616-79-5Relevant articles and documents
The cleavage of heterocyclic compounds in organic synthesis II [1] use of 5-nitroisatine for synthesis of various nitrogenous heterocycles
Hlavac, Jan,Soural, Miroslav,Hradil, Pavel,Frysova, Iveta,Slouka, Jan
, p. 633 - 636 (2004)
The reactions of 5-nitroisatine were studied with nucleophiles like heterocyclic amines and alkaline hydroxide. With the use of alkaline hydroxide it was converted into 2-amino-5-nitrophenylglyoxylic acid 2, with piperidine, morpholine and carbethoxypiperazine to its amides 4a-4c or by oxidation to 5-nitroanthranilic acid 7. This acid was used for synthesis of 3-hydroxy-6-nitro-2-phenyl-1H-quinolin-4-one 10. Semicarbazone of 5-nitroisatine 11 was converted to 5-(2-amino-5-nitrophenyl)-2,3,4,5-tetrahydro-1,2,4- triazine-3,5-dione 12. Cyclocondensation of this compound to afford 8-nitro-2,3-dihydro-5H-[1,2,4]triazino-[5,6-b]indol-3-one 13 was unsuccessful.
Isoxazole formamido-4 (3H)-quinazolinone derivative as well as synthesis method and application thereof
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, (2021/06/06)
The invention relates to a 6-(isoxazolyl-3-formamido)-4 (3H)-quinazolinone derivative as well as a synthesis method and application thereof, belongs to the technical field of medicines, and relates to a general formula (I) in which R1, R2 and R3 are different substituent groups. The invention discloses structures and synthesis methods of the compounds, inhibitory activity of acetylcholin esterase and inhibitory activity of protein tyrosine phosphatase, and the compounds can be further developed into drugs for treating Alzheimer's disease.
Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles
Han, Sheng,Sang, Yali,Wu, Yan,Tao, Yuan,Pannecouque, Christophe,De Clercq, Erik,Zhuang, Chunlin,Chen, Fen-Er
, (2019/11/11)
Molecular hybridization is a powerful strategy in drug discovery. A series of novel diarylbenzopyrimidine (DABP) analogues were developed by the hybridization of FDA-approved drugs etravirine (ETR) and efavirenz (EFV) as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). Substituent modifications resulted in the identification of new DABPs with the combination of the strengths of the two drugs, especially compound 12d, which showed promising activity toward the EFV-resistant K103N mutant. 12d also had a favorable pharmacokinetic (PK) profile with liver microsome clearances of 14.4 μL/min/mg (human) and 33.2 μL/min/mg (rat) and an oral bioavailability of 15.5% in rat. However, its activity against the E138K mutant was still unsatisfactory; E138K is the most prevalent NNRTI resistance-associated mutant in ETR treatment. Further optimizations resulted in a highly potent compound (12z) with no substituents on the phenyl ring and a 2-methyl-6-nitro substitution pattern on the 4-cyanovinyl-2,6-disubstitued phenyl motif. The antiviral activity of this compound was much higher than those of ETR and EFV against the WT, E138K, and K103N variants (EC50 = 3.4, 4.3, and 3.6 nM, respectively), and the cytotoxicity was decreased while the selectivity index (SI) was increased. In particular, this compound exhibited acceptable intrinsic liver microsome stability (human, 34.5 μL/min/mg; rat, 33.2 μL/min/mg) and maintained the good PK profile of its parent compound EFV and showed an oral bioavailability of 16.5% in rat. Molecular docking and structure-activity relationship (SAR) analysis provided further insights into the binding of the DABPs with HIV-1 reverse transcriptase and provided a deeper understanding of the key structural features responsible for their interactions.
Nickel-Catalyzed Regioselective C–H Bond Mono- and Bis-Nitration of Aryloxazolines with tert-Butyl Nitrite as Nitro Source
Wan, Li,Qiao, Kai,Yuan, Xin,Zheng, Ming-Wei,Fan, Bing-Bing,Di, Zhe Chen,Zhang, Dong,Fang, Zheng,Guo, Kai
, p. 2596 - 2604 (2017/08/16)
An efficient and regioselective nickel-catalyzed remote C–H nitration of 2-aryloxazoline amides using the non-corrosive tert-butyl nitrite (TBN) as nitro source has been developed. The protocol makes use of inexpensive nickel salts as catalysts and delivers the corresponding products in excellent yields. Notably, bis-nitration products were obtained by simply increasing the amount of tert-butyl nitrite. This reaction proceeds in air and features excellent functional group compatibility, broad substrate scope and is suitable for gram-scale synthesis. (Figure presented.).