Scaffold hopping and optimisation of 3',4'-dihydroxyphenyl- containing thienopyrimidinones: synthesis of quinazolinone derivatives as novel allosteric inhibitors of HIV-1 reverse transcriptase-associated ribonuclease H.
Scaffold hopping and optimisation of 3',4'-dihydroxyphenyl- containing thienopyrimidinones: synthesis of quinazolinone derivatives as novel allosteric inhibitors of HIV-1 reverse transcriptase-associated ribonuclease H.
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DOI：
10.1080/14756366.2020.1835884
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发表时间：
2020-12
影响因子：
5.6
通讯作者：
Tramontano E
中科院分区：
文献类型：
--
作者：
Tocco G;Esposito F;Caboni P;Laus A;Beutler JA;Wilson JA;Corona A;Le Grice SFJ;Tramontano E
Bioisosteric replacement and scaffold hopping are powerful strategies in drug design useful for rationally modifying a hit compound towards novel lead therapeutic agents. Recently, we reported a series of thienopyrimidinones that compromise dynamics at the p66/p51 HIV-1 reverse transcriptase (RT)-associated Ribonuclease H (RNase H) dimer interface, thereby allosterically interrupting catalysis by altering the active site geometry. Although they exhibited good submicromolar activity, the isosteric replacement of the thiophene ring, a potential toxicophore, is warranted. Thus, in this article, the most active 2-(3,4-dihydroxyphenyl)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one 1 was selected as the hit scaffold and several isosteric substitutions of the thiophene ring were performed. A novel series of highly active RNase H allosteric quinazolinone inhibitors was thus obtained. To determine their target selectivity, they were tested against RT-associated RNA-dependent DNA polymerase (RDDP) and integrase (IN). Interestingly, none of the compounds were particularly active on (RDDP) but many displayed micromolar to submicromolar activity against IN.
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影响因子：
4.7
作者：
Corona, Angela;Ballana, Ester;Tramontano, Enzo
通讯作者：
Tramontano, Enzo
影响因子：
4.2
作者：
Corona A;Masaoka T;Tocco G;Tramontano E;Le Grice SF
通讯作者：
Le Grice SF
吡咯烷二酮酸衍生物作为HIV-1整合酶双重抑制剂和逆转录酶核糖核酸酶H结构蛋白H结构域的结构活性关系。
影响因子：
7.3
作者：
Cuzzucoli Crucitti G;Métifiot M;Pescatori L;Messore A;Madia VN;Pupo G;Saccoliti F;Scipione L;Tortorella S;Esposito F;Corona A;Cadeddu M;Marchand C;Pommier Y;Tramontano E;Costi R;Di Santo R
通讯作者：
Di Santo R
影响因子：
3.1
作者：
Distinto, Simona;Maccioni, Elias;Tramontano, Enzo
通讯作者：
Tramontano, Enzo
DOI：
10.1007/bf03189993
发表时间：
1998-10-01
影响因子：
1.9
作者：
Dansette, PM;Bonierbale, E;Mansuy, D
通讯作者：
Mansuy, D