合成了一系列茚并[1,2 - b ]吲哚-9,10-二酮衍生物作为人酪蛋白激酶II(CK2)抑制剂。最有效的抑制剂在C环上包含一个N 5-异丙基取代基。发现相同系列的化合物也可以抑制乳腺癌抗性蛋白ABCG2,但具有完全不同的结构-活性关系:N 5-苯乙基取代基很关键,D环的7或8位或在邻或间苯乙基位置的甲氧基也有抑制作用。最好的ABCG2抑制剂,例如4c,4h,4i,4j和4k,作为CK2的非常弱的抑制剂,而最有效的CK2抑制剂,如4a,4p和4e,与ABCG2的相互作用有限。因此,可以通过茚并[1,2 - b ]吲哚-9,10-二酮支架的适当取代,将有效的CK2抑制剂转化为选择性ABCG2抑制剂,反之亦然。另外,一些最好的ABCG2抑制剂表现出非常低的细胞毒性,因此具有很高的治疗率,并且似乎不被转运,构成了有希望进行进一步研究的候选药物。
Due to their system of annulated 6-5-5-6-membered rings, indenoindoles have sparked great interest for the design of ATP-competitive inhibitors of human CK2. In the present study, we prepared twenty-one indeno[1,2-b]indole derivatives, all of which were tested in vitro on human CK2. The indenoindolones 5a and 5b inhibited human CK2 with an IC50 of 0.17 and 0.61 µM, respectively. The indeno[1,2-b]indoloquinone 7a also showed inhibitory activity on CK2 at a submicromolar range (IC50 = 0.43 µM). Additionally, a large number of indenoindole derivatives was evaluated for their cytotoxic activities against the cell lines 3T3, WI-38, HEK293T and MEF.
The Reactions of Group V Metal Amide with Sulfur Dioxide
作者:Fumio Ando、Jugo Koketsu、Yoshio Ishii
DOI:10.1246/bcsj.51.1481
日期:1978.5
Tris(dialkylamino)-arsines (I), -stibines (II), and -bismuthines (III) react with sulfurdioxide to give the corresponding tetraalkylsulfurous diamides and the corresponding metal oxides or polymers containing the metals. The reactivity of these metal amides in view of the fastness of the initial reactions follows the order III>II>I, however, the yields decrease in the order I>II>III. Tris(dialkylamino)phosphines
diethylamine and morpholine with diphenyl, methyl phenyl, ethyl phenyl, and isopropyl phenyl sulfites was studied. It was established that two reactions, substitution and alkylation, can occur in parallel. Diphenyl sulfites react with amines to give only substitution products, while other sulfites react with substitution at the sulfur atom and with alkylation of the amines.