Design, synthesis, anti-HIV evaluation and molecular modeling of piperidine-linked amino-triazine derivatives as potent non-nucleoside reverse transcriptase inhibitors

Abstract

A novel series of piperidine-linked amino-triazine derivatives were designed, synthesized and evaluated for in vitro anti-HIV activity as non-nucleoside reverse transcriptase inhibitors on the basis of our previous work. Screening results indicated that most compounds showed excellent activity against wild-type HIV-1 with EC(50) values in low nanomolar concentration range (especially compound 6b3, EC(50) = 4.61 nM, SI = 5945) and high activity against K103N/Y181C resistant mutant strain of HIV-1 with EC(50) values in low micromolar concentration range. In addition, preliminary structure-activity relationship and molecular modeling of these new analogs were detailed in this manuscript.

Ninhydrin in synthesis of heterocyclic compounds

“…[472][473][474] They also show excellent photonic, and electronic properties due to the high electron affinity, and symmetrical structure. The hetero-Diels-Alder reaction of 2-methyl-1-(1-phenylalkoxy)-butadienes containing a chiral center with ninhydrin to afford 1-alkoxy-5,6-dihydro-2H-pyrans 448 proceeds smoothly at room temperature in excellent yield and high diastereoselectivity.…”

3D-QSAR and docking studies on piperidine-substituted diarylpyrimidine analogues as HIV-1 reverse transcriptase inhibitors

“…In the development of this series of compounds, we replaced the core ring with different bioisosteric hexaheterocyclic and phenyl groups, several of which showed inhibition at low nanomolar concentration range against the wild-type HIV-1 as well as low micromolar concentration range against the drug-resistant mutant viruses (Chen et al, 2012a(Chen et al, , b, 2013Zhang et al, 2014). In continuation of our previous work, we built 3D-QSAR models on this series of compounds by CoMFA and CoMSIA methods with two different (substructure-based and docking-based) alignments, aiming at guiding our further work on structure modification and predicting the biological activity of newly designed compounds.…”

Study of new β-lactams-substituted s-triazine derivatives as potential bioactive agents

“…Besides its wellknown antibiotic activity, this ring system exhibits a wide range of activities, attracting the attention of researchers (Chimento et al, 2013;Jaishree et al, 2012;Bhati and Kumar, 2008;Halve et al, 2007). Moreover, s-triazine derivatives have gained great therapeutic importance in the field of medicinal chemistry since they display a fascinating array of pharmacological properties, such as antimicrobial (Patel et al, 2013b), antifungal (Saleh et al, 2010), antibacterial (Patel et al, 2012), anticancer (Kumar et al, 2013), anti-HIV (Chen et al, 2012), anti-inflammatory (Shanmugakala et al, 2014), antimalarial (Ojha et al, 2011), etc. In our continuous effort toward synthesis of bioactive s-triazine derivatives (Patel et al, 2014b), we report the synthesis of various benzonitrile/nicotinonitrile and azetidin-2-one incorporated s-triazine compounds by applying an efficient Pd-catalyzed C-C Suzuki coupling using catalyst system Pd(OAC) 2 , Xphos (2-dicyclohexylphosphino-2 0 ,4 0 ,6 0 -triisopropylbiphenyl), and K 3 PO 4 as a base in toluene solvent. The antimicrobial activity of synthesized compounds has been carried out against two Gram-positive bacteria, three Gram-negative bacteria, and two fungal species.…”