Design, parallel synthesis and SAR of novel urotensin II receptor agonists
(2007) In European Journal of Medicinal Chemistry 42(2). p.276-285- Abstract
A 30-membered library of amides based on the potent urotensin II (UII) receptor agonist FL104, has been synthesized from ten different carboxylic acids and three amines. A synthetic protocol producing the amides in 47-98% yield has been developed in which the purification involved only extractions and in a few cases filtration through an ion-exchange resin. It was found that 5 mg of starting material was enough to obtain reproducible results and excellent purities. Thus, the procedure is estimated to be transferable to fully automated systems. The synthesized compounds were evaluated for their UII receptor agonistic activities using a cell-based assay (R-SAT). The most active compounds were the 4-trifluoromethylcinnamic amides of... (More)
A 30-membered library of amides based on the potent urotensin II (UII) receptor agonist FL104, has been synthesized from ten different carboxylic acids and three amines. A synthetic protocol producing the amides in 47-98% yield has been developed in which the purification involved only extractions and in a few cases filtration through an ion-exchange resin. It was found that 5 mg of starting material was enough to obtain reproducible results and excellent purities. Thus, the procedure is estimated to be transferable to fully automated systems. The synthesized compounds were evaluated for their UII receptor agonistic activities using a cell-based assay (R-SAT). The most active compounds were the 4-trifluoromethylcinnamic amides of 1-(4-chlorophenyl)-3-dimethylamino-propylamine and 1-(2-naphthyl)-3-dimethylamino-propylamine, both showed EC50 values of 130 nM.
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- author
- Lehmann, Fredrik ; Lake, Lisa ; Currier, Erika A. ; Olsson, Roger LU ; Hacksell, Uli and Luthman, Kristina
- publishing date
- 2007-02-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Amidation, Library synthesis, Solid supported reagents, Structure-activity relationships, Urotensin II
- in
- European Journal of Medicinal Chemistry
- volume
- 42
- issue
- 2
- pages
- 10 pages
- publisher
- Elsevier Masson SAS
- external identifiers
-
- scopus:33847107720
- pmid:17112638
- ISSN
- 0223-5234
- DOI
- 10.1016/j.ejmech.2006.09.015
- language
- English
- LU publication?
- no
- id
- c9ba441c-f343-4910-acbf-0db5d35cc37c
- date added to LUP
- 2019-10-02 10:28:17
- date last changed
- 2024-08-21 08:51:57
@article{c9ba441c-f343-4910-acbf-0db5d35cc37c, abstract = {{<p>A 30-membered library of amides based on the potent urotensin II (UII) receptor agonist FL104, has been synthesized from ten different carboxylic acids and three amines. A synthetic protocol producing the amides in 47-98% yield has been developed in which the purification involved only extractions and in a few cases filtration through an ion-exchange resin. It was found that 5 mg of starting material was enough to obtain reproducible results and excellent purities. Thus, the procedure is estimated to be transferable to fully automated systems. The synthesized compounds were evaluated for their UII receptor agonistic activities using a cell-based assay (R-SAT). The most active compounds were the 4-trifluoromethylcinnamic amides of 1-(4-chlorophenyl)-3-dimethylamino-propylamine and 1-(2-naphthyl)-3-dimethylamino-propylamine, both showed EC<sub>50</sub> values of 130 nM.</p>}}, author = {{Lehmann, Fredrik and Lake, Lisa and Currier, Erika A. and Olsson, Roger and Hacksell, Uli and Luthman, Kristina}}, issn = {{0223-5234}}, keywords = {{Amidation; Library synthesis; Solid supported reagents; Structure-activity relationships; Urotensin II}}, language = {{eng}}, month = {{02}}, number = {{2}}, pages = {{276--285}}, publisher = {{Elsevier Masson SAS}}, series = {{European Journal of Medicinal Chemistry}}, title = {{Design, parallel synthesis and SAR of novel urotensin II receptor agonists}}, url = {{http://dx.doi.org/10.1016/j.ejmech.2006.09.015}}, doi = {{10.1016/j.ejmech.2006.09.015}}, volume = {{42}}, year = {{2007}}, }