N-Hydroxy Aryl Carbamates. A Class of Hydroxamic Acids Which Form Stable Phosphorylated and Sulfated Derivatives<sup>1</sup>

Steinberg, George M.; Bolger, James W.

doi:10.1021/jo01112a019

Cited by 15 publications

(7 citation statements)

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“…Hydroxysemicarbazide. A modified procedure of Grobner and Steinberg 24,25 was used in the synthesis of hydroxysemicarbazide. Yield 7.8 g (86%); mp 129-131 °C (reported mp 126 °C24 ).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Biological Evaluation, and Quantitative Structure−Activity Relationship Analysis of New Schiff Bases of Hydroxysemicarbazide as Potential Antitumor Agents

et al. 2001

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Thirty Schiff bases of hydroxysemicarbazide (Ar-CH=NNHCONHOH) have been synthesized and tested against L1210 murine leukemia cells. The IC(50) values were found to be in a range from 2.7 x 10(-6) to 9.4 x 10(-4) M. A total of 17 out of the 30 compounds had higher inhibitory activities than hydroxyurea (an anticancer drug currently used for the treatment of melanoma, leukemia, and ovarian cancer) against L1210 cells. Six compounds with IC(50) values in micromolar range were 11- to 30-fold more potent than hydroxyurea (IC(50) = 8.2 x 10(-5) M). The partition coefficient (log P) and ionization constants (pK(a)) of a model compound [1-(3-trifluoromethylbenzylidene)-4-hydroxysemicarbazide, 1] were measured by the shake-flask method, and the measured log P was used to derive Hansch-Fujita pi constant of -CH=NNHCONHOH. On the basis of the newly derived pi and those of other moieties, the partition coefficients (SlogP) of the other 29 compounds were calculated by the summation of pi values. Quantitative structure-activity relationship (QSAR) analysis showed that, besides the essential pharmacophore (-NHCONHOH), hydrophobicity (SlogP), molecular size/polarizability (calculated molar refractivity), and the presence of an oxygen-containing group at the ortho position (I) were important determinants for the antitumor activities. In conclusion, the results obtained in this study show that several Schiff bases of hydroxysemicarbazide are potent inhibitors of tumor cells and warrant further investigation as cancer chemotherapeutic agents.

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“…Hydroxysemicarbazide. A modified procedure of Grobner and Steinberg 24,25 was used in the synthesis of hydroxysemicarbazide. Yield 7.8 g (86%); mp 129-131 °C (reported mp 126 °C24 ).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Biological Evaluation, and Quantitative Structure−Activity Relationship Analysis of New Schiff Bases of Hydroxysemicarbazide as Potential Antitumor Agents

et al. 2001

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“…Based on the chemistry of related HNO donors, 19,20 we propose that the first step of decomposition is deprotonation which leads to release of nitrosocarbonyl plus pyrazolone. If the barrier to dissociation from anionic 48 indicates that the pKa of OHPY 1a is likely lower than that of OHPY 1c. Although these two donors have the same pyrazolone leaving group, the longer half-life for OHPY 1a (t1/2 = 25 min) compared with 1c (t1/2 = 0.6 min) suggests that the barrier to dissociation may also affect the observed half-lives.…”

Section: Decomposition Of Ohpy Compoundsmentioning

confidence: 99%

Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups

et al. 2016

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A new class of nitrosocarbonyl precursors, O-substituted hydroxamic acids with pyrazolone leaving groups (OHPY), is described.These compounds generate nitrosocarbonyl intermediates, which upon hydrolysis release nitroxyl (azanone, HNO) under physiologically relevant conditions. Pyrazolones have been used to confirm the generation of nitrosocarbonyls by competitive trapping to form isomeric N-substituted hydroxamic acids (NHPY) via an N-selective nitrosocarbonyl aldol reaction. The rate of nitrosocarbonyl release from OHPY donors is impacted by donor substituents, including the pyrazolone leaving group.

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“…(DMSO-d6) 7.45 (3 H, m), 7.75 (2 H, m). Phenyl 3V-hydroxycarbamate was synthesized by reaction of phenyl chlorocarbonate with hydroxylamine (9). Yield 57%; mp 104-105 °C (from benzene);…”

Section: Methodsmentioning

confidence: 99%

A chemical comparison of methanesulfonyl fluoride with organofluorophosphorus ester anticholinesterase compounds

Snow¹,

Barger²

1988

Chem. Res. Toxicol.

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The chemical reactivity and physical properties of methanesulfonyl fluoride (MSF) were quantitatively measured for direct comparison with those of isopropyl methylphosphonofluoridate (GB, sarin) and diisopropyl phosphorofluoridate (DFP). The chemistry involved reaction rate constant measurements of MSF hydrolysis and for reactions with phenolic, amine, oxime, hydroxamic acid, phenyl N-hydroxycarbamate, and hydroxylamine compounds and cupric imidazole and bipyridyl complexes. Analogous chemistry with GB and DFP occurred only for the nucleophilic reactions. MSF was substantially less reactive toward interactions involving hydrogen bonding, cupric complex coordination, and quaternary amine formation. Physical characterization included water solubility, vapor pressure, heat of vaporization, solubility parameter, hydrogen bond basicity, UV, IR, and NMR measurements. MSF is a much weaker hydrogen bond acceptor than the phosphorus esters. The hydrogen bond basicity beta-scale measurement provides a key insight to the chemical reactivity divergence of MSF and DFP or GB. Its unexpectedly low value is interpreted that MSF does not possess a site with sufficient basicity to be protonated by strong acid, to enter into hydrogen bonding, or for coordination with the cupric ion.

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N-Hydroxy Aryl Carbamates. A Class of Hydroxamic Acids Which Form Stable Phosphorylated and Sulfated Derivatives¹

Cited by 15 publications

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Synthesis, Biological Evaluation, and Quantitative Structure−Activity Relationship Analysis of New Schiff Bases of Hydroxysemicarbazide as Potential Antitumor Agents

Synthesis, Biological Evaluation, and Quantitative Structure−Activity Relationship Analysis of New Schiff Bases of Hydroxysemicarbazide as Potential Antitumor Agents

Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups

A chemical comparison of methanesulfonyl fluoride with organofluorophosphorus ester anticholinesterase compounds

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N-Hydroxy Aryl Carbamates. A Class of Hydroxamic Acids Which Form Stable Phosphorylated and Sulfated Derivatives1

Cited by 15 publications

References 0 publications

Synthesis, Biological Evaluation, and Quantitative Structure−Activity Relationship Analysis of New Schiff Bases of Hydroxysemicarbazide as Potential Antitumor Agents

Synthesis, Biological Evaluation, and Quantitative Structure−Activity Relationship Analysis of New Schiff Bases of Hydroxysemicarbazide as Potential Antitumor Agents

Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups

A chemical comparison of methanesulfonyl fluoride with organofluorophosphorus ester anticholinesterase compounds

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N-Hydroxy Aryl Carbamates. A Class of Hydroxamic Acids Which Form Stable Phosphorylated and Sulfated Derivatives¹