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

Kensuke Okuda, Hiroshi Deguchi, Setsuo Kashino, Takashi Hirota, Kenji Sasaki

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)685-689
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Volume58
Issue number5
DOIs
Publication statusPublished - May 2010

Fingerprint

Heterocyclic Compounds
Lipoprotein Lipase
Bronchodilator Agents
Carbachol
Trachea
Amines
Chlorides
X-Rays
Derivatives
Messenger RNA
X rays
potassium tert-butoxide
imidazole
furo(2,3-c)isoquinoline

Keywords

  • Bronchodilator activity
  • Cyclization
  • Furo[2,3-b]pyridine
  • Lipoprotein lipase
  • Ring cleavage
  • Truce-Smiles rearrangement

ASJC Scopus subject areas

  • Drug Discovery
  • Chemistry(all)

Cite this

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title = "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",
abstract = "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.",
keywords = "Bronchodilator activity, Cyclization, Furo[2,3-b]pyridine, Lipoprotein lipase, Ring cleavage, Truce-Smiles rearrangement",
author = "Kensuke Okuda and Hiroshi Deguchi and Setsuo Kashino and Takashi Hirota and Kenji Sasaki",
year = "2010",
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pages = "685--689",
journal = "Chemical and Pharmaceutical Bulletin",
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T1 - Polycyclic N-heterocyclic compounds. Part 64

T2 - 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

AU - Okuda, Kensuke

AU - Deguchi, Hiroshi

AU - Kashino, Setsuo

AU - Hirota, Takashi

AU - Sasaki, Kenji

PY - 2010/5

Y1 - 2010/5

N2 - 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.

AB - 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.

KW - Bronchodilator activity

KW - Cyclization

KW - Furo[2,3-b]pyridine

KW - Lipoprotein lipase

KW - Ring cleavage

KW - Truce-Smiles rearrangement

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