19371-31-4Relevant academic research and scientific papers
Modification of the lead molecule: Tryptophan and piperidine appended triazines reversing inflammation and hyeperalgesia in rats
Kumari, Priya,Kaur, Sukhmeet,Kaur, Jashanpreet,Bhatti, Rajbir,Singh, Palwinder
, (2020)
The structural optimization of the molecules making them to fit into the active site pocket of COX-2 occupying the same space as covered by the natural substrate arachidonic acid helped in the emergence of compound 10 as an efficacious anti-inflammatory a
Enantioseparation of amino acids and amino alcohols on a chiral stationary phase derived from L-alanyl- and piperidinyl-disubstituted cyanuric chloride
Lin, Chen-Hsing,Lin, Ching-Erh,Chen, Chia-Chong,Liao, Li-Fang
, p. 1069 - 1075 (2001)
A silica-base chiral stationary phase (CSP) derived from L-alanyl- and piperidinyl-disubstituted cyanuric chloride was prepared for the enantioseparation of methyl esters of N-(3,5-dinitrobenzoyl)amino acids and amino alcohols. This CSP provides good chiral recognition and effective separation of enantiomers of both methyl esters of N-(3,5-dinitrobenzoyl)amino acids, except for proline, and N-(3,5-dinitrobenzoyl)amino alcohols by high-performance liquid chromatography. The enantioselectivity depends mainly on three preferential interactions which include a π-π interaction and two hydrogen-bonding interactions. However, steric interaction between substituents attached to the chiral center of chiral selectands and the chiral selector also plays a significant role in chiral recognition. Comparison of chromatographic results of the CSP prepared in this study with those of the CSP containing pyrrolidinyl group attached to the s-triazine moiety, reported previously (J. Chromatogr. A, 722 (1996) 189), reveals that influences of steric interaction and the basic nature of piperidinyl substituent attached to the s-triazine ring of the chiral selector on chiral discrimination may not be neglected.
Convenient syntheses of cyanuric chloride-derived NHC ligands, their Ag(i) and Au(i) complexes and antimicrobial activity
Almalioti, Foteini,MacDougall, James,Hughes, Stephen,Hasson, Mohammed M.,Jenkins, Robert L.,Ward, Benjamin D.,Tizzard, Graham J.,Coles, Simon J.,Williams, David W.,Bamford, Sarah,Fallis, Ian A.,Dervisi, Athanasia
, p. 12370 - 12380 (2013)
Convenient syntheses of mono- and bis-imidazolium 1,3,5-triazine derivatives bearing piperidine and morpholine substituents are reported. In situ deprotonation of the mono-imidazolium salts and reaction with Ag2O or Au(tht)Cl (tht = tetrahydrothiophene) precursors affords the corresponding Ag(NHC)Cl and Au(NHC)Cl carbene complexes. In the presence of Ag(i) or Au(i) salts the bis-imidazolium pincers eliminate the imidazolium group to afford -OMe or -NMe2 substituted triazines depending on the solvent used. In solution, the Ag(i) and Au(i) complexes show a barrier to rotation about the Ctriazine-Namine bonds, with calculated ΔG ≠ barriers in the region of 70 kJ mol-1. Single crystal X-ray structures of several of the proligands and their corresponding Ag(i) and Au(i) complexes were obtained. These universally reveal an extended, rigidly planar π-conjugated network between the triazine core, imidazolium/ imidazolylidene substituents and exocyclic amine functions, to which the origin of the rotational barrier observed in solution is attributed. Only very weak Ntriazine-metal interactions are observed in the solid state, as indicated by small deviations of the CNHC-Ag-Cl bond angles from 180°and also supported by DFT calculations on the Ag(NHC)Cl complex (NHC = 4,6-dipiperidinyl-2-methylimidazolylidene triazine). Preliminary antimicrobial susceptibility studies against five microorganisms (methicillin resistant Staphylococcus aureus NCTC 13277, S. aureus NCTC 6571, Pseudomonas aeruginosa NCTC 10662, Proteus mirabilis NCTC 11938 and Candida albicans ATCC 90028) show that the above triazine-based Ag-NHC complexes are active antimicrobial and antifungal agents.
Synthesis and comparative anion binding profiles of two di-aqua Eu(iii) complexes
Imperio, Daniela,Giovenzana, Giovanni B.,Law, Ga-Lai,Parker, David,Walton, James W.
, p. 9897 - 9903 (2010)
Two di-aqua Eu(iii) complexes of heptadentate ligands are reported that show differing reactivity profiles towards various anions; a cationic complex with two azaxanthone moieties exhibits pronounced selectivity towards bicarbonate with an affinity constant, logK = 2.65 (295 K, 0.1 M NaCl).
Design and synthesis of new s-triazine polymers and their application as nanoparticulate drug delivery systems
Khattab, Sherine N.,Abdel Naim, Samar E.,El-Sayed, Mousa,El Bardan, Aly A.,Elzoghby, Ahmed O.,Bekhit, Adnan A.,El-Faham, Ayman
, p. 9565 - 9578 (2016)
Herein, we report the synthesis of a library of new s-triazine polyamides containing glycine and thioglycolic acid. The reaction of s-triazine dicarboxylic acid derivatives with ethylenediamine, benzidine, piperazine, or p-phenylenediamine, afforded the t
Synthesis of new 5-aza-isosteres of guanine containing aryl and hetaryl substituents on the 1,2,4-triazole ring
Zavodskaya, Anna V.,Bakharev, Vladimir V.,Parfenov, Victor E.,Gidaspov, Alexander A.,Slepukhin, Pavel A.,Isenov, Maksim L.,Eltsov, Oleg S.
, p. 1103 - 1106 (2015)
The oxidative cyclization of 4-amino-substituted 6-arylidene(hetarylmethylidene)hydrazinyl-1,3,5-triazin-2-ones with lead(IV) tetraacetate proceeds via a Dimroth-type rearrangement to give 5-amino-substituted 2-aryl(hetaryl)-1,2,4-triazolo[1,5-a]-1,3,5-tr
Synthesis and preliminary biological evaluation of 1,3,5-triazine amino acid derivatives to study their MAO inhibitors
Khattab, Sherine N.,Khalil, Hosam H.,Bekhit, Adnan A.,El-Rahman, Mohamed Mokbel Abd,El-Faham, Ayman,Albericio, Fernando
, p. 15976 - 15988 (2015)
Three series of 4,6-dimethoxy-, 4,6-dipiperidino- and 4,6-dimorpholino-1,3,5-triazin- 2-yl) amino acid derivatives were synthesized and characterized. A preliminary study for their monoamine oxidase inhibitory activity showed that compounds 7, 18, and 25 had MAO-A inhibition activity comparable to that of the standard clorgyline, with apparently more selective inhibitory activity toward MAO-A than MAO-B and no significant acute toxicity.
Hybrid Quinazoline 1,3,5-Triazines as Epidermal Growth Factor Receptor (EGFR) Inhibitors with Anticancer Activity: Design, Synthesis, and Computational Study
Pathak, Prateek,Rimac, Hrvoje,Grishina, Maria,Verma, Amita,Potemkin, Vladimir
, p. 822 - 838 (2020/12/07)
We report a series of hybrid quinazoline-1,3,5-triazine derivatives as EGFR inhibitors, which were synthesised and tested by using a variety of in vitro, in silico, and in vivo techniques. The derivatives were found to be active against different cancer cell lines and nontoxic against normal ones, with compounds 7 c, 7 d, 7 e, and 7 j being the most potent ones. The derivatives were also evaluated for angiogenesis inhibition potency in chicken eggs, and molecular docking and dynamics simulation studies were carried out to elucidate the fundamental substituent groups essential for their bioactivity. Additionally, a SAR study of the derivatives was performed for future compound optimisation. These studies suggested that the derivatives have a high affinity towards EGFR with favourable pharmacological properties. The most active compound (7 e) was further evaluated for in vivo anticancer activity against DMBA-induced tumours in female Sprague-Dawley rats as well as its effects on plasma antioxidant status, biotransformation enzymes, and lipid profile. The study suggested that 7 e has lead properties against breast cancer and can serve as a starting compound for further development of anti-EGFR compounds.
(S)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530), a Potent, Orally Bioavailable, and Brain-Penetrable Dual Inhibitor of Class i PI3K and mTOR Kinase
Rageot, Denise,Bohnacker, Thomas,Keles, Erhan,McPhail, Jacob A.,Hoffmann, Reece M.,Melone, Anna,Borsari, Chiara,Sriramaratnam, Rohitha,Sele, Alexander M.,Beaufils, Florent,Hebeisen, Paul,Fabbro, Doriano,Hillmann, Petra,Burke, John E.,Wymann, Matthias P.
, p. 6241 - 6261 (2019/07/04)
The phosphoinositide 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) pathway is frequently overactivated in cancer, and drives cell growth, proliferation, survival, and metastasis. Here, we report a structure-activity relationship study, which led to the discovery of a drug-like adenosine 5′-triphosphate-site PI3K/mTOR kinase inhibitor: (S)-4-(difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530, compound 6), which qualifies as a clinical candidate due to its potency and specificity for PI3K and mTOR kinases, and its pharmacokinetic properties, including brain penetration. Compound 6 showed excellent selectivity over a wide panel of kinases and an excellent selectivity against unrelated receptor enzymes and ion channels. Moreover, compound 6 prevented cell growth in a cancer cell line panel. The preclinical in vivo characterization of compound 6 in an OVCAR-3 xenograft model demonstrated good oral bioavailability, excellent brain penetration, and efficacy. Initial toxicity studies in rats and dogs qualify 6 for further development as a therapeutic agent in oncology.
Design and synthesis of mono-and di-pyrazolyl-s-triazine derivatives, their anticancer profile in human cancer cell lines, and in vivo toxicity in zebrafish embryos
Farooq, Muhammad,Sharma, Anamika,Almarhoon, Zainab,Al-Dhfyan, Abudalla,El-Faham, Ayman,Taha, Nael Abu,Wadaan, Mohammad A.M.,Torre, Beatriz G. de la,Albericio, Fernando
, p. 457 - 464 (2019/03/27)
s-Triazine is considered a privileged structure, as it is found in several FDA-approved drugs. In the framework of our ongoing medicinal chemistry project based on the use of s-triazine as a scaffold, we synthesized a series of mono- and di-pyrazolyl-s-triazine derivatives and tested them against four human cancer cell lines, namely Human breast carcinoma (MCF 7 and MDA-MB-231), hepatocellular carcinoma (HepG2), colorectal carcinoma (LoVo), and leukemia (K562). The cell viability assay revealed that most of the s-triazine compounds induced cytotoxicity in all four types of human cancer cell lines, however, compounds 4a, and 6g, both of them have a piperidine moiety in their structure were most effective. These two compounds affected the cell viability of cancer cells, with IC50 values within the range between 5 to 9 μM. The cell cycle analysis showed that 4a and 6g induced S and G2/M phase cell cycle arrest in K562 cells. This could be the mechanism by which these molecules induced cytotoxicity in tested cancer cells. The prepared compounds were tested in zebrafish embryos to evaluate in vivo and developmental toxicity of the pyrazolyl-s-triazine derivatives in animals. None of the derivatives were lethal in the concentration range tested.
