Structure-activity relationships for antiplasmodial activity among 7-substituted 4-aminoquinolines
Structure-activity relationships for antiplasmodial activity among 7-substituted 4-aminoquinolines
复制标题
DOI：
10.1021/jm980146x
复制
发表时间：
1998-12-03
影响因子：
7.3
通讯作者：
Krogstad, DJ
中科院分区：
文献类型：
--
作者：
De, DYD;Krogstad, FM;Krogstad, DJ
二氨基烷烃侧链（-HNRNEt2）比氯喹的异戊基侧链[-HNCHMe(CH2)(3)NEt2]短或长的氨基喹啉（AQs）对氯喹敏感和耐药恶性疟原虫都有活性。De， D.；等。点。j .太多。医学卫生杂志，1996,55,579-583)。在本文报道的研究中，我们研究了氯喹中具有不同N，N-二乙基二氨基烷烃侧链和不同取代基的AQs之间的构效关系（sar）。具有二氨基烷烃侧链的7-碘-和7-溴- aqs [- hn (CH2)(2)NEt2, - hn (CH2)(3)NEt2，或- hnchmech2net2]对氯喹敏感和耐药恶性疟原虫（IC(50)s为3-12 nM）的活性与相应的7-氯- aqs相同。相比之下，除了一个例外，7-氟- aqs和7-三氟甲基- aqs对氯喹敏感的恶性疟原虫（IC(50)s为15-50 nM）的活性较低，对氯喹耐药的恶性疟原虫（IC(50)s为18-500 nM）的活性较低。大多数7-OMe-AQs对氯喹敏感型（IC(50)s为17 ~ 150 nM）和耐药型恶性疟原虫（IC(50)s为90 ~ 3000 nM）均无活性。
Aminoquinolines (AQs) with diaminoalkane side chains (-HNRNEt2) shorter or longer than the isopentyl side chain [-HNCHMe(CH2)(3)NEt2] of chloroquine are active against both chloroquine-susceptible and -resistant Plasmodium falciparum. (De, D.; et al. Am. J. Trop. Med. Hyg. 1996, 55, 579-583). In the studies reported here, we examined structure-activity relationships (SARs) among AQs with different N,N-diethyldiaminoalkane side chains and different substituents at the 7-position occupied by Cl in chloroquine. 7-Iodo- and 7-bromo-AQs with diaminoalkane side chains [-HN(CH2)(2)NEt2, -HN(CH2)(3)NEt2, or -HNCHMeCH2NEt2] were as active as the corresponding 7-chloro-AQs against both chloroquine-susceptible and -resistant P. falciparum (IC(50)s of 3-12 nM). In contrast, with one exception, 7-fluoro-AQs and 7-trifluoromethyl-AQs were less active against chloroquine-susceptible P. falciparum (IC(50)s of 15-50 nM) and substantially less active against chloroquine-resistant P. falciparum (IC(50)s of 18-500 nM). Furthermore, most 7-OMe-AQs were inactive against both chloroquine-susceptible (IC(50)s of 17-150 nM) and -resistant P. falciparum (IC(50)s of 90-3000 nM).