Snader K M, Chakrin L W, Cramer R D, Gelernt Y M, Miao C K, Shah D H, Venslavsky J W, Willis C R, Sutton B M
J Med Chem. 1979 Jun;22(6):706-14. doi: 10.1021/jm00192a018.
Condensation of 3,5-diacylpyrantriones with various aromatic amines gave a new class of potent, orally active, antiallergic compounds, the 3-[(arylamino)ethylidene]-5-acylpyrantriones, hereafter referred to as pyranenamines, as evaluated not only in the traditional rat passive cutaneous anaphylaxis (PCA) assay but also in the in vitro fragmented rat and primate lung assay. Potencies in the PCA system, when measured intravenously, reached a maximum ID50 of 0.9 mu/kg (1000 times more potent than disodium chromoglycate) with 5-acetyl-4-hydroxy-3-[1-[(3,5-bis-glyceramoylphenyl)amino]ethylidene]-2H-pyran-2,6(3H)-dione (100), as predicted by structure-activity relationship (SAR) analysis. Potencies in the iv PCA system correlated well with potencies in the in vitro rat lung system but not with potencies in the oral PCA system or the in vitro primate lung system. Several compounds had good oral potency, and one analogue, 3-acetyl-4-hydroxy-3-[1-[3-amino-4-hydroxyphenyl)amino]ethylidene]-2H-pyran-2,6(3H)-dione hydrochloride (78), reached an oral ID50 of less than 1 mg/kg and was better than 10 times more effective than disodium chromoglycate at inhibiting the release of histamine and slow-reacting substance of anaphylaxis in the fragmented primate lung assay.
3,5 - 二酰基吡喃三酮与各种芳香胺缩合得到了一类新型的强效、口服活性抗过敏化合物，即3 - [(芳基氨基)亚乙基]-5 - 酰基吡喃三酮，以下简称吡喃烯胺。这类化合物不仅在传统的大鼠被动皮肤过敏反应（PCA）试验中得到评估，还在体外大鼠和灵长类动物肺碎片试验中进行了评估。在PCA系统中，静脉注射时，5 - 乙酰基 - 4 - 羟基 - 3 - [1 - [(3,5 - 双甘油酰胺基苯基)氨基]亚乙基]-2H - 吡喃 - 2,6(3H)-二酮（100）的效力达到最大ID50为0.9μg/kg（比色甘酸钠强1000倍），这是通过构效关系（SAR）分析预测的。静脉注射PCA系统中的效力与体外大鼠肺系统中的效力相关性良好，但与口服PCA系统或体外灵长类动物肺系统中的效力无关。几种化合物具有良好的口服效力，其中一种类似物，3 - 乙酰基 - 4 - 羟基 - 3 - [1 - [(3 - 氨基 - 4 - 羟基苯基)氨基]亚乙基]-2H - 吡喃 - 2,6(3H)-二酮盐酸盐（78），口服ID50小于1mg/kg，在体外灵长类动物肺碎片试验中，其抑制组胺和过敏反应慢反应物质释放的效果比色甘酸钠好10倍以上。
