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Items: 40

1.

Correction to Application of Structure-Based Design and Parallel Chemistry to Identify a Potent, Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor.

Helal CJ, Arnold EP, Boyden TL, Chang C, Chappie TA, Fennell KF, Forman MD, Hajos M, Harms JF, Hoffman WE, Humphrey JM, Kang Z, Kleiman RJ, Kormos BL, LaChapelle EA, Lee CW, Lu J, Maklad N, McDowell L, Mente S, O'Connor RE, Pandit J, Piotrowski M, Schmidt AW, Schmidt CJ, Ueno H, Verhoest PR, Yang EX.

J Med Chem. 2018 Apr 26;61(8):3753. doi: 10.1021/acs.jmedchem.8b00475. Epub 2018 Apr 6. No abstract available.

PMID:
29624389
2.

Late-Stage Microsomal Oxidation Reduces Drug-Drug Interaction and Identifies Phosphodiesterase 2A Inhibitor PF-06815189.

Stepan AF, Tran TP, Helal CJ, Brown MS, Chang C, O'Connor RE, De Vivo M, Doran SD, Fisher EL, Jenkinson S, Karanian D, Kormos BL, Sharma R, Walker GS, Wright AS, Yang EX, Brodney MA, Wager TT, Verhoest PR, Obach RS.

ACS Med Chem Lett. 2018 Jan 4;9(2):68-72. doi: 10.1021/acsmedchemlett.7b00343. eCollection 2018 Feb 8.

3.

Identification of a Potent, Highly Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor Clinical Candidate.

Helal CJ, Arnold E, Boyden T, Chang C, Chappie TA, Fisher E, Hajos M, Harms JF, Hoffman WE, Humphrey JM, Pandit J, Kang Z, Kleiman RJ, Kormos BL, Lee CW, Lu J, Maklad N, McDowell L, McGinnis D, O'Connor RE, O'Donnell CJ, Ogden A, Piotrowski M, Schmidt CJ, Seymour PA, Ueno H, Vansell N, Verhoest PR, Yang EX.

J Med Chem. 2018 Feb 8;61(3):1001-1018. doi: 10.1021/acs.jmedchem.7b01466. Epub 2018 Jan 16.

PMID:
29293004
4.

The Discovery of a Novel Phosphodiesterase (PDE) 4B-Preferring Radioligand for Positron Emission Tomography (PET) Imaging.

Zhang L, Chen L, Beck EM, Chappie TA, Coelho RV, Doran SD, Fan KH, Helal CJ, Humphrey JM, Hughes Z, Kuszpit K, Lachapelle EA, Lazzaro JT, Lee C, Mather RJ, Patel NC, Skaddan MB, Sciabola S, Verhoest PR, Young JM, Zasadny K, Villalobos A.

J Med Chem. 2017 Oct 26;60(20):8538-8551. doi: 10.1021/acs.jmedchem.7b01050. Epub 2017 Oct 9.

PMID:
28957634
5.

Discovery and Characterization of (R)-6-Neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (PF-06462894), an Alkyne-Lacking Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator Profiled in both Rat and Nonhuman Primates.

Stepan AF, Claffey MM, Reese MR, Balan G, Barreiro G, Barricklow J, Bohanon MJ, Boscoe BP, Cappon GD, Chenard LK, Cianfrogna J, Chen L, Coffman KJ, Drozda SE, Dunetz JR, Ghosh S, Hou X, Houle C, Karki K, Lazzaro JT, Mancuso JY, Marcek JM, Miller EL, Moen MA, O'Neil S, Sakurada I, Skaddan M, Parikh V, Smith DL, Trapa P, Tuttle JB, Verhoest PR, Walker DP, Won A, Wright AS, Whritenour J, Zasadny K, Zaleska MM, Zhang L, Shaffer CL.

J Med Chem. 2017 Sep 28;60(18):7764-7780. doi: 10.1021/acs.jmedchem.7b00604. Epub 2017 Sep 13.

PMID:
28817277
6.

Application of Structure-Based Design and Parallel Chemistry to Identify a Potent, Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor.

Helal CJ, Arnold EP, Boyden TL, Chang C, Chappie TA, Fennell KF, Forman MD, Hajos M, Harms JF, Hoffman WE, Humphrey JM, Kang Z, Kleiman RJ, Kormos BL, Lee CW, Lu J, Maklad N, McDowell L, Mente S, O'Connor RE, Pandit J, Piotrowski M, Schmidt AW, Schmidt CJ, Ueno H, Verhoest PR, Yang EX.

J Med Chem. 2017 Jul 13;60(13):5673-5698. doi: 10.1021/acs.jmedchem.7b00397. Epub 2017 Jun 16. Erratum in: J Med Chem. 2018 Apr 26;61(8):3753.

PMID:
28574706
7.

Discovery of cyclopropyl chromane-derived pyridopyrazine-1,6-dione γ-secretase modulators with robust central efficacy.

Pettersson M, Johnson DS, Rankic DA, Kauffman GW, Am Ende CW, Butler TW, Boscoe B, Evrard E, Helal CJ, Humphrey JM, Stepan AF, Stiff CM, Yang E, Xie L, Bales KR, Hajos-Korcsok E, Jenkinson S, Pettersen B, Pustilnik LR, Ramirez DS, Steyn SJ, Wood KM, Verhoest PR.

Medchemcomm. 2016 Nov 2;8(4):730-743. doi: 10.1039/c6md00406g. eCollection 2017 Apr 1.

8.

Quantitative Assessment of the Impact of Fluorine Substitution on P-Glycoprotein (P-gp) Mediated Efflux, Permeability, Lipophilicity, and Metabolic Stability.

Pettersson M, Hou X, Kuhn M, Wager TT, Kauffman GW, Verhoest PR.

J Med Chem. 2016 Jun 9;59(11):5284-96. doi: 10.1021/acs.jmedchem.6b00027. Epub 2016 May 26.

PMID:
27228214
9.

Central Nervous System Multiparameter Optimization Desirability: Application in Drug Discovery.

Wager TT, Hou X, Verhoest PR, Villalobos A.

ACS Chem Neurosci. 2016 Jun 15;7(6):767-75. doi: 10.1021/acschemneuro.6b00029. Epub 2016 Apr 4.

PMID:
26991242
10.

Identification of Phosphorylation Consensus Sequences and Endogenous Neuronal Substrates of the Psychiatric Risk Kinase TNIK.

Wang Q, Amato SP, Rubitski DM, Hayward MM, Kormos BL, Verhoest PR, Xu L, Brandon NJ, Ehlers MD.

J Pharmacol Exp Ther. 2016 Feb;356(2):410-23. doi: 10.1124/jpet.115.229880. Epub 2015 Dec 8.

PMID:
26645429
11.

Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway.

Dounay AB, Tuttle JB, Verhoest PR.

J Med Chem. 2015 Nov 25;58(22):8762-82. doi: 10.1021/acs.jmedchem.5b00461. Epub 2015 Aug 5. Review.

PMID:
26207924
12.

Design of Pyridopyrazine-1,6-dione γ-Secretase Modulators that Align Potency, MDR Efflux Ratio, and Metabolic Stability.

Pettersson M, Johnson DS, Humphrey JM, Butler TW, Am Ende CW, Fish BA, Green ME, Kauffman GW, Mullins PB, O'Donnell CJ, Stepan AF, Stiff CM, Subramanyam C, Tran TP, Vetelino BC, Yang E, Xie L, Bales KR, Pustilnik LR, Steyn SJ, Wood KM, Verhoest PR.

ACS Med Chem Lett. 2015 Apr 3;6(5):596-601. doi: 10.1021/acsmedchemlett.5b00070. eCollection 2015 May 14.

13.

Discovery of indole-derived pyridopyrazine-1,6-dione γ-secretase modulators that target presenilin.

Pettersson M, Johnson DS, Humphrey JM, Am Ende CW, Evrard E, Efremov I, Kauffman GW, Stepan AF, Stiff CM, Xie L, Bales KR, Hajos-Korcsok E, Murrey HE, Pustilnik LR, Steyn SJ, Wood KM, Verhoest PR.

Bioorg Med Chem Lett. 2015 Feb 15;25(4):908-13. doi: 10.1016/j.bmcl.2014.12.059. Epub 2014 Dec 25.

PMID:
25582600
14.

Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor.

Henderson JL, Kormos BL, Hayward MM, Coffman KJ, Jasti J, Kurumbail RG, Wager TT, Verhoest PR, Noell GS, Chen Y, Needle E, Berger Z, Steyn SJ, Houle C, Hirst WD, Galatsis P.

J Med Chem. 2015 Jan 8;58(1):419-32. doi: 10.1021/jm5014055. Epub 2014 Nov 17.

PMID:
25353650
15.

Chemoproteomics demonstrates target engagement and exquisite selectivity of the clinical phosphodiesterase 10A inhibitor MP-10 in its native environment.

Schülke JP, McAllister LA, Geoghegan KF, Parikh V, Chappie TA, Verhoest PR, Schmidt CJ, Johnson DS, Brandon NJ.

ACS Chem Biol. 2014 Dec 19;9(12):2823-32. doi: 10.1021/cb500671j. Epub 2014 Oct 20.

PMID:
25295858
16.

Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a [1,2,4]triazolo[4,3-b]pyridazine scaffold.

Galatsis P, Henderson JL, Kormos BL, Han S, Kurumbail RG, Wager TT, Verhoest PR, Noell GS, Chen Y, Needle E, Berger Z, Steyn SJ, Houle C, Hirst WD.

Bioorg Med Chem Lett. 2014 Sep 1;24(17):4132-40. doi: 10.1016/j.bmcl.2014.07.052. Epub 2014 Jul 30.

PMID:
25113930
17.

1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile derivatives as potent and tissue selective androgen receptor modulators.

Piatnitski Chekler EL, Unwalla R, Khan TA, Tangirala RS, Johnson M, St Andre M, Anderson JT, Kenney T, Chiparri S, McNally C, Kilbourne E, Thompson C, Nagpal S, Weber G, Schelling S, Owens J, Morris CA, Powell D, Verhoest PR, Gilbert AM.

J Med Chem. 2014 Mar 27;57(6):2462-71. doi: 10.1021/jm401625b. Epub 2014 Mar 10.

PMID:
24527807
18.

Design, synthesis, and pharmacological evaluation of a novel series of pyridopyrazine-1,6-dione γ-secretase modulators.

Pettersson M, Johnson DS, Subramanyam C, Bales KR, am Ende CW, Fish BA, Green ME, Kauffman GW, Mullins PB, Navaratnam T, Sakya SM, Stiff CM, Tran TP, Xie L, Zhang L, Pustilnik LR, Vetelino BC, Wood KM, Pozdnyakov N, Verhoest PR, O'Donnell CJ.

J Med Chem. 2014 Feb 13;57(3):1046-62. doi: 10.1021/jm401782h. Epub 2014 Jan 28.

PMID:
24428186
19.

Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): a highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator.

Zhang L, Balan G, Barreiro G, Boscoe BP, Chenard LK, Cianfrogna J, Claffey MM, Chen L, Coffman KJ, Drozda SE, Dunetz JR, Fonseca KR, Galatsis P, Grimwood S, Lazzaro JT, Mancuso JY, Miller EL, Reese MR, Rogers BN, Sakurada I, Skaddan M, Smith DL, Stepan AF, Trapa P, Tuttle JB, Verhoest PR, Walker DP, Wright AS, Zaleska MM, Zasadny K, Shaffer CL.

J Med Chem. 2014 Feb 13;57(3):861-77. doi: 10.1021/jm401622k. Epub 2014 Jan 22.

PMID:
24392688
20.

Evaluating the differences in cycloalkyl ether metabolism using the design parameter "lipophilic metabolism efficiency" (LipMetE) and a matched molecular pairs analysis.

Stepan AF, Kauffman GW, Keefer CE, Verhoest PR, Edwards M.

J Med Chem. 2013 Sep 12;56(17):6985-90. doi: 10.1021/jm4008642. Epub 2013 Aug 21.

PMID:
23886251
21.

Design and selection parameters to accelerate the discovery of novel central nervous system positron emission tomography (PET) ligands and their application in the development of a novel phosphodiesterase 2A PET ligand.

Zhang L, Villalobos A, Beck EM, Bocan T, Chappie TA, Chen L, Grimwood S, Heck SD, Helal CJ, Hou X, Humphrey JM, Lu J, Skaddan MB, McCarthy TJ, Verhoest PR, Wager TT, Zasadny K.

J Med Chem. 2013 Jun 13;56(11):4568-79. doi: 10.1021/jm400312y. Epub 2013 May 28.

PMID:
23651455
22.

PF-04859989 as a template for structure-based drug design: identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency.

Dounay AB, Anderson M, Bechle BM, Evrard E, Gan X, Kim JY, McAllister LA, Pandit J, Rong S, Salafia MA, Tuttle JB, Zawadzke LE, Verhoest PR.

Bioorg Med Chem Lett. 2013 Apr 1;23(7):1961-6. doi: 10.1016/j.bmcl.2013.02.039. Epub 2013 Feb 15.

PMID:
23466229
23.

Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New Potency-Enhancing Interactions.

Tuttle JB, Anderson M, Bechle BM, Campbell BM, Chang C, Dounay AB, Evrard E, Fonseca KR, Gan X, Ghosh S, Horner W, James LC, Kim JY, McAllister LA, Pandit J, Parikh VD, Rago BJ, Salafia MA, Strick CA, Zawadzke LE, Verhoest PR.

ACS Med Chem Lett. 2012 Oct 24;4(1):37-40. doi: 10.1021/ml300237v. eCollection 2013 Jan 10.

24.

Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors.

Claffey MM, Helal CJ, Verhoest PR, Kang Z, Fors KS, Jung S, Zhong J, Bundesmann MW, Hou X, Lui S, Kleiman RJ, Vanase-Frawley M, Schmidt AW, Menniti F, Schmidt CJ, Hoffman WE, Hajos M, McDowell L, O'Connor RE, Macdougall-Murphy M, Fonseca KR, Becker SL, Nelson FR, Liras S.

J Med Chem. 2012 Nov 8;55(21):9055-68. doi: 10.1021/jm3009635. Epub 2012 Oct 12.

PMID:
23025719
25.

Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disorders.

Verhoest PR, Fonseca KR, Hou X, Proulx-Lafrance C, Corman M, Helal CJ, Claffey MM, Tuttle JB, Coffman KJ, Liu S, Nelson F, Kleiman RJ, Menniti FS, Schmidt CJ, Vanase-Frawley M, Liras S.

J Med Chem. 2012 Nov 8;55(21):9045-54. doi: 10.1021/jm3007799. Epub 2012 Jul 25.

PMID:
22780914
26.

Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia.

Dounay AB, Anderson M, Bechle BM, Campbell BM, Claffey MM, Evdokimov A, Evrard E, Fonseca KR, Gan X, Ghosh S, Hayward MM, Horner W, Kim JY, McAllister LA, Pandit J, Paradis V, Parikh VD, Reese MR, Rong S, Salafia MA, Schuyten K, Strick CA, Tuttle JB, Valentine J, Wang H, Zawadzke LE, Verhoest PR.

ACS Med Chem Lett. 2012 Jan 25;3(3):187-92. doi: 10.1021/ml200204m. eCollection 2012 Mar 8.

27.

Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo.

Kleiman RJ, Chapin DS, Christoffersen C, Freeman J, Fonseca KR, Geoghegan KF, Grimwood S, Guanowsky V, Hajós M, Harms JF, Helal CJ, Hoffmann WE, Kocan GP, Majchrzak MJ, McGinnis D, McLean S, Menniti FS, Nelson F, Roof R, Schmidt AW, Seymour PA, Stephenson DT, Tingley FD, Vanase-Frawley M, Verhoest PR, Schmidt CJ.

J Pharmacol Exp Ther. 2012 May;341(2):396-409. doi: 10.1124/jpet.111.191353. Epub 2012 Feb 10.

PMID:
22328573
28.

Pharmacological characterization of 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine (PF-04455242), a high-affinity antagonist selective for κ-opioid receptors.

Grimwood S, Lu Y, Schmidt AW, Vanase-Frawley MA, Sawant-Basak A, Miller E, McLean S, Freeman J, Wong S, McLaughlin JP, Verhoest PR.

J Pharmacol Exp Ther. 2011 Nov;339(2):555-66. doi: 10.1124/jpet.111.185108. Epub 2011 Aug 5.

PMID:
21821697
29.

Design and discovery of a selective small molecule κ opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242).

Verhoest PR, Basak AS, Parikh V, Hayward M, Kauffman GW, Paradis V, McHardy SF, McLean S, Grimwood S, Schmidt AW, Vanase-Frawley M, Freeman J, Van Deusen J, Cox L, Wong D, Liras S.

J Med Chem. 2011 Aug 25;54(16):5868-77. doi: 10.1021/jm2006035. Epub 2011 Jul 22.

PMID:
21744827
30.

A general strategy for the synthesis of cyclic N-aryl hydroxamic acids via partial nitro group reduction.

McAllister LA, Bechle BM, Dounay AB, Evrard E, Gan X, Ghosh S, Kim JY, Parikh VD, Tuttle JB, Verhoest PR.

J Org Chem. 2011 May 6;76(9):3484-97. doi: 10.1021/jo200530j. Epub 2011 Apr 11.

PMID:
21452845
31.

Strategies to optimize the brain availability of central nervous system drug candidates.

Wager TT, Villalobos A, Verhoest PR, Hou X, Shaffer CL.

Expert Opin Drug Discov. 2011 Apr;6(4):371-81. doi: 10.1517/17460441.2011.564158. Epub 2011 Mar 22.

PMID:
22646015
32.

Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties.

Wager TT, Hou X, Verhoest PR, Villalobos A.

ACS Chem Neurosci. 2010 Jun 16;1(6):435-49. doi: 10.1021/cn100008c. Epub 2010 Mar 25.

33.

Defining desirable central nervous system drug space through the alignment of molecular properties, in vitro ADME, and safety attributes.

Wager TT, Chandrasekaran RY, Hou X, Troutman MD, Verhoest PR, Villalobos A, Will Y.

ACS Chem Neurosci. 2010 Jun 16;1(6):420-34. doi: 10.1021/cn100007x. Epub 2010 Mar 25.

34.

Identification of a brain penetrant PDE9A inhibitor utilizing prospective design and chemical enablement as a rapid lead optimization strategy.

Verhoest PR, Proulx-Lafrance C, Corman M, Chenard L, Helal CJ, Hou X, Kleiman R, Liu S, Marr E, Menniti FS, Schmidt CJ, Vanase-Frawley M, Schmidt AW, Williams RD, Nelson FR, Fonseca KR, Liras S.

J Med Chem. 2009 Dec 24;52(24):7946-9. doi: 10.1021/jm9015334.

PMID:
19919087
35.

Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia.

Verhoest PR, Chapin DS, Corman M, Fonseca K, Harms JF, Hou X, Marr ES, Menniti FS, Nelson F, O'Connor R, Pandit J, Proulx-Lafrance C, Schmidt AW, Schmidt CJ, Suiciak JA, Liras S.

J Med Chem. 2009 Aug 27;52(16):5188-96. doi: 10.1021/jm900521k.

PMID:
19630403
36.

Preclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia.

Schmidt CJ, Chapin DS, Cianfrogna J, Corman ML, Hajos M, Harms JF, Hoffman WE, Lebel LA, McCarthy SA, Nelson FR, Proulx-LaFrance C, Majchrzak MJ, Ramirez AD, Schmidt K, Seymour PA, Siuciak JA, Tingley FD 3rd, Williams RD, Verhoest PR, Menniti FS.

J Pharmacol Exp Ther. 2008 May;325(2):681-90. doi: 10.1124/jpet.107.132910. Epub 2008 Feb 20.

PMID:
18287214
37.

Total synthesis of (+)-phorboxazole A exploiting the Petasis-Ferrier rearrangement.

Smith AB 3rd, Minbiole KP, Verhoest PR, Schelhaas M.

J Am Chem Soc. 2001 Nov 7;123(44):10942-53.

PMID:
11686698
38.

Total synthesis of (+)-phorboxazole A.

Smith AB 3rd, Verhoest PR, Minbiole KP, Schelhaas M.

J Am Chem Soc. 2001 May 23;123(20):4834-6. No abstract available.

PMID:
11457294
39.

Phorboxazole synthetic studies. 2. Construction of a C(20-28) subtarget, a further extension of the Petasis-Ferrier rearrangement.

Smith AB 3rd, Minbiole KP, Verhoest PR, Beauchamp TJ.

Org Lett. 1999 Sep 23;1(6):913-6.

PMID:
10823222
40.

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