Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Design, parallel synthesis and SAR of novel urotensin II receptor agonists

Lehmann, Fredrik ; Lake, Lisa ; Currier, Erika A. ; Olsson, Roger LU orcid ; Hacksell, Uli and Luthman, Kristina (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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
publishing date
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
2024-05-14 23:47:38
@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}},
}