59807-18-0Relevant 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.
Iron-Catalyzed Alkyne-Based Multicomponent Synthesis of Pyrimidines under Air
Chakraborty, Gargi,Guin, Amit Kumar,Mondal, Rakesh,Paul, Nanda D.,Sarkar, Susmita
, p. 13186 - 13197 (2021/10/01)
An iron-catalyzed sustainable, economically affordable, and eco-friendly synthetic protocol for the construction of various trisubstituted pyrimidines is described. A wide range of trisubstituted pyrimidines were prepared using a well-defined, easy to prepare, bench-stable, and phosphine-free iron catalyst featuring a redox-noninnocent tridentate arylazo pincer under comparatively mild aerobic conditions via dehydrogenative functionalization of alcohols with alkynes and amidines.
Metal-free cascade synthesis of unsymmetrical 2-aminopyrimidines from imidazolate enaminones
Cui, Xue,Li, Youbin,Ma, Jianting,Wang, Xuesong,Xu, Junyu,Zeng, Tingting
, p. 24247 - 24253 (2021/07/29)
A convenient metal-free synthesis of unsymmetrical 2-aminopyrimidines from imidazolate enaminones has been developed. In this procedure, various structural 2-aminopyrimidines, as well as 4,5-dihydroisoxazol-5-ols and pyrazoles were synthesized in moderate to excellent yields. A plausible mechanism was also proposed for the cascade reaction. This method represents an effective strategy towards the synthesis of unsymmetrical 2-aminopyrimidines.
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.
Iron Catalyzed Synthesis of Pyrimidines Under Air
Mondal, Rakesh,Sinha, Suman,Das, Siuli,Chakraborty, Gargi,Paul, Nanda D.
supporting information, p. 594 - 600 (2019/12/15)
Herein we report an iron-catalyzed multicomponent dehydrogenative functionalization of alcohols to pyrimidines under atmospheric conditions. Using a well-defined Fe(II)-complex featuring redox noninnocent 2-phenylazo-(1,10-phenanthroline) ligand, as a cat
Ultrasound-mediated synthesis, biological evaluation, docking and in vivo acute oral toxicity study of novel indolin-2-one coupled pyrimidine derivatives
Nikalje, Anna Pratima G.,Tiwari, Shailee V.,Sangshetti, Jaiprakash N.,Damale, Manoj D.
, p. 3031 - 3059 (2018/02/06)
The work reports ultrasound-mediated greener synthesis of 11 novel 3-(4-(4-chlorophenyl)-6-(substituted phenyl/heteryl)pyrimidin-2-ylimino)indolin-2-one (7a–7k) derivatives. The synthesized derivatives were evaluated for their in vitro anticancer activity against a panel of selected human cancer cell lines of breast (MCF-7), cervix (HeLa), prostate (PC-3) and lung (A-549). Among the tested compounds, 7b exhibited most promising in vitro anticancer activity against HeLa, PC-3 and A-549 with GI50 value 15.38, 19.67 and 4.37?μM, respectively. The compounds (7a–7k) were also screened for induction of apoptosis and morphological changes in cancer cells at their GI50 concentration. The treatment of HeLa, PC-3 and A549 cancer cells with 7b and treatment of MCF-7 cancer cells with 7h showed apoptosis and morphological changes such as cell shrinkage, cell wall deformation and reduced number of viable cells. The compound 7b has shown almost 5.00 times more selectivity for PC-3 cancer cell lines in comparison to the RWPE-1 normal prostate epithelial cells. Molecular docking study has been carried out, which replicates results of biological activity in cases of initial hits 7b, 7c and 7d, suggesting that these compounds have a potential to become lead molecules in the drug discovery process. In silico ADMET study was performed for predicting pharmacokinetic properties and toxicity profile of the synthesized compounds and expressed good oral drug-like behaviour. An in vivo acute oral toxicity study was performed using Swiss albino mice for the most active compounds 7b and 7c, and results indicate that the compounds are non-toxic in nature.
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
CsOH/γ-Al2O3: A heterogeneous reusable basic catalyst for one-pot synthesis of 2-amino-4,6-diaryl pyrimidines
Nimkar, Amey,Ramana,Betkar, Rahul,Ranade, Prasanna,Mundhe, Balaji
, p. 2541 - 2546 (2016/03/22)
A new strategy for a one-pot synthesis of 2-amino-4, 6-diaryl pyrimidines using CsOH/γ-Al2O3 as a heterogeneous, reusable basic catalyst is presented. The developed synthetic protocol for pyrimidines is a one-pot three-component reac
One-Pot Three-Component Synthesis of 2-Amino Pyrimidines in Aqueous PEG-400 at Ambient Temperature
Jawale, Dhanaji V.,Pratap, Umesh R.,Bhosale, Manisha R.,Mane, Ramrao A.
, p. 1626 - 1630 (2016/09/23)
Amino pyrimidines have been synthesized by a one-pot procedure under environmentally friendly reaction conditions at room temperature. The use of aqueous PEG-400 circumvents the problems associated with the toxic, hazardous organic solvents and oxidizing agents.
Synthesis, characterization of 4,6-disubstituted aminopyrimidines and their sulphonamide derivatives as anti-Amoebic agents
Siddiqui, Shadab Miyan,Azam, Amir
, p. 2976 - 2984 (2014/05/06)
The present study describes the synthesis and anti-Amoebic activity of 4,6-disubstituted aminopyrimidines (1b-10b) and their sulphonamide derivatives (1-20). All the desired compounds were characterized by spectral data and their purity was confirmed by e
