2,4,6-Trisubstituted Triazines as Protein A Mimetics for the Treatment of Autoimmune Diseases

Abstract

A first-in-class series of low molecular weight trisubstituted triazines were synthesized and evaluated for their ability to mimic protein A binding to human IgG antibody. The structure-activity relationship (SAR) demonstrates that the 1,3-phenylenediamine component was essential for robust activity. Twenty-two compounds, represented by lead molecule 34, displayed significant activity compared to protein A. These compounds may prove useful for the treatment of autoimmune disease.

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

“…The intermediate 6-chloro-N 2 -mesityl-N 4 -(1-Boc-piperidin-4-yl)-1,3,5-triazine-2,4-diamine (3) was prepared from structurally symmetrical 2,4,6-trichloro-1,3, 5-triazine (1) by substitution reaction with 2,4,6-trimethylaniline and 4-amino-1-Boc-piperidine successively in mild reaction conditions. 20 Treatment of intermediate 3 with ammonia under high temperature in sealed reactor, 21 aqueous methylamine and sodium methoxide gave the intermediate 4a, 4b and 4c, respectively. 22 Boc group was removed in the presence of trifluoroacetic acid (TFA) at room temperature to afford 5a, 5b and 5c, which were alkylated at the N atom of piperidine, achieving the final compounds 6a1-6a8, 6b1-6b5 and 6c1-6c5, respectively.…”

Triazine as a promising scaffold for its versatile biological behavior

“…al. [110] has been synthesized and evaluated a number of bis-triazine derivatives of structural type 1 as protein A mimetic and displayed significant activity comparable to protein A. Amino function of 3-aminoaniline group appeared to be essential, and activity declined upon replacement of 3-aminoaniline with other groups such as 2-fluoroaniline (79a) or aminoethylamidine (79b) or 3-methylsulfonamidoaniline (79c). With 3-aminoaniline group at one of the triazine and substitution of 3-fluoroaniline (80a), 4-fluoroaniline (80b), 4-chloroaniline (80c), 3-methylsulfonylaniline (80d), ethylenediamine (80e) at another triazine ring, displayed less activity than compounds 3-aminoaniline (80f) and ethanolamine (80g, Fig.…”

Triazine–benzimidazole hybrids: Anticancer activity, DNA interaction and dihydrofolate reductase inhibitors

“…Similarly, compound 4b was treated with cyanuric chloride in the same reaction conditions to obtain (3-benzyl-2-methyl-3H-benzimidazol-5-yl)-(4,6-dichloro- [1,3,5]triazin-2-yl)-amine (5b) in 90% yield followed by nucleophilic substitution with morpholine to obtain compound 6b in 74% yield. Alternatively, poor overall yields of 6a-b were obtained with first nucleophilic substitution of cyanuric chloride with morpholine followed by substitution with aminobenzimidazoles (4).…”

“…To this mixture, 10% NaHCO 3 was added drop wise and stirred for 4 h. The resulted reaction mixture was then poured into crushed ice, filtered, dried and column chromatographed on silica gel in chloroform/methanol (50:1) to afford the desired product (1-benzyl-2-methyl-1H-benzimidazol-5-yl)-(4-chloro-6-morpholin-4-yl- [1,3,5]triazin-2-yl)-amine (6a) as white powder; (9.07 g, 80%); mp: >300°C; 1 …”

“…To a stirred solution of (1-benzyl-2-methyl-1H-benzimidazol-5-yl)-(4-chloro-6-morpholin-4-yl- [1,3,5]triazin-2-yl)-amine (6a) (0.200 g, 0.459 mmol) in 1,4-dioxane (20 mL), morpholine (0.059 g, 0.688 mmol) and potassium carbonate (0.076 g, 0.551 mmol) were added and heated at 110°C for 8 h. Extracted the reaction mixture with chloroform, dried over Na 2 SO 4 , filtered and concentrated to get crude product which was then purified through column chromatography using chloroform/methanol (50:1) as eluents to give (1-benzyl-2-methyl-1H-benzimidazol-5-yl)-(4,6-di-morpholin-4-yl- [1,3,5]triazin-2-yl)-amine (7) …”