Kawashima Y, Sato M, Yamamoto S, Shimazaki Y, Chiba Y, Satake M, Iwata C, Hatayama K
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Chem Pharm Bull (Tokyo). 1995 Jul;43(7):1132-6. doi: 10.1248/cpb.43.1132.
We have recently reported that 4-[2-(4-substituted phenylsulfonylamino) ethylthio]phenoxyacetic acids and related compounds showed potent thromboxane A2 (TXA2) receptor antagonist activity. To understand how substituents affect the biological activity, the quantitative structure-activity relationship (QSAR) was analyzed by using the Hansch-Fujita method for 36 compounds, including newly synthesized compounds. The positive coefficient for pi R and FR in the results of the QSAR study suggested that a hydrophobic an sigma electron-withdrawing substituent R at the para-position of the phenylsulfonyl moiety is required to improve the activity. Further, a substituent R which is long and moderately wide, was suggested to be preferable for the activity. The positive coefficients for pi X,Y,W-COOH and sigma Q(1)-(6) may indicate that the introduction of a hydrophobic and electron-withdrawing group on the benzene ring of the phenoxy acetic acid moiety enhances the activity. The length of the W-COOH moiety may also be important. On the other hand, the effect of the presence of methylene (n = 1) was not clear.
我们最近报道，4-[2-(4-取代苯磺酰氨基)乙硫基]苯氧基乙酸及相关化合物表现出强效血栓素A2（TXA2）受体拮抗活性。为了解取代基如何影响生物活性，采用Hansch-Fujita方法对包括新合成化合物在内的36种化合物进行了定量构效关系（QSAR）分析。QSAR研究结果中πR和FR的正系数表明，苯磺酰基部分对位需要一个疏水且吸电子的取代基R来提高活性。此外，对于活性而言，一个长且宽度适中的取代基R被认为是优选的。πX、Y、W-COOH和σQ(1)-(6)的正系数可能表明，在苯氧基乙酸部分的苯环上引入疏水且吸电子基团可增强活性。W-COOH部分的长度可能也很重要。另一方面，亚甲基（n = 1）存在的影响尚不清楚。
