日本岐阜药科大学访问团学术报告通知


报告题目:

1.“Big data analytics and pharmacovigilance: a retrospective study using spontaneous reporting system databases”

Dr. Mitsuhiro NAKAMURA, Prof.,

Lab. Drug Informatics

2.“Fluorescence Imaging of Fe(II) ion by small molecules: from molecular design to application”

Dr. Tasuku HIRAYAMA, Assoc. Prof.,

Lab. Pharmaceutical and Medicinal Chemistry

3.“Synthesis of Cyclic Ethynyl-λ3-iodane: N-Functionalization of Amino Acid Derivatives”

Dr. Norihiro TADA, Lecturer,

Lab. Pharmaceutical Synthetic Chemistry

报告时间:2019912(周四)15:30-17:00

报告地点:江宁校区多功能厅

报告摘要:

1.“Big data analytics and pharmacovigilance: a retrospective study using spontaneous reporting system databases”

  

Abstract:Spontaneous reporting systems (SRSs) have been recognized as primary tools for pharmacovigilance that reflect the realities of clinical practice. We analyzed the association of age, sex, and dosage with licorice-associated pseudoaldosteronism by using the Japanese Adverse Drug Event Report (JADER) database. Pseudoaldosteronism was reported frequently in female patients over the age of 50 years. The reporting odds ratios (RORs) (95% confidence interval) for doses of <2.5 g, 2.5–4.9 g, and ≥5 g were 20.9 (15.1–28.8), 26.1 (15.1–45.0), and 147.3 (150.3–206.0), respectively. These findings indicated that licorice dosage may be associated with pseudoaldosteronism.

Drug-induced photosensitivity (DIP) refers to the development of cutaneous disorders caused by the combined effects of different medications and light. Losartan/hydrochlorothiazide (HCTZ), valsartan/HCTZ, and ketoprofen should be used carefully in clinical practice to avoid DIP. For time-to-onset analysis, the median durations (interquartile range) for DIP caused by losartan/HCTZ, valsartan/HCTZ, and ketoprofen were 56 (41–78), 49 (38–88), and 8 (2–14) days, respectively. The seasonal variation of photosensitivity reactions was shown to follow an annual sinusoidal pattern with a peak in April and May. Despite the limitations inherent to SRS,the SRS is a rich resource and data mining indices provide a powerful means of identifying potential associations between drugs and adverse events.

  

  

2.“Fluorescence Imaging of Fe(II) ion by small molecules: from molecular design to application”

  

Abstract: Iron (Fe) is the most abundant transition metal in our body and plays various essential roles. The functions of Fe ion in our body range from oxygen transport to enzymatic reactions, most of which depend on the redox activity of Fe ion. The active redox property of Fe ion often causes cellular damages through an aberrant production of highly reactive oxygen species such as hydroxyl radical. Fe(II) ion rather than Fe(III) ion is the dominant redox state of labile Fe species in living cells due to an abundance of intracellular reductants.  In parallel, Fe(II) ion is a major reactant to produce the highly reactive oxygen species, which readily damage biomolecules such as DNA, proteins, and lipids. Thus, our group focus on the selective detection of Fe(II) ion in living cells to study the relationships between diseases and cellular homeostasis of iron. We established N-oxide chemistry as Fe(II)-responsive molecular switch and developed several fluorescent probes that show selective fluorescence turn-on in response to Fe(II) ion. In this seminar, the principle, design strategy, and the applications of our fluorescent sensor molecules will be presented.

  

3.“Synthesis of Cyclic Ethynyl-λ3-iodane: N-Functionalization of Amino Acid Derivatives”

  

Abstract: Amino acids have been broadly used as pharmaceuticals, agrochemicals, and chemical biology tools. For further application of amino acid derivatives, development of regio- and stereocontrolled amino acid-derived building brocks are desirable. For achieving the objective, we studied in the synthesis of very reactive hypervalent iodine compounds and N-functionalization of amino acids to give the reactive building blocks such as ynamide and enamide derivatives. The synthesis of a crystalline ethynyl benziodoxolone (EBX)−acetonitrile complex and N-ethynylation of a variety of sulfonamides including sterically demanding acyclic amino acid derivatives under mild reaction conditions are achieved. X-ray crystallography revealed the interesting structure of the EBX−acetonitrile complex. The synthesis of cis-β-amidevinyl benziodoxolone (VBX) from highly reactive EBX and sulfonamides is also achieved. These new compounds have the potential for the synthesis of various useful amino acid derivatives.

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