Physicochemical Approaches to Drug Design

Purcell, William P.; Clayton, John M.

doi:10.1021/ba-1971-0108.ch005

Cited by 4 publications

(4 citation statements)

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“…The octanol:water partition coefficient, a measure of drug lipophilicity, was measured by established methods 15 , 16 , 17 . Phosphate buffer (0.1 mol/L) was prepared from deionized water and dibasic sodium phosphate.…”

Section: Methodsmentioning

confidence: 99%

Preclinical investigation of the pharmacokinetics, metabolism, and protein and red blood cell binding of DRDE-07: a prophylactic agent against sulphur mustard

Verma

Vijayaraghavan

2014

Acta Pharmaceutica Sinica B

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DRDE-07, a newly synthesized amifostine analog currently under clinical investigation in a phase I trial, is a potent antidote against sulfur mustard toxicity. The purpose of this research was to evaluate the pharmacokinetic profile of DRDE-07 in female Swiss Albino mice after a single oral dose of 400 or 600 mg/kg. The physicochemical properties of DRDE-07, including solubility, pKa, Log P, plasma protein binding and plasma/blood partitioning, were determined to support the pharmacokinetic characterization. DRDE-07 concentration was determined by an HPLC-UV method. The profile of plasma concentration versus time was analyzed using a non-compartmental model. Plasma protein binding was assessed using ultrafiltration. DRDE-07 appeared rapidly in plasma after oral administration with peak plasma levels (Cmax) observed in less than 15 min. There was a rapid decline in the plasma levels followed by a smaller second peak about 90 min after dosing. The plasma protein binding of DRDE-07 was found to be less than 25% at all concentrations studied. Plasma clearance of DRDE-07 is expected to be ~1.5 fold higher than the blood clearance of DRDE-07. The probable metabolite of DRDE-07 was identified as phenyl-S-ethyl amine.

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Section: Methodsmentioning

confidence: 99%

Preclinical investigation of the pharmacokinetics, metabolism, and protein and red blood cell binding of DRDE-07: a prophylactic agent against sulphur mustard

Verma

Vijayaraghavan

2014

Acta Pharmaceutica Sinica B

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“…The partition coefficients of the three complexes were determined according to the published method [ 16 ] by mixing each complex with an equal-volume of 1-octanol and phosphate buffer (0.025 M, pH 7.4) in a centrifuge tube. The mixture was vortexed at room temperature for 1 min and then centrifuged at 5,000 rpm for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Pyrazolo[1,5-a]-pyrimidine-containing 99mTc Nitrido Radiopharmaceuticals as Imaging Agents for Tumors

Ding

et al. 2010

Molecules

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The compound 5-((2-aminoethylamino)methyl)-7-(4-bromoanilino)-3-cyano-pyrazolo[1,5-a]pyrimidine (ABCPP) was synthesized and conjugated with N-mercapto-acetylglycine (MAG), N-mercaptoacetylphenylalanine (MAF) and N-mercaptoacetylvaline (MAA), respectively. These three compounds were labeled successfully with [99mTcN]2+ intermediate in high radiochemical purities. Biodistribution in tumor-bearing mice demonstrated that the three new complexes showed tumor accumulation, high tumor-to-muscle (T/M) ratios and fast clearance from blood and muscle. Among them, the 99mTcN-MAG-ABCPP showed the most favorable characteristics, with tumor/blood and tumor/ muscle ratios reaching 1.51 and 2.97 at 30 min post-injection, 1.84 and 2.49 at 60 min post-injection, suggesting it could be further studied as potential tumor imaging agent for single photon emission computed tomography (SPECT).

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“…The determination of the partition coefficient P by the "shake flask" method with presaturated solvents is generally used, and extensive experimental details for this method have been published. 83 For compounds that are partially ion- ized at physiological pH, the use of distribution coefficients D, i.e. apparent partition coefficients at a given pH, was proposed.…”

Section: A Assays Of Chemical and Biological Parametersmentioning

confidence: 99%

“…Percentage of animals surviving on day 60 after tumor implantation. g Partition coefficient: P ) [compound in 1-octanol]/[compound in water], as measured by a UV method 83. h Alkylating activity determined as the absorbance at 560 nm according to a literature procedure.97 i Carbamoylating activity determined by an EPR procedure.613,614 j Half-life determined by a literature procedure 97.…”

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confidence: 99%