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

41 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",

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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/inward/citedby.url?scp=33746509098&partnerID=8YFLogxK

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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