Synthesis and anti-influenza virus activity of 7-O-alkylated derivatives related to zanamivir

被引：66

作者：

Honda, T

Masuda, T

Yoshida, S

Arai, M

Kaneko, S

Yamashita, M

机构：

[1] Sankyo Co Ltd, Med Chem Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

[2] Sankyo Co Ltd, Biol Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(02)00329-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 7-alkyl ether derivatives related to zanamivir were synthesized using direct alkylation of the C-7 alcohol of sialic acid. Alkyl ether moiety of less than 12 carbons in length showed low nanomolar inhibitory activity against influenza A virus sialidase. Furthermore, their moiety improved influenza A virus plaque reduction activity compared to zanamivir. However, removal of the 8,9-diol of the 7-O-alkyl derivatives resulted in loss of antiviral potency. This result suggests that 8,9-diol must play an important role in binding with both influenza A and B virus sialidases. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1925 / 1928

页数：4

共 20 条

[1]

ANAZAWA K, 1988, CHEM PHARM BULL, V36, P4976

[2] BCX-1812 (RWJ-270201): Discovery of a novel, highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design [J].

Babu, YS ;

Chand, P ;

Bantia, S ;

Kotian, P ;

Dehghani, A ;

El-Kattan, Y ;

Lin, TH ;

Hutchison, TL ;

Elliott, AJ ;

Parker, CD ;

Ananth, SL ;

Horn, LL ;

Laver, GW ;

Montgomery, JA .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (19) :3482-3486

[3]

BABU YS, Patent No. 9747194

[4] Systematic structure-based design and stereoselective synthesis of novel multisubstituted cyclopentane derivatives with potent antiinfluenza activity [J].

Chand, P ;

Kotian, PL ;

Dehghani, A ;

El-Kattan, Y ;

Lin, TH ;

Hutchison, TL ;

Babu, YS ;

Bantia, S ;

Elliott, AJ ;

Montgomery, JA .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (25) :4379-4392

[5]

CUBERO II, 1993, CARBOHYD RES, V242, P281

[6] Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza [J].

Hayden, FG ;

Treanor, JJ ;

Betts, RF ;

Lobo, M ;

Esinhart, JD ;

Hussey, EK .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1996, 275 (04) :295-299

[7] Synthesis and anti-influenza virus activity of 4-guanidino-7-substituted Neu5Ac2en derivatives [J].

Honda, T ;

Masuda, T ;

Yoshida, S ;

Arai, M ;

Kobayashi, Y ;

Yamashita, M .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (15) :1921-1924

[8] Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors [J].

Kim, CU ;

Lew, W ;

Williams, MA ;

Wu, HW ;

Zhang, LJ ;

Chen, XW ;

Escarpe, PA ;

Mendel, DB ;

Laver, WG ;

Stevens, RC .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (14) :2451-2460

[9] Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: Design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity [J].

Kim, CU ;

Lew, W ;

Williams, MA ;

Liu, HT ;

Zhang, LJ ;

Swaminathan, S ;

Bischofberger, N ;

Chen, MS ;

Mendel, DB ;

Tai, CY ;

Laver, WG ;

Stevens, RC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (04) :681-690

[10] Synthesis and biological evaluation of sulfur isosteres of the potent influenza virus sialidase inhibitors 4-amino-4-deoxy- and 4-deoxy-4-guanidino-Neu5Ac2en [J].

Kok, GB ;

Campbell, M ;

Mackey, B ;

vonItzstein, M .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1996, (23) :2811-2815

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