Protein kinase C modulators bearing dicarba-closo-dodecaborane as a hydrophobic pharmacophore

被引：41

作者：

Endo, Y

Yoshimi, T

Kimura, K

Itai, A

机构：

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

[2] Inst Med Mol Design, Bunkyo Ku, Tokyo 1130033, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 17期

关键词：

D O I：

10.1016/S0960-894X(99)00436-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The size and position of a hydrophobic moiety on a benzolactam skeleton, which reproduces the active conformation and biological activity of teleocidins, play an important role in the appearance of the activity. We have designed and synthesized benzolactams bearing dicarba-closo-dodecaborane. These compounds showed potent binding affinity to protein kinase C, providing a further example of the application of carborane as the hydrophobic pharmacophore of biologically active molecules. (C) 1999 Elsevier Science Ltd. All rights reserved.

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页码：2561 / 2564

页数：4

相关论文

共 19 条

[1]

ASHENDEL CL, 1983, CANCER RES, V43, P4333

[2]

DRIEDGER PE, 1994, RECEPTOR CHANNEL, V2, P99

[3]

Endo Y, 1996, CHEM PHARM BULL, V44, P1138

[4] CHIRAL REQUIREMENTS FOR TUMOR PROMOTERS - CONFORMATIONS AND ACTIVITY OF BENZOLACTAMS [J].

ENDO, Y ;

OHNO, M ;

HIRANO, M ;

TAKEDA, M ;

ITAI, A ;

SHUDO, K .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (03) :491-494

[5] Clarification of the binding mode of teleocidin and benzolactams to the Cys2 domain of protein kinase Cδ by synthesis of hydrophobically modified, teleocidin-mimicking benzolactams and computational docking simulation [J].

Endo, Y ;

Takehana, S ;

Ohno, M ;

Driedger, PE ;

Stabel, S ;

Mizutani, MY ;

Tomioka, N ;

Itai, A ;

Shudo, K .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (09) :1476-1496

[6] Potent estrogenic agonists bearing dicarba-closo-dodecaborane as a hydrophobic pharmacophore [J].

Endo, Y ;

Iijima, T ;

Yamakoshi, Y ;

Yamaguchi, M ;

Fukasawa, H ;

Shudo, K .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (09) :1501-1504

[7]

Endo Y, 1999, CHEM PHARM BULL, V47, P585

[8] Synthesis, conformation, and biological activity of teleocidin mimics, benzolactams. A clarification of the conformational flexibility problem in structure-activity studies of teleocidins [J].

Endo, Y ;

Ohno, M ;

Hirano, M ;

Itai, A ;

Shudo, K .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (08) :1841-1855

[9] Fluoride-ion deboronation of p-fluorophenyl-ortho- and -meta-carboranes. NMR evidence for the new fluoroborate, HOBHF2- [J].

Fox, MA ;

MacBride, JAH ;

Wade, K .

POLYHEDRON, 1997, 16 (14) :2499-2507

[10] TUMOR PROMOTING ACTIVITIES OF NEW SYNTHETIC ANALOGS OF TELEOCIDIN [J].

FUJIKI, H ;

SUGANUMA, M ;

HAKII, H ;

NAKAYASU, M ;

ENDO, Y ;

SHUDO, K ;

IRIE, K ;

KOSHIMIZU, K ;

SUGIMURA, T .

PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES, 1985, 61 (01) :45-47