title: SAR based design of nicotinamides as a novel class of androgen receptor antagonists for prostate cancer.
abstract: Molecular knowledge of pure antagonism and systematic SAR study offered a direction for structural optimization of DIMN to provide nicotinamides as a novel series of AR antagonists. Nicotinamides with extended linear scaffold bearing sterically bulky alkoxy groups on isoquinoline end were synthesized for H12 displacement. AR binding affinity and molecular basis of antiandrogenic effect establish the optimized derivatives, 7au and 7bb, as promising candidates of second generation AR antagonists for advanced prostate cancer.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwang-ju 500-757, Republic of Korea.
authors.forename: Su Hui
authors.initials: SH
authors.lastname: Yang
authors.forename: Chin-Hee
authors.initials: CH
authors.lastname: Song
authors.forename: Hue Thi My
authors.initials: HT
authors.lastname: Van
authors.forename: Eunsook
authors.initials: E
authors.lastname: Park
authors.forename: Daulat Bikram
authors.initials: DB
authors.lastname: Khadka
authors.forename: Eun-Yeung
authors.initials: EY
authors.lastname: Gong
authors.forename: Keesook
authors.initials: K
authors.lastname: Lee
authors.forename: Won-Jea
authors.initials: WJ
authors.lastname: Cho
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D059002:Androgen Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011944:Receptors, Androgen / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: C576268:6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl)nicotinamide; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D007546:Isoquinolines; D011944:Receptors, Androgen; D009536:Niacinamide