The Preparation of 2-(2-Oxo-2-Phenylethyl) Benzoic Acids from Dilithiated<i>Ortho-</i>Toluic Acid.

Guion, Tina S.; Koller, M. U.; Lachicotte, Rene J.; Hildebran, Karen C.; Le, Phuong Hong; Beam, Charles F.

doi:10.1080/00397919608002615

Cited by 4 publications

(1 citation statement)

References 17 publications

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“…Introduction of strongly electronegative substituents to this aryl ring was achieved by direct nitration of the diacetate 24 derived from 7b (Ac 2 O, H 2 SO 4 , 77%) which afforded a separable mixture of 4‘- and 2‘-nitro isomers 25 and 26 (ratio ∼ 1:1, 45% combined yield). Construction of the skeleton of the 2‘-carboxyl derivative 27 was achieved by lateral lithiation of o -toluic acid and reaction with methyl vanillate . Exposure of 27 to warm acid effected cyclization to 28 (both Scheme ).…”

Section: Chemistrymentioning

confidence: 99%

Synthesis of 1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and Derivatives as Potent and Long-Acting Peripheral Inhibitors of Catechol-O-methyltransferase

et al. 2001

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A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone) was found to exhibit the most potent and selective inhibition of peripheral COMT, with an inhibition profile more similar to entacapone 2 than tolcapone 1 (an equipotent peripheral and central inhibitor) but with much improved duration of action (7b, 70% inhibition and 2, 25% inhibition at 9 h after administration). The effects of structural modifications to 7b on COMT inhibitory profile were investigated, and it is concluded that the carbonyl group and preferably unsubstituted aromatic ring are essential features to maintain prolonged peripheral COMT inhibition. The introduction of the alpha-methylene group, the major structural difference between 7b and 1, would appear responsible for the observed enhancement in selectivity of peripheral COMT inhibition of 7b, which has more limited access to the brain than 1.

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Section: Chemistrymentioning

confidence: 99%