Novel potent and efficacious nonpeptidic urotensin II receptor agonists
(2006) In Journal of Medicinal Chemistry 49(7). p.2232-2240- Abstract
Six different series of nonpeptidic urotensin II receptor agonists have been synthesized and evaluated for their agonistic activity in a cell-based assay (R-SAT). The compounds are ring-opened analogues of the isochromanone-based agonist AC-7954 with different functionalities constituting the linker between the two aromatic ring moieties. Several of the compounds are highly potent and efficacious, with N-[1-(4-chlorophenyl)-3-(dimethylamino)- propyl]-4-phenylbenzamide oxalate (5d) being the most potent. The pure enantiomers of 5d were obtained from the corresponding diastereomeric amides. It was shown by a combination of X-ray crystallography and chemical correlation that the activity resides in the S-enantiomer of 5d (pEC50... (More)
Six different series of nonpeptidic urotensin II receptor agonists have been synthesized and evaluated for their agonistic activity in a cell-based assay (R-SAT). The compounds are ring-opened analogues of the isochromanone-based agonist AC-7954 with different functionalities constituting the linker between the two aromatic ring moieties. Several of the compounds are highly potent and efficacious, with N-[1-(4-chlorophenyl)-3-(dimethylamino)- propyl]-4-phenylbenzamide oxalate (5d) being the most potent. The pure enantiomers of 5d were obtained from the corresponding diastereomeric amides. It was shown by a combination of X-ray crystallography and chemical correlation that the activity resides in the S-enantiomer of 5d (pEC50 7.49).
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- author
- Lehmann, Fredrik ; Pettersen, Anna ; Currier, Erika A. ; Sherbukhin, Vladimir ; Olsson, Roger LU ; Hacksell, Uli and Luthman, Kristina
- publishing date
- 2006-04-06
- type
- Contribution to journal
- publication status
- published
- in
- Journal of Medicinal Chemistry
- volume
- 49
- issue
- 7
- pages
- 9 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:16570919
- scopus:33645669146
- ISSN
- 0022-2623
- DOI
- 10.1021/jm051121i
- language
- English
- LU publication?
- no
- id
- adf28454-70e4-4762-9dfe-9706dc64357a
- date added to LUP
- 2019-10-02 10:30:50
- date last changed
- 2024-03-19 22:11:07
@article{adf28454-70e4-4762-9dfe-9706dc64357a, abstract = {{<p>Six different series of nonpeptidic urotensin II receptor agonists have been synthesized and evaluated for their agonistic activity in a cell-based assay (R-SAT). The compounds are ring-opened analogues of the isochromanone-based agonist AC-7954 with different functionalities constituting the linker between the two aromatic ring moieties. Several of the compounds are highly potent and efficacious, with N-[1-(4-chlorophenyl)-3-(dimethylamino)- propyl]-4-phenylbenzamide oxalate (5d) being the most potent. The pure enantiomers of 5d were obtained from the corresponding diastereomeric amides. It was shown by a combination of X-ray crystallography and chemical correlation that the activity resides in the S-enantiomer of 5d (pEC<sub>50</sub> 7.49).</p>}}, author = {{Lehmann, Fredrik and Pettersen, Anna and Currier, Erika A. and Sherbukhin, Vladimir and Olsson, Roger and Hacksell, Uli and Luthman, Kristina}}, issn = {{0022-2623}}, language = {{eng}}, month = {{04}}, number = {{7}}, pages = {{2232--2240}}, publisher = {{The American Chemical Society (ACS)}}, series = {{Journal of Medicinal Chemistry}}, title = {{Novel potent and efficacious nonpeptidic urotensin II receptor agonists}}, url = {{http://dx.doi.org/10.1021/jm051121i}}, doi = {{10.1021/jm051121i}}, volume = {{49}}, year = {{2006}}, }