Abstract:
:Different green synthesis of alkyl esters of acyclovir (acyclovir prodrugs) is described. Hexanoic, decanoic, dodecanoic and tetradecanoic acyclovir esters were synthesized reacting acyclovir and the respective acid anhydride in dimethyl sulfoxide (DMSO), in solvents from renewable sources and without solvent (T=30 °C). Yields in prodrugs after 10 min of reaction were >95% using DMSO as solvent. The purification methodology was very simple, shorter and greener than previously described. The biosolvent, N,N-dimethylamide of decanoic acid, let us to obtain >95% yield at 24 h. This oily biosolvent is not dermotoxic and the reaction crude can directly be used in topic formulations. Syntheses without solvent proceeded successfully for acyclovir esters. Indeed, dodecanoate and tetradecanoate yielding >98% conversion of reactants in 30 min. In spite of requiring mild temperature (65 °C), substrate molar ratios were lowered to 1 : 1, thus conducing to a more efficient use of raw materials. The synthetic procedures were scaled up to a 300 g batch (yield 98-99% isolated ester). These esters can be used as acyclovir prodrugs in topic formulations. The esters release from an oil/water micro-emulsion and a hydrogel formulation were tested with good results.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
de Regil-Hernández R,Martínez-Lagos F,Rodríguez-Bayón A,Sinisterra JVdoi
10.1248/cpb.59.1089subject
Has Abstractpub_date
2011-01-01 00:00:00pages
1089-93issue
9eissn
0009-2363issn
1347-5223pii
JST.JSTAGE/cpb/59.1089journal_volume
59pub_type
杂志文章abstract::Novel 1,2,3,4-tetrahydroisoquinoline derivatives bearing directly a cyclic amine at the 2-position were prepared and examined for their bradycardic activities in isolated right atria and in anesthetized rats. The structure-activity relationships (SAR) study revealed that the 2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinol...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.51.390
更新日期:2003-04-01 00:00:00
abstract::The effect of the surface layering time of lactose carrier particles on the dry powder inhalation properties of salbutamol sulfate was investigated. Lactose carrier particles were layered with vegetable magnesium stearate by physical mixing. In the present study, drug/carrier powder mixtures were designed consisting o...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.52.350
更新日期:2004-03-01 00:00:00
abstract::Doxazosin mesylate (DXM) sustained release pellets were prepared by an extrusion-spheronization and fluid-bed coating technique. The core pellets containing DXM were prepared by extrusion-spheronization technique, and coated by a fluid-bed coater to control the release of DXM. The factors affecting to properties of pe...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c12-00767
更新日期:2013-01-01 00:00:00
abstract::From the herb of Luffa acutangula ROXB. (Cucurbitaceae), seven oleanane-type triterpene saponins, acutosides A--G, were isolated and their structures were determined. Acutoside A is oleanolic acid 3-O-beta-D-glucopyranosyl-(1----2)-beta-D-glucopyranoside. Acutosides B, D, E, F and G have a common prosapogenin structur...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.39.599
更新日期:1991-03-01 00:00:00
abstract::A series of diarylureas and diarylamides possessing pyrrolo[2,3-d]pyrimidine scaffold was designed and synthesized. The in vitro antiproliferative activities of a selected group of the target compounds against NCI-60 cell line panel were tested and compared with Sorafenib and Imatinib as reference compounds. Most of t...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c13-00249
更新日期:2014-01-01 00:00:00
abstract::Tin(IV) complexes 2a--q derived from pyridine Schiff bases were prepared and characterized. Four complexes of this series were evaluated in vitro against different carcinogenic cell lines; besides their anti-inflammatory and antioxidant properties were also tested. Combination of mass spectrometry, multinuclear NMR an...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.57.5
更新日期:2009-01-01 00:00:00
abstract::Our aim is to test the characteristics and expression activity in brain capillary endothelial cells (BCECs) of DNA-loaded nanoparticles before and after the modification with Antennapedia peptide (Antp). Chitosan (CH), polyethylenimine (PEI) and polyamidoamine (PAMAM) were chosen to prepare the nanoparticles; Lipofect...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.54.1254
更新日期:2006-09-01 00:00:00
abstract::A facile stereoselective synthesis of (Z)- and (E)-allyl sulfides has been accomplished from Morita-Baylis-Hillman acetates in one-pot by treatment with benzene thiol in the presence of catalytic amounts of 15% aqueous NaOH and TBAI in DMSO at room temperature. The method has been applied for the synthesis of (Z)-3-(4...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.55.1274
更新日期:2007-08-01 00:00:00
abstract::We developed new intravenous sedative-hypnotic compounds with the isoindolin-1-one skeleton focusing on the water-soluble property and in vivo safety. We synthesized approximately 170 derivatives and evaluated their hypnotic effects by intravenous administration of the compounds to mice. A series of the 2-phenyl-3-[2-...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.55.1682
更新日期:2007-12-01 00:00:00
abstract::Intramolecular [2+2] cycloaddition of γ,δ-unsaturated ketenes derived from hex-5-enoyl chloride derivatives gave bicyclo[2.1.1]hexan-5-ones with complete regioselectivity. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.60.548
更新日期:2012-01-01 00:00:00
abstract::A new cycloartane bisdesmoside and two new trinorcycloartane glycosides, along with four known cycloartane compounds, were isolated from the rhizomes of Cimicifuga dahurica (Ranunculaceae). The structures of the new compounds were elucidated as 3-O-alpha-L-arabinopyranosyl cimigenol 15-O-beta-D-glucopyranoside, 24-hyd...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.49.1468
更新日期:2001-11-01 00:00:00
abstract::A new isoflavone, 4'-gamma,gamma-dimethylallyloxy-5,7,2',5'-tetramethoxyisoflavone, brandisianin A (1), was isolated from the leaves of Millettia brandisiana, along with one synthetically known isoflavone, 7,4'-di-O-prenylgenistein (2) and twelve known compounds. The structures were elucidated on the basis of extensiv...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.56.835
更新日期:2008-06-01 00:00:00
abstract::A novel series of N-arylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic properties were evaluated. Reporter assays indicated that trans-2,5-dimethylpiperazine derivatives are potent AR antagonists, and in this series trans-N-4-[4-cy...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.53.402
更新日期:2005-04-01 00:00:00
abstract::A series of joro spider toxins, novel polyamines sharing a common moiety of 2,4-dihydroxyphenylacetyl cadaverine, have been identified using various bioassays, such as inhibition of a glutamatergic transmission and insecticidal activity. In this paper, we tried to chemically find still unknown polyamine toxins in the ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.42.1864
更新日期:1994-09-01 00:00:00
abstract::Eight new guaipyridine sesquiterpene alkaloids, rupestines F-M (1-8) were isolated from the leaves of Artemisia rupestris and their structures were elucidated on the basis of 2D-NMR data. The absolute configurations of 1-8 have been assigned by comparison of their experimental and calculated circular dichroism (CD) sp...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.60.213
更新日期:2012-01-01 00:00:00
abstract::A novel Fourier transform infrared (FT-IR) microspectroscopy equipped with a micro hot stage (thermal FT-IR microscopic system) was used to quickly study the phase transformation of acetaminophen polymorphs by a one-step process. Acetaminophen was sealed in KBr disc on the first and second heating processes under this...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.50.153
更新日期:2002-02-01 00:00:00
abstract::Nuclear factor-κB (NF-κB) is an inducible transcription factor activated by a variety of cytokines, and promotes the transcription of genes involved in cancer, inflammation, autoimmune disease, and viral infection, among others. Because of its involvement in numerous disease processes, considerable research has focuse...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.59.1555
更新日期:2011-01-01 00:00:00
abstract::Synthesis and pharmacological evaluation of novel thienopyridazinones and related compounds are described. A thiophene ring was found to be able to replace the benzene ring of a phthalazinone without loss of biological activities. This observation supports our hypothesis that the benzene ring plays an important role i...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.43.236
更新日期:1995-02-01 00:00:00
abstract::Electron spin resonance studies showed that addition of rat liver microsomes to the reaction system of alloxan with reduced nicotinamide adenine dinucleotide phosphate (NADPH) resulted in a marked increase in the generation of alloxan radicals (AH.), whereas heat-denatured microsomes were without such effect. Oxidatio...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.40.432
更新日期:1992-02-01 00:00:00
abstract::In the course of our research on spiro-compounds as neurokinin receptor antagonists, N-[2-aryl-4-(spiro-substituted piperidin-1'-yl)butyl]carboxamides were designed, based on YM-35375 (3) as a lead compound, and evaluated for NK2 receptor-antagonistic activities. Some derivatives inhibited the binding of radio-labeled...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.46.242
更新日期:1998-02-01 00:00:00
abstract::A new class of mono and bis heterocycles-styrylsulfonylmethyl 1,3,4-oxadiazoles, pyrazolyl/isoxazolyl-1,3,4-oxadiazoles were prepared and studied their antioxidant activity. The compound methyl substituted 2-(p-methylphenylamino-sulfonylmethyl)-5-[Z-(p-methylstyrylsulfonylmethyl)]-1,3,4-oxadiazole displayed slightly h...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c13-00652
更新日期:2013-01-01 00:00:00
abstract::A series of novel benzo[4,5]canthin-6-ones, bearing the N'-(substituted benzylidene)-carbohydrazide (11a-e) and N-alkylcarboxamide (13a-g) moieties at position-2, were synthesized and screened for their in vitro antitumor activity, against seven human cancer cell lines, and for antitrypanosomal and antileishmanial act...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c12-00356
更新日期:2012-01-01 00:00:00
abstract::From the air-dried roots of Glycyrrhiza uralensis Fischer collected in Xinjiang province, China ("Shinkyo-Kanzo" in Japanese), a new oleanene-type triterpene oligoglycoside named licorice-saponin L3 and a new chalcone oligoglycoside named isoliquiritin apioside were isolated together with glycyrrhizin, 18 alpha-glycyr...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.41.1567
更新日期:1993-09-01 00:00:00
abstract::A new phenolic glycoside, 3,4,5-trimethoxyphenol-1-(6-xylopyranosyl)glucopyranoside, was isolated together with twenty known compounds identified as koaburaside, 3,4,5-trimethoxyphenol, 5,7-dihydroxychromone-7-neohesperidoside, naringin, neoeriocitrin, p-coumaric acid, vanillin, vanillic acid, coniferyl aldehyde, feru...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.42.1669
更新日期:1994-08-01 00:00:00
abstract::Three new hydronaphthalenone derivatives (1-3) and one new dihydroramulosin derivative (4), were isolated from the endophytic fungus PSU-N24 together with eight known compounds. Their structures were elucidated by spectroscopic methods. Griseofulvin (9) displayed strong antifungal activity against Microsporum gypseum ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.56.1687
更新日期:2008-12-01 00:00:00
abstract::Three new glycosides, 7-deoxyloganic acid beta-D-glucopyranosyl ester (1), (3R)-hydrangenol 8,4'-di-O-beta-D-glucopyranoside (2), and (6R,7E,9R)-megastigma-4,7-dien-3-one 9,13-di-O-beta-D-glucopyranoside (3), have been isolated from the leaves of Hydrangea macrophylla subsp. serrata (THUNB.) MAKINO (Saxifragaceae). Th...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.56.610
更新日期:2008-04-01 00:00:00
abstract::The purpose of this study was to develop and test a novel and simple method for evaluating the disintegration time of rapidly disintegrating tablets (RDTs) in vitro, since the conventional disintegration test described in the pharmacopoeia produces poor results due to the difference of its environmental conditions fro...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c13-00441
更新日期:2013-01-01 00:00:00
abstract::The involvement of prostanoids in the improvement of adenine-induced renal failure in rats by magnesium lithospermate B was studied. After intraperitoneal administration of magnesium lithospermate B to renal failure rats, the levels of glomerular filtration rate, renal plasma flow and renal blood flow were increased. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.37.1568
更新日期:1989-06-01 00:00:00
abstract::Tranilast, a lipophilic drug with various ophthalmic applications, was used as a model drug to establish the possibility of delivering lipophilic drugs through the eyelid skin. Pharmacokinetics and tissue distribution studies were conducted employing three application methods (topical application onto eyelid skin, eye...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c20-00289
更新日期:2020-01-01 00:00:00
abstract::Three new 15,16-seco-cycloartane glycosides, which were constructed by a C-C bond cleavage in the D ring, have been isolated from Cimicifuga Rhizome for the first time. Their structures were determined by the use of 2D NMR techniques and chemical evidence. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.55.789
更新日期:2007-05-01 00:00:00