Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores

Sean W. Reilly; Suzy Griffin; Michelle Taylor; Kristoffer Sahlholm; Chi Chang Weng; Kuiying Xu; Daniel A. Jacome; Robert R. Luedtke; Robert H. Mach

doi:10.1021/acs.jmedchem.7b01248

Highly Selective Dopamine D₃ Receptor Antagonists with Arylated Diazaspiro Alkane Cores

Sean W. Reilly
, Suzy Griffin
, Michelle Taylor
, Kristoffer Sahlholm
, Chi Chang Weng
, Kuiying Xu
, Daniel A. Jacome
, Robert R. Luedtke
, Robert H. Mach^*

^*Corresponding author for this work

University of Pennsylvania
University of North Texas

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

32 Scopus citations

Abstract

A series of potent and selective D₃ receptor (D₃R) analogues with diazaspiro alkane cores were synthesized. Radioligand binding of compounds 11, 14, 15a, and 15c revealed favorable D₃R affinity (K_i = 12-25.6 nM) and were highly selective for D₃R vs D₃R (ranging from 264- to 905-fold). Variation of these novel ligand architectures can be achieved using our previously reported 10-20 min benchtop C-N cross-coupling methodology, affording a broad range of arylated diazaspiro precursors.

Original language	English
Pages (from-to)	9905-9910
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	60
Issue number	23
DOIs	https://doi.org/10.1021/acs.jmedchem.7b01248
State	Published - 14 12 2017
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2017 American Chemical Society.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1021/acs.jmedchem.7b01248

Cite this

@article{3e902659c29e41a59ba83e64eb0f9450,

title = "Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores",

abstract = "A series of potent and selective D3 receptor (D3R) analogues with diazaspiro alkane cores were synthesized. Radioligand binding of compounds 11, 14, 15a, and 15c revealed favorable D3R affinity (Ki = 12-25.6 nM) and were highly selective for D3R vs D3R (ranging from 264- to 905-fold). Variation of these novel ligand architectures can be achieved using our previously reported 10-20 min benchtop C-N cross-coupling methodology, affording a broad range of arylated diazaspiro precursors.",

author = "Reilly, \{Sean W.\} and Suzy Griffin and Michelle Taylor and Kristoffer Sahlholm and Weng, \{Chi Chang\} and Kuiying Xu and Jacome, \{Daniel A.\} and Luedtke, \{Robert R.\} and Mach, \{Robert H.\}",

note = "Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

year = "2017",

month = dec,

day = "14",

doi = "10.1021/acs.jmedchem.7b01248",

language = "英语",

volume = "60",

pages = "9905--9910",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "23",

}

TY - JOUR

T1 - Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores

AU - Reilly, Sean W.

AU - Griffin, Suzy

AU - Taylor, Michelle

AU - Sahlholm, Kristoffer

AU - Weng, Chi Chang

AU - Xu, Kuiying

AU - Jacome, Daniel A.

AU - Luedtke, Robert R.

AU - Mach, Robert H.

PY - 2017/12/14

Y1 - 2017/12/14

N2 - A series of potent and selective D3 receptor (D3R) analogues with diazaspiro alkane cores were synthesized. Radioligand binding of compounds 11, 14, 15a, and 15c revealed favorable D3R affinity (Ki = 12-25.6 nM) and were highly selective for D3R vs D3R (ranging from 264- to 905-fold). Variation of these novel ligand architectures can be achieved using our previously reported 10-20 min benchtop C-N cross-coupling methodology, affording a broad range of arylated diazaspiro precursors.

AB - A series of potent and selective D3 receptor (D3R) analogues with diazaspiro alkane cores were synthesized. Radioligand binding of compounds 11, 14, 15a, and 15c revealed favorable D3R affinity (Ki = 12-25.6 nM) and were highly selective for D3R vs D3R (ranging from 264- to 905-fold). Variation of these novel ligand architectures can be achieved using our previously reported 10-20 min benchtop C-N cross-coupling methodology, affording a broad range of arylated diazaspiro precursors.

UR - https://www.scopus.com/pages/publications/85038374273

U2 - 10.1021/acs.jmedchem.7b01248

DO - 10.1021/acs.jmedchem.7b01248

M3 - 文章

C2 - 29125762

AN - SCOPUS:85038374273

SN - 0022-2623

VL - 60

SP - 9905

EP - 9910

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 23

ER -