Synthesis and SAR studies of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl) acetamide vasopressin V1b receptor antagonists

Susan E. Napier; Jeffrey J. Letourneau; Nasrin Ansari; Douglas S. Auld; James Baker; Stuart Best; Leigh Campbell-Wan; Jui Hsiang Chan; Mark Craighead; Hema Desai; Katharine A. Goan; Koc Kan Ho; Ellen G.J. Hulskotte; Cliona P. MacSweeney; Rachel Milne; J. Richard Morphy; Irina Neagu; Michael H.J. Ohlmeyer; Ard W.M.M. Peeters; Jeremy Presland; Chris Riviello; Ge S.F. Ruigt; Fiona J. Thomson; Heather A. Zanetakos; Jiuqiao Zhao; Maria L. Webb

doi:10.1016/j.bmcl.2010.12.081

Synthesis and SAR studies of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl) acetamide vasopressin V_1b receptor antagonists

Susan E. Napier
, Jeffrey J. Letourneau
, Nasrin Ansari
, Douglas S. Auld
, James Baker
, Stuart Best
, Leigh Campbell-Wan
, Jui Hsiang Chan
, Mark Craighead
, Hema Desai
, Katharine A. Goan
, Koc Kan Ho
, Ellen G.J. Hulskotte
, Cliona P. MacSweeney
, Rachel Milne
, J. Richard Morphy
, Irina Neagu
, Michael H.J. Ohlmeyer
, Ard W.M.M. Peeters
, Jeremy Presland

Chris Riviello, Ge S.F. Ruigt, Fiona J. Thomson, Heather A. Zanetakos, Jiuqiao Zhao, Maria L. Webb

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

6 Scopus citations

Abstract

Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V_1b (V₃) antagonists are described. 2-(4-Oxo-2-aryl-quinazolin-3(4H)-yl)acetamides have been identified with low nanomolar affinity for the V_1b receptor and good selectivity with respect to related receptors V_1a, V₂ and oxytocin (OT). Optimised compound 12j demonstrates a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction.

Original language	English
Pages (from-to)	1871-1875
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2010.12.081
State	Published - 15 Mar 2011
Externally published	Yes

Keywords

HPA axis
Vasopressin

Access to Document

10.1016/j.bmcl.2010.12.081

Cite this

Napier, S. E., Letourneau, J. J., Ansari, N., Auld, D. S., Baker, J., Best, S., Campbell-Wan, L., Chan, J. H., Craighead, M., Desai, H., Goan, K. A., Ho, K. K., Hulskotte, E. G. J., MacSweeney, C. P., Milne, R., Morphy, J. R., Neagu, I., Ohlmeyer, M. H. J., Peeters, A. W. M. M., ... Webb, M. L. (2011). Synthesis and SAR studies of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl) acetamide vasopressin V_1b receptor antagonists. Bioorganic and Medicinal Chemistry Letters, 21(6), 1871-1875. https://doi.org/10.1016/j.bmcl.2010.12.081

@article{f1645e40aab44f42881ccbd8f059b63f,

title = "Synthesis and SAR studies of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl) acetamide vasopressin V1b receptor antagonists",

abstract = "Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V1b (V3) antagonists are described. 2-(4-Oxo-2-aryl-quinazolin-3(4H)-yl)acetamides have been identified with low nanomolar affinity for the V1b receptor and good selectivity with respect to related receptors V1a, V2 and oxytocin (OT). Optimised compound 12j demonstrates a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction.",

keywords = "HPA axis, Vasopressin",

author = "Napier, \{Susan E.\} and Letourneau, \{Jeffrey J.\} and Nasrin Ansari and Auld, \{Douglas S.\} and James Baker and Stuart Best and Leigh Campbell-Wan and Chan, \{Jui Hsiang\} and Mark Craighead and Hema Desai and Goan, \{Katharine A.\} and Ho, \{Koc Kan\} and Hulskotte, \{Ellen G.J.\} and MacSweeney, \{Cliona P.\} and Rachel Milne and Morphy, \{J. Richard\} and Irina Neagu and Ohlmeyer, \{Michael H.J.\} and Peeters, \{Ard W.M.M.\} and Jeremy Presland and Chris Riviello and Ruigt, \{Ge S.F.\} and Thomson, \{Fiona J.\} and Zanetakos, \{Heather A.\} and Jiuqiao Zhao and Webb, \{Maria L.\}",

year = "2011",

month = mar,

day = "15",

doi = "10.1016/j.bmcl.2010.12.081",

language = "English",

volume = "21",

pages = "1871--1875",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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}

Napier, SE, Letourneau, JJ, Ansari, N, Auld, DS, Baker, J, Best, S, Campbell-Wan, L, Chan, JH, Craighead, M, Desai, H, Goan, KA, Ho, KK, Hulskotte, EGJ, MacSweeney, CP, Milne, R, Morphy, JR, Neagu, I, Ohlmeyer, MHJ, Peeters, AWMM, Presland, J, Riviello, C, Ruigt, GSF, Thomson, FJ, Zanetakos, HA, Zhao, J & Webb, ML 2011, 'Synthesis and SAR studies of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl) acetamide vasopressin V_1b receptor antagonists', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 6, pp. 1871-1875. https://doi.org/10.1016/j.bmcl.2010.12.081

TY - JOUR

T1 - Synthesis and SAR studies of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl) acetamide vasopressin V1b receptor antagonists

AU - Napier, Susan E.

AU - Letourneau, Jeffrey J.

AU - Ansari, Nasrin

AU - Auld, Douglas S.

AU - Baker, James

AU - Best, Stuart

AU - Campbell-Wan, Leigh

AU - Chan, Jui Hsiang

AU - Craighead, Mark

AU - Desai, Hema

AU - Goan, Katharine A.

AU - Ho, Koc Kan

AU - Hulskotte, Ellen G.J.

AU - MacSweeney, Cliona P.

AU - Milne, Rachel

AU - Morphy, J. Richard

AU - Neagu, Irina

AU - Ohlmeyer, Michael H.J.

AU - Peeters, Ard W.M.M.

AU - Presland, Jeremy

AU - Riviello, Chris

AU - Ruigt, Ge S.F.

AU - Thomson, Fiona J.

AU - Zanetakos, Heather A.

AU - Zhao, Jiuqiao

AU - Webb, Maria L.

PY - 2011/3/15

Y1 - 2011/3/15

N2 - Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V1b (V3) antagonists are described. 2-(4-Oxo-2-aryl-quinazolin-3(4H)-yl)acetamides have been identified with low nanomolar affinity for the V1b receptor and good selectivity with respect to related receptors V1a, V2 and oxytocin (OT). Optimised compound 12j demonstrates a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction.

AB - Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V1b (V3) antagonists are described. 2-(4-Oxo-2-aryl-quinazolin-3(4H)-yl)acetamides have been identified with low nanomolar affinity for the V1b receptor and good selectivity with respect to related receptors V1a, V2 and oxytocin (OT). Optimised compound 12j demonstrates a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction.

KW - HPA axis

KW - Vasopressin

UR - https://www.scopus.com/pages/publications/79952363767

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DO - 10.1016/j.bmcl.2010.12.081

M3 - Article

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AN - SCOPUS:79952363767

SN - 0960-894X

VL - 21

SP - 1871

EP - 1875

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 6