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The present disclosure describes pyridineamine compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer, immune disorders and other diseases. Formula (I).

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

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Polo-like kinase-2 (Plk-2) is a potential therapeutic target for Parkinson’s disease and this Letter describes the SAR of a series of dihydropteridinone based Plk-2 inhibitors. By optimizing both the N-8 substituent and the biaryl region of the inhibitors we obtained single digit nanomolar compounds such as 37 with excellent selectivity for Plk-2 over Plk-1. When dosed orally in rats, compound 37 demonstrated a 41-45% reduction of pS129-alpha-synuclein levels in the cerebral cortex.

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

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Phosphodiesterase 4 catalyzes the hydrolysis of cyclic AMP and is a target for the development of anti-inflammatory agents. We have designed and synthesized a series of phenyl alkyl ketones as PDE4 inhibitors. Among them, 13 compounds were identified as having submicromolar IC50 values. The most potent compounds have IC50 values of in the mid- to low-nanomolar range. Compound 5v also showed preference for PDE4 with selectivity of >2000-fold over PDE7, PDE9, PDE2, and PDE5. Docking of 5v, 5zf, and 5za into the binding pocket of the PDE4 catalytic domain revealed a similar binding profile to PDE4 with rolipram except that the fluorine atoms of the difluoromethyl groups of 5v, 5za, and 5zf are within a reasonable range for hydrogen bond formation with the amide hydrogen of Thr 333 and the long alkyl chain bears additional van der Waals interactions with His 160, Asp 318, and Tyr 159.

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

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UV irradiation of bis(cis-1,2-dicyano-1,2-ethylenedithiolate)zinc bis(tetrabutylammonium) in aqueous tetrahydrofuran (THF) or 2,5-dihydrofuran (2,5-DHF) leads to the semiconductor n-ZnS which photocatalyses an efficient H2 evolution (Phi300nm =/>0.1) coupled to a chemoselective dehydrodimerization of the cyclic ether.The reacion does not occur in pure water nor in dry ethers. n-ZnS, which immediately photocorrodes in pure water, becames very stable in the presence of 2,5-DHF. 2,3-DHF and six-membered ethers do not dehydrodimerize or prevent photocorrosion.The H2-evolution rate increases linearity with light intensity and does not change as a function of temperature (20-50 deg C) or pH (4-10).In the case of 2,5-DHF, the previously unknown 2,2′-, 2,3′, and 3,3′-dehydrodimers are formed in the ratio of 1:2:1, respectively, on analytical and preparative scales.With THF, the reaction proceeds regioselectively with the exclusive formation of the 2,2′-dihydrodimer.A complete material balance shows that no water is consumed although the initial gas phase contains more than 90percent D2 when D2O is used.The latter value decreases with increasing turnover and is accompained by the formation of HD and H2.These results are compatible with the reduction of water to hydrogen by conduction band electrons.The dehydrodimers are produced by dimerization of the corresponding radicals formed most likely by hole oxidation of the cyclic ether with subsequent deprotonation.Comparison with reactions of OH<*> generated in homogeneous solution reveals a higher selectivity for the catalytic ZnS system.

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

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Provided herein are compounds and compositions useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

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Tetrahydrofuran – Wikipedia,
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The structure-activity relationship of HIV-1 protease (HIV-1 PR) inhibitors containing AHPBA (3-amino-2-hydroxy-4-phenylbutanoic acid) is discussed. In order to solve the problem of poor oral bioavailability, small-sized dipeptide HIV-1 protease inhibitors containing cyclic urethanes or benzamides at the P2 site were designed and prepared. The substitution patterns of the benzamides contributed significantly to their HIV-1 PR inhibitory activities, and it was shown that the choice of P2-residues was very important. Highly potent inhibitors possessing subnanomolar IC50 values and exhibiting good antiviral potency have been identified. In this class, inhibitor 18 was the most potent (IC90 (CEM/HIV-1 IIIb) 0.11muM) and showed good oral bioavailability in dogs. Copyright (C) 1998 Elsevier Science Ltd.

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Tetrahydrofuran – Wikipedia,
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This invention relates to a novel method for the preparation of 3-oxotetrahydrofuran comprising oxidating 3-hydroxy-tetrahydrofuran in the presence of a catalytic amount of TEMPO with trichloroisocyanuric acid.

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A highly efficient method to afford 2,3-unsaturated glycosides was described. In the presence of Hafnium(IV) triflate, a variety of 2,3-unsaturated-O- and S-glycosides have been obtained by stereoselective glycosylation of 3,4,6-tri-O-acetyl-d-glucal and hexa-O-acetyl-d-lactal with various acceptors in good isolated yields.

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

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Catalytic asymmetric reduction of prochiral ketones with the formation of enantio-pure secondary alcohols is of fundamental importance in organic chemistry, chiral man-made transition-metal catalysts, or organocatalysts and enzymes of the alcohol dehydrogenase (ADH) type. A distinct limitation is the traditional requirement that the alpha- and alpha?-moieties flanking the carbonyl function differ sterically and/or electronically. Difficult-to-reduce ketones such as tetrahydrofuran-3-one and tetrahydrothiofuran-3-one and related substrates are particularly challenging, irrespective of the catalyst type. The ADH from Thermoethanolicus brockii (TbSADH) is an attractive industrial biocatalyst, because of its high thermostability, but it also fails in the reduction of such ketones. We have successfully applied directed evolution using the previously developed concept of triple-code saturation mutagenesis at sites lining the TbSADH binding pocket with tetrahydrofuran-3-one serving as the model compound. Highly (R)- and (S)-selective variants were evolved (95%-99% ee) with minimal screening. These robust catalysts also proved to be effective in the asymmetric reduction of tetrahydrothiofuran-3-one and other challenging prochiral ketones as well. The chiral products, which are generally prepared by multistep routes, serve as synthons in the preparation of several important therapeutic drugs.

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

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Compounds according to formula (I) are useful in the treatment of phosphate homeostasis

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