Improving the oral efficacy of CNS drug candidates: Discovery of highly orally efficacious piperidinyl piperidine M2 muscarinic receptor antagonists

Journal of Medicinal Chemistry

Volumn 45, Issue 25, 2002, Pages 5415-5418

  Wang, Yuguang ^a   Chackalamannil, Samuel ^a   Hu, Zhiyong ^a   Greenlee, William J ^a   Clader, John ^a   Boyle, Craig D ^a   Kaminski, James J ^a   Billard, William ^a   Binch III, Herbert ^a   Crosby, Gordon ^a   Ruperto, Vilma ^a   Duffy, Ruth A ^a   Cohen Williams, Mary ^a   Coffin, Vicki L ^a   Cox, Kathleen A ^a   Grotz, Diane E ^a   Lachowicz, Jean E ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LEAD; MUSCARINIC M2 RECEPTOR ANTAGONIST; MUSCARINIC RECEPTOR BLOCKING AGENT; PIPERIDINE DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DRUG EFFICACY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIPOPHILICITY; MOLECULAR WEIGHT; NONHUMAN; RAT;

ACETYLCHOLINE; ADMINISTRATION, ORAL; ANIMALS; AUTORECEPTORS; AVOIDANCE LEARNING; CENTRAL NERVOUS SYSTEM AGENTS; CORPUS STRIATUM; HUMANS; MICRODIALYSIS; MOLECULAR CONFORMATION; MUSCARINIC ANTAGONISTS; PIPERIDINES; RATS; RECEPTOR, MUSCARINIC M2; RECEPTORS, MUSCARINIC; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037028048     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0255163     Document Type: Article

References (21)

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20. For details of chiral HPLC separation of 7, please see the Supporting Information.
21. Compounds were subjected to human liver microsomal incubation for 30 min. The metabolite characterization was done by LC MS/MS of the microsomal incubation. The details will be reported by Cox, K. A., et al.