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Development of a highly potent, novel M5 positive allosteric modulator (PAM) demonstrating CNS exposure: 1-((1H-indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380).
Gentry PR, Kokubo M, Bridges TM, Noetzel MJ, Cho HP, Lamsal A, Smith E, Chase P, Hodder PS, Niswender CM, Daniels JS, Conn PJ, Lindsley CW, Wood MR. Gentry PR, et al. Among authors: wood mr. J Med Chem. 2014 Sep 25;57(18):7804-10. doi: 10.1021/jm500995y. Epub 2014 Sep 3. J Med Chem. 2014. PMID: 25147929 Free PMC article.
Synthesis and biological characterization of a series of novel diaryl amide M₁ antagonists.
Poslusney MS, Sevel C, Utley TJ, Bridges TM, Morrison RD, Kett NR, Sheffler DJ, Niswender CM, Daniels JS, Conn PJ, Lindsley CW, Wood MR. Poslusney MS, et al. Among authors: wood mr. Bioorg Med Chem Lett. 2012 Nov 15;22(22):6923-8. doi: 10.1016/j.bmcl.2012.09.011. Epub 2012 Sep 23. Bioorg Med Chem Lett. 2012. PMID: 23062550 Free PMC article.
Targeting selective activation of M(1) for the treatment of Alzheimer's disease: further chemical optimization and pharmacological characterization of the M(1) positive allosteric modulator ML169.
Tarr JC, Turlington ML, Reid PR, Utley TJ, Sheffler DJ, Cho HP, Klar R, Pancani T, Klein MT, Bridges TM, Morrison RD, Blobaum AL, Xiang Z, Daniels JS, Niswender CM, Conn PJ, Wood MR, Lindsley CW. Tarr JC, et al. Among authors: wood mr. ACS Chem Neurosci. 2012 Nov 21;3(11):884-95. doi: 10.1021/cn300068s. Epub 2012 Jul 18. ACS Chem Neurosci. 2012. PMID: 23173069 Free PMC article.
Discovery of a selective M₄ positive allosteric modulator based on the 3-amino-thieno[2,3-b]pyridine-2-carboxamide scaffold: development of ML253, a potent and brain penetrant compound that is active in a preclinical model of schizophrenia.
Le U, Melancon BJ, Bridges TM, Vinson PN, Utley TJ, Lamsal A, Rodriguez AL, Venable D, Sheffler DJ, Jones CK, Blobaum AL, Wood MR, Daniels JS, Conn PJ, Niswender CM, Lindsley CW, Hopkins CR. Le U, et al. Among authors: wood mr. Bioorg Med Chem Lett. 2013 Jan 1;23(1):346-50. doi: 10.1016/j.bmcl.2012.10.073. Epub 2012 Nov 1. Bioorg Med Chem Lett. 2013. PMID: 23177787 Free PMC article.
Further exploration of M₁ allosteric agonists: subtle structural changes abolish M₁ allosteric agonism and result in pan-mAChR orthosteric antagonism.
Sheffler DJ, Sevel C, Le U, Lovell KM, Tarr JC, Carrington SJ, Cho HP, Digby GJ, Niswender CM, Conn PJ, Hopkins CR, Wood MR, Lindsley CW. Sheffler DJ, et al. Among authors: wood mr. Bioorg Med Chem Lett. 2013 Jan 1;23(1):223-7. doi: 10.1016/j.bmcl.2012.10.132. Epub 2012 Nov 9. Bioorg Med Chem Lett. 2013. PMID: 23200253 Free PMC article.
Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule.
Melancon BJ, Poslusney MS, Gentry PR, Tarr JC, Sheffler DJ, Mattmann ME, Bridges TM, Utley TJ, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Wood MR. Melancon BJ, et al. Among authors: wood mr. Bioorg Med Chem Lett. 2013 Jan 15;23(2):412-6. doi: 10.1016/j.bmcl.2012.11.092. Epub 2012 Dec 1. Bioorg Med Chem Lett. 2013. PMID: 23237839 Free PMC article.
Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule.
Poslusney MS, Melancon BJ, Gentry PR, Sheffler DJ, Bridges TM, Utley TJ, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Wood MR. Poslusney MS, et al. Among authors: wood mr. Bioorg Med Chem Lett. 2013 Mar 15;23(6):1860-4. doi: 10.1016/j.bmcl.2013.01.017. Epub 2013 Jan 11. Bioorg Med Chem Lett. 2013. PMID: 23416001 Free PMC article.
Discovery of ML326: The first sub-micromolar, selective M5 PAM.
Gentry PR, Bridges TM, Lamsal A, Vinson PN, Smith E, Chase P, Hodder PS, Engers JL, Niswender CM, Daniels JS, Conn PJ, Wood MR, Lindsley CW. Gentry PR, et al. Among authors: wood mr. Bioorg Med Chem Lett. 2013 May 15;23(10):2996-3000. doi: 10.1016/j.bmcl.2013.03.032. Epub 2013 Mar 16. Bioorg Med Chem Lett. 2013. PMID: 23562060 Free PMC article.
Discovery of the first M5-selective and CNS penetrant negative allosteric modulator (NAM) of a muscarinic acetylcholine receptor: (S)-9b-(4-chlorophenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-one (ML375).
Gentry PR, Kokubo M, Bridges TM, Kett NR, Harp JM, Cho HP, Smith E, Chase P, Hodder PS, Niswender CM, Daniels JS, Conn PJ, Wood MR, Lindsley CW. Gentry PR, et al. Among authors: wood mr. J Med Chem. 2013 Nov 27;56(22):9351-5. doi: 10.1021/jm4013246. Epub 2013 Nov 13. J Med Chem. 2013. PMID: 24164599 Free PMC article.
156 results