Synthesis and modeling study of (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy-8-(1-decynyl)-benzolactam-V8 as protein kinase C modulators

被引：7

作者：

Wei, ZL

Sakamuri, S

Petukhov, PA

George, C

Lewin, NE

Blumberg, PM

Kozikowski, AP

机构：

[1] Georgetown Univ, Med Ctr, Dept Neurol, Drug Discovery Program, Washington, DC 20007 USA

[2] USN, Res Lab, Washington, DC 20375 USA

[3] NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA

来源：

ORGANIC LETTERS | 2002年 / 4卷 / 13期

关键词：

D O I：

10.1021/ol026013u

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] Both (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy-8-(1-decynyl)benzolactam-V8 were designed and synthesized as PKC modulators. Biological assays reveal the (6R)-ligand to be 20-fold more potent than its (6S)-counterpart in binding to PKCalpha.

引用

页码：2169 / 2172

页数：4

共 36 条

[1]

ARMATO U, 1999, CURR T BIOCHEM RES, V1, P1

[2] From bench top to bedside [J].

Barinaga, M .

SCIENCE, 1997, 278 (5340) :1036-1039

[3] 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

[4] 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

[5] NEW CLASSES OF TUMOR PROMOTERS - TELEOCIDIN, APLYSIATOXIN, AND PALYTOXIN [J].

FUJIKI, H ;

SUGIMURA, T .

ADVANCES IN CANCER RESEARCH, 1987, 49 :223-264

[6]

Glazer RI, 1998, CURR PHARM DESIGN, V4, P277

[7]

Hinterding K, 1998, ANGEW CHEM INT EDIT, V37, P688, DOI 10.1002/(SICI)1521-3773(19980403)37:6<688::AID-ANIE688>3.0.CO

[8]

2-B

[9] Synthesis and biological activities of new conformationally restricted analogues of (-)-indolactam-V: Elucidation of the biologically active conformation of the tumor-promoting teleocidins [J].

Irie, K ;

Isaka, T ;

Iwata, Y ;

Yanai, Y ;

Nakamura, Y ;

Koizumi, F ;

Ohigashi, H ;

Wender, PA ;

Satomi, Y ;

Nishino, H .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (44) :10733-10743

[10] HALOGENATION USING QUATERNARY AMMONIUM POLYHALIDES .6. BROMINATION OF AROMATIC-AMINES BY USE OF BENZYLTRIMETHYLAMMONIUM TRIBROMIDE [J].

KAJIGAESHI, S ;

KAKINAMI, T ;

INOUE, K ;

KONDO, M ;

NAKAMURA, H ;

FUJIKAWA, M ;

OKAMOTO, T .

BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 1988, 61 (02) :597-599

← 1 2 3 4 →