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Can I read Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors on EtoBox?
Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors by Peter Ray; Jane Wright; Julia Adam; Johnathan Bennett; Sylviane Boucharens; Darcey Black; Andrew Cook; Angus R. Brown; Ola Epemolu; Dan Fletcher; Anders Haunso; Margaret Huggett; Phil Jones; Steven Laats; Amanda Lyons; Jordi Mestres; Jos de Man; Richard Morphy; Zoran Rankovic; Brad Sherborne; Lorcan Sherry; Nicole van Straten; Paul Westwood; Guido Z.R. Zaman is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors about?
Fragment-based NMR screening of a small literature focused library led to identification of a historical thrombin/FactorXa building block, 17A, that was found to be a ROCK-I inhibitor. In the absence of an X-ray structure, fragment growth afforded 6-substituted isoquinolin-1-amine derivatives which were profiled in the primary ROCK-I IMAP assay. Compounds 23A and 23E were selected as fragment optimized hits for further profiling. Compound 23A has similar ROCK-1 affinity, potency and cell based efficacy to the first generation ROCK inhibitors, however, it has a superior PK profile in C57 mouse. Compound 23E demonstrates the feasibility of improving ROCK-1 affinity, potency and cell based efficacy for the series, however, it has a poor PK profile relative to 23A.
Who reads Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Peter Ray; Jane Wright; Julia Adam; Johnathan Bennett; Sylviane Boucharens; Darcey Black; Andrew Cook; Angus R. Brown; Ola Epemolu; Dan Fletcher; Anders Haunso; Margaret Huggett; Phil Jones; Steven Laats; Amanda Lyons; Jordi Mestres; Jos de Man; Richard Morphy; Zoran Rankovic; Brad Sherborne; Lorcan Sherry; Nicole van Straten; Paul Westwood; Guido Z.R. Zaman
- Publisher
- Elsevier Science; Elsevier ; Elsevier Ltd.; Elsevier BV (ISSN 0960-894X)
- Published
- 2011
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)