Design, synthesis, and structure-activity relationship of new isobenzofuranone ligands of protein kinase C

被引：31

作者：

Baba, Y

Ogoshi, Y

Hirai, G

Yanagisawa, T

Nagamatsu, K

Mayumi, S

Hashimoto, Y

Sodeoka, M

机构：

[1] Tohoku Univ, IMRAM, Sendai, Miyagi 9808577, Japan

[2] Sagami Chem Res Ctr, Kanagawa, Japan

[3] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 11期

基金：

日本学术振兴会;

关键词：

D O I：

10.1016/j.bmcl.2004.02.097

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Protein kinase C (PKC) is a family of enzymes, which play important roles in intracellular signal transduction. We have designed novel PKC ligands having an isobenzofuranone template, based on the proposed interaction of DAG (1,2-diacyl-sn-glycerol) with the PKCdelta C1B ligand-binding domain. Several isobenzofuranone derivatives were synthesized and their PKCalpha binding activities were evaluated. The pivaloyl derivative 1f was found to be a strong PKCalpha ligand, and the structure-activity relationship is well explained by our proposed binding model. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：2963 / 2967

页数：5

共 35 条

[21] SHARKEY NA, 1985, CANCER RES, V45, P19
[22] Conformationally constrained analogues of diacylglycerol .10. Ultrapotent protein kinase C ligands based on a racemic 5-disubstituted tetrahydro-2-furanone template
Sharma, R
Lee, J
Wang, SM
Milne, GWA
Lewin, NE
Blumberg, PM
Marquez, VE
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (01) : 19 - 28
[23] BRYOSTATINS - POTENT, NEW MITOGENS THAT MIMIC PHORBOL ESTER TUMOR PROMOTERS
SMITH, JB
SMITH, L
PETTIT, GR
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1985, 132 (03) : 939 - 945
[24] Rational design, synthesis, and evaluation of a new type of PKC inhibitor
Sodeoka, M
Arai, MA
Adachi, K
Uotsu, K
Shibasaki, M
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (02) : 457 - 458
[25] PHOTOAFFINITY-LABELING OF PKC WITH A PHORBOL DERIVATIVE - IMPORTANCE OF THE 13-ACYL GROUP IN PHORBOL ESTER-PKC INTERACTION
SODEOKA, M
UOTSU, K
SHIBASAKI, M
[J]. TETRAHEDRON LETTERS, 1995, 36 (48) : 8795 - 8798
[26] Sugita K, 1996, CHEM PHARM BULL, V44, P463
[27] The C4 hydroxyl group of phorbol esters is not necessary for protein kinase C binding
Tanaka, M
Irie, K
Nakagawa, Y
Nakamura, Y
Ohigashi, H
Wender, PA
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (05) : 719 - 722
[28] CONFORMATIONALLY CONSTRAINED ANALOGS OF DIACYLGLYCEROL - INTERACTION OF GAMMA-LACTONES WITH THE PHORBOL ESTER RECEPTOR OF PROTEIN-KINASE-C
TENG, K
MARQUEZ, VE
MILNE, GWA
BARCHI, JJ
KAZANIETZ, MG
LEWIN, NE
BLUMBERG, PM
ABUSHANAB, E
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (03) : 1059 - 1070
[29] Photoaffinity labeling of PKC isozymes by phorbol ester derivatives
Uotsu, K
Sodeoka, M
Shibasaki, M
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 1998, 6 (07) : 1117 - 1126
[30] Synthesis and modeling study of (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy-8-(1-decynyl)-benzolactam-V8 as protein kinase C modulators
Wei, ZL
Sakamuri, S
Petukhov, PA
George, C
Lewin, NE
Blumberg, PM
Kozikowski, AP
[J]. ORGANIC LETTERS, 2002, 4 (13) : 2169 - 2172

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