Novel thieno[2,3-d]pyrimidines: Their design, synthesis, crystal structure analysis and pharmacological evaluation

Raju Adepu, D. Rambabu, Bagineni Prasad, Chandana Lakshmi T. Meda, Ajit Kandale, G. Rama Krishna, C. Malla Reddy, Lakshmi N. Chennuru, Kishore V.L. Parsa, Manojit Pal

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Novel thieno[2,3-d]pyrimidines containing a cyclohexane ring fused with a six- or five-membered heterocyclic moiety along with a benzylic nitrile were designed as potential inhibitors of PDE4. Expeditious synthesis of these compounds was carried out via a multi-step sequence consisting of a few key steps such as Gewald reaction, Dieckmann type cyclisation and Krapcho decarboxylation. This newly developed strategy involved construction of the thienopyrimidine ring followed by the cyclohexanone moiety and subsequently the fused heterocyclic ring. A number of thieno[2,3-d]pyrimidine based derivatives were synthesized using this method some of which showed promising PDE4B inhibitory properties. One of them was tested for PDE4D inhibition in vitro and dose dependent inhibition of TNF-α. A few selected molecules were docked into the PE4B protein the results of which showed good overall correlations to their observed PDE4B inhibitory properties in vitro. The crystal structure analysis of representative compounds along with hydrogen bonding patterns and molecular arrangement present within the molecule is described.

Original languageEnglish
Pages (from-to)5554-5569
Number of pages16
JournalOrganic and Biomolecular Chemistry
Volume10
Issue number29
DOIs
StatePublished - 7 Aug 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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