Abstract: The group of 18 new amide derivatives of mycophenolic acid (MPA) and selected heterocyclic amines was synthesised as potential immunosuppressive agents functioning as inosine-5′-monophosphate dehydrogenase (IMPDH) uncompetitive inhibitors. The synthesis of 14 of them employed uronium-type activating system (TBTU/HOBt/DIPEA) while 4 of them concerned phosphonic acid anhydride method (T3P/Py) facilitating amides to be obtained in moderate to excellent yields without the need of phenolic group protection. Most of optimised protocols did not require complicated reaction work-ups, including chromatographic, solvent-consuming methods. The biological activity assay was performed on the T-Jurkat cell line and peripheral mononuclear blood cells (PBMCs) which are both dedicated for antiproliferative activity determination. Each of designed derivatives was characterised by reduced cytotoxicity and benzoxazole analogue (A2) revealed the most promising activity. Subsequently, an observed structure-activity relationship was discussed.
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Example 170Preparation of 1-benzothiazol-6-yl-3-pyridin-3-yl-4-trifluoromethyl-imidazolidin-2-one (170A) Step-1: Synthesis of Intermediate 2-(Benzothiazol-6-ylaminomethyl)-3,3,3-trifluoro-propionic Acid (I-170a) Benzothiazol-6-ylamine (1 g, 6.66 mmol) was reacted with 2-trifluoromethyl-acrylic acid (1.39 g, 9.99 mmol), benzene-1,4-diol (51.3 mg, 0.46 mmol) and toluene (10 mL) to afford the crude product. Purification by column chromatography on silica gel (30% ethyl acetate in hexane) afforded 380 mg of the product (19.67% yield).1H NMR (300 MHz, DMSO-d6): delta 13.8-13.0 (bs, 1H), 8.95 (s, 1H), 7.8 (d, 1H), 7.2 (d, 1H), 6.95-6.85 (dd, 1H), 3.75-3.50 (m, 3H)LCMS: 100%, m/z=291.1 (M+1)
19.67%
With hydroquinone; In toluene;
Ben/othia/ol-6-ylamine ( Ig. 6.6<>mmol) was reacted with ^-trifluoromcth) l- acrylic acid ( 1.39g. y.99mmol). bouene- 1 ,4-diol (51.3mg.0 46mmoi) and toluene( 10ml-) to afford the crude product. Purification In column ehromatographs on silica gel (30% ethyl acetate in he.anc) afforded 380tng of the pr
2-((benzo[d]thiazol-6-ylimino)methyl)-4,6-diiodophenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
In methanol; at 40 - 50℃;
General procedure: L1H/L2H/L3H were synthesized by adding 3-nitro-salicylaldehyde/3,5-diiodo-salicylaldehyde/3-methoxy-5-bromo-salicylaldehyde (10 mM) into a stirred methanolic solution of 6-amino-benzothiazole (10 mM) in 1:1 M ratio (Scheme 1). The reaction mixture wasrefluxed on an oil bath for 3-4 h by maintaining temperature at 40-50 C and the progressof the reaction was monitored by TLC. The resulting solid product was isolatedand washed with petroleum ether and methanol. The Schiff bases were dried in a desiccatorover anhydrous CaCl2.
Chemistry
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Inhibitors/Agonists
Material Science
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