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Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): a temperature-neutral transient receptor potential vanilloid-1 (TRPV1) antagonist with analgesic efficacy.
Voight EA, Gomtsyan AR, Daanen JF, Perner RJ, Schmidt RG, Bayburt EK, DiDomenico S, McDonald HA, Puttfarcken PS, Chen J, Neelands TR, Bianchi BR, Han P, Reilly RM, Franklin PH, Segreti JA, Nelson RA, Su Z, King AJ, Polakowski JS, Baker SJ, Gauvin DM, Lewis LR, Mikusa JP, Joshi SK, Faltynek CR, Kym PR, Kort ME. Voight EA, et al. Among authors: polakowski js. J Med Chem. 2014 Sep 11;57(17):7412-24. doi: 10.1021/jm500916t. Epub 2014 Aug 21. J Med Chem. 2014. PMID: 25100568
Structure-activity studies of a novel series of 5,6-fused heteroaromatic ureas as TRPV1 antagonists.
Drizin I, Gomtsyan A, Bayburt EK, Schmidt RG, Zheng GZ, Perner RJ, DiDomenico S, Koenig JR, Turner SC, Jinkerson TK, Brown BS, Keddy RG, McDonald HA, Honore P, Wismer CT, Marsh KC, Wetter JM, Polakowski JS, Segreti JA, Jarvis MF, Faltynek CR, Lee CH. Drizin I, et al. Among authors: polakowski js. Bioorg Med Chem. 2006 Jul 15;14(14):4740-9. doi: 10.1016/j.bmc.2006.03.027. Epub 2006 Apr 18. Bioorg Med Chem. 2006. PMID: 16621571
Screening for cardiovascular safety: a structure-activity approach for guiding lead selection of melanin concentrating hormone receptor 1 antagonists.
Kym PR, Souers AJ, Campbell TJ, Lynch JK, Judd AS, Iyengar R, Vasudevan A, Gao J, Freeman JC, Wodka D, Mulhern M, Zhao G, Wagaw SH, Napier JJ, Brodjian S, Dayton BD, Reilly RM, Segreti JA, Fryer RM, Preusser LC, Reinhart GA, Hernandez L, Marsh KC, Sham HL, Collins CA, Polakowski JS. Kym PR, et al. Among authors: polakowski js. J Med Chem. 2006 Apr 6;49(7):2339-52. doi: 10.1021/jm0512286. J Med Chem. 2006. PMID: 16570930
Optimization of chromone-2-carboxamide melanin concentrating hormone receptor 1 antagonists: assessment of potency, efficacy, and cardiovascular safety.
Lynch JK, Freeman JC, Judd AS, Iyengar R, Mulhern M, Zhao G, Napier JJ, Wodka D, Brodjian S, Dayton BD, Falls D, Ogiela C, Reilly RM, Campbell TJ, Polakowski JS, Hernandez L, Marsh KC, Shapiro R, Knourek-Segel V, Droz B, Bush E, Brune M, Preusser LC, Fryer RM, Reinhart GA, Houseman K, Diaz G, Mikhail A, Limberis JT, Sham HL, Collins CA, Kym PR. Lynch JK, et al. Among authors: polakowski js. J Med Chem. 2006 Nov 2;49(22):6569-84. doi: 10.1021/jm060683e. J Med Chem. 2006. PMID: 17064075
Evoked changes in cardiovascular function in rats by infusion of levosimendan, OR-1896 [(R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide], OR-1855 [(R)-6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one], dobutamine, and milrinone: comparative effects on peripheral resistance, cardiac output, dP/dt, pulse rate, and blood pressure.
Segreti JA, Marsh KC, Polakowski JS, Fryer RM. Segreti JA, et al. Among authors: polakowski js. J Pharmacol Exp Ther. 2008 Apr;325(1):331-40. doi: 10.1124/jpet.107.132530. Epub 2008 Jan 2. J Pharmacol Exp Ther. 2008. PMID: 18171907
Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes.
Madar DJ, Kopecka H, Pireh D, Yong H, Pei Z, Li X, Wiedeman PE, Djuric SW, Von Geldern TW, Fickes MG, Bhagavatula L, McDermott T, Wittenberger S, Richards SJ, Longenecker KL, Stewart KD, Lubben TH, Ballaron SJ, Stashko MA, Long MA, Wells H, Zinker BA, Mika AK, Beno DW, Kempf-Grote AJ, Polakowski J, Segreti J, Reinhart GA, Fryer RM, Sham HL, Trevillyan JM. Madar DJ, et al. J Med Chem. 2006 Oct 19;49(21):6416-20. doi: 10.1021/jm060777o. J Med Chem. 2006. PMID: 17034148
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