Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 6, 2011, Pages 1844-1848

  Fang, Xingang ^a   Chen, Yen Ting ^a   Sessions, E Hampton ^a   Chowdhury, Sarwat ^a   Vojkovsky, Tomas ^a   Yin, Yan ^a   Pocas, Jennifer R ^a   Grant, Wayne ^a   Schröter, Thomas ^a   Lin, Li ^a   Ruiz, Claudia ^a   Cameron, Michael D ^a   Lograsso, Philip ^a   Bannister, Thomas D ^a   Feng, Yangbo ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

Protein kinase A; Pyrazole; Quinazolinone; Rho kinase; ROCK inhibitor

Indexed keywords

4(3H) QUINAZOLINONE DERIVATIVE; CYCLIC AMP DEPENDENT PROTEIN KINASE; QUINAZOLINONE DERIVATIVE; RHO KINASE; RHO KINASE II INHIBITOR; RHO KINASE INHIBITOR; UNCLASSIFIED DRUG;

AREA UNDER THE CURVE; ARTICLE; DISTRIBUTION VOLUME; DRUG CLEARANCE; DRUG HALF LIFE; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; HUMAN; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; STRUCTURE ACTIVITY RELATION;

PROTEIN KINASE INHIBITORS; QUINAZOLINONES; RHO-ASSOCIATED KINASES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79952361695     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.01.039     Document Type: Article

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25. Synthesis of quinazolines (S)-25 and (R)-25 involved modifications of the reactions described in Scheme 1. In brief, the carboxylic acid (prepared in Ref. 20) and aniline were coupled with EDC and HOAt in dichloromethane without the presence of base. The following Suzuki heteroarylation was then performed with sodium bicarbonate in place of potassium carbonate as the base.
26. Compounds 9 and 25 were also screened against three other kinases, MRCKα, JNK3, and p38 and no inhibition was observed at 20 μM concentration.