Discovery of N-aryl piperazines as selective mGluR5 potentiators with improved in vivo utility

ACS Medicinal Chemistry Letters

Volumn 1, Issue 8, 2010, Pages 433-438

  Zhou, Ya ^a,b   Manka, Jason T ^a,b   Rodriguez, Alice L ^a,b   Weaver, C David ^a,b   Days, Emily L ^a,b   Vinson, Paige N ^a,b   Jadhav, Satyawan ^a,b   Hermann, Elizabeth J ^a,b   Jones, Carrie K ^a,b,c   Conn, P Jeffrey ^a,b   Lindsley, Craig W ^a,b   Stauffer, Shaun R ^a,b  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^c DEPARTMENT OF VETERANS AFFAIRS   (United States)

Author keywords

hyperlocomotion; mGluR; positive allosteric modulator; potentiator; schizophrenia

Indexed keywords

ADX 47273; AMPHETAMINE; METABOTROPIC RECEPTOR 5; NEUROLEPTIC AGENT; PIPERAZINE DERIVATIVE; UNCLASSIFIED DRUG; VU 0364289;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PRIORITY JOURNAL; RAT; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION;

RATTUS; RODENTIA;

EID: 78649282776     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml100181a     Document Type: Article

References (26)

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21. 5 PAMs; see WO 087135, 2007; WO 152089, 2008; and WO 152090, 2008.
22. Experimental details are provided in the Supporting Information.
23. cLog P values were calculated using ChemBioDraw Ultra, version 12.0, available from CambridgeSoft.
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25. Although published accounts of plasma protein binding (PPB) and solubility data do not exist for ADX-47273, we have independently characterized ADX-47273 in-house and found PPB to be >98% in rat plasma and aqueous kinetic solubility to be <0.01 mg/mL.
26. Herman, E.; Gregory, K. J.; Jones, C. K.; Hammond, A. S.; Stauffer, S. R.; Manka, J.; Weaver, C. D.; Niswender, C. M.; Steckler, T.; Lavreysen, H.; MacDonald, G.; Bartolomé, J. M.; Mackie, C.; Lindsley, C. W.; Conn, P. J. Neuroscience 2010, Society for Neuroscience 40th Annual Meeting, 2010, San Diego, CA.