LY3154207   Click here for help

GtoPdb Ligand ID: 10506

Synonyms: compound 3 [PMID: 31532644] | LY-3154207
PDB Ligand
Compound class: Synthetic organic
Comment: LY3154207 is a potent, selective and orally active dopamine D1 receptor positive allosteric modulator (PAM) [1]. The allosteric binding site of LY3154207 has been determined to reside at the intracellular loop 2 (ICL2) region of the receptor.
D1 PAMs are being developed to address the poor drug-like properties of selective orthosteric D1 agonists. In particular, LY3154207 does not induce tachyphylaxis in preclinical models, whereas orthosteric agonists do. LY3154207 exhibits pro-cognitive and motor-enhancing effects in vivo, and is being considered for potential utility in the treatment of neuropsychiatric disorders [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 60.77
Molecular weight 449.15
XLogP 4.62
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES OCC1Cc2c(cccc2C(N1C(=O)Cc1c(Cl)cccc1Cl)C)CCC(O)(C)C
Isomeric SMILES OC[C@H]1Cc2c(cccc2[C@@H](N1C(=O)Cc1c(Cl)cccc1Cl)C)CCC(O)(C)C
InChI InChI=1S/C24H29Cl2NO3/c1-15-18-7-4-6-16(10-11-24(2,3)30)19(18)12-17(14-28)27(15)23(29)13-20-21(25)8-5-9-22(20)26/h4-9,15,17,28,30H,10-14H2,1-3H3/t15-,17+/m0/s1
InChI Key XHCSBQBBGNQINS-DOTOQJQBSA-N
References
1. Hao J, Beck JP, Schaus JM, Krushinski JH, Chen Q, Beadle CD, Vidal P, Reinhard MR, Dressman BA, Massey SM et al.. (2019)
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, 62 (19): 8711-8732. [PMID:31532644]
2. Svensson KA, Hao J, Bruns RF. (2019)
Positive allosteric modulators of the dopamine D1 receptor: A new mechanism for the treatment of neuropsychiatric disorders.
Adv Pharmacol, 86: 273-305. [PMID:31378255]