Pyrrole derivatives as potent inhibitors of lymphocyte-specific kinase: Structure, synthesis, and SAR

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 1, 2010, Pages 108-111

  Takayama, Tetsuo ^a   Umemiya, Hiroki ^a   Amada, Hideaki ^a   Yabuuchi, Tetsuya ^a   Shiozawa, Fumiyasu ^a   Katakai, Hironori ^a   Takaoka, Akiko ^a   Yamaguchi, Akie ^a   Endo, Mayumi ^a   Sato, Masakazu ^a  

^a TAISHO PHARMACEUTICAL CO LTD   (Japan)

Author keywords

Kinase inhibitor; Lck inhibitor

Indexed keywords

PROTEIN KINASE INHIBITOR; PROTEIN KINASE LCK; PYRROLE DERIVATIVE;

ARTICLE; DRUG BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; METHYLATION; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

ADENOSINE TRIPHOSPHATE; BINDING SITES; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; HYDROGEN BONDING; LYMPHOCYTE SPECIFIC PROTEIN TYROSINE KINASE P56(LCK); LYMPHOCYTES; PROTEIN KINASE INHIBITORS; PYRROLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 72049107793     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.11.014     Document Type: Article

References (18)

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13. 33P-ATP, and 10 μM poly (l-glutamic acid-l-tyrosine, 4:1) were added and incubated at 25 °C for 60 min and stopped with 100 μL of 100 mM phosphoric acid. The mixture was transferred to a MultiScreen-HA mixed cellulose ester membrane plate and harvested by filtration. Scintillation cocktail was added, and radioactivity was measured on a Packard Topcount instrument.
14. 3H-Thymidine incorporation into DNA was measured by Topcount. Compounds were added at the start of the culture.
15. 4, filtered, and concentrated in vacuo. The residue was purified by column chromatography to give 1, 7-31.
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17. The Binding Model was Examined and Visualized Using MOE™ (Molecular Operating Environment) Version 2007.09, Chemical Computing Group: Montreal, Canada.
18. Lck, Src, and Csk were purchased from Upstate (NY, USA). Kinase assays for ZAP-70, MEK1, PKA, PKB, PKC, Abl, CAMK2 and CDK1 were run by Cerep (Paris, France) using the Kinase profiler service according to the manufacturer's procedures.