Synthesis of bioactive polyheterocyclic ring systems as 5α-reductase inhibitors.
Simple synthetic strategies for the hitherto unreported [1,2,4]triazolo[4,3-a]pyrido[4,3-d]pyrimidines 8 and [1,2,4]triazolo[4',3':1,2]pyrimido[4,5-b][1,6]naphthyridine-5-one 15 are described based on reaction of thione 3 and 12 with hydrazonoyl chloride 1a-h, respectively. The structures of products 8 and 15 were confirmed by spectroscopic and X-ray crystallographic analyses. Also, the mechanism of such reactions was discussed. In addition, reaction of compound 12 with bromoacetic acid and hydrazine hydrate was investigated. Compounds were screened against 5α-reductase and showed activities with good LD(50) and LD(90) for all compounds.
Abdel Hafez
Naglaa A
NA
Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo, Egypt.
Farghaly
Thoraya A
TA
Al-Omar
Mohamed A
MA
Abdalla
Mohamed M
MM
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000187:drug effects*; D058891:5-alpha Reductase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D051381:Rats; D017207:Rats, Sprague-Dawley; D013055:Spectrophotometry, Infrared
D058891:5-alpha Reductase Inhibitors; D006571:Heterocyclic Compounds; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase