Parallel synthesis of DAPT derivatives and their γ-secretase-inhibitory activity

被引：34

作者：

Kan, T ^{[1
]}

Tominari, Y ^{[1
]}

Rikimaru, K ^{[1
]}

Morohashi, Y ^{[1
]}

Natsugari, H ^{[1
]}

Tomita, T ^{[1
]}

Iwatsubo, T ^{[1
]}

Fukuyama, T ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 08期

关键词：

D O I：

10.1016/j.bmcl.2004.01.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Parallel synthesis of the C-terminal-modified DAPT (1) derivatives was accomplished utilizing our novel resin 7. Condensation reaction of the N-acylamino acid 10 with the amines 11a-o proceeded smoothly to give the corresponding amides 6a-o without any epimerization. Among the analogues, the benzophenonemethyl amide derivative 6o showed 30 times more potent activity than the original DAPT (1). (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：1983 / 1985

页数：3

共 9 条

[1] Set back to Alzheimer vaccine studies [J].

Birmingham, K ;

Frantz, S .

NATURE MEDICINE, 2002, 8 (03) :199-200

[2] BENZOPHENONE PHOTOPHORES IN BIOCHEMISTRY [J].

DORMAN, G ;

PRESTWICH, GD .

BIOCHEMISTRY, 1994, 33 (19) :5661-5673

[3] Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain [J].

Dovey, HF ;

John, V ;

Anderson, JP ;

Chen, LZ ;

Andrieu, PD ;

Fang, LY ;

Freedman, SB ;

Folmer, B ;

Goldbach, E ;

Holsztynska, EJ ;

Hu, KL ;

Johnson-Wood, KL ;

Kennedy, SL ;

Kholedenko, D ;

Knops, JE ;

Latimer, LH ;

Lee, M ;

Liao, Z ;

Lieberburg, IM ;

Motter, RN ;

Mutter, LC ;

Nietz, J ;

Quinn, KP ;

Sacchi, KL ;

Seubert, PA ;

Shopp, GM ;

Thorsett, ED ;

Tung, JS ;

Wu, J ;

Yang, S ;

Yin, CT ;

Schenk, DB ;

May, PC ;

Altstiel, LD ;

Bender, MH ;

Boggs, LN ;

Britton, TC ;

Clemens, JC ;

Czilli, DL ;

Dieckman-McGinty, DK ;

Droste, JJ ;

Fuson, KS ;

Gitter, BD ;

Hyslop, PA ;

Johnstone, EM ;

Li, WY ;

Little, SP ;

Mabry, TE ;

Miller, FD ;

Ni, B .

JOURNAL OF NEUROCHEMISTRY, 2001, 76 (01) :173-181

[4] Total synthesis of polyamine toxin HO-416b utilizing the 2-nitrobenzenesulfonamide protecting group [J].

Hidai, Y ;

Kan, T ;

Fukuyama, T .

TETRAHEDRON LETTERS, 1999, 40 (25) :4711-4714

[5]

Hidai Y, 2000, CHEM PHARM BULL, V48, P1570, DOI 10.1248/cpb.48.1570

[6] Solid-phase synthesis of photoaffinity probes: highly efficient incorporation of biotin-tag and cross-linking groups [J].

Kan, T ;

Tominari, Y ;

Morohashi, Y ;

Natsugari, H ;

Tomita, T ;

Iwatsubo, T ;

Fukuyama, T .

CHEMICAL COMMUNICATIONS, 2003, (17) :2244-2245

[7]

Kan T, 2002, SYNLETT, P1338

[8] Sulindac sulfide is a noncompetitive γ-secretase inhibitor that preferentially reduces Aβ42 generation [J].

Takahashi, Y ;

Hayashi, I ;

Tominari, Y ;

Rikimaru, K ;

Morohashi, Y ;

Kan, T ;

Natsugari, H ;

Fukuyama, T ;

Tomita, T ;

Iwatsubo, T .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (20) :18664-18670

[9] Therapeutic strategies for Alzheimer's disease [J].

Wolfe, MS .

NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (11) :859-866

← 1 →