Design, synthesis, and evaluation of a novel 4-aminomethyl-4- fluoropiperidine as a T-type Ca2+ channel antagonist

William D. Shipe; James C. Barrow; Zhi Qiang Yang; Craig W. Lindsley; F. Vivien Yang; Kelly Ann S. Schlegel; Youheng Shu; Kenneth E. Rittle; Mark G. Bock; George D. Hartman; Cuyue Tang; Jeanine E. Ballard; Yuhsin Kuo; Emily D. Adarayan; Thomayant Prueksaritanont; Matthew M. Zrada; Victor N. Uebele; Cindy E. Nuss; Thomas M. Connolly; Scott M. Doran; Steven V. Fox; Richard L. Kraus; Michael J. Marino; Valerie Kuzmick Graufelds; Hugo M. Vargas; Patricia B. Bunting; Martha Hasbun-Manning; Rose M. Evans; Kenneth S. Koblan; John J. Renger

doi:10.1021/jm800419w

Design, synthesis, and evaluation of a novel 4-aminomethyl-4- fluoropiperidine as a T-type Ca²⁺ channel antagonist

William D. Shipe, James C. Barrow, Zhi Qiang Yang, Craig W. Lindsley, F. Vivien Yang, Kelly Ann S. Schlegel, Youheng Shu, Kenneth E. Rittle, Mark G. Bock, George D. Hartman, Cuyue Tang, Jeanine E. Ballard, Yuhsin Kuo, Emily D. Adarayan, Thomayant Prueksaritanont, Matthew M. Zrada, Victor N. Uebele, Cindy E. Nuss, Thomas M. Connolly, Scott M. DoranSteven V. Fox, Richard L. Kraus, Michael J. Marino, Valerie Kuzmick Graufelds, Hugo M. Vargas, Patricia B. Bunting, Martha Hasbun-Manning, Rose M. Evans, Kenneth S. Koblan, John J. Renger

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

Abstract

The novel T-type antagonist (S)-5 has been prepared and evaluated in in vitro and in vivo assays for T-type calcium ion channel activity. Structural modification of the piperidine leads 1 and 2 afforded the fluorinated piperidine (S)-5, a potent and selective antagonist that displayed in vivo CNS efficacy without adverse cardiovascular effects.

Original language	English (US)
Pages (from-to)	3692-3695
Number of pages	4
Journal	Journal of medicinal chemistry
Volume	51
Issue number	13
DOIs	https://doi.org/10.1021/jm800419w
State	Published - Jul 10 2008
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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Shipe, W. D., Barrow, J. C., Yang, Z. Q., Lindsley, C. W., Yang, F. V., Schlegel, K. A. S., Shu, Y., Rittle, K. E., Bock, M. G., Hartman, G. D., Tang, C., Ballard, J. E., Kuo, Y., Adarayan, E. D., Prueksaritanont, T., Zrada, M. M., Uebele, V. N., Nuss, C. E., Connolly, T. M., ... Renger, J. J. (2008). Design, synthesis, and evaluation of a novel 4-aminomethyl-4- fluoropiperidine as a T-type Ca²⁺ channel antagonist. Journal of medicinal chemistry, 51(13), 3692-3695. https://doi.org/10.1021/jm800419w

Design, synthesis, and evaluation of a novel 4-aminomethyl-4- fluoropiperidine as a T-type Ca²⁺ channel antagonist. / Shipe, William D.; Barrow, James C.; Yang, Zhi Qiang; Lindsley, Craig W.; Yang, F. Vivien; Schlegel, Kelly Ann S.; Shu, Youheng; Rittle, Kenneth E.; Bock, Mark G.; Hartman, George D.; Tang, Cuyue; Ballard, Jeanine E.; Kuo, Yuhsin; Adarayan, Emily D.; Prueksaritanont, Thomayant; Zrada, Matthew M.; Uebele, Victor N.; Nuss, Cindy E.; Connolly, Thomas M.; Doran, Scott M.; Fox, Steven V.; Kraus, Richard L.; Marino, Michael J.; Graufelds, Valerie Kuzmick; Vargas, Hugo M.; Bunting, Patricia B.; Hasbun-Manning, Martha; Evans, Rose M.; Koblan, Kenneth S.; Renger, John J.

In: Journal of medicinal chemistry, Vol. 51, No. 13, 10.07.2008, p. 3692-3695.

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

Shipe, WD, Barrow, JC, Yang, ZQ, Lindsley, CW, Yang, FV, Schlegel, KAS, Shu, Y, Rittle, KE, Bock, MG, Hartman, GD, Tang, C, Ballard, JE, Kuo, Y, Adarayan, ED, Prueksaritanont, T, Zrada, MM, Uebele, VN, Nuss, CE, Connolly, TM, Doran, SM, Fox, SV, Kraus, RL, Marino, MJ, Graufelds, VK, Vargas, HM, Bunting, PB, Hasbun-Manning, M, Evans, RM, Koblan, KS & Renger, JJ 2008, 'Design, synthesis, and evaluation of a novel 4-aminomethyl-4- fluoropiperidine as a T-type Ca²⁺ channel antagonist', Journal of medicinal chemistry, vol. 51, no. 13, pp. 3692-3695. https://doi.org/10.1021/jm800419w

Shipe, William D. ; Barrow, James C. ; Yang, Zhi Qiang ; Lindsley, Craig W. ; Yang, F. Vivien ; Schlegel, Kelly Ann S. ; Shu, Youheng ; Rittle, Kenneth E. ; Bock, Mark G. ; Hartman, George D. ; Tang, Cuyue ; Ballard, Jeanine E. ; Kuo, Yuhsin ; Adarayan, Emily D. ; Prueksaritanont, Thomayant ; Zrada, Matthew M. ; Uebele, Victor N. ; Nuss, Cindy E. ; Connolly, Thomas M. ; Doran, Scott M. ; Fox, Steven V. ; Kraus, Richard L. ; Marino, Michael J. ; Graufelds, Valerie Kuzmick ; Vargas, Hugo M. ; Bunting, Patricia B. ; Hasbun-Manning, Martha ; Evans, Rose M. ; Koblan, Kenneth S. ; Renger, John J. / Design, synthesis, and evaluation of a novel 4-aminomethyl-4- fluoropiperidine as a T-type Ca²⁺ channel antagonist. In: Journal of medicinal chemistry. 2008 ; Vol. 51, No. 13. pp. 3692-3695.

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title = "Design, synthesis, and evaluation of a novel 4-aminomethyl-4- fluoropiperidine as a T-type Ca2+ channel antagonist",

abstract = "The novel T-type antagonist (S)-5 has been prepared and evaluated in in vitro and in vivo assays for T-type calcium ion channel activity. Structural modification of the piperidine leads 1 and 2 afforded the fluorinated piperidine (S)-5, a potent and selective antagonist that displayed in vivo CNS efficacy without adverse cardiovascular effects.",

author = "Shipe, {William D.} and Barrow, {James C.} and Yang, {Zhi Qiang} and Lindsley, {Craig W.} and Yang, {F. Vivien} and Schlegel, {Kelly Ann S.} and Youheng Shu and Rittle, {Kenneth E.} and Bock, {Mark G.} and Hartman, {George D.} and Cuyue Tang and Ballard, {Jeanine E.} and Yuhsin Kuo and Adarayan, {Emily D.} and Thomayant Prueksaritanont and Zrada, {Matthew M.} and Uebele, {Victor N.} and Nuss, {Cindy E.} and Connolly, {Thomas M.} and Doran, {Scott M.} and Fox, {Steven V.} and Kraus, {Richard L.} and Marino, {Michael J.} and Graufelds, {Valerie Kuzmick} and Vargas, {Hugo M.} and Bunting, {Patricia B.} and Martha Hasbun-Manning and Evans, {Rose M.} and Koblan, {Kenneth S.} and Renger, {John J.}",

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AU - Barrow, James C.

AU - Yang, Zhi Qiang

AU - Lindsley, Craig W.

AU - Yang, F. Vivien

AU - Schlegel, Kelly Ann S.

AU - Shu, Youheng

AU - Rittle, Kenneth E.

AU - Bock, Mark G.

AU - Hartman, George D.

AU - Tang, Cuyue

AU - Ballard, Jeanine E.

AU - Kuo, Yuhsin

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AU - Uebele, Victor N.

AU - Nuss, Cindy E.

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AU - Doran, Scott M.

AU - Fox, Steven V.

AU - Kraus, Richard L.

AU - Marino, Michael J.

AU - Graufelds, Valerie Kuzmick

AU - Vargas, Hugo M.

AU - Bunting, Patricia B.

AU - Hasbun-Manning, Martha

AU - Evans, Rose M.

AU - Koblan, Kenneth S.

AU - Renger, John J.

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