Design of Aminobenzothiazole Inhibitors of Rho Kinases 1 and 2 by Using Protein Kinase A as a Structure Surrogate.

Autor: Judge RA; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Vasudevan A; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Scott VE; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Simler GH; AbbVie Bioresearch Center, 100 Research Drive, Worcester, MA, 01605, USA., Pratt SD; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Namovic MT; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Putman CB; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Aguirre A; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Stoll VS; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Mamo M; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.; Current address: Novartis Institute for Biomedical Research, 4560 Horton Street, Emeryville, CA, 94608, USA., Swann SI; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.; Current address: Takeda Pharmaceuticals, 10410 Science Center Drive, San Diego, CA, 92121, USA., Cassar SC; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Faltynek CR; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Kage KL; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.; Current address: Altor Bioscience, 2810 North Commerce Parkway, Miramar, FL, 33025, USA., Boyce-Rustay JM; AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.; Current address: Genentech, 1 DNA Way, South San Francisco, CA, 94080, USA., Hobson AD; AbbVie Bioresearch Center, 100 Research Drive, Worcester, MA, 01605, USA.
Jazyk: angličtina
Zdroj: Chembiochem : a European journal of chemical biology [Chembiochem] 2018 Mar 16; Vol. 19 (6), pp. 613-621. Date of Electronic Publication: 2018 Jan 30.
DOI: 10.1002/cbic.201700547
Abstrakt: We describe the design, synthesis, and structure-activity relationships (SARs) of a series of 2-aminobenzothiazole inhibitors of Rho kinases (ROCKs) 1 and 2, which were optimized to low nanomolar potencies by use of protein kinase A (PKA) as a structure surrogate to guide compound design. A subset of these molecules also showed robust activity in a cell-based myosin phosphatase assay and in a mechanical hyperalgesia in vivo pain model.
(© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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