27129-49-3Relevant academic research and scientific papers
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.
Efficient Amination of Activated and Non-Activated C(sp3)?H Bonds with a Simple Iron–Phenanthroline Catalyst
Jarrige, Lucie,Zhou, Zijun,Hemming, Marcel,Meggers, Eric
supporting information, p. 6314 - 6319 (2021/02/01)
A readily available catalyst consisting of iron dichloride in combination with 1,10-phenanthroline catalyzes the ring-closing C?H amination of N-benzoyloxyurea to form imidazolidin-2-ones in high yields. The C?H amination reaction is very general and applicable to benzylic, allylic, propargylic, and completely non-activated aliphatic C(sp3)?H bonds, and it also works for C(sp2)?H bonds. The surprisingly simple method can be performed under open flask conditions.
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.
An easy one-step synthesis of imidazolin-2-ones from phthalic anhydrides and their antioxidant evaluation
López, Héctor S.,Enciso, José E.,Ochoa-Terán, Adrián,Velazquez, Juan I.,Sarmiento, Juan I.
, p. 69 - 71 (2016/02/12)
Treatment of phthalic anhydride derivatives with trimethylsilyl azide affords benzimidazolin-2-ones in 45-91% yield, which is the result of two consecutive Curtius reactions. Within the series obtained, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one showed highest antioxidant activity.
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
A NEW AND EFFICIENT SYNTHESIS OF 4-ARYLIMIDAZOLIDIN-2-ONES
Rault, Sylvain,Tembo, Olivier N.,Dallemagne, Patrick,Robba, Max
, p. 1301 - 1305 (2007/10/02)
Curtius rearrangement of 3-trifluoroacetylamino-3-arylpropionyl azides gave 4-arylimidazolidin-2-ones via an anchimeric assistance reaction.
Selective Reductions of 3-Substituted Hydantoins to 4-Hydroxy-2-imidazolidinones and Vicinal Diamines
Cortes, Sergio,Kohn, Harold
, p. 2246 - 2254 (2007/10/02)
N3-Substituted hydantoins (1) have been shown to undergo LiAlH4 reduction (THF, room temperature, 2 days) to give 4-hydroxy-2-imidazolidinones (3) in good yields.Reduction of 3,5-disubstituted hydantoins in which an aliphatic substituent was present at nitrogen 3 led to the preferential formation of the cis adduct 3.Conversely, disubstituted hydantoins possessing an aryl moiety at nitrogen 3 gave the trans derivative 3 as the major product.Treatment of the N3-substituted hydantoins (1) under more vigorous conditions (THF, reflux, 3 days) led to selective ring opening of 1 to yield N-methylethylenediamines (7).The scope of both of these reductive processes has been explored, and explanations are offered to account for the observed results.Full spectral (infrared, 1H and 13C NMR, and mass spectra) data on all three classes of compounds (1, 3, and 7) have been collected.Together this information provides a consistent data set which is useful in structure elucidation.Moreover, various NMR aids have been discerned for the isomeric cis- and trans-4-hydroxy-2-imidazolidinones (3) which permitted stereochemical assignments for these compounds.
