Abstract：
:A number of arylidene derivatives of alicyclic ketones and some corresponding oximes, oxime esters, and related compounds were prepared as candidate cytotoxic agents. All of the compounds were evaluated against murine L1210 lymphoid leukemia cells. In general, cytotoxicity was greatest with the alpha,beta-unsaturated ketones and diminished with the oximes, and the oxime esters had little or no activity in this screen. When the same compounds were examined in both the in vitro L1210 and P388 leukemia screens, in the majority of cases the L1210 cells were more sensitive to these derivatives. Over half of the compounds prepared were evaluated against approximately 55 human tumors in vitro and showed selective toxicity toward one or more groups of neoplastic diseases, particularly leukemia. Some correlations between structure and bioactivity were discerned. The cytotoxicity screening and stability studies of representative compounds suggested that the ketones, oximes, and oxime esters were stable under the conditions of bioevaluation. X-ray crystallography of four representative compounds revealed structural features associated with cytotoxicity which may be considered in the design of future candidate cytotoxins.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Dimmock JR,Sidhu KK,Chen M,Li J,Quail JW,Allen TM,Kao GYdoi
10.1002/jps.2600830619subject
Has Abstractpub_date
1994-06-01 00:00:00pages
852-8issue
6eissn
0022-3549issn
1520-6017pii
S0022-3549(15)49503-6journal_volume
83pub_type
杂志文章abstract：:The metabolic fate of aprophen hydrochloride (2-diethylaminoethyl 2,2-diphenylpropionate) was studied in rats after intravenous administration. Both 14C-labeled and unlabeled aprophen were used in these studies. Blood samples were collected and analyzed to determine the identities of the metabolites formed. Utilizing ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770210
更新日期：1988-02-01 00:00:00
abstract：:A simultaneous GLC determination for methyl salicylate and menthol in a topical analgesic formulation is reported. n-Nonadecane is used as the internal standard. The method is rapid, accurate, precise, and selective in the presence of salicylic acid and ethyl salicylate. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680431
更新日期：1979-04-01 00:00:00
abstract：:Maintaining good content uniformity (CU) is a significant challenge for low-dose oral tablets in particular when using direct compression (DC). Using 6 model active pharmaceutical ingredients, we show that a platform DC tablet formulation suitable for developing low-dose API with excellent CU can be developed. This pl...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.03.005
更新日期：2017-07-01 00:00:00
abstract：:The chemical stability of the novel anticancer agent carzelesin in aqueous buffer/acetonitrile (1:1, v/v) mixtures has been investigated utilizing a stability-indicating reversed-phase high-performance liquid chromatographic assay. The degradation kinetics of carzelesin has been studied as a function of pH, buffer com...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js960005n
更新日期：1996-11-01 00:00:00
abstract：:A fluorescence method is presented for the determination of nitrofurantoin based on conversion of the drug to a fluorescent substance. The method requires 0.1-0.5 ml of plasma or diluted urine and is 10 times more sensitive than the commonly used colorimetric method. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690134
更新日期：1980-01-01 00:00:00
abstract：:Various concentrations of salicylic acid in hydrophilic ointment were applied repeatedly at daily or weekly intervals to rats in vivo. Salicylic acid absorption through treated skin was monitored by determining the penetration fluxes of salicylic acid through skin excised at various times. A gradual decrease in the sa...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600671213
更新日期：1978-12-01 00:00:00
abstract：:The permeability coefficient, Kp, of pure unbranched alkanoic acids (C2-C7) applied to isolated porcine skin, reached a maximum in the solubility parameter (delta 2) range of 9.7-10 cal1 /2/cm3/2. When these and other penetrants were delivered from a solvent vehicle, the following linear relationships could be demonst...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730426
更新日期：1984-04-01 00:00:00
abstract：:The recently developed hydrogen-bonding propensity tool in the Cambridge Structural Database software package (Mercury) was tested to predict polymorphs. The compounds for the study were chosen from a list of approximately 300 pharmaceutically important compounds, for which multiple crystal forms had not been previous...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24449
更新日期：2015-06-01 00:00:00
abstract：:Locally recurrent prostate cancer can lead to significant morbidity, metastasis, and even death. The objective of this study was to evaluate the efficacy of an injectable polymeric paste formulation containing paclitaxel against orthotopic prostate tumor in rats. The Dunning R-3327 rat prostate adenocarcinoma is exper...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21492
更新日期：2009-03-01 00:00:00
abstract：:A stereoselective and sensitive method for the determination of nilvadipine, a new dihydropyridine calcium antagonist, in human plasma was developed. An internal standard, the deuterated analogue of racemic nilvadipine, was added to the plasma and extracted with an n-hexane:ethyl acetate (92.5:7.5) mixture under alkal...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600760410
更新日期：1987-04-01 00:00:00
abstract：:Live attenuated influenza vaccine (LAIV) is considered one of the most effective vaccines and can be manufactured quickly and inexpensively to counter seasonal or pandemic influenza. Lyophilization is widely used in vaccine production. However, it requires a longer production cycle and large-scale equipment, thus posi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.02.017
更新日期：2019-07-01 00:00:00
abstract：:Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24257
更新日期：2015-02-01 00:00:00
abstract：:Statistical assessment of bioavailability and bioequivalence of drug products is generally carried out with a univariate analysis by independently comparing each relevant parameter [such as, area under the drug concentration curve (AUC) and peak drug concentration (Cmax)] of the test and reference products. The assump...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600840620
更新日期：1995-06-01 00:00:00
abstract：:The disposition kinetics of nicotine and cotinine enantiomers was determined in rabbits. The clearance of (R)-nicotine was similar to that of (S)-nicotine, but clearance of (R)-cotinine was twice that of (S)-cotinine. Fractional conversions of both enantiomers of nicotine to cotinine were approximately 50%. These resu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770508
更新日期：1988-05-01 00:00:00
abstract：:A randomized, two-way, crossover study was performed on 18 normal volunteers to assess the influence of food on the bioavailability of lisinopril, (1-[N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl]-L-proline), a long-acting nonsulfhydryl angiotensin converting enzyme inhibitor. A single, 20-mg oral dose of lisinopril was ...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/jps.2600750416
更新日期：1986-04-01 00:00:00
abstract：:The aim of this study was to evaluate a strategy based on static and dynamic physiologically based pharmacokinetic (PBPK) modeling for the prediction of metabolite and parent drug area under the time-concentration curve ratio (AUCm/AUCp) and their PK profiles in humans using in vitro data when active transport process...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.03.032
更新日期：2017-09-01 00:00:00
abstract：:Dissolution profiles are classified in accordance with the shape of fractional dissolution rate function. This function is constant in time for the classical first-order model and, in this case, the dissolution is described by a monoexponential function. Therefore, any deviation of the fractional dissolution rate from...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10419
更新日期：2003-08-01 00:00:00
abstract：:Nonionic surfactants (caprylocaproyl macrogol-8 glycerides, octoxynol-12, polysorbate-20, and polyethylene glycol-40 hydrogenated castor oil) (47.03%, w/w), costabilizer (poloxamer 407) (12%-20%, w/w), oil (isopropyl myristate) (5.22%, w/w), water (q.s. ad 100%, w/w), and ibuprofen (5%, w/w) were used to develop oil-i...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24494
更新日期：2015-08-01 00:00:00
abstract：:The objective of the present research was to investigate the stability of an amorphous drug, Delta(9)-tetrahydrocannabinol (THC) in polymer-based transmucosal systems. THC was incorporated in polyethylene oxide and hydroxypropylcellulose matrices by a hot-melt fabrication procedure, utilizing various processing aids. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20667
更新日期：2006-08-01 00:00:00
abstract：:A set of nonionic cellulose ethers with varying hydrophobicity and molecular weight has been investigated by principal component analysis (PCA). Several experimental variables such as dynamic surface tension, diffusion coefficient, microviscosity as monitored by a fluorescence probe technique, and intrinsic viscosity ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js9804922
更新日期：1999-08-01 00:00:00
abstract：:The relationship between the concentration of a drug and its pharmacologic effect is of central interest in pharmacodynamics. Various compartmental and noncompartmental methods have been proposed for elucidating this relationship when the plasma drug concentration and effects are both measured. Although the relationsh...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830317
更新日期：1994-03-01 00:00:00
abstract：:This whitepaper highlights current challenges and opportunities associated with continuous synthesis, workup, and crystallization of active pharmaceutical ingredients (drug substances). We describe the technologies and requirements at each stage and emphasize the different considerations for developing continuous proc...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24252
更新日期：2015-03-01 00:00:00
abstract：:Iontophoretic transdermal delivery of sumatriptan was investigated in vitro. Among the conditions tested, 0.25 mA/cm2 and low ionic strength (NaCl 25 mM) was the best experimental condition to increase its transport across the skin. The flux increased 385-fold respective to passive diffusion, thus resulting in a trans...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20447
更新日期：2005-10-01 00:00:00
abstract：:This study aims to investigate the drug-drug interactions (DDIs) between orally administered atorvastatin (ATV) and rifampicin (RIF) in rats. The isotope-IV method was used for the analysis of the increased systemic exposure (AUCpo) of ATV, in which a small amount of deuterium-labeled ATV (ATV-d5) was intravenously in...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.04.027
更新日期：2017-09-01 00:00:00
abstract：:4,5-Dimethoxykynuramine was synthesized in a three-step sequence originating with veratrole. Indirect evidence indicates that the drug was converted in vivo to the hypotensive agent 6,7-dimethoxy-4-quinolinol by the action of monoamine oxidase. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670344
更新日期：1978-03-01 00:00:00
abstract：:The secondary structure content of microparticulate insulin powders produced by the supercritical antisolvent (SAS) precipitation technique was investigated via Raman spectroscopy. Precipitate samples were generated at 25 and 35 degrees C processing temperatures. Both precipitate samples gave amide I band spectra that...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600831203
更新日期：1994-12-01 00:00:00
abstract：:A spectrophotofluorometric method is described for the quantitative analysis of coumarin, umbelliferone, and mixtures thereof in whole blood. The two drugs were selectively isolated from blood by solvent extraction. Analysis of the isolated coumarin was based on the measurement of the fluorophore at activation and emi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650104
更新日期：1976-01-01 00:00:00
abstract：:A column-switching high-performance liquid chromatographic assay combined with a heart-cutting technique and UV detection (LC/LC/UV) was developed to determine ceftibuten, a new oral cephalosporin, in human plasma. Plasma samples were directly injected into the first chromatographic column for sample cleanup and extra...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810715
更新日期：1992-07-01 00:00:00
abstract：:A method for the measurement, in human plasma, of all tertiary and secondary tricyclic antidepressants prescribed in the United States is described. The method uses electron beam ionization GLC-mass spectrometry, employing a computer-controlled multiple-ion detector. This method, mass fragmentography, is used with int...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650221
更新日期：1976-02-01 00:00:00
abstract：:Hydrogen triiodide adducts were prepared from N,N-dimethylacetamide, N-alkylpyrrolidone derivatives, and polyvinylpyrrolidone, and their structures were investigated by IR spectra and X-ray structure analyses and compared with the structure of povidone-iodine USP. The results suggest that the iodine in povidone-iodine...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600681211
更新日期：1979-12-01 00:00:00
