Synthesis of 4-aryl-3,4-dihydropyrimidin-2(1H)-thione derivatives as potential calcium channel blockers

Zorkun İ. S., Sarac S., Celebi S., Erol K.

BIOORGANIC & MEDICINAL CHEMISTRY, cilt.14, sa.24, ss.8582-8589, 2006 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 14 Sayı: 24
  • Basım Tarihi: 2006
  • Doi Numarası: 10.1016/j.bmc.2006.08.031
  • Dergi Adı: BIOORGANIC & MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.8582-8589
  • Anahtar Kelimeler: Biginelli reaction, dihydropyrimidin-2-thiones (DHPM-2-thiones), ferric chloride, boric acid, calcium channel blocker activity, ONE-POT SYNTHESIS, BIGINELLI DIHYDROPYRIMIDINE SYNTHESIS, ADRENOCEPTOR-SELECTIVE ANTAGONISTS, IMPROVED PROTOCOL CONDITIONS, SOLVENT-FREE CONDITIONS, ACID-ESTERS, CHROMATOGRAPHIC RESOLUTION, PHARMACOLOGICAL-PROPERTIES, ANTIHYPERTENSIVE AGENTS, CONDENSATION REACTION
  • Karadeniz Teknik Üniversitesi Adresli: Hayır

Özet

Biginelli reaction which involves condensation of methyl 3-oxopentanoate, aromatic aldehydes and thiourea with a catalytic amount of HCl at reflux temperature has been used for the synthesis of 4-aryl-6-ethyl-5-(methoxycarbonyl)-3,4-dihydropyrimidin-2(1H)-thiones (1-16). In addition, Lewis acids such as FeCl(3)(.)6 H2O and/or H3BO3 were also used as. catalysts for one-pot synthesis of the products. Compared to the classical Biginelli reaction conditions, the usage of Lewis acids has the advantage of good yields and short reaction times. The calcium channel blocker activities of 1-16 were screened by the tests performed on isolated rat ileum and thoracic aorta. Although product 11, 2-nitrophenyl-derivative, has potent antispasmodic activity on BaCl2-stimulated rat ileum, it does not have vasodilator activity on KCl-stimulated rat thoracic aorta. Product 15, 2-ethoxyphenyl-derivative, exhibited significant antispasmodic and vasodilator activities in both screening paradigms. (c) 2006 Elsevier Ltd. All rights reserved.