Optimization of isochromanone based urotensin II receptor agonists
Lehmann, Fredrik ; Currier, Erika A. ; Olsson, Roger LU
; Ma, Jian Nong
; Burstein, Ethan S.
; Hacksell, Uli
and Luthman, Kristina
(2010)
In Bioorganic and Medicinal Chemistry
18(13).
p.4844-4854
- Abstract
A series of novel isochromanone based urotensin II receptor agonists have been synthesized and evaluated for their activity using a functional cell based assay (R-SAT). Several potent and efficacious derivatives were identified with 3-(3,4-dichlorophenyl)-6,7-dimethyl-3-(2-dimethylaminoethyl)isochroman-1-one (28) being the most potent compound showing an EC50-value of 51 nM, thereby being the most potent compound so far within the isochromanone series. In addition, two other heterocyclic systems (isochromanes and tetrahydroisoquinolinones) were investigated and these derivatives were found to be both potent and efficacious. The activity of the isochromane derivatives implies that the carbonyl group of the isochromanone is not... (More)
A series of novel isochromanone based urotensin II receptor agonists have been synthesized and evaluated for their activity using a functional cell based assay (R-SAT). Several potent and efficacious derivatives were identified with 3-(3,4-dichlorophenyl)-6,7-dimethyl-3-(2-dimethylaminoethyl)isochroman-1-one (28) being the most potent compound showing an EC50-value of 51 nM, thereby being the most potent compound so far within the isochromanone series. In addition, two other heterocyclic systems (isochromanes and tetrahydroisoquinolinones) were investigated and these derivatives were found to be both potent and efficacious. The activity of the isochromane derivatives implies that the carbonyl group of the isochromanone is not necessary for activity. Furthermore it was found that the geometry of the heterocycles was more important for receptor interaction than the composition of the heteroatoms present.
(Less)
- author
- Lehmann, Fredrik
; Currier, Erika A.
; Olsson, Roger
LU
; Ma, Jian Nong
; Burstein, Ethan S.
; Hacksell, Uli
and Luthman, Kristina
- publishing date
- 2010-05-31
- type
- Contribution to journal
- publication status
- published
- keywords
- Agonist, GRP14, Isochromane, Isochromanone, SAR, Tetrahydroisoquinolinone, Urotensin II, UT-receptor
- in
- Bioorganic and Medicinal Chemistry
- volume
- 18
- issue
- 13
- pages
- 11 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:20570157
- scopus:77954218912
- ISSN
- 0968-0896
- DOI
- 10.1016/j.bmc.2010.04.041
- language
- English
- LU publication?
- no
- id
- c66ddadf-86f4-4603-b82c-f3f98a1c6468
- date added to LUP
- 2019-10-02 10:12:26
- date last changed
- 2024-04-16 21:18:51
@article{c66ddadf-86f4-4603-b82c-f3f98a1c6468,
abstract = {{<p>A series of novel isochromanone based urotensin II receptor agonists have been synthesized and evaluated for their activity using a functional cell based assay (R-SAT). Several potent and efficacious derivatives were identified with 3-(3,4-dichlorophenyl)-6,7-dimethyl-3-(2-dimethylaminoethyl)isochroman-1-one (28) being the most potent compound showing an EC<sub>50</sub>-value of 51 nM, thereby being the most potent compound so far within the isochromanone series. In addition, two other heterocyclic systems (isochromanes and tetrahydroisoquinolinones) were investigated and these derivatives were found to be both potent and efficacious. The activity of the isochromane derivatives implies that the carbonyl group of the isochromanone is not necessary for activity. Furthermore it was found that the geometry of the heterocycles was more important for receptor interaction than the composition of the heteroatoms present.</p>}},
author = {{Lehmann, Fredrik and Currier, Erika A. and Olsson, Roger and Ma, Jian Nong and Burstein, Ethan S. and Hacksell, Uli and Luthman, Kristina}},
issn = {{0968-0896}},
keywords = {{Agonist; GRP14; Isochromane; Isochromanone; SAR; Tetrahydroisoquinolinone; Urotensin II; UT-receptor}},
language = {{eng}},
month = {{05}},
number = {{13}},
pages = {{4844--4854}},
publisher = {{Elsevier}},
series = {{Bioorganic and Medicinal Chemistry}},
title = {{Optimization of isochromanone based urotensin II receptor agonists}},
url = {{http://dx.doi.org/10.1016/j.bmc.2010.04.041}},
doi = {{10.1016/j.bmc.2010.04.041}},
volume = {{18}},
year = {{2010}},
}