1374102-53-0Relevant articles and documents
Potent, selective and orally bioavailable leucine-rich repeat kinase 2 (LRRK2) inhibitors
Greshock, Thomas J.,Sanders, John M.,Drolet, Robert E.,Rajapakse, Hemaka A.,Chang, Ronald K.,Kim, Boyoung,Rada, Vanessa L.,Tiscia, Heather E.,Su, Hua,Lai, Ming-Tain,Sur, Sylvie M.,Sanchez, Rosa I.,Bilodeau, Mark T.,Renger, John J.,Kern, Jonathan T.,McCauley, John A.
, p. 2631 - 2635 (2016)
Familial Parkinson's disease cases have recently been associated with the leucine rich repeat kinase 2 (LRRK2) gene. It has been hypothesized that inhibition of the LRRK2 protein may have the potential to alter disease pathogenesis. A dihydrobenzothiophene series of potent, selective, orally bioavailable LRRK2 inhibitors were identified from a high-throughput screen of the internal Merck sample collection. Initial SAR studies around the core established the series as a tractable small molecule lead series of LRRK2 inhibitors for potential treatment of Parkinson's disease. It was also found that incorporation of a lactam into the core drastically improved the CNS and DMPK properties of these small molecules.
LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY
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Page/Page column 45, (2012/05/19)
Disclosed are compounds of Formula (I): and the pharmaceutically acceptable salts thereof, wherein "A" is S-; -SO-, -SO2-, -O- or NRac-, wherein Rac is H, or C1-20 alkyl and R1 through R5 are defined
