Synthesis and antilipolytic activities of quinolyl carbanilates and related analogs

Abstract

A series of quinolyl carbanilates was prepared and tested as antilipolytic agents. These compounds inhibited production of glycerol from rat adipocytes and inhibited liberation of free fatty acids from triolein by canine cardiac triglyceride lipases. An extensive structure-activity relationship study indicated that 8-quinolyl 4-methoxycarbanilate (1) contained features necessary for maximum potency in vitro. Substituting a benzofuranyl group for the quinolyl group of 1 provided the most interesting compound on the basis of both potency and structural novelty. 7-Benzofuranyl 4-methoxycarbanilate (44) has IC50's of 16 and 0.3 microM in the myocardial lipase and rat adipocyte assays, respectively. In vivo, compound 44 was orally active as an inhibitor (97% at 25 mg/kg) of lipolysis in the rat.

Palladium-Catalyzed Hydroxylation of Aryl and Heteroaryl Halides Enabled by the Use of a Palladacycle Precatalyst

“…13 Benzofuran-7-ol (3k). 29 Following general procedure A, the title compound was prepared using 7-chlorobenzofuran (153 mg, 1.0 mmol); EtOAc/hexanes (1:4); 125 mg, 93%; pale-yellow oil. 1 H NMR (400 MHz, DMSO-d 6 ) δ: 9.96 (br s, 1 H), 7.91 (d, J = 2.0 Hz, 1 H), 7.06 (d, J = 7.6 Hz, 1 H), 7.02 (t, J = 7.6 Hz, 1 H), 6.87 (d, J = 2.0 Hz, 1 H), 6.74 (d, J = 7.6 Hz, 1 H).…”

Synthetic Models Related to Methoxalen and Menthofuran–Cytochrome P450 (CYP) 2A6 Interactions. Benzofuran and Coumarin Derivatives as Potent and Selective Inhibitors of CYP2A6

“…We selected menthofuran 26) (1) and methoxalen (2) as lead compounds and prepared various benzofuran and coumarin derivatives (Chart 1). A series of benzofuran derivatives (3, 8,9) 4, 10,11) 5, 12) 6, 13) 7, 14,15) 8, 14,15) 9, 16) 10, 17,18) and 11 19) ) and coumarin derivatives (13,20) 14, 21) 15, 22) 16, 23) and 17 22) ) were prepared by the reported procedure. Assays of inhibition of CYP2A6 activity by benzofuran and coumarin derivatives were based on microsomal coumarin 7-hydroxylation.…”

Hypoxia-Activated Prodrug Derivatives of Carbonic Anhydrase Inhibitors in Benzenesulfonamide Series: Synthesis and Biological Evaluation

“…2-and 5-nitroimidazole, nitrofuran, nitrothiophene and nitrogen mustard were conjugated with benzene sulfonamides using a carbamate linker. Because of the low reactivity observed, the introduction of the carbamate linker proved to be challenging for some derivatives and two approaches were used to achieve the synthesis of these inhibitors starting from the nitroaromatic alcohols: (i) a reaction with carbonyldiimidazole to access to the carbamoyl imidazole derivatives that reacted, in a one-pot reaction, with aminomethyl-or aminoethyl-benzenesulfonamide, or (ii) a reaction with phosgene to yield to the chloroformates which were then reacted with aminomethyl-or aminoethyl-benzenesulfonamide in the presence of triethylamine (Scheme 1) [31]. Compounds 1b-5b and 2c-3c were isolated with yields ranging from 43% to 88% and characterized extensively by spectroscopic and spectrometric methods (see materials and methods part).…”