Niel N, Rechencq E, Muller A, Vidal J P, Escale R, Durand T, Girard J P, Rossi J C, Bonne C
Laboratoire de Chimie des Mediateurs et Physicochimie des Interactions Biologiques associe au C.N.R.S., Faculte de Pharmacie, Universite Montpellier I, France.
Prostaglandins. 1992 Jan;43(1):45-54. doi: 10.1016/0090-6980(92)90063-y.
Seven new pseudopeptido and thioaromatic leukotriene analogues were synthesized and their agonist-antagonist and binding activities investigated. The synthesis led to the pleasing observation that the analogue in which the cysteinyl-glycine moiety was replaced by a 6-mercapto-3-(E)-hexenoic acid, not only exhibited potent affinity (guinea-pig lung parenchyma, IC50: 5 x 10(-9) M) but also showed 30% of the LTD4 agonist activity (guinea-pig ileum, ED 50: 2.7 x 10(-9)) giving very important key information on LTD4 geometry to the receptor. This compound was the first stable new pseudopeptido-leukotriene with such agonist activity and should contribute to the understanding of the metabolism of leukotriene D4. In addition, inversion of chirality at C5 and C6 carbon atoms of the leukotriene chain or replacement of the cysteinyl-glycine moiety by a thioaromatic acid led to new weak antagonists of the LTD4.
合成了七种新的假肽和硫代芳香族白三烯类似物，并研究了它们的激动剂-拮抗剂和结合活性。合成过程中令人高兴地观察到，半胱氨酰-甘氨酸部分被6-巯基-3-(E)-己烯酸取代的类似物，不仅表现出强大的亲和力（豚鼠肺实质，IC50：5×10(-9) M），而且还显示出30%的LTD4激动剂活性（豚鼠回肠，ED50：2.7×10(-9)），为受体提供了关于LTD4几何结构的非常重要的关键信息。该化合物是首个具有此类激动剂活性的稳定新型假肽白三烯，应有助于对白三烯D4代谢的理解。此外，白三烯链中C5和C6碳原子的手性反转或用硫代芳香酸取代半胱氨酰-甘氨酸部分，导致了新的LTD4弱拮抗剂。
