Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists

Journal of Medicinal Chemistry

Volumn 51, Issue 19, 2008, Pages 5915-5918

  Jin, Jian ^a,b   Budzik, Brian ^a   Wang, Yonghui ^a   Shi, Dongchuan ^a   Wang, Feng ^a   Xie, Haibo ^a   Wan, Zehong ^a   Zhu, Chongye ^a   Foley, James J ^a   Webb, Edward F ^a   Berlanga, Manuela ^a   Burman, Miriam ^a   Sarau, Henry M ^a   Morrow, Dwight M ^a   Moore, Michael L ^a   Rivero, Ralph A ^a   Palovich, Michael ^a   Salmon, Michael ^a   Belmonte, Kristen E ^a   Lainé, Dramane I ^a  

^a GLAXOSMITHKLINE   (United States)

^b UNIVERSITY OF NORTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIPHENYL DERIVATIVE; MUSCARINIC RECEPTOR BLOCKING AGENT; PIPERAZINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRONCHOSPASM; CHRONIC OBSTRUCTIVE LUNG DISEASE; CONTROLLED STUDY; DRUG INDICATION; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; IN VIVO STUDY; MOUSE; NONHUMAN; SINGLE DRUG DOSE;

ADMINISTRATION, INTRANASAL; ANIMALS; BRONCHIAL PROVOCATION TESTS; BRONCHOCONSTRICTION; BRONCHOCONSTRICTOR AGENTS; BRONCHODILATOR AGENTS; DISEASE MODELS, ANIMAL; DRUG EVALUATION, PRECLINICAL; METHACHOLINE CHLORIDE; MICE; MOLECULAR STRUCTURE; PIPERAZINES; RECEPTORS, MUSCARINIC; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 53549091063     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm800935u     Document Type: Article

References (26)

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14. 3 receptor. See supporting information for FLIPR assay details.
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19. The biological assay results in the paper are a mean of at least 2 determinations with standard deviation of <±0.3 unless otherwise noted.
20. 1 FLIPR assays and showed no agonism in the three assays.
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25. 5a, 5b, and 5c were single enantiomers with a (3S)-3-methylpiperazin-1-yl moiety at the right-hand side (RHS) similar to 4a, 4b, and 4c.
26. Measuring the permeation ability of compounds of interest across artificial phospholipid membranes. The technique is very similar to the widely used Caco-2 monolayer permeation technique.