Suzuki T, Nagaoka H, Kondo Y, Takahashi T, Takeuchi M, Hara H, Saito M, Yamada T, Tomioka K, Hamada M, Mase T
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan.
Chem Pharm Bull (Tokyo). 1998 Sep;46(9):1468-73. doi: 10.1248/cpb.46.1468.
Conversion of the 2-(3-pyridyl)thiazolidine part of 1-(3-phenylpropyl)-4-[2-(3-pyridyl)thiazolidine-4-carbonyl]piperazine (YM461), which is a potent platelet-activating factor (PAF) antagonist, to other rings was performed, and PAF antagonistic activities evaluated. The 2-(3-pyridyl)thiazolidine skeleton, which exists as a mixture of cis and trans diastereomers, played an important role in the potency of PAF antagonism. In this study, new effective skeletons were not uncovered, however, 2-(4-pyridyl)thiazolidine-4-carboxamides (1n and 1z) showed potent PAF antagonistic activities equal to the 3-pyridyl derivatives. From the results obtained for 1a, 1a(S), 1g and 1i, a cis-(2R,4R)-2-(3-pyridyl)thiazolidine-4-carboxamide was assumed to be the active configuration for PAF antagonism.
对强效血小板活化因子（PAF）拮抗剂1-(3-苯丙基)-4-[2-(3-吡啶基)噻唑烷-4-羰基]哌嗪（YM461）的2-(3-吡啶基)噻唑烷部分进行了环转化，并对PAF拮抗活性进行了评估。以顺式和反式非对映异构体混合物形式存在的2-(3-吡啶基)噻唑烷骨架在PAF拮抗效力中起重要作用。在本研究中，未发现新的有效骨架，然而，2-(4-吡啶基)噻唑烷-4-羧酰胺（1n和1z）显示出与3-吡啶基衍生物相当的强效PAF拮抗活性。从1a、1a(S)、1g和1i的结果推测，顺式-(2R,4R)-2-(3-吡啶基)噻唑烷-4-羧酰胺是PAF拮抗的活性构型。
