Probing the Physicochemical Boundaries of Cell Permeability and Oral Bioavailability in Lipophilic Macrocycles Inspired by Natural Products

Journal of Medicinal Chemistry

Volumn 58, Issue 11, 2015, Pages 4581-4589

  Bockus, Andrew T ^a   Lexa, Katrina W ^b   Pye, Cameron R ^a   Kalgutkar, Amit S ^c   Gardner, Jarret W ^a   Hund, Kathryn C R ^a   Hewitt, William M ^a   Schwochert, Joshua A ^a   Glassey, Emerson ^a   Price, David A ^c   Mathiowetz, Alan M ^c   Liras, Spiros ^c   Jacobson, Matthew P ^b   Lokey, R Scott ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPEPTIDE; CYCLOSPORIN A; HEXAPEPTIDE; MACROCYCLIC COMPOUND; PROPRANOLOL; STATINE; BIOLOGICAL PRODUCT; SOLVENT;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; CRYSTAL STRUCTURE; DIASTEREOISOMER; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG PENETRATION; DRUG SOLUBILITY; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; ELIMINATION HALF-LIFE; HUMAN; HUMAN CELL; HYDROGEN BOND; IN VITRO STUDY; IN VIVO STUDY; LIPOPHILICITY; LIVER MICROSOME; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PASSIVE TRANSPORT; PHYSICAL CHEMISTRY; RAT; STEREOCHEMISTRY; VOLUME OF DISTRIBUTION AT STEADY-STATE; ANIMAL; BIOAVAILABILITY; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; ORAL DRUG ADMINISTRATION; STRUCTURE ACTIVITY RELATION; WISTAR RAT;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; BIOLOGICAL PRODUCTS; CELL MEMBRANE PERMEABILITY; HYDROGEN BONDING; MACROCYCLIC COMPOUNDS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MICROSOMES, LIVER; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PEPTIDES, CYCLIC; PHYSICOCHEMICAL PHENOMENA; RATS; RATS, WISTAR; SOLVENTS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84935898517     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00128     Document Type: Article

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