Discovery of the first nonpeptide agonist of the GPR14/Urotensin-II receptor: 3-(4-Chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one (AC-7954)

Glenn E. Croston; Roger Olsson; Erika A. Currier; Ethan S. Burstein; David Weiner; Norman Nash; Daniel Severance; Stig G. Allenmark; Linda Thunberg; Jian Nong Ma; Nina Mohell; Brian O'Dowd; Mark R. Brann; Uli Hacksell

doi:10.1021/jm025551

Discovery of the first nonpeptide agonist of the GPR14/Urotensin-II receptor: 3-(4-Chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one (AC-7954)

Glenn E. Croston, Roger Olsson, Erika A. Currier, Ethan S. Burstein, David Weiner, Norman Nash, Daniel Severance, Stig G. Allenmark, Linda Thunberg, Jian Nong Ma, Nina Mohell, Brian O'Dowd, Mark R. Brann, Uli Hacksell

Research output: Contribution to journal › Article › peer-review

Abstract

A functional cell-based screen identified 3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one hydrochloride (AC-7954, 1) as a nonpeptidic agonist of the urotensin-II receptor. Racemic 1 had an EC50 of 300 nM at the human UII receptor and was highly selective. Testing of the enantiopure (+)- and (-)-1 revealed that the UII receptor activity of racemic 1 resides primarily in (+)-1. Being a selective nonpeptidic druglike UII receptor agonist, (+)-1 will be useful as a pharmacological research tool and a potential drug lead.

Original language	English
Pages (from-to)	4950-4953
Journal	Journal of Medicinal Chemistry
Volume	45
Issue number	23
DOIs	https://doi.org/10.1021/jm025551
Publication status	Published - 2002 Oct 9
Externally published	Yes

Subject classification (UKÄ)

Pharmaceutical Sciences

Access to Document

10.1021/jm025551

Cite this

Croston, G. E., Olsson, R., Currier, E. A., Burstein, E. S., Weiner, D., Nash, N., Severance, D., Allenmark, S. G., Thunberg, L., Ma, J. N., Mohell, N., O'Dowd, B., Brann, M. R., & Hacksell, U. (2002). Discovery of the first nonpeptide agonist of the GPR14/Urotensin-II receptor: 3-(4-Chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one (AC-7954). Journal of Medicinal Chemistry, 45(23), 4950-4953. https://doi.org/10.1021/jm025551

@article{919c0ec44c1f479eb5b8725b60802da2,

title = "Discovery of the first nonpeptide agonist of the GPR14/Urotensin-II receptor: 3-(4-Chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one (AC-7954)",

abstract = "A functional cell-based screen identified 3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one hydrochloride (AC-7954, 1) as a nonpeptidic agonist of the urotensin-II receptor. Racemic 1 had an EC50 of 300 nM at the human UII receptor and was highly selective. Testing of the enantiopure (+)- and (-)-1 revealed that the UII receptor activity of racemic 1 resides primarily in (+)-1. Being a selective nonpeptidic druglike UII receptor agonist, (+)-1 will be useful as a pharmacological research tool and a potential drug lead.",

author = "Croston, {Glenn E.} and Roger Olsson and Currier, {Erika A.} and Burstein, {Ethan S.} and David Weiner and Norman Nash and Daniel Severance and Allenmark, {Stig G.} and Linda Thunberg and Ma, {Jian Nong} and Nina Mohell and Brian O'Dowd and Brann, {Mark R.} and Uli Hacksell",

year = "2002",

month = oct,

day = "9",

doi = "10.1021/jm025551",

language = "English",

volume = "45",

pages = "4950--4953",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "The American Chemical Society (ACS)",

number = "23",

}

Croston, GE, Olsson, R, Currier, EA, Burstein, ES, Weiner, D, Nash, N, Severance, D, Allenmark, SG, Thunberg, L, Ma, JN, Mohell, N, O'Dowd, B, Brann, MR & Hacksell, U 2002, 'Discovery of the first nonpeptide agonist of the GPR14/Urotensin-II receptor: 3-(4-Chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one (AC-7954)', Journal of Medicinal Chemistry, vol. 45, no. 23, pp. 4950-4953. https://doi.org/10.1021/jm025551

TY - JOUR

T1 - Discovery of the first nonpeptide agonist of the GPR14/Urotensin-II receptor

T2 - 3-(4-Chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one (AC-7954)

AU - Croston, Glenn E.

AU - Olsson, Roger

AU - Currier, Erika A.

AU - Burstein, Ethan S.

AU - Weiner, David

AU - Nash, Norman

AU - Severance, Daniel

AU - Allenmark, Stig G.

AU - Thunberg, Linda

AU - Ma, Jian Nong

AU - Mohell, Nina

AU - O'Dowd, Brian

AU - Brann, Mark R.

AU - Hacksell, Uli

PY - 2002/10/9

Y1 - 2002/10/9

N2 - A functional cell-based screen identified 3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one hydrochloride (AC-7954, 1) as a nonpeptidic agonist of the urotensin-II receptor. Racemic 1 had an EC50 of 300 nM at the human UII receptor and was highly selective. Testing of the enantiopure (+)- and (-)-1 revealed that the UII receptor activity of racemic 1 resides primarily in (+)-1. Being a selective nonpeptidic druglike UII receptor agonist, (+)-1 will be useful as a pharmacological research tool and a potential drug lead.

AB - A functional cell-based screen identified 3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one hydrochloride (AC-7954, 1) as a nonpeptidic agonist of the urotensin-II receptor. Racemic 1 had an EC50 of 300 nM at the human UII receptor and was highly selective. Testing of the enantiopure (+)- and (-)-1 revealed that the UII receptor activity of racemic 1 resides primarily in (+)-1. Being a selective nonpeptidic druglike UII receptor agonist, (+)-1 will be useful as a pharmacological research tool and a potential drug lead.

UR - http://www.scopus.com/inward/record.url?scp=0037038316&partnerID=8YFLogxK

U2 - 10.1021/jm025551

DO - 10.1021/jm025551

M3 - Article

C2 - 12408704

AN - SCOPUS:0037038316

SN - 0022-2623

VL - 45

SP - 4950

EP - 4953

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 23

ER -

Discovery of the first nonpeptide agonist of the GPR14/Urotensin-II receptor: 3-(4-Chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one (AC-7954)

Abstract

Subject classification (UKÄ)

Access to Document

Other files and links

Fingerprint

Cite this