title: Discovery of 3-hydroxy-4-cyano-isoquinolines as novel, potent, and selective inhibitors of human 11β-hydroxydehydrogenase 1 (11β-HSD1).
abstract: Derived from the HTS hit 1, a series of hydroxyisoquinolines was discovered as potent and selective 11β-HSD1 inhibitors with good cross species activity. Optimization of substituents at the 1 and 4 positions of the isoquinoline group in addition to the core modifications, with a special focus on enhancing metabolic stability and aqueous solubility, resulted in the identification of several compounds as potent advanced leads.
authors: Bristol-Myers Squibb Research & Development, PO Box 5400, Hopewell, NJ 08534-5400, USA. shung.wu@bms.com
authors: Shung C
authors: SC
authors: Wu
authors: David
authors: D
authors: Yoon
authors: Janice
authors: J
authors: Chin
authors: Katy
authors: K
authors: van Kirk
authors: Ramakrishna
authors: R
authors: Seethala
authors: Rajasree
authors: R
authors: Golla
authors: Bin
authors: B
authors: He
authors: Thomas
authors: T
authors: Harrity
authors: Lori K
authors: LK
authors: Kunselman
authors: Nathan N
authors: NN
authors: Morgan
authors: Randolph P
authors: RP
authors: Ponticiello
authors: Joseph R
authors: JR
authors: Taylor
authors: Rachel
authors: R
authors: Zebo
authors: Timothy W
authors: TW
authors: Harper
authors: Wenying
authors: W
authors: Li
authors: Mengmeng
authors: M
authors: Wang
authors: Lisa
authors: L
authors: Zhang
authors: Bogdan G
authors: BG
authors: Sleczka
authors: Akbar
authors: A
authors: Nayeem
authors: Steven
authors: S
authors: Sheriff
authors: Daniel M
authors: DM
authors: Camac
authors: Paul E
authors: PE
authors: Morin
authors: John G
authors: JG
authors: Everlof
authors: Yi-Xin
authors: YX
authors: Li
authors: Cheryl A
authors: CA
authors: Ferraro
authors: Kasia
authors: K
authors: Kieltyka
authors: Wilson
authors: W
authors: Shou
authors: Marianne B
authors: MB
authors: Vath
authors: Tatyana A
authors: TA
authors: Zvyaga
authors: David A
authors: DA
authors: Gordon
authors: Jeffrey A
authors: JA
authors: Robl
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1