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Titolo:
Synthesis and biological evaluations of quinoline-based HMG-CoA reductase inhibitors
Autore:
Suzuki, M; Iwasaki, H; Fujikawa, Y; Kitahara, M; Sakashita, M; Sakoda, R;
Indirizzi:
Nissan Chem Ind Co Ltd, Cent Res Labs, Funabashi, Chiba 2748507, Japan Nissan Chem Ind Co Ltd Funabashi Chiba Japan 2748507 Chiba 2748507, Japan Nissan Chem Ind Co Ltd, Div Pharmaceut, Chiyoda Ku, Tokyo 1010054, Japan Nissan Chem Ind Co Ltd Tokyo Japan 1010054 yoda Ku, Tokyo 1010054, Japan Nissan Chem Ind Co Ltd, Biol Res Labs, Shiraoka, Saitama 3490294, Japan Nissan Chem Ind Co Ltd Shiraoka Saitama Japan 3490294 tama 3490294, Japan
Titolo Testata:
BIOORGANIC & MEDICINAL CHEMISTRY
fascicolo: 10, volume: 9, anno: 2001,
pagine: 2727 - 2743
SICI:
0968-0896(200110)9:10<2727:SABEOQ>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
COENZYME-A REDUCTASE; BETA-KETO-ESTERS; CHOLESTEROL-BIOSYNTHESIS; COMPETITIVE INHIBITOR; PRAVASTATIN; HYPERCHOLESTEROLEMIA; DERIVATIVES; METABOLISM; NUCLEUS; EVENTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Suzuki, M Nissan Chem Ind Co Ltd, Cent Res Labs, 722-1 Tsuboi Cho, Funabashi, Chiba 2748507, Japan Nissan Chem Ind Co Ltd 722-1 Tsuboi Cho Funabashi Chiba Japan 2748507
Citazione:
M. Suzuki et al., "Synthesis and biological evaluations of quinoline-based HMG-CoA reductase inhibitors", BIO MED CH, 9(10), 2001, pp. 2727-2743

Abstract

A series of quinoline-based 3,5-dihydroxyheptenoic acid derivatives were synthesized from quinolinecarboxylic acid esters by homologation, aldol condensation with ethyl acetoacetate dianion, and reduction of 3-hydroxyketone to evaluate their ability to inhibit the enzyme HMG-CoA reductase in vitro. In agreement with previous literature, a strict structural requirement exists on the external ring, and 4-fluorophenyl is the most active in this system. For the central ring, substitution on positions 6, 7, and 8 of the central quinoline nucleus moderately affected the potency, whereas the alkyl side chain on the 2-position had a more pronounced influence on activity. Among the derivatives, NK-104 (pitavastatin calcium), which has a cyclopropylgroup as the alkyl side chain, showed the greatest potency. We found that further modulation and improvement in potency at inhibiting HMG-CoA reductase was obtained by having the optimal substituents flanking the desmethylinevalonic acid portion, that is, 4-fluorophenyl and cyclopropyl, instead of the usual isopropyl group. (C) 2001 Elsevier Science Ltd, All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 11:08:22