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en: Synthesis and Pharmacological Evaluation of New 1-Hydroxy-1-phenyl-2, 3,4, 5-tetrahydro-1H-3-benzazepines as NE Potentiators

en: 4-Hydroxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (PI-OH) (1a) and its derivatives form a new class of compounds which possess norepinephrine (NE) potentiating activity. As a new series of compounds, 1-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines (2a--f) were synthesized by the intramolecular Barbier reaction of N-[2-(2-iodophenyl)ethyl]phenacylamines (6a--f) with n-BuLi as a key reaction step. The potentiating activities of the benzazepines 2a--f on the contraction of rat anococcygeus muscle induced by NE were tested. Among the compounds tested in this study, compound 2a showed moderate potentiating activity (the activity ratio was 7.3-fold at 3 x 10(-5) M).

en: Chemical & Pharmaceutical Bulletin

ja: Chemical & Pharmaceutical Bulletin


en: Prescribing patterns during pregnancy at Tokushima University Hospital

en: The purpose of this study was to investigate the drugs prescribed for pregnant women at Tokushima University Hospital in Japan, and to evaluate the risks associated with the use of these drugs during pregnancy according to the pregnancy risk classification systems of the PDA, ADEC and that used in manufacturers' package inserts. Of 496 female outpatients who gave birth at Tokushima University Hospital, 81% had been prescribed at least one drug, and the mean was 4.0 drugs per patient. Analysis of the prescriptions revealed a pattern of drug use very different from that in other countries, in that Kampo (Japanese herbal) medicines were also prescribed. For more than half of the oral drugs prescribed, risks were not given in the PDA and/or ADEC pregnancy risk systems. In addition, there was no listing of pregnancy risks in the package inserts of 20 drugs. We therefore consider it to be very important to develop a globally harmonized system for evaluating the risks associated with prescription drugs taken during pregnancy.

en: Japanese Journal of Pharmaceutical Health Care and Sciences


en: Synthesis of New 1,2-Diphenyl-4,5-dihydro-3H-benzazepines

en: 1, 2-Diphenyl-4, 5-dihydro-3H-3-benzazepine derivatives (2a-d) were synthesized via cyclization reaction of N-[2-(2-iodophenyl)ethyl]-α- phenylphenacylamines (5a-c) and (5e) with n-C4H9Li, followed by dehydration of the cyclization products, 1, 2-diphenyl-1-hydroxy-3-methyl-2, 3, 4, 5-tetrahydro- 1H-3-benzazepines (4a-d) with trifluoromethanesulfonic acid.

en: Heterocycles

ja: Heterocycles


en: A new synthesis of phenolic 1-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines


en: Defects in apoptotic signal transduction in cisplatin-resistant non-small cell lung cancer cells

en: Non-small cell lung cancer (NSCLC) often shows intrinsic multidrug resistance, which is one of the most serious problems in cisplatin-based adjuvant chemotherapy. Anticancer drugs exert at least part of their cytotoxic effect by triggering apoptosis. In order to understand the molecular alterations leading to heterogeneous cisplatin sensitivity and apoptosis inducibility in NSCLC cells, we analyzed various apoptotic pathways, including the activation of caspase-8, -9 and -3, the release of cytochrome c from mitochondria and the expression levels of pro- and anti-apoptotic proteins such as Bax, Bad, Bcl-2, Bcl-xL, Fas and p53 using heterogeneously apoptosis-sensitive cells (Ma-10, Ma-31 and Ma-46). Cisplatin treatment induced the activation of caspase-8, -9 and -3 and the release of cytochrome c in apoptosis-sensitive Ma-46. The expression of Bcl-xL was the highest and p53 was not expressed in apoptosis-resistant Ma-31, and Fas was not expressed in Ma-46. These expression levels were not correlated with the apoptosis inducibility of the three cell lines. These results suggest that blockage of the apoptotic signal from mitochondria is responsible for apoptosis resistance in NSCLC cell lines. Our findings also indicate that anti-apoptotic Bcl-xL and pro-apoptotic p53 are necessary but not sufficient for resistance to cisplatin-induced apoptosis in NSCLC cells.

en: Oncology Reports

ja: Oncology Reports


en: 徳島大学病院におけるTPN処方設計支援ソフトの使用評価と改良

ja: 徳島大学病院におけるTPN処方設計支援ソフトの使用評価と改良

en: Fluid therapy is a fundamental treatment for almost all inpatients, and nutritional therapy is the most important type of such therapy. Currently, total parenteral nutrition (TPN) is widely used to provide complete nutritional support but 30-40% of TPN recipients are considered to in a malnourished state due to inappropriate TPN prescriptions. Computer-assisted TPN prescription systems are thought to be useful to clinical professionals in solving this problem because they can perform complicated calculations that make it easy to draw up correct TPN prescriptions. So, we made a prototype system for aiding the preparation of TPN prescriptions based on Microsoft^[ !R] EXCEL and it was tested by physicians, pharmacists, dietitians and nurses engaged in TPN therapy at Tokushima University Hospital. We also had them fill out a questionnaire on the system in which they rated it for ease of operation and usefulness according to a scoring system in which 5 indicated full marks. Our Computer-Assisted TPN Prescription System was improved on the basis of the questionnaire results and is now being effectively used by the nutrition support team (NST) in Tokushima University Hospital.

ja: 医療薬学


en: Expression of multidrug resistance proteins and accumulation of cisplatin in human non-small cell lung cancer cells

en: In order to understand and overcome multidrug resistance (MDR) of human non-small cell lung cancer (NSCLC), mRNA and protein expression levels of P-glycoprotein (MDR1), multidrug resistance-associated protein 1 (MRP1), and lung resistance-related protein (LRP) were investigated and compared with the chemosensitivity and the intracellular/intranuclear cisplatin accumulation of three NSCLC cell lines (Ma-10, Ma-31, and Ma-46). Ma-31 was more resistant than Ma-10 and Ma-46 to cisplatin, carboplatin, etoposide, and paclitaxel. The mRNA level of MDR1 was extremely low, and MDR1 protein was not detected in all cell lines. MRP1 mRNA expression was highest in Ma-31 and lowest in Ma-10, but there was no notable difference between the MRP1 protein expression in three cell lines. LRP mRNA/protein was equally expressed in Ma-10 and Ma-31, but was nominal in Ma-46. The intracellular/intranuclear cisplatin accumulation of the cells was determined to be Ma-31>Ma-46>Ma-10. Thus, MDR1, MRP1, and LRP mRNA and protein expression levels were not correlated with the chemosensitivity or the intracellular/intranuclear cisplatin accumulation of each cell line. The present results indicate that MDR proteins (MDR1, MRP1, and LRP) may not play an important role in the chemoresistance and drug efflux of NSCLC cells.

en: Biological & Pharmaceutical Bulletin

ja: Biological & Pharmaceutical Bulletin


en: Overexpression of constitutive signal transducer and activator of transcription 3 mRNA in cisplatin-resistant human non-small cell lung cancer cells.

en: Non-small cell lung cancer (NSCLC) often shows intrinsic multidrug resistance, which is one of the most serious problems in cisplatin-based adjuvant chemotherapy. Recently, the constitutive activation of signal transducer and activator of transcription (STAT) factors has been found in a variety of human cancers. In the present study, the mRNA expression of STATs in various human NSCLC cell lines was investigated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) to determine whether STATs can be implicated in cisplatin resistance and apoptosis inducibility. Cisplatin triggered apoptosis in Ma-46 based on biochemical and morphological findings, but not in Ma-31. The mRNA expression of STAT3 was highest in cisplatin-resistant Ma-31 and lowest in cisplatin-sensitive Ma-46. A 6-hour exposure of cancer cells to cisplatin failed to stimulate STAT3 mRNA expression. Therefore, an increased transcriptional level of constitutive STAT3 may be related to the suppressive regulation of the apoptotic pathway in intrinsically chemo-resistant NSCLC cells.


en: New entry of coupling reaction of phenacylamine derivatives with silylstannane

en: The new coupling reaction of phenacylamines with silylstannane and lithium diisopropylamide (LDA) is reported. The treatment of a phenacylamine iodide 1 with (trimethylsilyl)tributylstannane (Me_3SiSnBu_3) and cesium fluoride (CsF) gave a dimerization product 2 having no iodine atom. Reaction of 1 with LDA afforded a dimerization product 3 with an iodine atom. The products 2 and 3 were separated to the meso and racemic isomers, respectively.

en: Chemical & Pharmaceutical Bulletin


en: Tissue Distribution of and Species Differences in Deacetylation of N-Acetyl-L-Cysteine and Immunohistochemical Localisation of Acylase I in the Primate Kidney

en: Species differences in the biotransformation of N-acetyl-L-cysteine (NAC) have been investigated to evaluate the usefulness of NAC as a constituent in parenteral nutrition solutions in place of cysteine. The activity of NAC-deacetylating enzyme (acylase) was measured in various tissues of different species (rat, rabbit, dog, monkey, and man). Acylase activity was highest in the kidney in all species studied. Enzyme activity in the liver was 10 %-22 % of that in the kidney in the rat, rabbit, monkey, and man, but almost no hepatic activity was seen in the dog. NAC-deacetylating activity was very low in other organs. The tissue distribution of acylase I was determined by Western blotting and an immunohistochemical method employing specific antibody against porcine acylase I (EC 3.5.1.14). The immunoblotting study showed a 46-kDa protein band corresponding to porcine acylase I in the kidney of all species. In liver cytosol, 46 kDa and/or 29 kDa bands were observed in the rat, rabbit, monkey, and man, but not in the dog. In the immunohistochemical study, positive staining with anti-acylase I antibody was observed clearly in the renal proximal tubules in the monkey and man. These results suggested that the kidney and liver were the main organs responsible for the biotransformation of NAC to cysteine in mammals other than the dog.

en: The Journal of Pharmacy and Pharmacology


en: New Reduction Reaction of Benzylic Alcohols with Acid and Proof of the Intermolecular Hydride Shift Mechanism

en: Heterocycles


en: Phytochemical flavones isolated from Scutellaria barbata and antibacterial activity against methicillin-resistant Staphylococcus aureus.

en: A crude extract prepared from Scutellaria barbata D. Don (Lamiaceae) was analyzed in the effort to discover antibacterial compounds against high-level strains of methicillin-resistant Staphylococcus aureus (MRSA). Apigenin and luteolin were isolated from the plant as active constituents against the bacteria. These flavonoid congeners were selectively toxic to S. aureus, including the MRSA and methicillin-sensitive S. aureus strains.

en: Journal of Ethnopharmacology

ja: Journal of Ethnopharmacology


en: Biotransformation of N-acetyl-L-cysteine:Tissue distribution and species difference of its deacetylation

en: Drug Metabolism Reviews

ja: Drug Metabolism Reviews


en: Stereoselective Intermolecular Hydiride Shift Mecahnism of the New Reduction of Benzylic Alcohols with Acid


en: A Xanthanolide with Potent Antibacterial Activity against Methicillin-resistant Staphylococcus aureus.

ja: The Journal of Pharmacy and Pharmacology


en: Synthesis and biological evaluation of 7-hydroxy-3,4-diphenyl-1,2-dihydroquinolines as new 4-hydroxytamoxifen analogues


en: Extraction and Purification of Effective Antimicrobial Constituents of Terminalia chebula RETS. against Methicillin-Resistant Staphylococcus aureus.

en: Biological & Pharmaceutical Bulletin


en: Synthesis and Biological Evaluation of 3,4-Diphenyl-1,2-dihydroisoquinolines as a New Tamoxifen Analogue

en: 3,4-Diphenyl-1,2-dihydroisoquinoline derivatives (1) as a new tamoxifen analogue were synthesized with trifluoromethanesulfonic acid from 3,4-diphenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (2), which were prepared by intramolecular Barbier reaction of N-(2-iodobenzyl)phenacylamines. Anti-proliferative activities of 1 and 2, and 3,4-diphenyl-1,2,3,4-tetrahydroisoquinolines (3) prepared by NaBH4 reduction of 1 against human mammary carcinoma MCF-7 cell line and human nasopharyngeal carcinoma KB cell line were evaluated. 1,2-Dihydroisoquinoline (1a) was the most active against MCF-7 cells in the compounds tested and the activity [IC50(micrograms/mL) 0.94] was nearly equipotent to that of tamoxifen. The structure-activity relationships of the compounds 1,2 and 3 were discussed.

en: Drug Design and Discovery

ja: Drug Design and Discovery


en: Synthesis and Enantioselectivity of Optically Active 1- and 3-Substituted 4-Phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols and Related Compounds as Norepinephrine Potentiators

en: Chemical & Pharmaceutical Bulletin


en: A New Synthesis of 3-Substituted Indolines and Indoles


en: Alkaloidal Constituents of Leucojum autumnale L.(Amaryllidaceae)


en: New Norepinephrine Potentiators:Synthesis and Structure-Activity Relationships of a series of 4-Phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols


en: Synthesis and Pharmacological Evaluation of Phenolic 2-Methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols


en: Isolation and Structure Elucidation of a Novel Alkaloid, Incartine, a Supposed Biosynthetic Intermediate, from Flowers of Lycoris incarnata


en: One-Pot Synthesis of New 1,3-Imidazolidines Possessing Three Aryl Groups via a 1,3-

en: Heterocycles


en: セフェム系抗生物質のラット脳脊髄腔液移行性に関するQSAR解析

ja: セフェム系抗生物質のラット脳脊髄腔液移行性に関するQSAR解析

en: SAR NEWS

ja: SAR NEWS