2. Academic Validation
  3. Design and synthesis of poly ADP-ribose polymerase-1 inhibitors. 2. Biological evaluation of aza-5[H]-phenanthridin-6-ones as potent, aqueous-soluble compounds for the treatment of ischemic injuries

Design and synthesis of poly ADP-ribose polymerase-1 inhibitors. 2. Biological evaluation of aza-5[H]-phenanthridin-6-ones as potent, aqueous-soluble compounds for the treatment of ischemic injuries

  • J Med Chem. 2003 Jul 3;46(14):3138-51. doi: 10.1021/jm030109s.
Dana Ferraris 1,  Yao-Sen Ko,  Thomas Pahutski,  Rica Pargas Ficco,  Larisa Serdyuk,  Christina Alemu,  Chadwick Bradford,  Tiffany Chiou,  Randall Hoover,  Shirley Huang,  Susan Lautar,  Shi Liang,  Qian Lin,  May X-C Lu,  Maria Mooney,  Lisa Morgan,  Yongzhen Qian,  Scott Tran,  Lawrence R Williams,  Qi Yi Wu,  Jie Zhang,  Yinong Zou,  Vincent Kalish
Affiliations

Affiliation

  • 1 Guilford Pharmaceuticals Inc, 6611 Tributary Street, Baltimore, Maryland 21224, USA. ferraisd@guildfordpharm.com
PMID: 12825952 DOI: 10.1021/jm030109s
Abstract

A series of aza-5[H]-phenanthridin-6-ones were synthesized and evaluated as inhibitors of poly ADP-ribose polymerase-1 (PARP-1). Inhibitory potency of the unsubstituted aza-5[H]-phenanthridin-6-ones (i.e., benzonaphthyridones) was dependent on the position of the nitrogen atom within the core structure. The A ring nitrogen analogues (7-, 8-, and 10-aza-5[H]-phenanthridin-6-ones) were an order of magnitude less potent than C ring nitrogen analogues (1-, 2-, 3-, and 4-aza-5[H]-phenanthridin-6-ones). Preliminary stroke results from 1- and 2-aza-5[H]-phenanthridin-6-one prompted structure-activity relationships to be established for several 2- and 3-substituted 1-aza-5[H]-phenanthridin-6-ones. The 2-substituted 1-aza-5[H]-phenanthridin-6-ones were designed to improve the solubility and pharmacokinetic profiles for this series of PARP-1 inhibitors. Most importantly, three compounds from this series demonstrated statistically significant protective effects in rat models of stroke and heart ischemia.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z