Piperazinyl-glutamate-pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation

John J. Parlow; Mary W. Burney; Brenda L. Case; Thomas J. Girard; Kerri A. Hall; Ronald R. Hiebsch; Rita M. Huff; Rhonda M. Lachance; Deborah A. Mischke; Stephen R. Rapp; Rhonda S. Woerndle; Michael D. Ennis

doi:10.1016/j.bmcl.2009.09.017

Piperazinyl-glutamate-pyrimidines as potent P2Y₁₂ antagonists for inhibition of platelet aggregation

John J. Parlow, Mary W. Burney, Brenda L. Case, Thomas J. Girard, Kerri A. Hall, Ronald R. Hiebsch, Rita M. Huff, Rhonda M. Lachance, Deborah A. Mischke, Stephen R. Rapp, Rhonda S. Woerndle, Michael D. Ennis

Department of Pediatrics

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

17 Scopus citations

Abstract

Piperazinyl-glutamate-pyrimidines were prepared with oxygen, nitrogen, and sulfur substitution at the 4-position of the pyrimidine leading to highly potent P2Y₁₂ antagonists. In particular, 4-substituted piperidine-4-pyrimidines provided compounds with exceptional potency. Pharmacokinetic and physicochemical properties were fine-tuned through modifications at the 4-position of the piperidine ring leading to compounds with good human PRP potency, selectivity, clearance and oral bioavailability.

Original language	English
Pages (from-to)	6148-6156
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2009.09.017
State	Published - Nov 1 2009

Keywords

Antiplatelet
Antithrombotic
Cardiovascular disease
GPCR antagonist
P2Y12 antagonist
P2Y12 receptor

Access to Document

10.1016/j.bmcl.2009.09.017

Cite this

Parlow, J. J., Burney, M. W., Case, B. L., Girard, T. J., Hall, K. A., Hiebsch, R. R., Huff, R. M., Lachance, R. M., Mischke, D. A., Rapp, S. R., Woerndle, R. S., & Ennis, M. D. (2009). Piperazinyl-glutamate-pyrimidines as potent P2Y₁₂ antagonists for inhibition of platelet aggregation. Bioorganic and Medicinal Chemistry Letters, 19(21), 6148-6156. https://doi.org/10.1016/j.bmcl.2009.09.017

@article{002f969f439f4aadbc9ef247ab38ddec,

title = "Piperazinyl-glutamate-pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation",

abstract = "Piperazinyl-glutamate-pyrimidines were prepared with oxygen, nitrogen, and sulfur substitution at the 4-position of the pyrimidine leading to highly potent P2Y12 antagonists. In particular, 4-substituted piperidine-4-pyrimidines provided compounds with exceptional potency. Pharmacokinetic and physicochemical properties were fine-tuned through modifications at the 4-position of the piperidine ring leading to compounds with good human PRP potency, selectivity, clearance and oral bioavailability.",

keywords = "Antiplatelet, Antithrombotic, Cardiovascular disease, GPCR antagonist, P2Y12 antagonist, P2Y12 receptor",

author = "Parlow, {John J.} and Burney, {Mary W.} and Case, {Brenda L.} and Girard, {Thomas J.} and Hall, {Kerri A.} and Hiebsch, {Ronald R.} and Huff, {Rita M.} and Lachance, {Rhonda M.} and Mischke, {Deborah A.} and Rapp, {Stephen R.} and Woerndle, {Rhonda S.} and Ennis, {Michael D.}",

year = "2009",

month = nov,

day = "1",

doi = "10.1016/j.bmcl.2009.09.017",

language = "English",

volume = "19",

pages = "6148--6156",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

number = "21",

}

TY - JOUR

T1 - Piperazinyl-glutamate-pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation

AU - Parlow, John J.

AU - Burney, Mary W.

AU - Case, Brenda L.

AU - Girard, Thomas J.

AU - Hall, Kerri A.

AU - Hiebsch, Ronald R.

AU - Huff, Rita M.

AU - Lachance, Rhonda M.

AU - Mischke, Deborah A.

AU - Rapp, Stephen R.

AU - Woerndle, Rhonda S.

AU - Ennis, Michael D.

PY - 2009/11/1

Y1 - 2009/11/1

N2 - Piperazinyl-glutamate-pyrimidines were prepared with oxygen, nitrogen, and sulfur substitution at the 4-position of the pyrimidine leading to highly potent P2Y12 antagonists. In particular, 4-substituted piperidine-4-pyrimidines provided compounds with exceptional potency. Pharmacokinetic and physicochemical properties were fine-tuned through modifications at the 4-position of the piperidine ring leading to compounds with good human PRP potency, selectivity, clearance and oral bioavailability.

AB - Piperazinyl-glutamate-pyrimidines were prepared with oxygen, nitrogen, and sulfur substitution at the 4-position of the pyrimidine leading to highly potent P2Y12 antagonists. In particular, 4-substituted piperidine-4-pyrimidines provided compounds with exceptional potency. Pharmacokinetic and physicochemical properties were fine-tuned through modifications at the 4-position of the piperidine ring leading to compounds with good human PRP potency, selectivity, clearance and oral bioavailability.

KW - Antiplatelet

KW - Antithrombotic

KW - Cardiovascular disease

KW - GPCR antagonist

KW - P2Y12 antagonist

KW - P2Y12 receptor

UR - http://www.scopus.com/inward/record.url?scp=71749090236&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2009.09.017

DO - 10.1016/j.bmcl.2009.09.017

M3 - Article

C2 - 19796941

AN - SCOPUS:71749090236

SN - 0960-894X

VL - 19

SP - 6148

EP - 6156

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 21

ER -

Piperazinyl-glutamate-pyrimidines as potent P2Y₁₂ antagonists for inhibition of platelet aggregation

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this