63500-32-3Relevant academic research and scientific papers
Design, synthesis and evaluation of 2,4,6-substituted pyrimidine derivatives as BACE-1 inhibitor: Plausible lead for alzheimer’s disease
Jadhav, Hemant R.,Jain, Priti,Wadhwa, Pankaj K.
, p. 1194 - 1206 (2021/12/21)
Alzheimer’s disease is one of the most common neurodegenerative disorder afflicting a large mass of population. BACE-1 (β-secretase) is an aspartyl protease of the amyloidogenic pathway considered responsible for Alzheimer’s disease (AD). Since it catalyzes the rate-limiting step of Aβ-42 production from amyloid precursor protein (APP), its inhibition is considered a viable thera-peutic strategy. We have reported the design of small molecular weight compounds supposed to be blood brain permeable as BACE-1 inhibitors. The clue for the design of this series is drawn from the previously designed series from our research group. Objective: Design and synthesis of 2,4,6-substituted pyrimidine derivatives has been reported. In vitro FRET-based screening of synthesized derivatives was performed to evaluate the BACE-1 inhibition profile. Methods: Based on the docking simulation studies, a library of derivatives was designed, synthesized and evaluated for BACE-1 inhibition in-vitro. The docking studies were performed on Glide (Schrodinger suite) and Molegro virtual docker. Theoretical toxicity was predicted using Osiris Property Explorer. The synthesized compounds were tested for BACE-1 inhibition using in vitro assay based on Fluorescence Resonance Energy Transfer technique. The percent inhibition was cal-culated as a measure of activity. Results: The designed compounds revealed strong interactions with the desired amino acids of BACE-1 active sites. The aromatic rings placed at the fourth and sixth position of the pyrimidine ring occupied S1 and S3 substrate-binding clefts while the amino group formed hydrogen bonding interactions with Asp32 and Asp228. In silico data ensured that the compounds were orally bioavailable and brain permeable. The in vitro testing showed that the compounds inhibited BACE-1 at 10μM concentration. Conclusion: Compounds substituted with m-benzyloxy on one aromatic ring and o,p-di-chloro on another aromatic ring displayed maximum BACE-1 inhibition. Compound 2.13A displayed high docking score and was found to be most potent with IC50 of 6.92μM. The series displayed a good correlation between the docking score and BACE-1 inhibition profile.
Photocatalytic synthesis of 2-amino-4,6-diarylpyrimidines using nanoTiO2
E. P., Aparna,K. S., Devaky,Mathew, Divya,N, Rakesh,Thomas, Ashly
, (2020/06/05)
Photocatalytic synthesis of 2-amino-4,6-diarylpyrimidines was carried out by using nano TiO2. The method follows a green route by avoiding the use of toxic organic solvents and tedious experimental conditions. Compared with conventional methods the present strategy offers excellent yield under UV irradiation for a period of 20 min in ethanolic medium. Only a small quantity of nanocatalyst (1 mol%) is sufficient to achieve the completion of the reaction. The nanocatalyst can be reused up to four reaction cycles without much loss in the activity.
Secondary amines immobilized inside magnetic mesoporous materials as a recyclable basic and oxidative heterogeneous nanocatalyst for the synthesis of trisubstituted pyrimidine derivatives
Aryan, Reza,Beyzaei, Hamid,Nojavan, Masoomeh,Dianatipour, Tahereh
, p. 4417 - 4431 (2016/07/06)
A novel magnetic MCM-41 nanocomposite-based catalyst is reported for the first time in the multicomponent synthesis of trisubstituted pyrimidines in which piperazine is immobilized inside the mesochannels of magnetic MCM-41 as an organic base (α-Fe2
Synthesis, characterization, and anti-amoebic activity of N-(pyrimidin-2-yl)benzenesulfonamide derivatives
Roouf Bhat, Abdul,Arshad, Mohammad,Ju Lee, Eun,Pokharel, Smritee,Choi, Inho,Athar, Fareeda
, p. 2267 - 2277 (2014/01/06)
A new series of N-(pyrimidin-2-yl)benzenesulfonamide derivatives, 3a-3i and 4a-4i, was synthesized from pyrimidin-2-amines, 2a-2i, with the aim to explore their effects on in vitro growth of Entamoeba histolytica. The chemical structures of the compounds
Synthesis and characterization of some new 2-amino-4-(4′-substituted) -6-(4″-substituted)diphenyl pyrimidines
Hasan, Aurangzeb,Khaleeq, Musfirah,Riaz, Uzma
, p. 5581 - 5587 (2012/08/07)
Synthesis and characterization of some novel 2-amino-4-(4′- substituted)-6-(4″-substituted)diphenyl pyrimidines has been carried out by the conversion of variably substituted acetophenones and benzaldehydes into corresponding chalcones followed by cyclization with guanidine hydrochloride in the presence of an oxidizing agent.
Reaction of α,β-Unsaturated Ketones with Guanidine. Substituent Effects on the Protonation Constants of 2-Amino-4,6-diarylpyrimidines
Al-Hajjar, Farouk H.,Sabri, Salim S.
, p. 1087 - 1092 (2007/10/02)
1.3-Diaryl-2-propen-1-ones, I, reacted with guanidine hydrochloride (II) in the presence of 3 moles of sodium hydroxide to give the corresponding 2-amino-4,6-diarylpyrimidines, III.The structure and configuration of the products are based on chemical and
