Wichrowski B, Jouquey S, Broquet C, Heymans F, Godfroid J J, Fichelle J, Worcel M
Laboratoire de Pharmacochimie Moléculaire, Université Paris, France.
J Med Chem. 1988 Feb;31(2):410-5. doi: 10.1021/jm00397a025.
The synthesis and biological characterization of some 3-carboxylate isosteres of PAF-acether structurally modified in positions 1 (ether, carbamate), 2 (acetoyl, ethoxy), and 3 (chain length and polar head group) are reported. All derivatives present antagonist activities against PAF-acether-induced effects in vitro (platelet aggregation) and in vivo (bronchoconstriction and thrombocytopenia in guinea pig and, to a lesser extent, hypotension in rat). The functional modifications presented here do not modify dramatically the potency of antagonist activities, and there is no enantioselectivity. All of the isosteres are specific PAF-acether antagonists, except the 1-carbamoyl analogue, which is also potent against acetylcholine-induced hypotension and bronchoconstriction.
报道了一些在1位（醚、氨基甲酸酯）、2位（乙酰基、乙氧基）和3位（链长和极性头部基团）进行结构修饰的PAF-乙醚3-羧酸酯类似物的合成及生物学特性。所有衍生物在体外（血小板聚集）和体内（豚鼠支气管收缩和血小板减少，以及在较小程度上大鼠低血压）均表现出对PAF-乙醚诱导效应的拮抗活性。本文呈现的功能修饰并未显著改变拮抗活性的效力，且不存在对映体选择性。除1-氨基甲酰基类似物外，所有类似物均为特异性PAF-乙醚拮抗剂，该1-氨基甲酰基类似物对乙酰胆碱诱导的低血压和支气管收缩也有强效作用。
