Fretland D J, Widomski D L, Anglin C P, Yu S, Djuric S W
Department of ImmunoInflammatory Diseases Research, Searle Research and Development, Skokie, Illinois 60077.
Chirality. 1992;4(6):353-5. doi: 10.1002/chir.530040605.
Leukotriene B4 (LTB4) is a proinflammatory product of arachidonic acid metabolism that has been implicated in a number of inflammatory diseases. When injected intradermally into the guinea pig, LTB4 has been shown to elicit a dose-dependent infiltration of granulocytes as assessed by the level of the neutrophil marker enzyme myeloperoxidase. SC-41930 [7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-3,4-dihydro-8- propyl-2H-1-benzopyran-2-carboxylic acid] is a potent LTB4 receptor antagonist. When compounds were coadministered along with LTB4 (35 ng) into the dermal site, racemic SC-41930, (+)-SC-41930, and (-)-SC-41930 each inhibited granulocyte accumulation with ED50 values of 340 +/- 30, 98 +/- 5.7, and 1000 +/- 142 ng, respectively; when given intravenously inhibited with ED50 values of 0.5 +/- 0.06, 0.3 +/- 0.04, and 1.4 +/- 0.19 mg/kg, respectively; and when given intragastrically inhibited with ED50 values of 1.7 +/- 0.20, 1.4 +/- 0.23, and 3.0 +/- 0.41 mg/kg, respectively.
白三烯B4（LTB4）是花生四烯酸代谢产生的一种促炎产物，与多种炎症性疾病有关。将LTB4皮内注射到豚鼠体内时，已证明其可引发剂量依赖性的粒细胞浸润，这可通过中性粒细胞标记酶髓过氧化物酶的水平来评估。SC-41930 [7-[3-(4-乙酰基-3-甲氧基-2-丙基苯氧基)丙氧基]-3,4-二氢-8-丙基-2H-1-苯并吡喃-2-羧酸]是一种强效的LTB4受体拮抗剂。当将化合物与LTB4（35 ng）共同给药至皮肤部位时，外消旋SC-41930、(+)-SC-41930和(-)-SC-41930均可抑制粒细胞聚集，其半数有效剂量（ED50）值分别为340±30、98±5.7和1000±142 ng；静脉给药时，其ED50值分别为0.5±0.06、0.3±0.04和1.4±0.19 mg/kg；胃内给药时，其ED50值分别为1.7±0.20、1.4±0.23和3.0±0.41 mg/kg。
