Cyclobutane derivatives as potent NK1 selective antagonists

Michelle Laci Wrobleski; Gregory A. Reichard; Sunil Paliwal; Sapna Shah; Hon Chung Tsui; Ruth A. Duffy; Jean E. Lachowicz; Cynthia A. Morgan; Geoffrey B. Varty; Neng Yang Shih

doi:10.1016/j.bmcl.2006.04.031

Cyclobutane derivatives as potent NK₁ selective antagonists

Michelle Laci Wrobleski
, Gregory A. Reichard
, Sunil Paliwal
, Sapna Shah
, Hon Chung Tsui
, Ruth A. Duffy
, Jean E. Lachowicz
, Cynthia A. Morgan
, Geoffrey B. Varty
, Neng Yang Shih

Department of Chemistry and Chemical Biology

Merck

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

43 Scopus citations

Abstract

A series of novel cyclobutane derivatives as potent and selective NK₁ receptor antagonists is described. Several compounds in this series exhibited high in vitro binding affinity (K_i {less-than or slanted equal to} 1 nM), and potent inhibition of central NK₁ receptor following oral administration. Syntheses of these compounds are also described herein.

Original language	English
Pages (from-to)	3859-3863
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2006.04.031
State	Published - 15 Jul 2006

Keywords

CNS penetration
Cyclobutane
NK antagonist
Oral in vivo activity
Substance P

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10.1016/j.bmcl.2006.04.031

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title = "Cyclobutane derivatives as potent NK1 selective antagonists",

abstract = "A series of novel cyclobutane derivatives as potent and selective NK1 receptor antagonists is described. Several compounds in this series exhibited high in vitro binding affinity (Ki \{less-than or slanted equal to\} 1 nM), and potent inhibition of central NK1 receptor following oral administration. Syntheses of these compounds are also described herein.",

keywords = "CNS penetration, Cyclobutane, NK antagonist, Oral in vivo activity, Substance P",

author = "Wrobleski, \{Michelle Laci\} and Reichard, \{Gregory A.\} and Sunil Paliwal and Sapna Shah and Tsui, \{Hon Chung\} and Duffy, \{Ruth A.\} and Lachowicz, \{Jean E.\} and Morgan, \{Cynthia A.\} and Varty, \{Geoffrey B.\} and Shih, \{Neng Yang\}",

year = "2006",

month = jul,

day = "15",

doi = "10.1016/j.bmcl.2006.04.031",

language = "English",

volume = "16",

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T1 - Cyclobutane derivatives as potent NK1 selective antagonists

AU - Wrobleski, Michelle Laci

AU - Reichard, Gregory A.

AU - Paliwal, Sunil

AU - Shah, Sapna

AU - Tsui, Hon Chung

AU - Duffy, Ruth A.

AU - Lachowicz, Jean E.

AU - Morgan, Cynthia A.

AU - Varty, Geoffrey B.

AU - Shih, Neng Yang

PY - 2006/7/15

Y1 - 2006/7/15

N2 - A series of novel cyclobutane derivatives as potent and selective NK1 receptor antagonists is described. Several compounds in this series exhibited high in vitro binding affinity (Ki {less-than or slanted equal to} 1 nM), and potent inhibition of central NK1 receptor following oral administration. Syntheses of these compounds are also described herein.

AB - A series of novel cyclobutane derivatives as potent and selective NK1 receptor antagonists is described. Several compounds in this series exhibited high in vitro binding affinity (Ki {less-than or slanted equal to} 1 nM), and potent inhibition of central NK1 receptor following oral administration. Syntheses of these compounds are also described herein.

KW - CNS penetration

KW - Cyclobutane

KW - NK antagonist

KW - Oral in vivo activity

KW - Substance P

UR - https://www.scopus.com/pages/publications/33746509098

UR - https://www.scopus.com/pages/publications/33746509098#tab=citedBy

U2 - 10.1016/j.bmcl.2006.04.031

DO - 10.1016/j.bmcl.2006.04.031

M3 - Article

C2 - 16682196

AN - SCOPUS:33746509098

SN - 0960-894X

VL - 16

SP - 3859

EP - 3863

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 14

ER -

Cyclobutane derivatives as potent NK₁ selective antagonists

Abstract

Keywords

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