2014年1月19日日曜日

薬学愛論その2


☆ Face Book に書いた旧友への 薬学・ナウ。


ボクは高校の時は、1年から3年まで一番勉強したのは生物。
NHKテキストも集めた。化学は 試験のためだけの勉強だったし、化学でメシを食おうとは思わなかった!ボクが薬学に入った70年代は、薬学の生物系は、フォーカスが定まっていなかった。おまけに、薬学4年の時に、微生物の教室に入ることも考えたが、教室配属で女性陣のスクラムが強く、ハジキ飛ばされて合成系へと進んだので、薬品合成化学が修士までの専門になった。後は帝京大でズルズルと 製造化学をやり、大塚では 医薬生産部に属したが、圧倒的に面白かったのは 大塚製薬・医薬生産部での仕事、三度のメシより面白かったし、カラオケも格段にうまくなったよ。
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  • 高崎にきてから、薬物代謝、動態の大先輩に出会ったので 
  • なんとか薬を教えられるようになった。
    6年制薬学は化学の上に、薬理学や病理学という臨床的な 花 が咲くようになった。もはや 創薬研究は薬学部ではできない。薬剤師養成という名の おもてなし教育が主流となった。
  • この辺の6年制薬学・ナウ という憂うべき現状について 原稿を作っています。薬剤師という資格と、メシの種を求めて、医学部と同じお金をつぎ込むようなご時世だから、テンションの高い学生は、医学部へ流れていく。濁流の中の6年制薬学だな。教員も、私の周りに限れば、『薬学部が良くなった『という人は、きわめて少ない。
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  • おまけに、スマホ学習の横行がある。おととし薬学7年生(一期生)のリクエストで薬学ブログを始めた。看護学部の授業では、終りの30分だけ、スマホ解禁にして 自習という名の まとめ を行っている。講義はどこでも、PPT、おまけに PPTを配布資料にしている。これをやると、城報収集力とそれと一番重要な、テイスト即ち、情報選別力がつかない。
  • 誰かの意見や考えに イイネ しいているだけだ。 イイネじゃないね!という力量がないと、医療人としては 不十分だ。医師や看護師に イイネ するだけの薬剤師はイラナイ。

  • 2014年1月18日土曜日

    Imidazole Containing Statins

    The Imidazole-Based Statins



    Abstract Image



    Development work toward an enabling synthesis of preparative scale batches of an imidazole-based HMG-CoA reductase inhibitor is described.

    The desired target was synthesized in 16% yield over 7 steps, highlighted by an imidazole-forming condensation reaction in which the yield was improved from 20% to >70% via modification of the solvent, acid, and amine equivalents. The step 2 acylation was improved, and a problematic benzyl ester in step 4 was converted into the corresponding benzyl amide to decrease trans-amidation during the step 5 imidazole formation. A highly effective salt formation and crystallization protocol was also developed.


    Citing Articles

    Citation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.
    This article has been cited by 2 ACS Journal articles (2 most recent appear below).

    Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles by a Sequential Aza-Wittig/Michael/Isomerization Reaction

    Yi-BoNie, LongWang, and Ming-WuDing
    The Journal of Organic Chemistry2012 77 (1), 696-700
    Carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3 with aryl isocyanates, reacted with secondary amines in the presence of a catalytic amount of sodium alkoxide to give 1,2,4,5-tetrasubstituted imidazoles 7 in good yields.
    • Cover Image

      Development of an Early Enabling Synthesis for PF-03052334-02: A Novel Hepatoselective HMG-CoA Reductase Inhibitor

      Daniel M. Bowles, David C. Boyles, Chulho Choi, Jeffrey A. Pfefferkorn, and Stephanie Schuyler, Edward J. Hessler
      Organic Process Research & Development2011 15 (1), 148-157
      • Development of an Early Enabling Synthesis for PF-03052334-02: A Novel Hepatoselective HMG-CoA Reductase Inhibitor

        Daniel M.Bowles, David C.Boyles, ChulhoChoi, Jeffrey A.Pfefferkorn, and StephanieSchuyler, Edward J.Hessler
        Organic Process Research & Development2011 15 (1), 148-157
        Early process development work toward a promising pyrazole-based HMG-CoA reductase inhibitor is described. PF-03052334-02 (1) was prepared in 14 synthetic steps with a 21% overall yield, highlighted by a modified three-step hydroxypyrazole formation in ...

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    COX-2 Inhibitor: NS-398 and Meloxican



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    Over expression of COX-2 has been implicated in inflammation and reported in a number of human cancers including lung, breast, skin, prostate and colon cancers.183



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    Nonetheless, it has been suggested that COX-2
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    Liang et al.191 reported the downregulation of B7-H1 expression in
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    They showed that COX-2 inhibitors other than nimesulide
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    Furthermore, addition of PG-E2 to IFN-c treated breast cancer cells did not inhibit nimesulidemediated B7-H1 downregulation, which indicated
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    2014年1月13日月曜日

    Glutathione Analogue against Amyloid-β Toxicity


    The antioxidant properties of glutathione (GSH) and their relevance to oxidative stress induced pathological states such as Alzheimer’s disease is well-established.
     
    The utility of GSH itself as a pharmacotherapeutic agent for such disorders is limited because of the former’s lability to breakdown through amide cleavage by the ubiquitous enzyme γ-glutamyl transpeptidase (γ-GT).
     
    In the present study, a GSH analogue, Ψ-GSH, where the γ-glutamylcysteine amide linkage is replaced with a ureide linkage, was synthesized.
     
     
    Ψ-GSH was found to be stable toward γ-GT mediated breakdown. Ψ-GSH fulfilled four cardinal properties of GSH, namely, traversing across the blood brain barrier (BBB) via the GSH active uptake machinery, replacing GSH in the glyoxalase-I mediated detoxification of methylglyoxal, protecting cells against chemical oxidative insult, and finally lowering the cytotoxicity of amyloid-β peptide. These results validate Ψ-GSH as a viable metabolically stable replacement for GSH and establish it as a potential preclinical candidate for treatment of oxidative stress mediated pathology.
     
     

    Abstract Image