依西美坦衍生物——芳香酶抑制作用的合成与评价
[Derivatives of exemestane--synthesis and evaluation of aromatase inhibition].
作者信息
Görlitzer K, Bonnekessel Ch, Jones P G, Palusczak A, Hartmann R W
机构信息
Institut für Pharmazeutische Chemie' Analytische Chemie der Technischen Universität Braunschweig, Germany.
出版信息
Pharmazie. 2006 Jul;61(7):575-81.
The irreversible aromatase inhibitor exemestane (6) reacts with nitromethane and sodium ethanolate to yield the Michael adduct 9. The aldehyde 10 is obtained by Nef reaction of the nitro compound 9 and affords the 1,4-dihydropyridine (DHP) 11 by Hantzsch reaction using methyl beta-aminocrotonate in acetic acid. The new compounds showed a reduced inhibitory potency towards aromatase (IC50 values: 9, 0.91 microM; 10, 2.5 microM; 11, 10 microM) compared to 6 (IC50 = 0.23 microM). The 1,4-DHP 11 was dehydrogenated with CAN or electrochemically (E1/2 =1.18 V) to yield the corresponding pyridine 12.
不可逆芳香酶抑制剂依西美坦（6）与硝基甲烷和乙醇钠反应生成迈克尔加成物9。通过硝基化合物9的内夫反应得到醛10，并在乙酸中使用β-氨基巴豆酸甲酯通过汉茨希反应得到1,4-二氢吡啶（DHP）11。与6（IC50 = 0.23 μM）相比，新化合物对芳香酶的抑制效力降低（IC50值：9，0.91 μM；10，2.5 μM；11，10 μM）。1,4-DHP 11用CAN脱氢或通过电化学方法（E1/2 = 1.18 V）脱氢生成相应的吡啶12。
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