Ku T W, McCarthy M E, Weichman B M, Gleason J G
J Med Chem. 1985 Dec;28(12):1847-53. doi: 10.1021/jm00150a016.
A series of structural analogues of 4(R)-hydroxy-5(S)-cysteinylglycyl-6(Z)-nonadecenoic acid [4R,5S,6Z)-2-nor-LTD1 (10b), SK&F 101132) has been synthesized and pharmacologically characterized. (4R,5S,6Z)-2-nor-LTD1 significantly antagonized LTD4-induced contractile responses on isolated guinea pig trachea. The cis double-bond geometry appears to be critical for antagonist activity, whereas the trans isomer 17 exhibited weak contractile activity. Replacement of the cysteinylglycyl moiety with cysteine afforded 20, which retained significant antagonist activity, while lengthening or shortening the lipid tail by five methylene groups resulted in complete loss of activity. The eicosanoid amide 15, glycinamide 14, and C-1 carbinol 18 analogues all possessed antagonist activity, whereas the diol derivative 19 exhibited increased intrinsic agonist activity.
已合成并对4(R)-羟基-5(S)-半胱氨酰甘氨酰-6(Z)-十九碳烯酸[4R,5S,6Z)-2-去甲-LTD1(10b)，SK&F 101132]的一系列结构类似物进行了药理学表征。(4R,5S,6Z)-2-去甲-LTD1能显著拮抗LTD4对离体豚鼠气管的收缩反应。顺式双键构型似乎是拮抗剂活性的关键，而反式异构体17表现出较弱的收缩活性。用半胱氨酸取代半胱氨酰甘氨酰部分得到20，其保留了显著的拮抗剂活性，而脂质尾延长或缩短五个亚甲基则导致活性完全丧失。类二十烷酰胺15、甘氨酰胺14和C-1甲醇18类似物均具有拮抗剂活性，而二醇衍生物19表现出增强的内在激动剂活性。
