2. Academic Validation
  3. Dual functional cholinesterase and PDE4D inhibitors for the treatment of Alzheimer's disease: Design, synthesis and evaluation of tacrine-pyrazolo[3,4-b]pyridine hybrids

Dual functional cholinesterase and PDE4D inhibitors for the treatment of Alzheimer's disease: Design, synthesis and evaluation of tacrine-pyrazolo[3,4-b]pyridine hybrids

  • Bioorg Med Chem Lett. 2019 Aug 15;29(16):2150-2152. doi: 10.1016/j.bmcl.2019.06.056.
Tingting Pan 1,  Shishun Xie 1,  Yan Zhou 1,  Jinhui Hu 1,  Haibin Luo 1,  Xingshu Li 1,  Ling Huang 2
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • 2 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: [email protected].
PMID: 31281020 DOI: 10.1016/j.bmcl.2019.06.056
Abstract

A series of tacrine-pyrazolo[3,4-b]pyridine hybrids were synthesised and evaluated as dual cholinesterase (ChE) and phosphodiesterase 4D (PDE4D) inhibitors for the treatment of Alzheimer's disease (AD). Compound 10j, which is tacrine linked with pyrazolo[3,4-b]pyridine moiety by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) with IC50 value of 0.125 μM. Moreover, compound 10j provided a desired balance of AChE and butylcholinesterase (BuChE) and PDE4D inhibition activities, with IC50 value of 0.449 and 0.271 μM, respectively. The above results indicated that this hybrid was a promising dual functional agent for the treatment of AD.

Keywords

Alzheimer's disease; Cholinesterase inhibitor; PDE4D inhibitors; Tacrine-pyrazolo[3,4-b]pyridine hybrids.

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