Synthesis of N-alkylated pyrazolo[3,4-d]pyrimidine analogs and evaluation of acetylcholinesterase and carbonic anhydrase inhibition properties

Aydin B. O., ANIL D., Demir Y.

ARCHIV DER PHARMAZIE, cilt.354, sa.5, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 354 Sayı: 5
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/ardp.202000330
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: acetylcholinesterase, carbonic anhydrase, enzyme inhibition, pyrazolopyrimidine
  • Atatürk Üniversitesi Adresli: Evet

Özet

Fused pyrimidines, especially pyrazolo[3,4-d]pyrimidines, are among the most preferred building blocks for pharmacology studies, as they exhibit a broad spectrum of biological activity. In this study, new derivatives of pyrazolo[3,4-d]pyrimidine were synthesized by alkylation of the N1 nitrogen atom. We synthesized 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine 2 from commercially available aminopyrazolopyrimidine 1 using N-iodosuccinimide as an iodinating agent. The synthesis of compound 2 started with nucleophilic substitution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine with R-X (X: -OMs, -Br, -Cl), affording N-alkylated pyrazolo[3,4-d]pyrimidine. We performed this synthesis using a weak inorganic base and the mild temperature was also used for a two-step procedure to generate N-alkylated pyrazolo[3,4-d]pyrimidine derivatives. Also, all compounds were tested for their ability to inhibit acetylcholinesterase (AChE) and the human carbonic anhydrase (hCA) isoforms I and II, with K-i values in the range of 15.41 +/- 1.39-63.03 +/- 10.68 nM for AChE, 17.68 +/- 1.92-66.27 +/- 5.43 nM for hCA I, and 8.41 +/- 2.03-28.60 +/- 7.32 nM for hCA II. Notably, compound 10 was the most selective and potent CA I inhibitor with a significant selectivity ratio of 26.90.