Abstract
A series of psoralens and structurally related 5,7-disubstituted coumarins was synthesized and investigated for their K+ channel blocking activity as well as for their phototoxicity to Artemia salina and their ability to generate singlet oxygen and to photomodify DNA. After screening the compounds on Ranvier nodes of the toad Xenopus laevis, the affinities of the most promising compounds, which proved to be psoralens bearing alkoxy substituents in the 5-position or alkoxymethyl substituents in the neighboring 4- or 4'-position, to a number of homomeric K+ channels were characterized. All compounds exhibited the highest affinity to Kv1.2. 5,8- Diethoxypsoralen (10d) was found to be an equally potent inhibitor of Kv1.2 and Kv1.3, while lacking the phototoxicity normally inherent in psoralens. The reported compounds represent a novel series of nonpeptide blockers of Shaker-type K+ channels that could be further developed into selective inhibitors of Kv1.2 or Kv1.3.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4542-4549 |
| Number of pages | 8 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 41 |
| Issue number | 23 |
| DOIs | |
| State | Published - Nov 5 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
Alkoxypsoralens, novel nonpeptide blockers of Shaker-type K+ channels : Synthesis and photoreactivity. / Wulff, Heike; Rauer, Heiko; Düring, Tim; Hanselmann, Christine; Ruff, Katharina; Wrisch, Anja; Grissmer, Stephan; Hänsel, Wolfram.
In: Journal of Medicinal Chemistry, Vol. 41, No. 23, 05.11.1998, p. 4542-4549.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alkoxypsoralens, novel nonpeptide blockers of Shaker-type K+ channels
T2 - Synthesis and photoreactivity
AU - Wulff, Heike
AU - Rauer, Heiko
AU - Düring, Tim
AU - Hanselmann, Christine
AU - Ruff, Katharina
AU - Wrisch, Anja
AU - Grissmer, Stephan
AU - Hänsel, Wolfram
PY - 1998/11/5
Y1 - 1998/11/5
N2 - A series of psoralens and structurally related 5,7-disubstituted coumarins was synthesized and investigated for their K+ channel blocking activity as well as for their phototoxicity to Artemia salina and their ability to generate singlet oxygen and to photomodify DNA. After screening the compounds on Ranvier nodes of the toad Xenopus laevis, the affinities of the most promising compounds, which proved to be psoralens bearing alkoxy substituents in the 5-position or alkoxymethyl substituents in the neighboring 4- or 4'-position, to a number of homomeric K+ channels were characterized. All compounds exhibited the highest affinity to Kv1.2. 5,8- Diethoxypsoralen (10d) was found to be an equally potent inhibitor of Kv1.2 and Kv1.3, while lacking the phototoxicity normally inherent in psoralens. The reported compounds represent a novel series of nonpeptide blockers of Shaker-type K+ channels that could be further developed into selective inhibitors of Kv1.2 or Kv1.3.
AB - A series of psoralens and structurally related 5,7-disubstituted coumarins was synthesized and investigated for their K+ channel blocking activity as well as for their phototoxicity to Artemia salina and their ability to generate singlet oxygen and to photomodify DNA. After screening the compounds on Ranvier nodes of the toad Xenopus laevis, the affinities of the most promising compounds, which proved to be psoralens bearing alkoxy substituents in the 5-position or alkoxymethyl substituents in the neighboring 4- or 4'-position, to a number of homomeric K+ channels were characterized. All compounds exhibited the highest affinity to Kv1.2. 5,8- Diethoxypsoralen (10d) was found to be an equally potent inhibitor of Kv1.2 and Kv1.3, while lacking the phototoxicity normally inherent in psoralens. The reported compounds represent a novel series of nonpeptide blockers of Shaker-type K+ channels that could be further developed into selective inhibitors of Kv1.2 or Kv1.3.
UR - http://www.scopus.com/inward/record.url?scp=0032487929&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032487929&partnerID=8YFLogxK
U2 - 10.1021/jm981032o
DO - 10.1021/jm981032o
M3 - Article
C2 - 9804693
AN - SCOPUS:0032487929
VL - 41
SP - 4542
EP - 4549
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 23
ER -