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

Junya Ishida; Kouji Hattori; Hirofumi Yamamoto; Akinori Iwashita; Kayoko Mihara; Nobuya Matsuoka

doi:10.1016/j.bmcl.2005.06.094

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

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4221-5. doi: 10.1016/j.bmcl.2005.06.094.

Authors

Junya Ishida¹, Kouji Hattori, Hirofumi Yamamoto, Akinori Iwashita, Kayoko Mihara, Nobuya Matsuoka

Affiliation

¹ Medicinal Chemistry Research Laboratories, 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. junya_ishida@po.fujisawa.co.jp

PMID: 16098744
DOI: 10.1016/j.bmcl.2005.06.094

Abstract

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) polymerase-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.

MeSH terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / analogs & derivatives*
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / chemical synthesis
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
Antipyrine
Benzamides
Humans
Inhibitory Concentration 50
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerase Inhibitors*
Structure-Activity Relationship

Substances

Benzamides
Poly(ADP-ribose) Polymerase Inhibitors
4-phenyl-1,2,3,6-tetrahydropyridine
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
PARP1 protein, human
Poly (ADP-Ribose) Polymerase-1
Antipyrine