Structural investigation of 3,5‐disubstituted isoxazoles by ¹H‐nuclear magnetic resonance

Abstract

This work is dedicated to the memory of Prof. Paolo Sanna HIV-1 integrase (IN) is a very promising and validated target for the development of therapeutic agents against AIDS. In an effort to design and synthesize biological isosteric analogs of β-diketoacid-containing inhibitors of IN, we prepared a series of substituted isoxazole carboxylic acids. Several of these compounds inhibited catalytic activities of purified IN at micromolar concentration range. With an aim to prepare a large number of analogues based on the isoxazole pharmacophore we focused our study on a series of 3,5-disubstituted isoxazole isomers. For a rapid structural analysis we discovered a convenient 1 H-nmr method for distinguishing between isomeric structures based on their H-4 assignments. This "finger print" approach to isomer identification will be useful in combinatorial chemistry settings where a mixture can be further derivatized.

From Renewable Levulinic Acid to a Diversity of 3‐(Azol‐3‐yl)Propanoates

“…This was confirmed by a 1 H NMR spectrum in DMSO, which exhibits a singlet signal at δ 7.08 ppm representing the aromatic isoxazole 4‐H and a broad singlet at 10.58 ppm representing the carboxyl group at the 5‐C position of the isoxazole ring. A 13 C NMR spectrum exhibits two signals at δ 164.2 and δ 173.7 ppm, both for carboxyl groups .…”

Design and synthesis of novel polycycles based on the 3H‐pyrrolo/6,7‐dihydropyrido[1,2‐a]indole scaffold as templates for pharmaceutical development

“…2) [13], which bears two carbonyl groups, suitable to be functionalized (''two-armed'' approach) giving compound 4 and related derivatives [14]. Both computational studies and viscosimetric analysis seem to support the hypothesis that these compounds could interfere with DNA, and further studies are currently in progress to investigate their biological properties [15].…”

“…The precipitate obtained was filtered to give a pale brown solid, 0.11 g, (59%); (c) To a solution of 11 (0.60 g, 2.23 mmol) in ethanol (12 mL), 37% HCl (12 mL) was added and the reaction mixture was stirred at reflux for 1.5 h. After this period, the reaction mixture was allowed to cool down, diluted with water, and the precipitate formed was filtered and purified by column flash chromatography gradient elution of petroleum ether/ethyl acetate (80/20 then 70/30) to give a brown solid, 0.30 g (72%), mp 140À142 C for products from (a), (b), and (c) (lit. [17] (E/Z)-9-(2-(4,5-dihydro-1H-imidazol-2-yl)hydrazono)-6,7,8,9-tetrahydropyrido[1,2-a]indole bromohydrate (13). To a solution of 6 (0.20 g, 1.08 mmol) in absolute ethanol (10 mL), 2-amine-2-imidazoline bromohydrate (0.39 g, 2.16 mmol) was added and the reaction mixture was stirred at reflux for 48 h. After this period, the precipitate formed was filtered to give a dark yellow solid, 0.10 g (27%), mp 295À297 Ethyl 9-(2-(dimethylamino)ethylamino)-6,7-dihydropyrido[1,2-a]indole-8-carboxylate (14).…”

Five‐Membered Heterocycles: 1,2‐Azoles. Part 2. Isoxazoles and Isothiazoles

“…The 1 H NMR spectrum of isoxazole (1), neat or dissolved in various solvents, has been reported in many papers (Table 9.2) [34,[47][48][49]. The signals of H4 (d, 6.28-6.41 ppm) appear at lower frequency values than those of H3 (d, 8.15-8.40 ppm) and H5 (d, 8.39-8.61 ppm), but all of them are in the aromatic region.…”