Correlation Engine 2.0
Clear Search sequence regions


  • 122.17, 29.87, 20.52. 3-( 5- bromo- 4-(( 4- bro... (1)
  • 19.10. 3-( 5- bromo- 4-( 4- ethylnaphth- 1- yl)... (1)
  • 4 and (1)
  • acceptors (1)
  • acetyl (1)
  • acid (54)
  • acyl (5)
  • adduct (1)
  • aldehyde (6)
  • alkyl (1)
  • allantoin (1)
  • allopurinol (1)
  • aluminum (1)
  • amine (7)
  • anhydrides (1)
  • anion (2)
  • antibodies (1)
  • arthritis (2)
  • attacks (1)
  • br 4 (1)
  • brine (13)
  • bromide (2)
  • brs 3 (2)
  • brs 8 (11)
  • carbon (1)
  • cardiovascular diseases (1)
  • case (3)
  • cell plates (1)
  • cells human (1)
  • CH2 (4)
  • cocl 2 (2)
  • colorless (19)
  • corticosteroids (1)
  • crystals (1)
  • d 400 (129)
  • dicyclohexylcarbodiimide (2)
  • dimethylaminopyridine (2)
  • direct (3)
  • dmso (2)
  • ester (10)
  • ethanol (3)
  • ethanol (1)
  • febuxostat (1)
  • g 15 (1)
  • gout (12)
  • gout lead (1)
  • halogen (1)
  • heparin (1)
  • humans (2)
  • hydrolysis (1)
  • hyperlipidemia (1)
  • hyperuricemia (8)
  • impairment (1)
  • inhibit (1)
  • ion (1)
  • isomer (1)
  • joint pain (1)
  • lactones (1)
  • lialh4 (2)
  • lithium (1)
  • lithium diisopropylamide (2)
  • m 35 (1)
  • m 75 (1)
  • m 8 (21)
  • mass (20)
  • methanol (4)
  • methyl (67)
  • n buli (4)
  • olefin (3)
  • osmium (1)
  • oxide (2)
  • parent (5)
  • patient (6)
  • penicillin (2)
  • phase (3)
  • phosphate (1)
  • physicians (1)
  • potassium (2)
  • precipitates (3)
  • probenecid (3)
  • propen (4)
  • proton (1)
  • reflux (6)
  • risk factor (1)
  • salt (3)
  • serum uric acid (3)
  • signals (2)
  • silica gel (4)
  • sodium (25)
  • sodium nitrite (1)
  • sodium phosphate (1)
  • solvent (4)
  • streptomycin (1)
  • switzerland (1)
  • tempo (3)
  • tetrahydrofuran (1)
  • trypsin (1)
  • URAT1 (35)
  • uric acid (7)
  • uricosuria (1)
  • vessel (2)
  • xanthine oxidase inhibitors (4)
  • Sizes of these terms reflect their relevance to your search.

    In order to systematically explore and understand the structure-activity relationship (SAR) of a lesinurad-based hit (1c) derived from the replacement of the S atom in lesinurad with CH₂, 18 compounds (1a-1r) were designed, synthesized and subjected to in vitro URAT1 inhibitory assay. The SAR exploration led to the discovery of a highly potent flexible URAT1 inhibitor, 1q, which was 31-fold more potent than parent lesinurad (IC50 = 0.23 μM against human URAT1 for 1q vs 7.18 μM for lesinurad). The present study discovered a flexible molecular scaffold, as represented by 1q, which might serve as a promising prototype scaffold for further development of potent URAT1 inhibitors, and also demonstrated that the S atom in lesinurad was not indispensable for its URAT1 inhibitory activity.

    Citation

    He Tian, Wei Liu, Zhixing Zhou, Qian Shang, Yuqiang Liu, Yafei Xie, Changying Liu, Weiren Xu, Lida Tang, Jianwu Wang, Guilong Zhao. Discovery of a Flexible Triazolylbutanoic Acid as a Highly Potent Uric Acid Transporter 1 (URAT1) Inhibitor. Molecules (Basel, Switzerland). 2016 Nov 16;21(11)

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 27854343

    View Full Text