A series of 6-aralkyl substituted 2,4-diaminothieno[2,3-d]pyrimidines in which the 6-aryl group is separated from the thieno[2,3-d]pyrimidine ring by two to five methylene groups were synthesized and studied as inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and rat liver. Compounds in which the thieno[2,3-d]pyrimidine ring is separated from the 6-aryl substituent by three methylene groups were the most potent inhibitors of the series (with IC(50) values ranging from 0.24 and 11.0 microM) but those with two methylene groups between the aromatic rings were the most selective agents.

中文翻译：

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一系列6-取代的2,4-二氨基噻吩并[2,3-d]嘧啶的合成及DHFR抑制活性。

合成了一系列6-芳烷基取代的2,4-二氨基噻吩并[2,3-d]嘧啶，其中6-芳基与噻吩并[2,3-d]嘧啶环被2至5个亚甲基隔开，并用作卡氏肺孢子虫，弓形虫，鸟分枝杆菌和大鼠肝脏中二氢叶酸还原酶的抑制剂。噻吩并[2,3-d]嘧啶环与6-芳基取代基被三个亚甲基隔开的化合物是该系列中最有效的抑制剂（IC（50）值为0.24至11.0 microM），但这些抑制剂在芳环之间具有两个亚甲基的化合物是最具选择性的试剂。