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Novel and potent small-molecule urotensin II receptor agonists

Lehmann, Fredrik ; Currier, Erika A. ; Clemons, Bryan ; Hansen, Lars K. ; Olsson, Roger LU ; Hacksell, Uli and Luthman, Kristina (2009) In Bioorganic and Medicinal Chemistry 17(13). p.4657-4665
Abstract


A series of analogs of the non-peptidic urotensin II receptor agonist N-[1-(4-chlorophenyl)-3-(dimethylamino)propyl]-4-phenylbenzamide (FL104) has been synthesized and evaluated pharmacologically. The enantiomers of the two most potent racemic analogues were obtained from the corresponding diastereomeric mandelic amides. In agreement with previously observed SAR, most of the agonist potency resided in the (S) enantiomers. The most potent UII receptor agonist in the new series was (S)-N-[3-dimethylamino-1-(2-naphthyl)propyl]-4-(4-chlorophenyl)benzamide (EC
50
= 23 nM at the urotensin II receptor).

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Agonists, Parallel synthesis, R-SAT, SAR, Urotensin II
in
Bioorganic and Medicinal Chemistry
volume
17
issue
13
pages
4657 - 4665
publisher
Elsevier
external identifiers
  • pmid:19481466
  • scopus:66449132432
ISSN
0968-0896
DOI
10.1016/j.bmc.2009.04.062
language
English
LU publication?
no
id
6794f8c6-aa10-400f-a73a-e44086158dcf
date added to LUP
2019-10-02 10:14:57
date last changed
2021-01-06 07:37:39
@article{6794f8c6-aa10-400f-a73a-e44086158dcf,
  abstract     = {<p><br>
                            A series of analogs of the non-peptidic urotensin II receptor agonist N-[1-(4-chlorophenyl)-3-(dimethylamino)propyl]-4-phenylbenzamide (FL104) has been synthesized and evaluated pharmacologically. The enantiomers of the two most potent racemic analogues were obtained from the corresponding diastereomeric mandelic amides. In agreement with previously observed SAR, most of the agonist potency resided in the (S) enantiomers. The most potent UII receptor agonist in the new series was (S)-N-[3-dimethylamino-1-(2-naphthyl)propyl]-4-(4-chlorophenyl)benzamide (EC<br>
                            <sub>50</sub><br>
                             = 23 nM at the urotensin II receptor).</p>},
  author       = {Lehmann, Fredrik and Currier, Erika A. and Clemons, Bryan and Hansen, Lars K. and Olsson, Roger and Hacksell, Uli and Luthman, Kristina},
  issn         = {0968-0896},
  language     = {eng},
  month        = {07},
  number       = {13},
  pages        = {4657--4665},
  publisher    = {Elsevier},
  series       = {Bioorganic and Medicinal Chemistry},
  title        = {Novel and potent small-molecule urotensin II receptor agonists},
  url          = {http://dx.doi.org/10.1016/j.bmc.2009.04.062},
  doi          = {10.1016/j.bmc.2009.04.062},
  volume       = {17},
  year         = {2009},
}