3262-03-1Relevant articles and documents
Discovery and Characterization of Potent Pan-Genotypic HCV NS5A Inhibitors Containing Novel Tricyclic Central Core Leading to Clinical Candidate
Ramdas, Vidya,Talwar, Rashmi,Banerjee, Moloy,Joshi, Advait Arun,Das, Amit Kumar,Walke, Deepak Sahebrao,Borhade, Prashant,Dhayagude, Usha,Loriya, Rajesh,Gote, Ganesh,Bommakanti, Apparao,Sivaram, Aruna,Agarwal, Gautam,Goswami, Arnab,Nigade, Prashant,Mehta, Maneesh,Patil, Vinod,Modi, Dipak,Kumar, Hemant,Mallurwar, Sadanand,Dash, Amruta,Modi, Falguni,Kuldharan, Sandip,Srivastava, Pratima,Singh, Minakshi,Narasimham, Lakshmi,Gundu, Jayasagar,Sharma, Sharad,Kamboj, Rajender Kumar,Palle, Venkata P.
, p. 10563 - 10582 (2019)
The identification of a novel class of potent pan-genotypic NS5A inhibitors with good pharmacokinetic profile suitable for potential use in treating HCV infections is disclosed here. The present series of compounds are with less complex tricyclic central core, identified through a systematic SAR study carried out on biphenyl moiety. The SAR outcome has confirmed the requirement of near planar and linear conformation of the molecule to achieve the best pan-genotypic activity. In addition, SAR with substituted imidazoles on improvement of antiviral activity is disclosed. The newly identified compounds 12, 16, 19-21 have shown desirable pharmacokinetic profiles with a favorable uptake of compounds in liver and maintained a significant concentration for up to 8 h in the liver. In addition, compounds 20 and 21 have shown superior pan-genotypic anti-HCV activity compared to ledipasvir and daclatasvir. Additional characterization and preliminary safety assessment resulted in the identification of compound 20 as a potential clinical candidate.
Synthesis of amides from (E)-3-(1-chloro-3,4-dihydronaphthalen-2-yl)acrylic acid and substituted amino acid esters as NorA efflux pump inhibitors of Staphylococcus aureus
Rath, Santosh K.,Singh, Samsher,Kumar, Sunil,Wani, Naiem A.,Rai, Rajkishor,Koul, Surrinder,Khan, Inshad A.,Sangwan, Payare L.
, p. 343 - 353 (2019)
Inhibitors for NorA efflux pump of Staphylococcus aureus have attracted the attention of many researchers towards the discovery and development of novel efflux pump inhibitors (EPIs). In an attempt to find specific potent inhibitors of NorA efflux pump of S. aureus, a total of 15 amino acid conjugates of 3-(1-chloro-3,4-dihydronaphthalen-2-yl)acrylic acid (4–18) were synthesized using a simple convenient synthetic approach and bioevaluated against NorA efflux pump. Two compounds 7 and 8 (each having MEC of 1.56 μg/mL) were found to restore the activity of ciprofloxacin through reduction of the MIC elucidated by comparing the ethidium bromide efflux in dose dependent manner in addition to ethidium bromide efflux inhibition and accumulation study using NorA overexpressing strain SA-1199B. Most potent compounds among these were able to restore the antibacterial activity of ciprofloxacin completely against SA-1199B. Structure activity relationship (SAR) studies and docking study of potent compounds 7 and 8 could elucidate the structural requirements necessary for interaction with the NorA efflux pumps. On the whole, compounds 7 and 8 have ability to reverse the NorA efflux mediated resistance and could be further optimized for development of potent efflux pump inhibitors.
Photoactuators based on the dynamic molecular crystals of naphthalene acrylic acids driven by stereospecific [2+2] cycloaddition reactions
Liu, Jiaxi,Ye, Kaiqi,Shen, Yanbing,Peng, Jiang,Sun, Jingbo,Lu, Ran
supporting information, p. 3165 - 3175 (2020/03/19)
The photomechanical effects of the dynamic molecular crystals of halogen-substituted naphthalene acrylic acids (1FNaAA, 1ClNaAA, 1BrNaAA, 1INaAA and 6BrNaAA) have been investigated. Upon UV irradiation, the needle-like crystal of 1FNaAA curls away from the light source, while the slice-like crystal of 6BrNaAA bends towards the light source. Moreover, the light-induced bending, flipping and bursting are observed for the elongated needle-like crystals of 1FNaAA, and the slice-like crystals of 1ClNaAA and 1BrNaAA show bending, cracking, coiling, rotating and twisting triggered by 365 nm light. It is found that stereospecific [2+2] cycloaddition reactions take place in the crystals to afford one stereoisomer of β-type cyclobutanes, since 1FNaAA, 1ClNaAA, 1BrNaAA and 6BrNaAA pack in a head-to-head mode, which satisfies the Schmidt's topo-photochemical criteria. The strain can be generated and accumulated during the photodimerization, and the release of the strain leads to the photomechanical effects. This provides new clues for the development of photomechanical molecular crystals based on acrylic acids bearing halogen-substituted aromatic units.
Two-Step Synthesis of 3,4-Dihydropyrrolopyrazinones from Ketones and Piperazin-2-ones
Sandoval, Cosme,Lim, Ngiap-Kie,Zhang, Haiming
, p. 1252 - 1255 (2018/02/22)
An expedient two-step synthesis of 3,4-dihydropyrrolopyrazinones has been achieved via a Vilsmeier-Haack reaction of ketones, followed by an annulation of the corresponding chloroaldehydes with commercially available piperazin-2-ones. A variety of cyclic and acyclic ketones and piperazin-2-ones participated in this two-step chemistry, affording the desired 3,4-dihydropyrrolopyrazinones in up to 78% yield.
