Ring-fused pyrazole derivatives as potent inhibitors of lymphocyte-specific kinase (Lck): Structure, synthesis, and SAR

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 1, 2010, Pages 112-116

  Takayama, Tetsuo ^a   Umemiya, Hiroki ^a   Amada, Hideaki ^a   Yabuuchi, Tetsuya ^a   Koami, Takeshi ^a   Shiozawa, Fumiyasu ^a   Oka, Yusuke ^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; PYRAZOLE DERIVATIVE;

ARTICLE; DEPROTECTION REACTION; DRUG IDENTIFICATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HYDROLYSIS; METHYLATION; STRUCTURE ACTIVITY RELATION;

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: 72049098176     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.11.013     Document Type: Article

References (19)

1. Molina T.J., Kishihara K., Siderovskid D.P., van Ewijk W., Narendran A., Timms E., Wakeham M.A., Paige C.J., Hartmann K.-U., Veillette A., Davidson D., and Mak T.W. Nature 357 (1992) 161
2. Straus D.B., and Weiss A. Cell 70 (1992) 585
3. Levin D.S., Anderson S.J., Forbushm K.A., and Perlmutter R.M. EMBO J. 12 (1993) 1671
4. Goldberg D.R., Butz T., Cardozo M.G., Eckner R.J., Hammach A., Huang J., Jakes S., Kapadia S., Kashem M., Lukas S., Morwick T.M., Panzenbeck M., Patel U., Pav S., Peet G.W., Peterson J.D., Prokopowicz A.S., Snow R.J., Sellati R., Takahashi H., Tan J., Tschantz M.A., Wang X.-J., Wang Y., Wolak J., Xiong P., and Moss N. J. Med. Chem. 46 (2003) 1337
5. Chen P., Doweyko A.M., Norris D., Gu H.H., Spergel S.H., Das J., Moquin R.V., Lin J., Wityak J., Iwanowicz E.J., McIntyre K.W., Shuster D.J., Behnia K., Chong S., Fex H., Pang S., Pitt S., Shen D.R., Thrall S., Stanley P., Kocy O.R., Witmer M.R., Kanner S.B., Schieven G.L., and Barrish J.C. J. Med. Chem. 47 (2004) 4517
6. Borhani D.W., Calderwood D.J., Friedman M.M., Hirst G.C., Li B., Leung A.K.W., McRae B., Ratnofsky S., Ritter K., and Waegell W. Bioorg. Med. Chem. Lett. 14 (2004) 2613
7. Martin M.W., Newcomb J., Nunes J.J., McGowan D.C., Armistead D.M., Boucher C., Buchanan J.L., Buckner W., Chai L., Elbaum D., Epstein L.F., Faust T., Flynn S., Gallant P., Gore A., Gu Y., Hsieh F., Huang X., Lee J.H., Metz D., Middleton S., Mohn D., Morgenstern K., Morrison M.J., Novak P.M., Oliveira-dos-Santos A., Powers D., Rose P., Schneider S., Sell S., Tudor Y., Turci S.M., Welcher A.A., White R.D., Zack D., Zhao H., Zhu L., Zhu X., Ghiron C., Amouzegh P., Ermann M., Jenkins J., Johnston D., Napier S., and Power E. J. Med. Chem. 49 (2006) 4981
8. DiMauro E.F., Newcomb J., Nunes J.J., Bemis J.E., Boucher C., Buchanan J.L., Buckner W.H., Cee V.J., Chai L., Deak H.L., Epstein L.F., Faust T., Gallant P., Geuns-Meyer S.D., Gore A., Gu Y., Henkle B., Hodous B.L., Hsieh F., Huang X., Kim J.L., Lee J.H., Martin M.W., Masse C.E., McGowan D.C., Metz D., Mohn D., Morgenstern K.A., Oliveira-dos-Santos A., Patel V.F., Powers D., Rose P.E., Schneider S., Tomlinson S.A., Tudor Y.-Y., Turci S.M., Welcher A.A., White R.D., Zhao H., Zhu L., and Zhu X. J. Med. Chem. 49 (2006) 5671
9. Sabat M., VanRens J.C., Brugel T.A., Maier J., Laufersweiler M.J., Golebiowski A., De B., Easwaran V., Hsieh L.C., Rosegen J., Berberich S., Suchanek E., and Janusz M.J. Bioorg. Med. Chem. Lett. 16 (2006) 4257
10. Bamborough P., Angell R.M., Bhamra I., Brown D., Bull J., Christopher J.A., Cooper A.W.J., Fazal L.H., Giordano I., Hind L., Patel V.K., Ranshaw L.I., Sims M.J., Skone P.A., Smith K.J., Vickerstaff E., and Washington M. Bioorg. Med. Chem. Lett. 17 (2007) 4363
11. Martin M.W., Newcomb J., Nunes J.J., Boucher C., Chai L., Epstein L.F., Faust T., Flores S., Gallant P., Gore A., Gu Y., Hsieh F., Huang X., Kim J.L., Middleton S., Morgenstern K., Oliveira-dos-Santos A., Patel V.F., Powers D., Rose P., Tudor Y., Turci S.M., Welcher A.A., Zack D., Zhao H., Zhu L., Zhu X., Ghiron C., Ermann M., Johnston D., and Saluste C.-G.P. J. Med. Chem. 51 (2008) 1637
12. DiMauro E.F., Newcomb J., Nunes J.J., Bemis J.E., Boucher C., Chai L., Chaffee S.C., Deak H.L., Epstein L.F., Faust T., Gallant P., Gore A., Gu Y., Henkle B., Hsieh F., Huang X., Kim J.L., Lee J.H., Martin M.W., McGowan D.C., Metz D., Mohn D., Morgenstern K.A., Oliveira-dos-Santos A., Patel V.F., Powers D., Rose P.E., Schneider S., Tomlinson S.A., Tudor Y.-Y., Turci S.M., Welcher A.A., Zhao H., Zhu L., and Zhu X. J. Med. Chem. 51 (2008) 1681
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. The two regioisomers were successfully separated by column purification.
16. 4, filtered, and concentrated in vacuo. The residue was purified by column chromatography to give 12.
17. Jacobs M.D., Caron P.R., and Hare B.J. Proteins 70 (2008) 1451
18. The binding model was examined and visualized using MOE™ (Molecular Operating Environment) Version 2007.09, Chemical Computing Group: Montreal, Canada.
19. Lck, Src, and Csk were purchased from Upstate (NY, USA). Kinase assays for ZAP-70, MEK1, PKA, PKBα, PKCα, CDK1, CAMKIV and MAPK1 were run by Upstate (NY, USA) using Kinase profiler service in according to the manufacturer's procedures.