Activity of fosazepam, a soluble analogue of diazepam.

Nicholson, A. N.; Wright, C.

doi:10.1111/j.1365-2125.1977.tb00773.x

Cited by 9 publications

(6 citation statements)

References 6 publications

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“…1). 5,6 However, phosphorus can form stable bonds with multiple elements, including sulfur and boron, as well as carbon, oxygen and nitrogen. In particular, P–B substructures can be regarded as isosteric with alkanes because of their tetrahedral sp 3 –sp 3 character, and therefore phosphine borane derivatives might provide a variety of chemical options for structural development in drug discovery research.…”

Section: Introductionmentioning

confidence: 99%

Physicochemical characterization of B-hydroxyphenyl phosphine borane derivatives and their evaluation as nuclear estrogen receptor ligands

Miyajima,

Noguchi-Yachide,

Ochiai

et al. 2024

RSC Med. Chem.

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Section: Introductionmentioning

confidence: 99%

Physicochemical characterization of B-hydroxyphenyl phosphine borane derivatives and their evaluation as nuclear estrogen receptor ligands

Miyajima,

Noguchi-Yachide,

Ochiai

et al. 2024

RSC Med. Chem.

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“…In another development, substitutions limited to the 1-position were used, and with fosazepam involved a dimethylphosphinylmethyl group. This compound had a short half life, but like diazepam it was metabolized to the long-acting benzodiazepine, nordiazepam, which has persistent activity Nicholson, Stone, Clarke & Ferres, 1976;Nicholson & Wright, 1977). To avoid this metabolic pathway heterocyclic ring structures have been added to the 1-and 2-positions, and triazolam, an example of a triazolobenzodiazepine with an ortho-chlorophenyl group (Rudzik, Hester, Tang, Straw & Friis, 1973), like flunitrazepam, has also proved to be a powerful hypnotic.…”

Section: Introductionmentioning

confidence: 99%

Activity of the hypnotics, flunitrazepam and triazolam, in man.

Nicholson¹,

Stone²

1980

Brit J Clinical Pharma

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1 Effects of flunitrazepam and triazolam (0.25 and 0.5 mg) on sleep and on performance were studied in six healthy adult males. Sleep was assessed by electroencephalography and analogue scales, and performance by a visuo-motor coordination task. 2 Over the same dose range triazolam had a more pronounced effect than flunitrazepam. Total sleep time was increased by 0.25 and 0.5 mg triazolam, and by 0.5 mg flunitrazepam. Both drugs decreased awake activity and drowsy sleep, though the effect of flunitrazepam was limited to the 0.5 mg dose and restricted to the first 6 h after sleep onset. There were no changes in slow wave sleep. 3 Latency to the first period of rapid eye movement (REM) sleep was increased with 0.5 mg triazolam, and when doses were combined (0.25-0.5 mg) the latencies with both drugs were increased. Both doses of triazolam reduced the duration and percentage of REM sleep during the early part of the night, though the whole night duration of REM sleep was not changed. 4 After the morning ingestion of 0.25 mg flunitrazepam performance was impaired for 2.0 h, but there were no residual effects when 0.25 or 0.5 mg were taken at night. With the morning ingestion of 0.25 mg triazolam performance was impaired from 0.5 to at least 5.0 h after ingestion. There were no residual effects with 0.25 mg overnight, but with 0.5 mg triazolam there was an effect on performance 10 h after ingestion with recovery within 1.5 h (11.5 h of ingestion). 5 Triazolam (0.25 mg) and 0.5 mg flunitrazepam provide useful hypnotic activity when impaired performance the next day is to be avoided. The activity of 0.5 mg triazolam is accompanied by only limited residual sequelae compared with some other benzodiazepines of comparable efficacy, and so may prove to be useful when a more powerful effect is required.

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“…Recently, the anticancer drug brigatinib [20] with a dimethylphospine oxide moiety was approved by the Food and Drug Administration (FDA). Other examples include fosenazid [21], a neurodrug with potent serotonin and epinephrine inhibitory properties, and fosazepam [22], a water-soluble diazepam derivative with sedative and anti-anxiety effects. Two years ago, researchers demonstrated that incorporation of the POMe 2 substituent into prazosin increased its solubility and reduced its lipophilicity while maintaining its full biological profile [23].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Structural Elucidation of P-stereogenic Coumarins

Dziuba,

Frynas,

Kozioł

et al. 2024

Symmetry

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This paper presents the general synthesis of a comprehensive group of P-chiral phosphinyl derivatives with a natural coumarin-type motif. A chiral substituent was attached at the third position of the coumarin molecule via the Knoevenagel procedure using readily available P-chiral phoshinylacetic acid esters without loss of enantiomeric purity. The application of salicylaldehyde-based derivatives allowed the incorporation of substituents of different electron character into the backbone of these coumarins making them suitable for subsequent chemical modifications. As a result, we gained access to six achiral (2a–g) and a large number ((Sp)-4a–f, (Sp)-6a–e and (Rp)-8a) of new potential chiral ligand precursors, pharmaceuticals, etc. with an imbedded phosphinyl group with evidenced biological activity based on the natural coumarin backbone. The molecular structure, including absolute configuration, was determined for seven compounds.

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Activity of fosazepam, a soluble analogue of diazepam.

Cited by 9 publications

References 6 publications

Physicochemical characterization of B-hydroxyphenyl phosphine borane derivatives and their evaluation as nuclear estrogen receptor ligands

Physicochemical characterization of B-hydroxyphenyl phosphine borane derivatives and their evaluation as nuclear estrogen receptor ligands

Activity of the hypnotics, flunitrazepam and triazolam, in man.

Synthesis and Structural Elucidation of P-stereogenic Coumarins

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