this pathway. In this work, we discovered a series of novel 2-amino-4-methylquinazoline derivatives through a hybridization and subsequent scaffold hopping approach that were highly potent class I PI3K inhibitors. Lead optimization resulted in several promising compounds (e.g., 19, 20, 37, and 43) with nanomolar PI3K potencies, prominent antiproliferative activities, favorable PK profiles, and robust in vivo antitumor efficacies. More interestingly, compared with 19 and 20, 37 and 43 demonstrated improved brain penetration and in vivo efficacy in an orthotopic glioblastoma xenograft model. Furthermore, preliminary safety assessments including hERG channel inhibition, AMES, CYP450 inhibition, and single-dose toxicity were performed to characterize their toxicological properties.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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A tetrahydro – 3 – furan methanol synthesis method (by machine translation)

The invention discloses a tetrahydro – 3 – furan methanol synthesis method, solved in the prior art 3 – hydroxy methyl – tetrahydrofuran complex synthetic route, the operation is difficult, a plurality of “three wastes”, the problem of high cost. The present invention includes: (1) in the organic solvent, malonic acid chlorine ethanol in the catalyst A react to generate the malonic acid single chlorine ethyl ester; (2) the malonic acid single chlorine ethyl ester in alkali under the effect of the ring produced by the reaction of 3 – carboxylic acid – gamma – butyrolactone; (3) 3 – carboxylic acid – gamma – butyrolactone in reducing agent and catalyst B reduction under the condition of, purified to get the 3 – hydroxymethyl – tetrahydrofuran. The invention has after treatment is simple, environmental protection, low cost, simple operation, and high yield. (by machine translation)

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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SUBSTITUTED QUINAZOLINONE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR4

The present invention relates to novel quinazolinone derivatives of formula (I) as well as pharmaceutical compositions containing these compounds. The compounds of formula (I) as provided herein can act as positive allosteric modulators of metabotropic glutamate receptor subtype 4 (mGluR4), and can thus be used as therapeutic agents, particularly in the treatment or prevention of conditions associated with altered glutamatergic signalling and/or functions or conditions which can be affected by alteration of glutamate level or signalling.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Structure-activity relationship of a series of inhibitors of monoacylglycerol hydrolysis – Comparison with effects upon fatty acid amide hydrolase

A series of 32 heterocyclic analogues based on the structure of 2-arachidonoylglycerol (2-AG) were synthesized and tested for their ability to inhibit monoacylglycerol lipase and fatty acid amide hydrolase activities. The designed compounds feature a hydrophobic moiety and different heterocyclic subunits that mimic the glycerol fragment. This series has allowed us to carry out the first systematic structure-activity relationship study on inhibition of 2-AG hydrolysis. The most promising compounds were oxiran-2-ylmethyl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate (1) and tetrahydro-2H-pyran-2- ylmethyl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate (5). They inhibited cytosolic 2-oleoylglycerol (2-OG) hydrolysis completely (IC50 values of 4.5 and 5.6 muM, respectively). They also blocked, albeit less potently, 2-OG hydrolysis in membrane fractions (IC50 values of 19 and 26 muM, respectively) and anandamide hydrolysis (IC50 values of 12 and 51 muM, respectively). These compounds will be useful in delineating the importance of the cytosolic hydrolytic activity in the regulation of 2-AG levels and, hence, its potential as a target for drug development.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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A 3-hydroxy methyl tetrahydrofuran method for the synthesis of (by machine translation)

The invention discloses a synthetic method for 3-hydroxylmethal tetrahydrofuran. The synthetic method comprises the following steps: with 2-chloroethanol and diethyl malonate as raw materials, reacting under the action of alkaline in the presence of an organic solvent or in absence of a solvent to obtain an intermediate 2-ethoxy-diethyl succinate; then, reducing the intermediate 2-ethoxy-diethyl succinate by virtue of metal borohydride to obtain 2-hydroxymethyl-1,4-butanediol; and finally, producing 3-hydroxylmethal tetrahydrofuran under the action of a dehydrating agent. According to the synthetic method, the usage amount of the reducing agent metal borohydride is remarkably lowered, and yield of a byproduct sodium metaborate is reduced at the same time. The invention provides the synthetic method for the drug intermediate 3-hydroxylmethal tetrahydrofuran.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF

The present invention relates to compounds of formula (I), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, formula (I). wherein R1, R2, R3, R4, and L1 are defined in the specfication, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. The present invention also relates to compounds of formula (II), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, formula (II). wherein R1a, R2a, Rx, and n are as defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Process for the preparation of 3-methyltetrahydrofuran

Disclosed is a process for the preparation of 3-methyltetrahydrofuran (MeTHF) from 3-(hydroxymethyl)tetrahydrofuran (HOMeTHF) or 3-formyltetrahydrofuran (FTHF) by contacting HOMeTHF or 3-formyltetrahydrofuran with a secondary alcohol in the presence of a hydrous zirconia catalyst.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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INDOLE DERIVATIVE

The present invention provides an indole derivative having a melanin-concentrating hormone receptor antagonistic action, which is useful as an agent for the prophylaxis or treatment of obesity and the like.The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.The present invention provides an indole derivative having a melanin-concentrating hormone receptor antagonistic action, which is useful as an agent for the prophylaxis or treatment of obesity and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Related Products of 15833-61-1, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 15833-61-1, molcular formula is C5H10O2, introducing its new discovery.

THE USE OF N-ARYL DIAZASPIRACYCLIC COMPOUNDS IN THE TREATMENT OF ADDICTION

Compounds, compositions and methods for treating drug addiction, nicotine addiction, and/or obesity are disclosed. The compounds are N-aryl diazaspirocyclic compounds, bridged analogs of N-heteraryl diazaspirocyclic compounds, or prodrugs or metabolites of these compounds. The aryl group can be a five- or six-membered heterocyclic ring (heteroaryl). The compounds are effective at inhibiting dopamine production and/or secretion, and accordingly are effective at inhibiting the physiological “”reward”” process that is associated with ingestion of nicotine and/or illicit drugs. The compounds and compositions can be administered in effective amounts to inhibit dopamine release, wihout resulting in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Preparation of 1-alkyl- or 1-cycloalkylpiperazines

1-Alkyl- or 1-cycloalkylpiperazines are prepared by reacting piperazine with an alkanol or cycloalkanol in the presence of hydrogen and a hydrogenation/dehydrogenation catalyst by a process in which the reaction is carried out at from 130 to 190 C. under from 5 to 100 bar in the presence of from 5 to 40% by weight, based on the reaction mixture, of water, and the molar ratio of piperazine to alkanol or cycloalkanol is kept at from 1:1.5 to 1:8.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem