Pyrrolidine-carboxamides and oxadiazoles as potent hNK1 antagonists

Jonathan R. Young; Ronsar Eid; Cherilyn Turner; Robert J. DeVita; Marc M. Kurtz; Kwei Lan C. Tsao; Gary G. Chicchi; Alan Wheeldon; Emma Carlson; Sander G. Mills

doi:10.1016/j.bmcl.2007.08.028

Pyrrolidine-carboxamides and oxadiazoles as potent hNK₁ antagonists

Jonathan R. Young
, Ronsar Eid
, Cherilyn Turner
, Robert J. DeVita
, Marc M. Kurtz
, Kwei Lan C. Tsao
, Gary G. Chicchi
, Alan Wheeldon
, Emma Carlson
, Sander G. Mills

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

16 Scopus citations

Abstract

The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK₁ antagonists in vitro and efficacious in vivo with minimal interactions with P₄₅₀ liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK₁ binding affinity, functional activity, and a good PD response in vivo.

Original language	English
Pages (from-to)	5310-5315
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2007.08.028
State	Published - 1 Oct 2007
Externally published	Yes

Keywords

NK antagonists
Substance P

Access to Document

10.1016/j.bmcl.2007.08.028

Cite this

@article{06c9af1c827144a098c453f82a9c3663,

title = "Pyrrolidine-carboxamides and oxadiazoles as potent hNK1 antagonists",

abstract = "The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK1 antagonists in vitro and efficacious in vivo with minimal interactions with P450 liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK1 binding affinity, functional activity, and a good PD response in vivo.",

keywords = "NK antagonists, Substance P",

author = "Young, \{Jonathan R.\} and Ronsar Eid and Cherilyn Turner and DeVita, \{Robert J.\} and Kurtz, \{Marc M.\} and Tsao, \{Kwei Lan C.\} and Chicchi, \{Gary G.\} and Alan Wheeldon and Emma Carlson and Mills, \{Sander G.\}",

year = "2007",

month = oct,

day = "1",

doi = "10.1016/j.bmcl.2007.08.028",

language = "English",

volume = "17",

pages = "5310--5315",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "19",

}

TY - JOUR

T1 - Pyrrolidine-carboxamides and oxadiazoles as potent hNK1 antagonists

AU - Young, Jonathan R.

AU - Eid, Ronsar

AU - Turner, Cherilyn

AU - DeVita, Robert J.

AU - Kurtz, Marc M.

AU - Tsao, Kwei Lan C.

AU - Chicchi, Gary G.

AU - Wheeldon, Alan

AU - Carlson, Emma

AU - Mills, Sander G.

PY - 2007/10/1

Y1 - 2007/10/1

N2 - The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK1 antagonists in vitro and efficacious in vivo with minimal interactions with P450 liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK1 binding affinity, functional activity, and a good PD response in vivo.

AB - The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK1 antagonists in vitro and efficacious in vivo with minimal interactions with P450 liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK1 binding affinity, functional activity, and a good PD response in vivo.

KW - NK antagonists

KW - Substance P

UR - https://www.scopus.com/pages/publications/34548591161

U2 - 10.1016/j.bmcl.2007.08.028

DO - 10.1016/j.bmcl.2007.08.028

M3 - Article

C2 - 17723300

AN - SCOPUS:34548591161

SN - 0960-894X

VL - 17

SP - 5310

EP - 5315

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 19