Synthesis and evaluation of novel spiro derivatives for pyrrolopyrimidines as anti-hyperglycemia promising compounds

J Enzyme Inhib Med Chem. 2018 Dec;33(1):809-817. doi: 10.1080/14756366.2018.1461854.

Abstract

Pyrrolopyrimidin-4-ylidene-malononitriles IIad were prepared as important intermediates for preparation of a new series of spiro-pyrrolopyrimidines. These intermediates undergo cyclisation via reaction with acetylacetone, guanidine hydrochloride or hydrazine hydrate. Elemental and spectroscopic evidences for the structures of these compounds are presented. The final compounds have been monitored for in vivo anti-hyperglycemic activity, compared with Amaryl as standard drug. Among 12 tested compounds, both spiro (pyrano IIIb and pyrazlo Va) derivatives exhibit promising anti-hyperglycemic activity.

Keywords: Spiropyrimidines; anti-hyperglycemic assay; pyrrolopyrimidines.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Cyclization
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy
  • Glucose Tolerance Test
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Proton Magnetic Resonance Spectroscopy
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Rats, Wistar
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Infrared
  • Spiro Compounds / chemistry*
  • Streptozocin

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Pyrimidines
  • Pyrroles
  • Spiro Compounds
  • pyrrolopyrimidine
  • Streptozocin