Brubaker A N, DeRuiter J, Whitmer W L
J Med Chem. 1986 Jun;29(6):1094-9. doi: 10.1021/jm00156a031.
A number of 4,7-disubstituted benzopyran-2-ones were synthesized and evaluated for crude rat lens aldose reductase inhibitory activity. Substituents on position 4 included CH3, CO2H, CH2CO2H, CH = CHCO2H, and CH2CH2CO2H. The aromatic substituents included OH, OCH3, OCOCH3, CH2CH3, and Cl. Also included in the study were 3-oxo-3H-naphtho[2,1-b]pyran-1-acetic, 2-oxo-2H-naphtho[1,2-b]pyran-4-acetic, and 1-naphthylacetic acids. The benzopyran and naphthopyran derivatives were prepared by the classical von Pechmann reaction. General structure-activity relationships reveal that optimal enzyme inhibitory activity is displayed by those compounds possessing the acetic acid moiety. For example, the most potent derivative, 3-oxo-3H-naphtho[2,1-b]pyran-1-acetic acid with an IC50 of 0.020 microM, is as potent as sorbinil (IC50 = 0.017 microM) in the crude rat lens aldose reductase assay.
合成了多种4,7 - 二取代苯并吡喃 - 2 - 酮，并对其进行了大鼠晶状体醛糖还原酶抑制活性的评估。4位上的取代基包括CH3、CO2H、CH2CO2H、CH = CHCO2H和CH2CH2CO2H。芳环取代基包括OH、OCH3、OCOCH3、CH2CH3和Cl。该研究还包括3 - 氧代 - 3H - 萘并[2,1 - b]吡喃 - 1 - 乙酸、2 - 氧代 - 2H - 萘并[1,2 - b]吡喃 - 4 - 乙酸和1 - 萘乙酸。苯并吡喃和萘并吡喃衍生物通过经典的冯·佩希曼反应制备。一般构效关系表明，具有乙酸部分的那些化合物表现出最佳的酶抑制活性。例如，最有效的衍生物3 - 氧代 - 3H - 萘并[2,1 - b]吡喃 - 1 - 乙酸，IC50为0.020微摩尔，在大鼠晶状体醛糖还原酶粗酶检测中与索比尼尔（IC50 = 0.017微摩尔）效力相当。
