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-1 H -imidazo[2,1- a ]isoindol-5(9b H)-one (ML375)

Journal of Medicinal Chemistry

Volumn 56, Issue 22, 2013, Pages 9351-9355

  Gentry, Patrick R ^a,b   Kokubo, Masaya ^a,b   Bridges, Thomas M ^a,b   Kett, Nathan R ^a,b   Harp, Joel M ^a   Cho, Hyekyung P ^a,b   Smith, Emery ^d   Chase, Peter ^d   Hodder, Peter S ^d   Niswender, Colleen M ^a,b   Daniels, J Scott ^a,b   Conn, P Jeffrey ^a,b   Wood, Michael R ^a,b,c   Lindsley, Craig W ^a,b,c  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^c VANDERBILT UNIVERSITY   (United States)

^d SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

9 BETA (4 CHLOROPHENYL) 1 (3,4 DIFLUOROBENZOYL) 2,3 DIHYDRO 1H IMIDAZO[2,1 ALPHA ]ISOINDOL 5 (9 BETA H)ONE; CENTRAL NERVOUS SYSTEM AGENTS; ML 375; MUSCARINIC M5 RECEPTOR; MUSCARINIC RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG; VU 0483253; 9B-(4-CHLOROPHENYL)-1-(3,4-DIFLUOROBENZOYL)-2,3-DIHYDRO-1H-IMIDAZO(2,1-A)ISOINDOL-5(9BH)-ONE; IMIDAZOLE DERIVATIVE; INDOLE DERIVATIVE; 9B (4 CHLOROPHENYL) 1 (3,4 DIFLUOROBENZOYL) 2,3 DIHYDRO 1H IMIDAZO(2,1 A)ISOINDOL 5(9BH) ONE;

ANIMAL CELL; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CENTRAL NERVOUS SYSTEM; DRUG BINDING SITE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CLEARANCE; DRUG DEVELOPMENT; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; FEMALE; HUMAN; IC 50; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PROTEIN EXPRESSION; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; ALLOSTERISM; ANIMAL; BRAIN; CHEMISTRY; CHO CELL LINE; CRICETULUS; DRUG EFFECTS; ENZYME SPECIFICITY; HAMSTER; METABOLISM; STRUCTURE ACTIVITY RELATION; CHO CELL; DRUG EFFECT;

ALLOSTERIC REGULATION; ANIMALS; BRAIN; CHO CELLS; CRICETINAE; CRICETULUS; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; HUMANS; IMIDAZOLES; INDOLES; MALE; RATS; RECEPTOR, MUSCARINIC M5; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 84889245029     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm4013246     Document Type: Article

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19. For the MLPCN see http://mli.nih.gov/mli/mlpcn/. ML375 is an MLPCN probe and freely available upon request.
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