The Preparation of Substituted Hydrazines. IV. Arylhydrazines via Conventional Methods<sup>1</sup>

Hunsberger, I. Moyer; Shaw, Elwood R.; Fugger, J.; Ketcham, Roger; Lednicer, Daniel

doi:10.1021/jo01110a004

Cited by 54 publications

(22 citation statements)

References 6 publications

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“…Substituted phenylhydrazines were obtained from commercial sources or were synthesized as described (16) from the corresponding substituted anilines, except that the hydrochloride of ethyl 2-hydrazinobenzoate was synthesized from ethyl anthranilate (17). Each compound was purified by recrystallization from 2 M HCI or ethanol.…”

Section: Methodsmentioning

confidence: 99%

Ligands and oxidants in ferrihemochrome formation and oxidative hemolysis

Itano

Hirota

Vedvick

1977

Proc. Natl. Acad. Sci. U.S.A.

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We have investigated the effect of size of a single neutral ring substituent on the induction of hemolytic anemia and the formation of a ferrihemochrome by substituted phenylhydrazines. The severity of induced anemia decreased with increase in size of a halogen atom or an alkyl group ortho to the hydrazino group, little anemia resulting from 2-iodophenylhydrazine and no anemia from 2-tert-butylphenylhydrazine. The size of a halogen atom or an alkyl group at the meta or para position had relatively little effect on the severity of induced anemia. The ability of an arylhydrazine to induce hemolytic anemia paralleled its ability to produce a ferrihemochrome with an exogenous ligand, probably the corresponding aryldiazene. In general, rapid and complete formation of ferrihemochrome occurred-with arylhydrazines that induced severe anemia. The degree of hemolysis induced by an arylhydrazine was not related to its rate of autooxidation, i.e., the rate at which oxidants are formed by the reduction of oxygen. We propose a mechanism of arylhydrazine-induced oxidative denaturation based on the simultaneous formation of hydroxyl radical and aryldiazene ferrihemochrome in a reaction of oxyhemoglobin with arylhydrazine. We suggest that after oxidation of the porphyrin ring is initiated by a hydroxyl radical, oxidative cleavage of the ring is facilitated by the presence of a large li-

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Section: Methodsmentioning

confidence: 99%

Ligands and oxidants in ferrihemochrome formation and oxidative hemolysis

Itano

Hirota

Vedvick

1977

Proc. Natl. Acad. Sci. U.S.A.

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“…The hacmolytic activity of these and other riiig-substitutcd yheiiylliydrazines in rabbits is reported here. Itano, K. Hosokawa and K. Hirota chloride were synthesized from the corresponding anilines (Hunsberger et al, 1956), and ethyl 4-hydrazinobenzoate was obtained by the esterification of 4-hydrazinobenzoic acid (Wieland, 1934). Phenylhydrazine hydrochloride was purchased from Eastman Organic Chemicals, Rochester, New York, and all other substituted phenylhydrazines were purchased from Aldrich Chemical Company, Milwaukee, Wisconsin.…”

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confidence: 99%

Induction of Haemolytic Anaemia by Substituted Phenylhydrazines

1976

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The induction of anaemia and reticulocytosis by arylhydrazines was influenced by substituents on the benzene ring of phenylhydrazine. Arylhydrazines with ortho substituents, which would hinder the binding by haemoglobin of a ligand derived from the arylhydrazine, resulted in the least anaemia and reticulocytosis. These results are consistent with a previous finding that hydrazinobenzoic acid, which did not produce a ferrihaemochrome from ferrihaemoglobin, did not induce anaemia. The parallelism between the formation of a ferrihaemoglobin compound and the induction of anaemia supports the hypothesis that destabilization of haemoglobin by the binding of a ligand derived from the aryl portion of an arylhydrazine is an essential step in arylhydrazine-induced haemolytic anaemia.

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“…According to a similar literature procedure, [25][26][27] 1-(3Ј-iodophenyl)-3-methy-2-pyrazolin-5-one (2) was prepared in three steps from 3-iodoaniline, involving diazotization in hydrochloride-acetic acid, followed by reduction with stannous chloride and cyclization with ethyl acetoacetate in EtOH, in 49% overall yield of the three-step conversion, as presented in Chart 1. It was important to carry out this under a stream of argon gas for the reduction stage.…”

Section: Resultsmentioning

confidence: 99%

1-(3'-[125I]Iodophenyl)-3-methy-2-pyrazolin-5-one: Preparation, Solution Stability, and Biodistribution in Normal Mice

et al. 2010

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Recent studies indicate that reactive oxygen species (ROS), such as hydroxyl radical and hydrogen peroxide, are generated in a normal physiological process, and that the imbalance between the antioxidant defense system and excessive levels of ROS in cellular systems is involved in the initiation and progression of various diseases and disorders. [1][2][3][4][5] Various chemical probes of several methods have been developed to measure ROS in biological systems and the most common approach is the measurement of the levels of trapped molecules formed as a result of interception of ROS by probe molecules.6,7) Potential problems in detection and quantification of ROS by methods currently available have been reviewed, 8,9) in which the difficulties of precisely analyzing ROS-expression in the whole body are discussed, because of the low concentration of ROS formed in tissues and interference by the presence of endogenous reductants. Nevertheless, in vivo imaging technologies that allow visualization of localized production and accumulation of ROS in a living system provide useful information on the pathophysiological status of the living body, and they have attracted a great deal of interest.Of several biological imaging methods, nuclear imaging technology, such as positron emission tomography or single photon emission computed tomography using radiolabeled molecules, is well known for its ability to assess molecular pathways in vivo in both pre-clinical and clinical studies with very high sensitivity.10) The first reported work in developing radiotracers for free radical imaging in vivo includes 125 Ilabeled analogs of a-p-hydroxy-m-iodophenyl-N-t-butylnitrone 11) and a-p-iodophenyl-N-tert-butyl-nitrone, 12) based on the chemical characteristic that free radicals can be reacted with nitrone-based compounds at the nitrone-double bond to form organic radical adducts, but none of these proved to be useful as in vivo probes because of their limited free radical specificity. An 18 F-labeled analog of N-t-butylnitrone 13) or ethylmethylthiourea compound 14) has also been prepared, but with no information on its in vivo behavior. Thus, no appropriate radiotracers for nuclear imaging technology are currently available for detecting free radicals in vivo.3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone, 1, Fig. 1), known as a potent free radical scavenger, has been used clinically for the treatment of cerebral infarction in humans to prevent ischemic reperfusion injury [15][16][17] and has also been reported to be effective for myocardial and hepatic ischemia as well. 18,19) Biochemical and chemical studies have found that the free radical scavenging reaction of edaravone (1) with free radical species produces mainly 2-oxo-3-(phenylhydrazono)butanoic acid (OPB) with a more hydrophilic character as a stable oxidative product. 17,20,21) In addition, metabolite studies have indicated that edaravone, after intravenous administration in rats and humans, is exclusively metabolized into its glucuronide and/or sulfate conjugates which...

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The Preparation of Substituted Hydrazines. IV. Arylhydrazines via Conventional Methods¹

Cited by 54 publications

References 6 publications

Ligands and oxidants in ferrihemochrome formation and oxidative hemolysis

Ligands and oxidants in ferrihemochrome formation and oxidative hemolysis

Induction of Haemolytic Anaemia by Substituted Phenylhydrazines

1-(3'-[125I]Iodophenyl)-3-methy-2-pyrazolin-5-one: Preparation, Solution Stability, and Biodistribution in Normal Mice

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The Preparation of Substituted Hydrazines. IV. Arylhydrazines via Conventional Methods1

Cited by 54 publications

References 6 publications

Ligands and oxidants in ferrihemochrome formation and oxidative hemolysis

Ligands and oxidants in ferrihemochrome formation and oxidative hemolysis

Induction of Haemolytic Anaemia by Substituted Phenylhydrazines

1-(3'-[125I]Iodophenyl)-3-methy-2-pyrazolin-5-one: Preparation, Solution Stability, and Biodistribution in Normal Mice

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The Preparation of Substituted Hydrazines. IV. Arylhydrazines via Conventional Methods¹