27129-49-3Relevant articles and documents
Identification of (6S)-cyclopropyl-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxamines as new HBV capsid assembly modulators
Lv, Kai,Wu, Shuo,Tao, Zeyu,Wang, Aoyu,Xu, Shijie,Yang, Lu,Gao, Qiang,Wang, Apeng,Qin, Xiaoyu,Jiang, Bin,Wu, Wenhao,Jia, Xuedong,Li, Yuhuan,Jiang, Jiandong,Liu, Mingliang
supporting information, (2021/11/16)
GYH2-18 is a type II HBV CAM with 6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxamine (DPPC) skeleton discovered by Roche INC. A series of GYH2-18 derivatives were designed, synthesized and evaluated for their anti-HBV activity. Two compounds 2f and 3k exhibited excellent anti-HBV activity, low cytotoxicity and accepted oral PK profiles. Chiral separation of 2f and 3k was conducted successfully, and (6S)-cyclopropyl DPPC isomers 2f-1, 2f-3, 3k-1 and 3k-3 were identified to be much more active than the corresponding (6R)-ones. The preliminary structure-activity relationship, particle gel assay and molecular modeling studies were also discussed, which provide useful indications for guiding the further rational design of new (6S)-cyclopropyl DPPC analogues.
Enantioselective Ring-Closing C–H Amination of Urea Derivatives
Zhou, Zijun,Tan, Yuqi,Yamahira, Tatsuya,Ivlev, Sergei,Xie, Xiulan,Riedel, Radostan,Hemming, Marcel,Kimura, Masanari,Meggers, Eric
, p. 2024 - 2034 (2020/07/15)
An enantioselective intramolecular C(sp3)–H amination of N-benzoyloxyurea by using a chiral-at-metal ruthenium catalyst is reported, providing chiral 2-imidazolidinones in yields of up to 99percent and with up to 99percent ee. Catalyst loadings down to 0.05 mol percent are feasible. Control experiments support a stepwise nitrene insertion mechanism through hydrogen atom transfer of a ruthenium nitrenoid intermediate followed by a radical recombination. Chiral 2-imidazolidinones are prevalent in bioactive compounds and can be converted to chiral vicinal diamines in a single step. The synthetic value of the new method is demonstrated for the synthesis of intermediates of the drugs levamisole and dexamisole, the bisindole alkaloids topsentine D and spongotine A, and a chiral organocatalyst. Direct C–H functionalization offers the prospect for streamlined synthesis with high atom economy. In this respect, the transition-metal-catalyzed enantioselective insertion of nitrenoids into prochiral sp3 C–H bonds is a powerful tool for the efficient construction of non-racemic chiral nitrogen-containing molecules. Intramolecular versions have been used to synthesize chiral nitrogen heterocycles, but cyclic urea is still elusive through enantioselective nitrenoid insertion chemistry. Here, we fill this gap and report an enantioselective intramolecular C(sp3)–H amination of N-benzoyloxyurea to provide chiral 2-imidazolidinones in high yields and with high enantioselectivities. The synthetic utility of this new method is illustrated with the catalytic asymmetric synthesis of medicinal agents, natural products, and a chiral organocatalyst. Our work emphasizes the usefulness of transition-metal-controlled asymmetric nitrene chemistry and the importance of tailored catalyst design. Here, we report the first catalytic asymmetric ring-closing C(sp3)–H amination of urea derivatives to construct chiral 2-imidazolidinones, which are prevalent in bioactive compounds and can be converted to chiral vicinal diamines. The simple and mild transformation is catalyzed by a recently developed chiral-at-ruthenium complex in high yields and with high enantioselectivities. Applications to the drugs levamisole and dexamisole, the bisindole alkaloids topsentine D and spongotine A, and a chiral organocatalyst demonstrate the synthetic value of this new method.
5-HT RECEPTOR MODULATORS
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Page/Page column 63, (2011/09/15)
The invention relates to compounds of formula (I), useful for treating disorders mediated by the 5-hydroxytryptamine (serotonin) receptor 1B (5-HT1B), e.g. vascular disorders, cancer and CNS disorders. The invention also provides methods of treating such disorders, and componnds and compositions etc. for their treatment
