4-Phenyl-1,2,3,6-tetrahydropyridine, an excellent fragment to improve the potency of PARP-1 inhibitors.
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.
Ishida
Junya
J
Medicinal Chemistry Research Laboratories, 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. junya_ishida@po.fujisawa.co.jp
Hattori
Kouji
K
Yamamoto
Hirofumi
H
Iwashita
Akinori
A
Mihara
Kayoko
K
Matsuoka
Nobuya
N
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000983:Antipyrine; D001549:Benzamides; D006801:Humans; D020128:Inhibitory Concentration 50; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013329:Structure-Activity Relationship
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C040846:4-phenyl-1,2,3,6-tetrahydropyridine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D000983:Antipyrine