Synthesis of amino acids and related compounds. 29. Synthesis and hypolipidemic activities of 5-thienyl-4-oxazoleacetic acid derivatives

Abstract

A series of 2,5-disubstituted 4-oxazoleacetic acid derivatives was synthesized and evaluated for hypolipidemic activity. Among them, those with a thienyl group at C-5 of the oxazole ring exerted highly potent hypolipidemic effects in rats. 2-(4-Fluorophenyl)-5-(3-thienyl)-4-oxazoleacetic acid (88) was the most potent derivative: it was about 2 times as active in normal SD male rats and about 4 times as active in hereditary hyperlipidemic rats (THLR/1) as clofibrate with an improved antiarteriosclerosis index (HDL-Cho/Total-Cho). In addition, it showed inhibition of platelet aggregation ex vivo.

Synthesis of α-Amidoketones through the Cascade Reaction of Carboxylic Acids with Vinyl Azides under Catalyst-Free Conditions

“…Eluent: petroleum ether/ethyl acetate (5:1). 12 White solid (54.5 mg, 76%), mp: 123− 124 °C (lit. 12 124−125 °C).…”

“…12 White solid (54.5 mg, 76%), mp: 123− 124 °C (lit. 12 124−125 °C). 1 H NMR (400 MHz, CDCl 3 ) δ 7.98 (d, J = 7.6 Hz, 2H), 7.88 (d, J = 7.2 Hz, 2H), 7.60 (t, J = 7.2 Hz, 1H), 6H),4.92 (d,J = 4.4 Hz,2H).…”

“…Eluent: petroleum ether/ethyl acetate (3:1). 12 Yellowish solid (59.7 mg, 74%), mp: 133−135 °C (lit. 12 133−134 °C).…”

“…12 Yellowish solid (59.7 mg, 74%), mp: 133−135 °C (lit. 12 133−134 °C). 1 H NMR (600 MHz, CDCl 3 ) δ 8.04 (d, J = 7.2 Hz, 2H), 7.85−7.87 (m, 2H), 7.65 (t, J = 7.2 Hz, 1H), 7.53 (t, J = 7.8 Hz, 2H), 7.21 (br s, 1H), 6.95−6.97 (m, 2H), 4.96 (d, J = 4.2 Hz, 2H), 3.87 (s, 3H).…”

Synthesis and Hypolipidemic Activity of Novel 2‐(4‐(2‐Amino‐6‐(4‐Substituted Phenyl) Pyrimidin‐4‐yl)‐2‐Substituted Phenoxy) Acetic Acid Derivatives

“…It was observed that phenoxy acetic acid pharmacophore has been frequently used in the synthesis of hypolipidemic agent (4–6). Phenoxy acetic acid moiety was frequently coupled with heterocyclic nucleus such as pyrimidine (7), piperidine (8), pyridine (9), oxazole (10), indole (11), benzothiophene (12), benzisoxazole (13), and oxadiazole (14), which exhibited potent antihyperlipidemic activity.…”