Gangjee et al. recently reported a novel series of 2-amino-4-methyl-5-phenylethyl substituted-7-benzyl-pyrrolo[2,3-d]pyrimidines, some of which exhibited two digit nanomolar antitumor and antimitotic activity and were not subject to P-glycoprotein (Pgp) or multidrug resistance protein 1 (MRP1) mediated tumor resistance (unlike the Vinca alkaloids and taxanes). Some of these compounds, in addition to their antitumor activity, had the ability to reverse the Pgp-mediated resistance to clinically used antimitotic agents. This report consists of an attempt to optimize the various activities of the parent compounds by synthetic variations of the phenyl ring of the 5-phenylethyl side chain. The target compounds were synthesized via a nine-step synthesis involving a Sonogashira reaction. The substituted phenylacetylenes as coupling partners were in turn synthesized from unactivated aryl bromides or iodides. The target compounds exhibited moderate cytotoxicity against MCF-7 tumor cells. However, most of these compounds showed improved cytotoxicity against the resistant NCI/ADR and MCF-7/VP. This study afforded an analog which reversed both Pgp-mediated as well as MRP1-mediated resistance to clinically used antimitotic agents, along with its own antimitotic mediated antitumor activity. In addition, in the NCI-60 cell line panel one of the compounds inhibited the growth of MDA-MD-435 breast cancer cell line at submicromolar concentration.

刚吉等人。最近报道了一系列新的2-氨基-4-甲基-5-苯乙基取代-7-苄基-吡​​咯并[2,3 -d ]嘧啶，其中一些表现出两位数纳摩尔级的抗肿瘤和抗有丝分裂活性，并且不受P -糖蛋白 (Pgp) 或多药耐药蛋白 1 (MRP1) 介导肿瘤耐药性（与长春花生物碱和紫杉烷不同）。其中一些化合物除了具有抗肿瘤活性外，还能够逆转 Pgp 介导的对临床使用的抗有丝分裂剂的耐药性。该报告试图通过 5-苯乙基侧链苯环的合成变化来优化母体化合物的各种活性。通过涉及 Sonogashira 反应的九步合成合成了目标化合物。作为偶联配偶体的取代苯乙炔又由未活化的芳基溴或碘化物合成。目标化合物对 MCF-7 肿瘤细胞表现出中等的细胞毒性。然而，大多数这些化合物对耐药性 NCI/ADR 和 MCF-7/VP 表现出改善的细胞毒性。这项研究提供了一种类似物，可以逆转 Pgp 介导的以及 MRP1 介导的对临床使用的抗有丝分裂药物的耐药性，以及其自身的抗有丝分裂介导的抗肿瘤活性。此外，在 NCI-60 细胞系组中，其中一种化合物在亚微摩尔浓度下抑制 MDA-MD-435 乳腺癌细胞系的生长。