title: 2-Aminobenzimidazoles as potent Aurora kinase inhibitors.
abstract: This Letter describes the discovery and key structure-activity relationship (SAR) of a series of 2-aminobenzimidazoles as potent Aurora kinase inhibitors. 2-Aminobenzimidazole serves as a bioisostere of the biaryl urea residue of SNS-314 (1c), which is a potent Aurora kinase inhibitor and entered clinical testing in patients with solid tumors. Compared to SNS-314, this series of compounds offers better aqueous solubility while retaining comparable in vitro potency in biochemical and cell-based assays; in particular, 6m has also demonstrated a comparable mouse iv PK profile to SNS-314.
authors: Sunesis Pharmaceuticals, Inc., 395 Oyster Point Blvd., South San Francisco, CA 94080, USA. mzhong@presidiopharma.com
authors: Min
authors: M
authors: Zhong
authors: Minna
authors: M
authors: Bui
authors: Wang
authors: W
authors: Shen
authors: Subramanian
authors: S
authors: Baskaran
authors: Darin A
authors: DA
authors: Allen
authors: Robert A
authors: RA
authors: Elling
authors: W Michael
authors: WM
authors: Flanagan
authors: Amy D
authors: AD
authors: Fung
authors: Emily J
authors: EJ
authors: Hanan
authors: Shannon O
authors: SO
authors: Harris
authors: Stacey A
authors: SA
authors: Heumann
authors: Ute
authors: U
authors: Hoch
authors: Sheryl N
authors: SN
authors: Ivy
authors: Jeffrey W
authors: JW
authors: Jacobs
authors: Stuart
authors: S
authors: Lam
authors: Heman
authors: H
authors: Lee
authors: Robert S
authors: RS
authors: McDowell
authors: Johan D
authors: JD
authors: Oslob
authors: Hans E
authors: HE
authors: Purkey
authors: Michael J
authors: MJ
authors: Romanowski
authors: Jeffrey A
authors: JA
authors: Silverman
authors: Bradley T
authors: BT
authors: Tangonan
authors: Pietro
authors: P
authors: Taverna
authors: Wenjin
authors: W
authors: Yang
authors: Josh C
authors: JC
authors: Yoburn
authors: Chul H
authors: CH
authors: Yu
authors: Kristin M
authors: KM
authors: Zimmerman
authors: Tom
authors: T
authors: O'Brien
authors: Willard
authors: W
authors: Lew
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D064127:Aurora Kinases; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; C027391:2-aminobenzimidazole; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases