Cyclic urea derivatives as potent NK1 selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions

Ho Jane Shue; Xiao Chen; John H. Schwerdt; Sunil Paliwal; David J. Blythin; Ling Lin; Danlin Gu; Cheng Wang; Gregory A. Reichard; Hongwu Wang; John J. Piwinski; Ruth A. Duffy; Jean E. Lachowicz; Vicki L. Coffin; Amin A. Nomeir; Cynthia A. Morgan; Geoffrey B. Varty; Neng Yang Shih

doi:10.1016/j.bmcl.2005.10.072

Cyclic urea derivatives as potent NK₁ selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions

Ho Jane Shue, Xiao Chen, John H. Schwerdt, Sunil Paliwal, David J. Blythin, Ling Lin, Danlin Gu, Cheng Wang, Gregory A. Reichard, Hongwu Wang, John J. Piwinski, Ruth A. Duffy, Jean E. Lachowicz, Vicki L. Coffin, Amin A. Nomeir, Cynthia A. Morgan, Geoffrey B. Varty, Neng Yang Shih

Department of Chemistry and Chemical Biology

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

28 Scopus citations

Abstract

A series of novel five-membered urea derivatives as potent NK₁ receptor antagonists is described. The effects of substitution of a 4-fluoro group at the phenyl ring and the introduction of an α-methyl group at the benzylic position to improve potency and duration of in vivo activity are discussed. Several compounds with high affinity and sustained in vivo activity were identified.

Original language	English
Pages (from-to)	1065-1069
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2005.10.072
State	Published - 15 Feb 2006

Keywords

Improved potency
NK antagonist
Sustained in vivo activity

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10.1016/j.bmcl.2005.10.072

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Shue, H. J., Chen, X., Schwerdt, J. H., Paliwal, S., Blythin, D. J., Lin, L., Gu, D., Wang, C., Reichard, G. A., Wang, H., Piwinski, J. J., Duffy, R. A., Lachowicz, J. E., Coffin, V. L., Nomeir, A. A., Morgan, C. A., Varty, G. B., & Shih, N. Y. (2006). Cyclic urea derivatives as potent NK₁ selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions. Bioorganic and Medicinal Chemistry Letters, 16(4), 1065-1069. https://doi.org/10.1016/j.bmcl.2005.10.072

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title = "Cyclic urea derivatives as potent NK1 selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions",

abstract = "A series of novel five-membered urea derivatives as potent NK1 receptor antagonists is described. The effects of substitution of a 4-fluoro group at the phenyl ring and the introduction of an α-methyl group at the benzylic position to improve potency and duration of in vivo activity are discussed. Several compounds with high affinity and sustained in vivo activity were identified.",

keywords = "Improved potency, NK antagonist, Sustained in vivo activity",

author = "Shue, \{Ho Jane\} and Xiao Chen and Schwerdt, \{John H.\} and Sunil Paliwal and Blythin, \{David J.\} and Ling Lin and Danlin Gu and Cheng Wang and Reichard, \{Gregory A.\} and Hongwu Wang and Piwinski, \{John J.\} and Duffy, \{Ruth A.\} and Lachowicz, \{Jean E.\} and Coffin, \{Vicki L.\} and Nomeir, \{Amin A.\} and Morgan, \{Cynthia A.\} and Varty, \{Geoffrey B.\} and Shih, \{Neng Yang\}",

year = "2006",

month = feb,

day = "15",

doi = "10.1016/j.bmcl.2005.10.072",

language = "English",

volume = "16",

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Shue, HJ, Chen, X, Schwerdt, JH, Paliwal, S, Blythin, DJ, Lin, L, Gu, D, Wang, C, Reichard, GA, Wang, H, Piwinski, JJ, Duffy, RA, Lachowicz, JE, Coffin, VL, Nomeir, AA, Morgan, CA, Varty, GB & Shih, NY 2006, 'Cyclic urea derivatives as potent NK₁ selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions', Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 4, pp. 1065-1069. https://doi.org/10.1016/j.bmcl.2005.10.072

TY - JOUR

T1 - Cyclic urea derivatives as potent NK1 selective antagonists. Part II

T2 - Effects of fluoro and benzylic methyl substitutions

AU - Shue, Ho Jane

AU - Chen, Xiao

AU - Schwerdt, John H.

AU - Paliwal, Sunil

AU - Blythin, David J.

AU - Lin, Ling

AU - Gu, Danlin

AU - Wang, Cheng

AU - Reichard, Gregory A.

AU - Wang, Hongwu

AU - Piwinski, John J.

AU - Duffy, Ruth A.

AU - Lachowicz, Jean E.

AU - Coffin, Vicki L.

AU - Nomeir, Amin A.

AU - Morgan, Cynthia A.

AU - Varty, Geoffrey B.

AU - Shih, Neng Yang

PY - 2006/2/15

Y1 - 2006/2/15

N2 - A series of novel five-membered urea derivatives as potent NK1 receptor antagonists is described. The effects of substitution of a 4-fluoro group at the phenyl ring and the introduction of an α-methyl group at the benzylic position to improve potency and duration of in vivo activity are discussed. Several compounds with high affinity and sustained in vivo activity were identified.

AB - A series of novel five-membered urea derivatives as potent NK1 receptor antagonists is described. The effects of substitution of a 4-fluoro group at the phenyl ring and the introduction of an α-methyl group at the benzylic position to improve potency and duration of in vivo activity are discussed. Several compounds with high affinity and sustained in vivo activity were identified.

KW - Improved potency

KW - NK antagonist

KW - Sustained in vivo activity

UR - https://www.scopus.com/pages/publications/30344434044

UR - https://www.scopus.com/inward/citedby.url?scp=30344434044&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2005.10.072

DO - 10.1016/j.bmcl.2005.10.072

M3 - Article

C2 - 16290143

AN - SCOPUS:30344434044

SN - 0960-894X

VL - 16

SP - 1065

EP - 1069

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

ER -

Cyclic urea derivatives as potent NK₁ selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions

Abstract

Keywords

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