Polycyclic N-heterocyclic compounds. Part 64: synthesis of 5-amino-1,2,6,7-tetrahydrobenzo[f]furo[2,3-c]isoquinolines and related compounds. Evaluation of their bronchodilator activity and effects on lipoprotein lipase mRNA expression.
Reaction of 1-(3-cyanopropoxy)-3,4-dihydronaphthalene-2-carbonitriles with potassium tert-butoxide gave 5-amino-1,2,6,7-tetrahydrobenzo[f]furo[2,3-c]isoquinolines via a Truce-Smiles rearrangement. The 5-amino group was transformed to the bromo derivatives which were allowed to react with aliphatic cyclic amines to produce amino derivatives. In contrast, a combination of imidazole and NaH gave a dihydrofuran ring cleaved product, the structure of which was confirmed by X-ray crystallographic analysis. Effects of the newly synthesized compounds on carbamylcholine chloride-induced contractions of trachea and lipoprotein lipase mRNA expression were also evaluated and found one promising bronchodilator.
Okuda
Kensuke
K
Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. okuda@gifu-pu.ac.jp
Deguchi
Hiroshi
H
Kashino
Setsuo
S
Hirota
Takashi
T
Sasaki
Kenji
K
D016475:3T3 Cells; D000818:Animals; D001993:Bronchodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D005663:Furans / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006571:Heterocyclic Compounds; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000187:drug effects*
D001993:Bronchodilator Agents; D005663:Furans; D006571:Heterocyclic Compounds; D007546:Isoquinolines; D011083:Polycyclic Compounds; D012333:RNA, Messenger; D008071:Lipoprotein Lipase