Synthesis and evaluation of 3-halocyclophosphamides and analogous compounds as novel anticancer "pro-prodrugs".

Abstract:

:3-Fluoro-, 3-chloro-, and 3-bromocyclophosphamide were prepared from the reaction of trifluoromethylhypofluorite, sodium hypochlorite, and bromine with the anticancer drug cyclophosphamide. Treatment of cis- and trans-4-phenylcyclophosphamide and 5,6-benzocyclophosphamide with sodium hypochlorite afforded cis- and trans-3-chloro-4-phenylcyclophosphamide and 3-chloro-5,6-benzocyclophosphamide, respectively. 31P-NMR spectroscopy was used to study the reactivity of these compounds: the fluoro derivative was reduced to cyclophosphamide on incubation with mouse liver slices, and the reactivity order for sulfhydryl-induced reduction of the 3-halocyclophosphamides was Br approximately equal to Cl much greater than F. Compared with the therapeutic efficacy of cyclophosphamide against L-1210 and P-388 cancers in mice, 3-fluoro- and 3-chlorocyclophosphamide were less active, although the fluoro derivative was more efficacious than the 3-chloro compound. The individual R and S enantiomers of 3-chlorocyclophosphamide, prepared from (S)- and (R)-cyclophosphamide, respectively, showed no significant difference in therapeutic activity in the P-388 test system.

journal_name

J Pharm Sci

authors

Zon G,Ludeman SM,Ozkan G,Chandrasegaran S,Hammer CF,Dickerson R,Mizuta K,Egan W

doi

10.1002/jps.2600720622

subject

Has Abstract

pub_date

1983-06-01 00:00:00

pages

687-91

issue

6

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)44631-3

journal_volume

72

pub_type

杂志文章
  • Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

    abstract::Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, becaus...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1002/jps.24303

    authors: Al-Gousous J,Langguth P

    更新日期:2015-09-01 00:00:00

  • Liquid chromatographic determination of 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one in human plasma with fluorescence detection.

    abstract::A simple and sensitive assay for quantitating 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (1; BMY 26517) in human plasma was developed using high-performance liquid chromatography with fluorescence detection. The method involves precipitation of protein and reversed-phase chromatography. The method i...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600761216

    authors: Cheng H,Pittman KA,Dandekar KA

    更新日期:1987-12-01 00:00:00

  • Fluorometric assay for measuring biological half-life of coralyne sulfoacetate in dogs and monkeys.

    abstract::A spectrophotofluorometric assay for coralyne sulfoacetate was developed. Caralyne was extracted from serum samples with n-butyl alcohol, and the drug concentrations were determined fluorometrically at 475 nm when the extract was excited at 325 nm. A biphasic serum decay curve for coralyne was observed for both dogs a...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600670942

    authors: Finkel JM,Hill DL

    更新日期:1978-09-01 00:00:00

  • Investigation of protein/carbohydrate interactions in the dried state. 1. Calorimetric studies.

    abstract::Isoperibol calorimetry was used to evaluate protein/carbohydrate interactions after freeze drying. rh-DNase, rh-GH, rh-MetGH, and rh-IGF-I were freeze dried with either mannitol, sucrose, trehalose, or dextran at concentrations ranging from 0% to 100% (w/w). Enthalpies of solution for both freeze-dried and physical mi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.10023

    authors: Souillac PO,Costantino HR,Middaugh CR,Rytting JH

    更新日期:2002-01-01 00:00:00

  • A rapid HPLC method for the quantification of tyrothricin, menthol, and benzocaine in pharmaceutical formulations.

    abstract::A rapid, sensitive, and accurate reversed-phase HPLC method has been developed for the analysis and quantification of pharmaceutical formulations containing tyrothricin (1), an antibiotic used in antiseptic buccal compressed tablets for local application. The assay has been carried out under isocratic conditions, usin...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600830815

    authors: Caraballo I,Fernandez-Arevalo M,Holgado MA,Vela MT,Rabasco AM

    更新日期:1994-08-01 00:00:00

  • Dissolving Microneedles Integrated With Liquid Crystals Facilitate Transdermal Delivery of Sinomenine Hydrochloride.

    abstract::The purpose of this study was to investigate the feasibility of delivering sinomenine hydrochloride (SH) transdermally using composite dissolving microneedles (DM) which integrated with liquid crystals (H2). The fabricated SH-loaded composite DM was evaluated for their appearance, mechanical strength, irritation, and ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2017.07.027

    authors: Gui Z,Wu X,Wang S,Cao Y,Wan J,Shan Q,Yang Z,Zhang J,Gui S

    更新日期:2017-12-01 00:00:00

  • Evaluation of drug-polymer solubility curves through formal statistical analysis: comparison of preparation techniques.

    abstract::In this study, the influence of the preparation technique (ball milling, spray drying, and film casting) of a supersaturated amorphous dispersion on the quality of solubility determinations of indomethacin in polyvinylpyrrolidone was investigated by means of statistical analysis. After annealing of the amorphous dispe...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.24207

    authors: Knopp MM,Olesen NE,Holm P,Löbmann K,Holm R,Langguth P,Rades T

    更新日期:2015-01-01 00:00:00

  • Evaluation of PEGylated exendin-4 released from poly (lactic-co-glycolic acid) microspheres for antidiabetic therapy.

    abstract::Peptide-based therapies have the potential to induce antibody formation if the molecules differ from a native human peptide. Several reports have disclosed the occurrence of antibody generation in a patient treated with exenatide. The immune response can be problematic from a clinical stand point, particularly if the ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.24238

    authors: Lim SM,Eom HN,Jiang HH,Sohn M,Lee KC

    更新日期:2015-01-01 00:00:00

  • Constant returns to scale for prescription dispensing in U.S. community pharmacy.

    abstract::By using data from a sample of 1767 community pharmacies, a total cost function was estimated by a polynomial regression of total cost on output. The Cobb-Douglas production function was estimated by a multiple linear regression of natural logarithmic transformations of output on natural logarithmic transformation of ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600650208

    authors: Lohrisch D,Shull SC,Smith MC

    更新日期:1976-02-01 00:00:00

  • GLC determination of lidocaine in human plasma.

    abstract::A specific, sensitive, rapid, and reproducible analytical GLC method for lidocaine in human plasma, including pharmacokinetic parameters, is described. Aminopyrine is the internal standard. The method was used to study pharmacokinetics in four healthy volunteers following the administration of a lidocaine bolus at a d...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600661007

    authors: Caille G,Lelorier J,Latour Y,Besner JG

    更新日期:1977-10-01 00:00:00

  • Swelling and polymer erosion for poly(ethylene oxide) tablets of different molecular weights polydispersities.

    abstract::The aim of the study was to determine and compare the degree of swelling and the swelling kinetics of poly(ethylene oxide) (PEO) hydrophilic matrix tablets without any additives for matrixes with different molecular weight polydispersities. A wide range of "mixed" polydisperse PEO tablets were obtained by mixing two P...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21892

    authors: Körner A,Larsson A,Andersson A,Piculell L

    更新日期:2010-03-01 00:00:00

  • Mechanism of Drug Release From Temperature-Sensitive Formulations Composed of Low-Melting-Point Microcrystalline Wax.

    abstract::It was reported that wax matrix (WM) particles composed of low-melting-point microcrystalline wax showed unique release behaviors; the particles released only a small amount of the entrapped drug (non-diffusion-controlled release) at 37°C, whereas it showed comparatively fast drug release in a diffusion-controlled man...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2019.01.010

    authors: Matsumoto K,Kimura SI,Noguchi S,Itai S,Kondo H,Iwao Y

    更新日期:2019-06-01 00:00:00

  • Bioavailability of seocalcitol I: Relating solubility in biorelevant media with oral bioavailability in rats--effect of medium and long chain triglycerides.

    abstract::Simulated intestinal media (SIM) containing bile salt (BS) and phospholipids (PL) with and without medium chain lipolytic products (MC-LP) or long chain lipolytic products (LC-LP) were developed to study the solubility of seocalcitol. Both MC-LP and LC-LP were studied in order to investigate the influence of fatty aci...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20403

    authors: Grove M,Pedersen GP,Nielsen JL,Müllertz A

    更新日期:2005-08-01 00:00:00

  • Interleukin-1 receptor antagonist: a new therapy for type 2 diabetes mellitus.

    abstract::Various complex mechanisms and their multifactorial pathways decisively provoke low-grade local and systemic inflammation in β-cells of pancreatic islets and peripheral tissues to induce β-cells' dysfunction and apoptosis, insulin resistance, and ultimately, overt type 2 diabetes mellitus (T2DM). Conventional antidiab...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1002/jps.23057

    authors: Akash MS,Shen Q,Rehman K,Chen S

    更新日期:2012-05-01 00:00:00

  • Amphotericin B/emulsion admixture interactions: an approach concerning the reduction of amphotericin B toxicity.

    abstract::Mixing Fungizone with a fat emulsion used for nutritional purpose (Intralipid or Lipofundin ) was reported to decrease Amphotericin B (AmB) toxicity in clinical use. In an effort to understand the reason for this phenomenon, spectral and morphological analyses were done for the Fungizone and Fungizone /Lipofundin admi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.10223

    authors: Egito ES,Araújo IB,Damasceno BP,Price JC

    更新日期:2002-11-01 00:00:00

  • Modified NF method for quantitative determination of pentaerythritol tetranitrate.

    abstract::A modified NF method for the quantitative determination of pentaerythritol tetranitrate is reported. A solution of powder is made directly from the dosage form in glacial acetic acid and is then reacted with phenoldisulfonic acid TS. The proposed method saves approximately 75% of the time required with the NF method. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600670543

    authors: Gupta VD

    更新日期:1978-05-01 00:00:00

  • Dehydration behavior of eprosartan mesylate dihydrate.

    abstract::Eprosartan mesylate (SKF 108566-J; EM) is an antihypertensive agent approved for marketing in the USA. EM dihydrate was prepared by three methods, one of which included suspending the anhydrous drug in an aqueous solution of 1.0 M methanesulfonic acid to form a slurry, followed by filtration. The dehydration kinetics ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1021/js9900250

    authors: Sheng J,Venkatesh GM,Duddu SP,Grant DJ

    更新日期:1999-10-01 00:00:00

  • Tocainide conjugation in humans: novel biotransformation pathway for a primary amine.

    abstract::The metabolism of tocainide, an experimental antiarrhythmic drug, was studied in humans. Urinary excretion of unchanged drug was 28-55% in 24 hr after oral dosing. Urine hydrolysis with hydrochloric acid or beta-glucuronidase increased tocainide recovery to 55-79%. Saccharo-1,4-lactone inhibited the beta-glucuronidase...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600690113

    authors: Elvin AT,Keenaghan JB,Byrnes EW,Tenthorey PA,McMaster PD,Takman BH,Lalka D,Manion CV,Baer DT,Wolshin EM,Meyer MB,Ronfeld RA

    更新日期:1980-01-01 00:00:00

  • In vitro and in vivo availability of commercial prednisone tablets.

    abstract::A three-way crossover bioavailability study was performed using nine adult male volunteers with three different commercial prednisone tablets. Plasma samples were assayed for prednisolone, the active metabolite of prednisone, by a radioimmunoassay method. Statistical analysis showed significant differences in the rate...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 临床试验,杂志文章

    doi:10.1002/jps.2600641035

    authors: Sullivan TJ,Sakmar E,Albert KS,Blair DC,Wagner JG

    更新日期:1975-10-01 00:00:00

  • Assessing OATP1B1- and OATP1B3-Mediated Drug-Drug Interaction Potential of Vemurafenib Using R-Value and Physiologically-Based Pharmacokinetic Models.

    abstract::Organic anion transporting polypeptides (OATP) 1B1 and OATP1B3 are important determinants of transporter-mediated drug-drug interactions (DDIs). Current studies assessed the OATP1B1 and OATP1B3-mediated DDI potential of vemurafenib, a kinase inhibitor drug with high protein binding and low aqueous solubility, using R-...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2020.06.016

    authors: Kayesh R,Farasyn T,Crowe A,Liu Q,Pahwa S,Alam K,Neuhoff S,Hatley O,Ding K,Yue W

    更新日期:2021-01-01 00:00:00

  • Importance of viscosity in the dissolution rate of cholesterol in monooctanoin solutions.

    abstract::Several factors affecting the dissolution rate of cholesterol in monooctanoin were investigated. This solvent is used clinically for dissolution of residual cholesterol gallstones in the bile duct after cholecystectomy. The effect of added water on dissolution rate, measured using the static- or rotating-disk methods,...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600730711

    authors: Bogardus JB

    更新日期:1984-07-01 00:00:00

  • An examination of the thermodynamics of fusion, vaporization, and sublimation of (R,S)- and (R)-flurbiprofen by correlation gas chromatography.

    abstract::The vaporization, fusion, and sublimation enthalpies of (R,S)- and (R)-flurbiprofen at T = 298.15 K are reported and compared with literature values when available. Correlation gas chromatography experiments were first performed to identify appropriate standards that could be used for materials containing a single flu...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.23094

    authors: Umnahanant P,Hasty D,Chickos J

    更新日期:2012-06-01 00:00:00

  • Stability-indicating assay for phenylbutazone: high-performance liquid chromatographic determination of hydrazobenzene and azobenzene in degraded aqueous phenylbutazone solutions.

    abstract::A high-performance liquid chromatographic method was developed for the simultaneous determination of azobenzene, hydrazobenzene, and four other decomposition products in phenylbutazone injectable formulations. Separation was achieved on a C18 column, with 0.1 M Tris-citrate buffer (pH 5.25) and acetonitrile (52:48), a...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600731211

    authors: Fabre H,Hussam-Eddine N,Mandrou B

    更新日期:1984-12-01 00:00:00

  • A Simplified Model of Moisture Transport in Hydrophilic Porous Media With Applications to Pharmaceutical Tablets.

    abstract::This work establishes a predictive model that explicitly recognizes microstructural parameters in the description of the overall mass uptake and local gradients of moisture into tablets. Model equations were formulated based on local tablet geometry to describe the transient uptake of moisture. An analytical solution ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2016.05.030

    authors: Klinzing GR,Zavaliangos A

    更新日期:2016-08-01 00:00:00

  • Preparation and biological evaluation of tumor-specific Ara-C liposomal preparations containing RGDV motif.

    abstract::Arginine-glycine-aspartate (RGD) has been shown to be essential for the recognition of integrins overexpressed in tumor cells, especially during tumor invasion, angiogenesis, and metasis. In this study, a novel tetrapeptide, RGD-valine (RGDV), was designed and attached to the N position of 1-β-D-arabinofuranosylcytosi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.23326

    authors: Wang F,Cui C,Ren Z,Wang L,Liu H,Cui G

    更新日期:2012-12-01 00:00:00

  • Dissolution profiles and specifications for dihydroergotoxine sublingual tablets using a new in vitro method.

    abstract::A dissolution method (paddle method) for determining the dissolution rate profile for 0.5- and 1.0-mg dihydroergotoxine methanesulfonate sublingual tablets was developed. A fluorometric method was used for measuring drug concentration in the dissolution medium, distilled water. It was essential to filter the dissoluti...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600700722

    authors: Hunt JP,Shah VP,Prasad VK,Schuirmann DJ,Cabana BE

    更新日期:1981-07-01 00:00:00

  • Synthesis, cytotoxicity, and phase-solubility study of cyclodextrin click clusters.

    abstract::To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HT-β-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl}-β-cyclodextrin (...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.24107

    authors: Le HT,Jeon HM,Lim CW,Kim TW

    更新日期:2014-10-01 00:00:00

  • Stable isotope coadministration methodology for the estimation of the fraction of imipramine metabolized to desipramine.

    abstract::The application of a stable isotope coadministration technique for estimating the fraction (fm) of imipramine (IP) that is converted to desipramine (DMI) is described. Four healthy male subjects received 25 mg of IP-d4 hydrochloride orally with 25 mg of DMI hydrochloride. The plasma concentrations of IP-d4, DMI-d4, an...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600790203

    authors: Sasaki Y,Shinohara Y,Baba S

    更新日期:1990-02-01 00:00:00

  • Solid and Solution State Thermodynamics of Polymorphs of Butamben (Butyl 4-Aminobenzoate) in Pure Organic Solvents.

    abstract::The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-propanol, 1-butanol, and toluene over the temperature range 268-298 K. Polymorph transition and melting temperatures, associated enthalpy changes, and the heat capacity of the solid forms and the supercooled melt have been mea...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2019.02.013

    authors: Svärd M,Zeng L,Valavi M,Krishna GR,Rasmuson ÅC

    更新日期:2019-07-01 00:00:00

  • Association efficiency of three ionic forms of oxytetracycline to cationic and anionic oil-in-water nanoemulsions analyzed by diafiltration.

    abstract::The association efficiency of oxytetracycline (OTC) to pharmaceutical available, ionic oil-in-water nanoemulsions is studied. Theoretical mathematical developments allowed us to differentiate by diafiltration (DF) between thermodynamically and kinetically controlled binding of the drug to the nanoemulsions, and relate...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.24255

    authors: Orellana SL,Torres-Gallegos C,Araya-Hermosilla R,Oyarzun-Ampuero F,Moreno-Villoslada I

    更新日期:2015-03-01 00:00:00