13161-30-3Relevant academic research and scientific papers
Pattern of Addition of Hydroxyl Radicals to the Spin Traps α-Pyridyl 1-Oxide N-tert-Butyl Nitrone
Neta, P.,Steenken, S.,Janzen, Edward G.,Shetty, Raghav V.
, p. 532 - 534 (1980)
Hydroxyl radicals react with α-2, α-3, and α-4-pyridyl 1-oxide N-tert-butyl nitrones (POBN) with rate constants of 3.2E9, 4.8E9, and 3.5E9 M-1 s-1, respectively, via addition to two distinct sites.Addition to the pyridine ring yields short-lived radicals of the hydroxyazacyclohexadienyl type, while addition to the nitrone function in the side chain yields long-lived nitroxide radicals.The distribution of OH addition at the two molecular sites was determined by using differences in reducing power upon reaction of the different types of radicals with IrCl62-.The fraction of OH attack on the pyridine ring is ca. 0.6, relatively independent of the isomeric structure of the POBN.
Experimental and theoretical study of the dissociation enthalpy of the N-O bond on 2-hydroxypyridine N-oxide: Theoretical analysis of the energetics of the N-O bond for hydroxypyrydine N-oxide isomers
Ribeiro da Silva, Maria D.M.C.,Matos, M. Agostinha R.,Miranda, Margarida S.,Morais, Victor M.F.,Acree Jr.
, p. 107 - 113 (2004)
The standard (p° = 0.1 MPa) molar enthalpy of formation of crystalline 2-hydroxypyridine N-oxide was measured, at T = 298.15 K, by static bomb calorimetry and the standard molar enthalpy of sublimation, at T = 298.15 K, was obtained using Calvet microcalorimetry. These values were used to derive the standard molar enthalpy of formation of 2-hydroxypyridine N-oxide in gaseous phase, and to evaluate the dissociation enthalpy of the N-O bond. Additionally, high-level density functional theory calculations using the B3LYP hybrid exchange-correlation energy functional have been performed for the three isomers of hydroxypyridine N-oxide in order to confirm the experimental trend for the dissociation enthalpy of the (N-O) bond.
Alkyl transfer with retention and inversion of configuration: Reexamination of a putative [1s,4s] sigmatropic rearrangement
Wolfe, Saul,Yang, Kiyull,Weinberg, Noham,Shi, Zheng,Hsieh, Yih-Huang,Sharma, Rajendra Dev,Ro, Stephen,Kim, Chan-Kyung
, p. 886 - 902 (1998)
The thermal rearrangement of 2-alkoxypyridine-1-oxides to 1-alkoxy-2-pyridones, which has been reported to proceed by an intramolecular [1s,4s] sigmatropic migration of the alkyl group with retention of configuration and first-order kinetics, has been reexamined. The intramolecular barriers have been computed to be at least 20 kcal mol-1 higher than the reported experimental barriers. An alternative bimolecular mechanism, discovered computationally, has been confirmed by a variety of experiments including crossover studies, determination of solvent effects and secondary H/D isotope effects, and new kinetic and stereochemical studies. In the new mechanism there is an initial intermolecular transfer of the alkyl group, with inversion of configuration, to the N-oxide. Depending on the nature of the alkyl group and the solvent, this is followed by a second transfer, also with inversion of configuration, of one of the alkyl groups of the cationic intermediate to one of the oxygens of the anionic intermediate. The product is then formed either without crossover, by a double inversion of one alkyl group, or with crossover by two single inversions of different alkyl groups. The proposed intermediates of this mechanism can be synthesized; they react to form a 1-alkoxy-2-pyridone at room temperature.
STIMULUS-TRIGGERED PRODRUGS
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Page/Page column 56-57, (2012/01/13)
Set forth herein, inter alia, are compositions and methods for treating diseases with prodrugs. Provided herein are prodrug compositions for inhibiting the function of proteins, compositions and methods for treating diseases associated with oxidative compounds, oxidatively-sensitive prodrugs of inhibitors of metalloproteases. and methods of inhibiting metalloproteases using oxidatively-sensitive prodrugs.
Activation of sulfonate ester based matrix metalloproteinase proinhibitors by hydrogen peroxide
Daniel, Kevin B.,Major Jourden, Jody L.,Negoescu, Kimberly E.,Cohen, Seth M.
body text, p. 313 - 323 (2012/01/13)
This study details the development of matrix metalloproteinase inhibitor prodrugs (proMMPi) that are activated in the presence of reactive-oxygen species (ROS). Conventional matrix metalloproteinase inhibitors (MMPi) utilize a zinc-binding group (ZBG) that chelates to the catalytic zinc(II) ion of matrix metalloproteinases (MMPs) to inhibit their activity. To create ROS-sensitive prodrugs, sulfonate esters were used as a protecting group for the ZBG to block their metal binding ability. Surprisingly, these sulfonate esters were found to be cleaved by H2O2 only when the ZBG contained an N-oxide donor atom moiety. Sulfonate ester derivatives of full-length MMPi based on these ROS-triggerable systems were synthesized. It was found that proMMPi with sulfonate ester protecting groups showed relatively high rates of cleavage in the presence of H2O2 to release the active MMPi. In vitro MMP inhibition studies confirmed a significant increase in inhibitory activity of proMMPi upon addition of H2O2, demonstrating the use of sulfonate esters to act as cleavable triggers for ROS-activated prodrugs.
Ruthenium catalyzed oxidation of tertiary nitrogen compounds with molecular oxygen: An easy access to N-oxides under mild conditions
Jain, Suman L.,Sain, Bir
, p. 1040 - 1041 (2007/10/03)
A variety of tertiary nitrogen compounds have been efficiently oxidized to their corresponding N-oxides in excellent yields with molecular oxygen as a sole oxidant and ruthenium trichloride as catalyst.
An efficient synthesis of heterocyclic N-oxides over molecular sieve catalyst
Prasad, M. Ramakrishna,Kamalakar, G.,Madhavi, G.,Kulkarni, S. J.,Raghavan, K. V.
, p. 1577 - 1578 (2007/10/03)
Heterocyclic N-oxides have been synthesized in very high yields over redox molecular sieve catalysts in the presence of H2O2.
Thiapyran formation via an unexpected thioaldehyde intermediate by the thermal decomposition of phenacyl sulfoxides bearing some heterocycles
Morita, Hiroyuki,Takeda, Masahiro,Kamiyama, Hideo,Hashimoto, Tadaaki,Yoshimura, Toshiaki,Shimasaki, Choichiro,Tsukurimichi, Eiichi
, p. 3739 - 3740 (2007/10/03)
Thermolysis of phenacyl sulfoxide bearing some nitrogen-containing heterocycles in the presence of 2,3-dimethyl-2,3-butadiene led to 6-benzoyl-5,6-dihydro-3,4-dimethyl-2H-thiapyran. This product was considered to be formed by the Diels-Alder reaction of the diene with thioaldehyde formed initially by the thermal decomposition of the sulfoxide.
Studies on 1,3-Benzoxazines. I. Synthesis of Primary 2-Amino-pyridines via the Reaction of Imidoyl Chlorides of 1,3-Benzoxazines with Pyridine N-Oxides
Wachi, Kazuyuki,Terada, Atsusuke
, p. 465 - 472 (2007/10/02)
A new synthetic method for primary 2-aminopyridine derivatives is described.Treatment of the imidoyl chlorides of 1,3-benzoxazines (1a-i) with pyridine N-oxides resulted in the introduction of an oxazine moiety into the α-position of the pyridine ring through rearrangement of the initially formed reaction adduct.Acid hydrolysis of the rearrangement products afforded 2-aminopyridine derivatives in excellent yields.When methoxypyridine N-oxides were used, products of a different type (10 and 14) were obtained.
KINETICS OF THE N OXIDATION OF SOME COMPOUNDS OF THE PYRIDINE SERIES WITH PERBENZOIC ACID IN CHLOROFORM AND AQUEOUS DIOXANE
Lohkov, R.E.
, p. 264 - 271 (2007/10/02)
A comparative study of the kinetics of the N oxidation of 19 derivatives of the pyridine series with perbenzoic acid in choroform and aqueous dioxane at 20, 25, 30, and 35 deg C was made.The rate constants, the parameters of the Arrhenius equation, and the activation energies of the N oxidation of the indicated monoazines were determined.The scale of the reactivities of the derivatives of the pyridine series was calculated within the framework of the Pearson hard-soft acid-base concept.
