- Cu(II)-Catalyzed Ortho-Selective Amination of Simple Phenols with O-Benzoylhydroxylamines
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A Cu(II)-catalyzed ortho-selective amination of simple phenols with O-benzoylhydroxylamines has been developed, which provides access to 2-aminophenols under mild conditions. Various functional groups on the phenol and electrophilic amine are compatible, and the protocol typically delivers the products in moderate to good yields. The mechanistic detail of this process are discussed.
- Shao, Nan-Qi,Yao, Zhi-Li,Wang, Dong-Hui
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- PRMT5 INHIBITORS AND USES THEREOF
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Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
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- PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF
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Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.
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- 4,5-DIHYDROISOXAZOLE DERIVATIVES AS NAMPT INHIBITORS
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The present invention provides substituted 4,5-dihydroisoxazole derivatives of formula (I), which may be therapeutically useful, more particularly NAMPT inhibitors and in which R1 R2, Y, X, "Het" and "p" have the meanings given in the specification, and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention of diseases or disorder caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPT) in a mammal. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of the substituted 4,5-dihydroisoxazole derivatives of formula (I) or a pharmaceutically acceptable salts or stereoisomers or N-oxide thereof.
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Page/Page column 215
(2014/08/06)
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- Function-oriented synthesis of a didesmethyl triazacryptand analogue for fluorescent potassium ion sensing
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Triazacryptand (TAC)-based fluorescent K+ sensors have broad biomedical utility, yet their advancement has been hindered because of their challenging synthesis. Herein, an efficient synthesis is reported that delivers a didesmethyl triazacrypta
- Carpenter, Richard D.,Verkman, Alan S.
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experimental part
p. 1242 - 1248
(2011/04/17)
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- An exploratory and mechanistic study of the defluorination of an (aminofluorophenyl)oxazolidinone: SN1(Ar*) vs. S R+N1(Ar*) mechanism
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The morpholinofluorophenyloxazolidinone 1 (the antibacterial drug linezolid) is found to undergo reductive defluorination upon irradiation in water (Φ 0.33), in some of the products accompanied by the simultaneous oxidative degradation of the morpholine side chain. In the presence of chloride, iodide and pyrrole, the fluorine is substituted by these groups (with pyrrole, in position 2). The defluorination is less efficient in methanol and mainly leads to reduction (Φ 0.053). These data can be accommodated through two different mechanisms, viz. either C-F bond heterolysis to give a phenyl cation [SN1(Ar*)], or ionization to give a radical cation [S R+N1(Ar*)]. Steady-state and time resolved data have been gathered for clarifying this issue. It is found that, indeed, ionization of 1 is efficient and proceeds from the singlet, but leads to no irreversible change. On the contrary, triplet 31 (lifetime 0.5 μs in MeOH, 0.1 μs in water) fragments and gives the corresponding triplet phenyl cation. The last intermediate explains well the observed hydrogen abstraction both inter- (from the solvent, when this is reducing) and intramolecularly (from the morpholine group), as well as addition to a charged anion or to a neutral π nucleophile such as pyrrole. The rationalization is supported by the study of some related molecules. Thus, the only photochemical reaction from the non fluorinated analogue of linezolid (that ionizes just as 1) is an inefficient degradation of the morpholine chain (Φ 0.001), while a simple model such as N-(2-fluorophenyl)morpholine undergoes photosolvolysis in water and is not trapped by pyrrole.
- Fasani, Elisa,Tilocca, Fedele,Protti, Stefano,Merli, Daniele,Albini, Angelo
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experimental part
p. 4634 - 4642
(2009/03/12)
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- Production of keto acids
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A method for the production of a keto acid having the general formula STR1 wherein R1 and R2 independently represent a straight or branched chain alkyl of 1-18 carbon atoms, a cycloalkyl of 4-8 carbon atoms or a phenyl, each of which may be substituted by at least one substituent selected from the group consisting of halogen atoms and alkyls having 1-4 carbon atoms, an aralkyl of 7-10 carbon atoms, alkoxyalkyl having 2-20 carbon atoms, tetrahydrofuryl alkyl, alkylcarboxy alkyl, alkylcarboxy benzyl, or R1 and R2 together with the adjacent nitrogen atom may form a heterocyclic ring, or one of R1 and R2 is hydrogen, but R1 and R2 may not simultaneously be methyl or ethyl or benzyl which comprises reacting a m-amino phenol having the general formula STR2 wherein R1 and R2 are the same as above, with phthalic anhydride, in an organic solvent in an amount of less than 0.5 parts by weight per part of m-amino phenol.
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- The Willgerodt-Kindler Reactions. 6. Isomerization of the Carbonyl Group in Alkanones and Cycloalkanones
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The most unusual feature of the Willgerodt-Kindler Reactions is the facile isomerization of the carbonyl function along a chain of unbranched methylene groups, or around a cycloaliphatic ring containing several connected methylene groups.We have demonstrated that the first step in the Kindler process is the formation of enamines by reaction of the carbonyl function with secondary aliphatic amines, followed by reaction of the enamine with certain sulfur-amine catalysts to form reactive heterocyclic sulfur intermediates that facilitate the elimination-readdition of the amines reversibly along the chain.It was shown that compounds of the type R2N-S-S-NR2 are effective catalysts but not compounds of the type R2N-S-NR2.Some cyclohexanone derivatives undergo aromatization, with anomalous results in certain cases.
- Carmack, Marvin,Behforouz, Mohammad,Berchtold, Glenn A.,Berkowitz, Samuel M.,Wiesler, Donald,Barone, Ralph
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p. 1305 - 1318
(2007/10/02)
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