Y3154207 is a potent, and subtype selective human D1 positive allosteric modulator (PAM) with minimal allosteric agonist activity (EC50 = 3 nM). In contrast to orthosteric agonists, LY3154207 showed a distinct pharmacological profile without a bell-shaped dose-response relationship or tachyphylaxis in preclinical models. Identification of a crystalline form of free LY3154207 from the discovery lots was not successful. Instead, a novel cocrystal form with superior solubility was discovered and determined to be suitable for development. LY3154207 is now in clinical development as a potential first-in-class D1 PAM for Lewy body dementia. References: Hao J, Beck JP, Schaus JM, Krushinski JH, Chen Q, Beadle CD, Vidal P, Reinhard MR, Dressman BA, Massey SM, Boulet SL, Cohen MP, Watson BM, Tupper D, Gardinier KM, Myers J, Johansson AM, Richardson J, Richards DS, Hembre EJ, Remick DM, Coates DA, Bhardwaj RM, Diseroad BA, Bender D, Stephenson G, Wolfangel CD, Diaz N, Getman BG, Wang XS, Heinz BA, Cramer JW, Zhou X, Maren DL, Falcone JF, Wright RA, Mitchell SN, Carter G, Yang CR, Bruns RF, Svensson KA. Synthesis and Pharmacological Characterization of 2-(2,6-Dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1 -methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a Potent, Subtype Selective, and Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor. J Med Chem. 2019 Sep 30. doi: 10.1021/acs.jmedchem.9b01234. [Epub ahead of print] PubMed PMID: 31532644.

纯度：≥98%

CAS：1638667-79-4