A Low Hazard Procedure for the Laboratory Preparation of Polynitrate Esters

Marken, Craig; Kristofferson, Clifford E.; ROLAND, M. M.; Manzara, Anthony P.; Barnes, Michael W.

doi:10.1055/s-1977-24454

Cited by 19 publications

(9 citation statements)

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“…In our search for a relatively low-hazard batch method to synthesise small quantities of dry, analytically pure NG, we have evaluated and optimized an existing literature method 1 with a view to synthesise milligram to gram quantities of pure NG. Whilst the original procedure was developed to prepare batch quantities up to 450 g of various nitrate esters free of less stable nitrite (ester) impurities, and which relied on a Redox potentiometric probe to regulate the glycerol addition rate, we have adapted the method to prepare much smaller amounts of product down to 250 mg, without using microreactors and without potentiometric control.…”

Section: Resultsmentioning

confidence: 99%

Low hazard small-scale synthesis and chemical analysis of high purity nitroglycerine (NG)

et al. 2015

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A previously reported two-phase (99.5% fuming nitric acid/dichloromethane) batch method 1 to prepare high purity 1,2,3propanetriyl trinitrate (nitroglycerine, NG) was evaluated, simplified and adapted specifically for low hazard small-scale synthesis. The purity of the product, as determined by NMR spectroscopy, HPLC and IR spectroscopic analysis was found to be greater than 99%. The quick synthetic method is highly recommended when small amounts of highly pure NG are required for analytical and related purposes in the absence of a microreactor.

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Section: Resultsmentioning

confidence: 99%

Low hazard small-scale synthesis and chemical analysis of high purity nitroglycerine (NG)

et al. 2015

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“…[23] mp 142–143°C (Hex/CHCl 3 )). Products 3 and 4 were synthesized from N ‐propanol and 1,2‐propanediol respectively according to the procedure described in literature [24]; product 8 was synthesized from 4‐phenyl‐3‐phenylsulfonylfuroxan according to the procedure described in literature [25].…”

Section: Methodsmentioning

confidence: 99%

“…[23] mp 142-143°C (Hex/CHCl 3 )). Products 3 and 4 were synthesized from N-propanol and 1,2-propanediol respectively according to the procedure described in literature [24]; product 8 was synthesized from 4-phenyl-3-phenylsulfonylfuroxan according to the procedure described in literature [25]. 3-(Nitrooxy)propyl 4-methylbenzenesulfonate (10) 9 (1.10 g, 9.1 mmol) was dissolved in dry pyridine (10 mL) at 0°C and p-toluensulfonyl chloride (2.50 g, 13.1 mmol) was added in one portion.…”

Section: Chemistrymentioning

confidence: 99%

NO‐donor melatonin derivatives: synthesis and in vitro pharmacological characterization

Chegaev

Lazzarato

Rolando

et al. 2007

Journal of Pineal Research

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Numerous studies document that melatonin possesses a broad-spectrum antioxidant activity. It traps a number of reactive oxygen species (ROS) such as hydroxyl and peroxyl radicals, singlet oxygen and hypochlorous acid. It also inhibits peroxynitrite-induced reactions. It is known that atherosclerosis progression involves ROS-induced oxidation of low-density lipoproteins in sub-endothelial space and the depletion of nitric oxide (NO) in blood vessels, as well as a decreased sensitivity of the vessels to the actions of NO. Considering this, a series of new NO-donor antioxidants were designed and synthesized by joining melatonin with NO-donor nitrooxy and furoxan moieties as polyvalent agents potentially useful for the treatment of cardiovascular diseases involving atherosclerotic vascular changes. The in vitro antioxidant properties of the resulting products were assessed in the thiobarbituric acid reactive substances assay (TBARS), the ABTS(+.) as well as in the alkaline phosphatase (ALP) assay. The antioxidant capacities of NO-donor melatonins to inhibit lipoperoxidation (TBARS-IC(50)) was predominantly dependent on their lipophilicity, and therefore on their partitioning process into membranes. On the other hand, their comparable capacity to inhibit protein oxidation (ALP-IC(50)) was independent of their lipophilicity and was consistent with their similar ability to participate in electron transfer reactions. All the NO-donor melatonins were also evaluated for their ability to relax rat aorta strips precontracted with 1 microM phenylephrine. Finally, binding affinities and intrinsic activity studies, carried out at MT(1) and MT(2) receptor subtypes, showed a rather complex picture in need of further investigation.

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“…Silica gel column chromatography was performed using Silicycle silica gel (70-230 mesh). Glycerol trinitrate [Marken et al, 1977], 3,4-bis(benzenesulfonyl)furoxan (7) [Kelly et al, 1977], 4-bromo-1-butanol (10) [Nguyen et al, 2000], nitroacetone (17) [Hurd and Nilson, 1955], 2-cyanoethyl 3-aminocrotonate (19) [Ogawa et al, 1993], benzofurazan-4-carboxaldehyde (25) [Heitzmann, 1987], 2-amino-1-nitroprop-1-ene (26) [Miri et al, 2000], and 2-cyanoethyl acetoacetate (27) [Yiu and Knaus, 1997] were prepared according to procedures reported in the literature. All other reagents were purchased from Aldrich Chemical (Milawukee, WI).…”

Section: Methodsmentioning

confidence: 99%

Syntheses, calcium channel agonist‐antagonist modulation effects, and nitric oxide release studies of [3‐(Benzenesulfonyl)furoxan‐4‐yloxy]alkyl 1,4‐Dihydro‐2,6‐dimethyl‐5‐nitro‐4‐(2‐trifluoromethylphenyl, benzofurazan‐4‐yl, 2‐, 3‐, or 4‐pyridyl)‐3‐pyridinecarboxylates

Nguyen

McEwen

et al. 2002

Drug Development Research

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A group of racemic 1,4-dihydro-2,6-dimethyl-5-nitro-3-pyridinecarboxylates possessing either a C-4 2-trifluoromethylphenyl (22-24), benzofurazan-4-yl (42-44), 2-pyridyl (45-47), 3-pyridyl (48-50), or 4-pyridyl (51-53), substituent in conjunction with a nitric oxide donor C-3 ester [3-(benzenesulfonyl)furoxan-4-yloxy]alkyl substituent were synthesized using modified Hantzsch reactions. Compounds 45-53 having a C-4 2-, 3-, or 4-pyridyl substituent exhibited more potent in vitro calcium channel antagonist activity (IC 50 's in the 0.46 to 5.23 mM range) on guinea pig ileum longitudinal smooth muscle (GPILSM) than related analogs having a C-4 2-trilfuoromethylphenyl (22-24) or benzofurazan-4-yl (42, 44) substituent (IC 50 Z 29.91 mM). The point of attachment of the pyridyl ring (2-, 3-, or 4-), and the length of the C-3 ester alkyl spacer [-CH 2 (CH 2 )n, n ¼ 1-3], were not determinants of smooth muscle calcium channel antagonist activity. Replacement of the C-3 ester methyl substituent of Bay K 8644, or the ester isopropyl substituent of the 4-(pyridyl) isomers 4a-c by a [3-(benzensulfonyl)furoxan-4-yloxy]alkyl moiety retained the desired calcium channel agonist (positive inotropic) effect on guinea pig left atrium (GPLA). Compounds having C-4 3-pyridyl (48-50), or 4-pyridyl (51-53), substituents were the most potent cardiac positive inotropes (EC 50 's in the 3.02 to 19.74 mM range) relative to the reference drug Bay K 8644 IC 50 ¼ 0.77 mM). The % nitric oxide released in vitro in the presence of L-cysteine for this group of compounds was higher (36-74% range) than for the reference drug glycerol trinitrate (20%). A quantitative structure-activity analysis showed an inverse correlation between a molecular weight (MW) descriptor and % nitric oxide released. Model hybrid (calcium channel modulation, nitric oxide donor) compounds that show dual cardioselective agonist (positive inotropic)/smooth muscle selective antagonist activities constitute a novel type of 1,4-dihydropyridine calcium channel modulator that provides a potential drug design concept targeted toward the treatment of congestive heart failure, and is a useful probe to study the structure-function relationship of calcium channels. Drug. Dev. Res. 56:1-16, 2002.

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A Low Hazard Procedure for the Laboratory Preparation of Polynitrate Esters

Cited by 19 publications

References 0 publications

Low hazard small-scale synthesis and chemical analysis of high purity nitroglycerine (NG)

Low hazard small-scale synthesis and chemical analysis of high purity nitroglycerine (NG)

NO‐donor melatonin derivatives: synthesis and in vitro pharmacological characterization

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