Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor

Journal of Medicinal Chemistry

Volumn 58, Issue 1, 2015, Pages 419-432

  Henderson, Jaclyn L ^a   Kormos, Bethany L ^a   Hayward, Matthew M ^a   Coffman, Karen J ^a   Jasti, Jayasankar ^a   Kurumbail, Ravi G ^a   Wager, Travis T ^a   Verhoest, Patrick R ^a   Noell, G Stephen ^a   Chen, Yi ^a   Needle, Elie ^a   Berger, Zdenek ^a   Steyn, Stefanus J ^a   Houle, Christopher ^a   Hirst, Warren D ^a   Galatsis, Paul ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [4 (MORPHOLIN 4 YL) 7H PYRROLO[2,3 D]PYRIMIDIN 5 YL]BENZONITRILE; LEUCINE RICH REPEAT KINASE 2; PHOSPHOTRANSFERASE INHIBITOR; UNCLASSIFIED DRUG; 3-(4-(MORPHOLIN-4-YL)-7H-PYRROLO(2,3-D)PYRIMIDIN-5-YL)BENZONITRILE; BENZONITRILE; LRRK2 PROTEIN, HUMAN; NITRILE; PROTEIN BINDING; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE; PROTEOME; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DRUG STRUCTURE; GENETIC ASSOCIATION; IN VIVO STUDY; KIDNEY DISEASE; LIVER MICROSOME; NONHUMAN; RAT; SEQUENCE ALIGNMENT; SUZUKI REACTION; WHOLE CELL; AMINO ACID SEQUENCE; ANIMAL; ANTAGONISTS AND INHIBITORS; AREA UNDER THE CURVE; BRAIN; C57BL MOUSE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; DRUG SCREENING; GENETICS; HEK293 CELL LINE; HUMAN; METABOLISM; MISSENSE MUTATION; MOLECULAR GENETICS; PARKINSON DISEASE; PROTEIN TERTIARY STRUCTURE; TRANSGENIC MOUSE; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANIMALS; AREA UNDER CURVE; BRAIN; CRYSTALLOGRAPHY, X-RAY; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; HEK293 CELLS; HUMANS; MICE, INBRED C57BL; MICE, TRANSGENIC; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; MUTATION, MISSENSE; NITRILES; PARKINSON DISEASE; PROTEIN BINDING; PROTEIN KINASE INHIBITORS; PROTEIN STRUCTURE, TERTIARY; PROTEIN-SERINE-THREONINE KINASES; PROTEOME; PYRIMIDINES; PYRROLES; RATS;

EID: 84920809166     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5014055     Document Type: Article

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47. Compounds 14 (PF-06447475) and 28 (PF-06454589) are now available from Sigma Aldrich.