4-Phenyl-1,2,3,6-tetrahydropyridine, an excellent fragment to improve the potency of PARP-1 inhibitors

被引：40

作者：

Ishida, J

Hattori, K

Yamamoto, H

Iwashita, A

Mihara, K

Matsuoka, N

机构：

[1] Med Chem Res Labs, Yodogawa Ku, Osaka 5328514, Japan

[2] Fujisawa Pharmaceut Co Ltd, Med Biol Res Labs, Yodogawa Ku, Osaka 5328514, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 19期

关键词：

PARP-1; poly(ADP-ribose) polymerase; 4-phenyl-1,2,3,6-tetrahydropyridine;

D O I：

10.1016/j.bmcl.2005.06.094

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have shown that a 4-phenyl-1,2,3,6-tetrahydropyridine fragment plays an important role in improving inhibitory potency against poly(ADP-ribose) polymerise-1 (PARP-1). Various benzamide analogues linked with this fragment via alkyl spacers have been prepared and evaluated. As a result, some of them have been found to be highly potent PARP-1 inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4221 / 4225

页数：5

相关论文

共 25 条

[1]

ADBELKARIM GE, 2001, INT J MOL MED, V7, P255

[2]

AM CYANAMID CO, 2000, Patent No. 0044716

[3] Nonsteroidal antiinflammatory agents -: Part 1:: Antiinflammatory, analgesic and antipyretic activity of some new 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-ones [J].

Badawey, ESAM ;

El-Ashmawey, IM .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1998, 33 (05) :349-361

[4] Poly(ADP-ribose) polymerase: killer or conspirator? The 'suicide hypothesist' revisited [J].

Chiarugi, A .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2002, 23 (03) :122-129

[5] New inhibitors of poly(ADPribose) polymerase and their potential therapeutic targets [J].

Cosi, C .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2002, 12 (07) :1047-1071

[6] Poly(ADP-ribose) polymerase inhibitors protect against MPTP-induced depletions of striatal dopamine and cortical noradrenaline in C57B1/6 mice [J].

Cosi, C ;

Colpaert, F ;

Koek, W ;

Degryse, A ;

Marien, M .

BRAIN RESEARCH, 1996, 729 (02) :264-269

[7]

DEMURCAI G, 2000, DNA DAMAGE STRESS SI

[8] AN EFFICIENT CONVERSION OF NITRILES TO AMIDINES [J].

GARIGIPATI, RS .

TETRAHEDRON LETTERS, 1990, 31 (14) :1969-1972

[9] Rational approaches to discovery of orally active and brain-penetrable quinazolinone inhibitors of poly(ADP-ribose)polymerase [J].

Hattori, K ;

Kido, Y ;

Yamamoto, H ;

Ishida, J ;

Kamijo, K ;

Murano, K ;

Ohkubo, M ;

Kinoshita, T ;

Iwashita, A ;

Mihara, K ;

Yamazaki, S ;

Matsuoka, N ;

Teramura, Y ;

Miyake, H .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (17) :4151-4154

[10] Neuroprotective effects of a novel poly(ADP-ribose) polymerase-1 inhibitor, 2-{3-[4-(4-chlorophenyl)-l-piperazinyl] propyl}-4(3H)-quinazolinone (FR255595), in an in Vitro model of cell death and in Mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease [J].

Iwashita, A ;

Yamazaki, S ;

Mihara, K ;

Hattori, K ;

Yamamoto, H ;

Ishida, J ;

Matsuoka, N ;

Mutoh, S .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2004, 309 (03) :1067-1078