2386 Journal of Medicinal Chemistry, 2005, Vol. 48, No. 7
VanderWel et al.
(32) Schultz, C.; Link, A.; Loest, M.; Zaharevitz, D. W.; Gussio, R.;
Sausville, E. A.; Meijer, L.; Kunick, C. Paullones, A Series of
Cyclin-Dependent Kinase Inhibitors: Synthesis, Evaluation of
CDK1/Cyclin B Inhibition, and in Vitro Antitumor Activity. J.
Med. Chem. 1999, 42, 2909-2919.
(33) Kunick, C.; Schultz, C.; Lemcke, T.; Zaharevitz, D. W.; Gussio,
R.; Jalluri, R. K.; Sausville, E. A.; Loest, M.; Meijer, L.
2-Substituted Paullones: CDK1/Cyclin B-Inhibiting Property
and In Vitro Antiproliferative Activity. Bioorg. Med. Chem. Lett.
2000, 10, 567-569.
(34) Sayle, K. L.; Bentley, J.; Boyle, F. T.; Calvert, A. H.; Cheng, Y.;
Curtin, N. J.; Endicott, J. A.; Golding, B. T.; Hardcastle, I. R.;
Jewsbury, P.; Mesguiche, V.; Newell, D. R.; Noble, M. E. M.,
Parsons, R. J., Pratt, D. J.; Wang, L. Z.; Griffin, R. J. Structure-
Based Design of 2-Arylamino-4-cyclohexylmethyl-5-nitroso-6-
aminopyrimidine Inhibitors of Cyclin-Dependent Kinases 1 and
2. Bioorg. Med. Chem. Lett. 2003, 13, 3079-3082.
(48) Seong, Y.-S.; Min, C.; Li, L.; Yang, J. Y.; Kim, S.-Y.; C, X.; Kim,
K.; Yuspa, S. H.; Chung, H.-H.; Lee, K. S. Characterization of a
Novel Cyclin-Dependent Kinase 1 Inhibitor, BMI-1026. Cancer
Res. 2003, 63, 7384-7391.
(49) Murthi, K. K.; Dubay, M.; McClure, C.; Brizuela, L.; Boisclair,
M. D.; Worland, P. J.; Mansuri, M. M.; Pal, K. Structure-
Activity Relationship Studies of Flavopiridol Analogues. Bioorg.
Med. Chem. Lett. 2000, 10, 1037-1041.
(50) Li, X.; Huang, P.; Cui, J. J.; Zhang, J.; Tang, C. Novel Pyrrolyl-
lactone and Pyrrolyllactam Indolinones as Potent Cyclin-De-
pendent Kinase 2 Inhibitors. Bioorg. Med. Chem. Lett. 2003, 13,
1939-1942.
(51) Liu, J.-J.; Dermatakis, A.; Lukacs, C.; Konzelmann, F.; Chen,
Y.; Kammlott, U.; Depinto, W.; Yang, H.; Yin, X.; Chen, Y.;
Schutt, A.; Simcox, M. E.; Luk, K.-C. 3,5,6-Trisubstituted
Naphthostyrils as CDK2 Inhibitors. Bioorg. Med. Chem. Lett.
2003, 13, 2465-2468.
(35) Anderson, M.; Beattie, J. F.; Breault, G. A.; Breed, J.; Byth, K.
F.; Culshaw, J. D.; Ellston, R. P. A.; Green, S.; Minshull, C. A.;
Norman, R. A.; Pauptit, R. A.; Stanway, J.; Thomas, A. P.;
Jewsbury, P. J. Imidazo[1,2-a]pyridines: A Potent and Selective
Class of Cyclin-Dependent Kinase Inhibitors Indentified Through
Structure-Based Hybridisation. Bioorg. Med. Chem. Lett. 2003,
13, 3021-3026.
(36) Tang, J.; Shewchuk, L. M.; Sato, H.; Hasegawa, M.; Washio, Y.;
Nishigaki, N. Anilinopyrazole as Selective CDK2 Inhibitors:
Design, Synthesis, Biological Evaluation, and X-ray Crystal-
lographic Analysis. Bioorg. Med. Chem. Lett. 2003, 13, 2985-
2988.
(37) Misra, R. N.; Xiao, H.; Rawlins, D. B.; Shan, W.; Kellar, K. A.;
Mulheron, J. G.; Sack, J. S.; Tokarski, J. S.; Kimball, S. D.;
Webster, K. R. 1H-Pyrazolo[3,4-b]pyridine Inhibitors of Cyclin-
Dependent Kinases: Highly Potent 2,6-Difluorophenacyl Ana-
logues. Bioorg. Med. Chem. Lett. 2003, 13, 2405-2408.
(38) Misra, R. N.; Rawlins, D. B.; Xiao, H.; Shan, W.; Bursuker, I.;
Kellar, K. A.; Mulheron, J. G.; Sack, J. S.; Tokarski, J. S.;
Kimball, S. D.; Webster, K. R. 1H-Pyrazolo[3,4-b]pyridine In-
hibitors of Cyclin-Dependent Kinases. Bioorg. Med. Chem. Lett.
2003, 13, 1133-1136.
(39) Mesguiche, V.; Parsons, R. J.; Arris, C. E.; Bentley, J.; Boyle, F.
T.; Curtin, N. J.; Davies, T. G.; Endicott, J. A.; Gibson, A. E.;
Golding, B. T.; Griffin, R. J.; Jewsbury, P.; Johnson, L. N.;
Newell, D. R.; Noble, M. E. M.; Wang, L. Z.; Hardcastle, I. R.
4-Alkoxy-2,6-diaminopyrimidine Derivatives: Inhibitors of Cy-
clin Dependent Kinases 1 and 2. Bioorg. Med. Chem. Lett. 2003,
13, 217-222.
(52) Bramson, H. N.; Corona, J.; Davis, S. T.; Dickerson, S. H.;
Edelstein, M.; Frye, S. V.; Gampe, R. T., Jr.; Harris, P. A.;
Hassell, A.; Holmes, W. D.; Hunter, R. N.; Lackey, K. E.; Lovejoy,
B.; Luzzio, M. J.; Montana, V.; Rocque, W. J.; Rusnak, D.;
Shewchuk, L.; Veal, J. M.; Walker, D. H.; Kuyper, L. F. Oxindole-
Based Inhibitors of Cyclin-Dependent Kinase 2 (CDK2): Design,
Synthesis, Enzymatic Activities, and X-ray Crystallographic
Analysis. J. Med. Chem. 2001, 44, 4339-4358.
(53) Yue, E. W.; Higley, C. A.; DiMeo, S. V.; Carini, D. J.; Nugiel, D.
A.; Benware, C.; Benfield, P. A.; Burton, C. R.; Cox, S.; Graf-
strom, R. H.; Sharp, D. M.; Sisk, L. M.; Boylan, J. F.; Muckel-
bauer, J. K.; Smallwood, A. M.; Chen, H.; Chang, C.-H.; Seitz,
S. P.; Trainor, G. L. Synthesis and Evaluation of Indenopyrazoles
as Cyclin-Dependent Kinase Inhibitors. 3.Structure Activity
Relationships at C3. J. Med. Chem. 2002, 45, 5233-5248.
(54) Nugiel, D. A.; Vidwans, A.; Etzkorn, A.-M.; Rossi, K. A.; Benfield,
P. A.; Burton, C. R.; Cox, S.; Doleniak, D.; Seitz, S. P. Synthesis
and Evaluation of Indenopyrazoles as Cyclin-Dependent Kinase
Inhibitors. 2. Probing the Indeno Ring Substituent Pattern. J.
Med. Chem. 2002, 45, 5224-5232.
(55) Nugiel, D. A.; Etzkorn, A.-M.; Vidwans, A.; Benfield, P. A.;
Boisclair, M.; Burton, C. R.; Cox, S.; Czerniak, P. M.; Doleniak,
D.; Seitz, S. P. Indenopyrazoles as Novel Cyclin Dependent
Kinase (CDK) Inhibitors. J. Med. Chem. 2001, 44, 1334-1336.
(56) Lane, M. E.; Yu, B.; Rice, A.; Lipson, K. E.; Liang, C.; Sun, L.;
Tang, C.; McMahon, G.; Pestell, R. G.; Wadler, S. A Novel cdk2-
selective Inhibitor, SU9516, Induces Apoptosis in Colon Carci-
noma Cells. Cancer Res. 2001, 61, 6170-6177.
(57) Andreani, A.; Cavalli, A.; Granaiola, M.; Leoni, A.; Locatelli, A.;
Morigi, R.; Rambaldi, M.; Recanatini, M.; Garnier, M.; Meijer,
L. Imidazo[2,1-b]thiazolylmethylene- and indolylmethylene-2-
indolinones: a new class of cyclin-dependent kinase inhibitors.
Design, synthesis, and CDK/cyclin B inhibition. Anti-Cancer
Drug Des. 2000, 15, 447-452.
(58) Honma, T.; Hayaski, K.; Aoyama, T.; Hashimoto, N.; Machida,
T.; Fukasawa, K.; Iwama, T.; Ikeura, C.; Ikuta, M.; Suzuki-
Takahashi, I.; Iwasawa, Y.; Hayama, T.; Nishimura, S.; Mor-
ishima, H. Structure-Based Generation of a New Class of Potent
Cdk4 Inhibitors: New de Novo Design Strategy and Library
Design. J. Med. Chem. 2001, 44, 4615-4627.
(59) Honma, T.; Yoshizumi, T.; Hashimoto, N.; Hayashi, K.; Kawa-
nishi, N.; Fukasawa, K.; Takaki, T.; Ikeura, C.; Ikuta, M.;
Suzuki-Takahashi, I.; Hayama, T.; Nishimura, S.; Moroshima,
H. A Novel Approach for the Development of Selective Cdk4
Inhibitors: Library Design Based on Locations of Cdk4 Specific
Amino Acid residues. J. Med. Chem. 2001, 44, 4628-4640.
(60) Soni, R.; O’Reilly, T.; Furet, P.; Muller, L.; Stephan, C.; Zum-
stein-Mecker, S.; Fretz, H.; Fabbro, D.; Chaudhuri, B. Selective
In Vivo and In Vitro Effects of a Small Molecule Inhibitor of
Cyclin-Dependent Kinase 4. J. Natl. Cancer Inst. 2001, 93, 436-
446.
(61) Beattie, J. F.; Breault, G. A.; Ellston, R. P. A.; Green, S.;
Jewsbury, P. J.; Midgley, C. J.; Naven, R. T.; Minshull, C. A.;
Pauptit, R. A.; Tucker, J. A.; Pease, J. E. Cyclin-Dependent
Kinase 4 Inhibitors as a Treatment for Cancer. Part 1: Identi-
fication and Optimisation of Substituted 4,6-Bis Anilino Pyrim-
idines. Bioorg. Med. Chem. Lett. 2003, 13, 2955-2960.
(62) Breault, G. A.; Ellston, R. P. A.; Green, S.; James, S. R.;
Jewsbury, P. J.; Midgley, C. J.; Pauptit, R. A.; C. A.; Minshull,
Tucker, J. A.; Pease, J. E. Cyclin-Dependent Kinase 4 Inhibitors
as a Treatment for Cancer. Part 2: Identification as Optimisa-
tion of Substituted 2,4-Bis Anilino Pyrimidines. Bioorg. Med.
Chem. Lett. 2003, 13, 2961-2966.
(63) Sanchez-Martinez, C.; Shih, C.; Faul, M. M.; Zhu, G.; Paal, M.;
Somoza, C.; Li, T.; Kumrich, C. A.; Winneroski, L. L.; Xun, Z.;
Brooks, H. B.; Patel, B. K. R.; Schultz, R. M.; DeHahn, T. B.;
Spencer, C. D.; Watkins, S. A.; Considine, E.; Dempsey, J. A.;
Ogg, C. A.; Campbell, R. M.; Anderson, B. A.; Wagner, J. Aryl-
[a]pyrrolo[3,4,-c]carbazoles as Selective Cyclin D1-CDK4 Inhibi-
tors. Bioorg. Med. Chem. Lett. 2003, 13, 3835-3839.
(40) Song, Y.; Wang, J.; Teng, S. F.; Kesuma, D.; Deng, Y.; Duan, J.;
Wang, J. H.; Qi, R. Z.; Sim, M. M. â-Carbolines as Specific
Inhibitors of Cyclin-Dependent Kinases. Bioorg. Med. Chem.
Lett. 2002, 12, 1129-1132.
(41) Kim, K. S.; Kimball, S. D.; Misra, R. N.; Rawlins, D. B.; Hunt,
J. T.; Xiao, H.-Y.; Lu, S.; Qian, L.; Han, W.-C.; Shan, W.; Mitt,
T.; Cai, Z.-W.; Poss, M. A.; Zhu, H.; Sack, J. S.; Tokarski, J. S.;
Chang, C. Y.; Pavletich, N.; Kamath, A.; Humphreys, W. G.;
Marathe, P.; Bursuker, I.; Kellar, K. A.; Roongta, U.; Batorsky,
R.; Mulheron, J. G.; Bol, D.; Fairchild, C. R.; Lee, F. Y.; Webster,
K. R. Discovery of Aminothiazole Inhibitors of Cyclin-Dependent
Kinase 2: Synthesis, X-ray Crystallographic Analysis, and
Biological Activities. J. Med. Chem. 2002, 45, 3905-3927.
(42) Ortega, M. A.; Montoya, M. E.; Zarranz, B.; Jaso, A.; Aldana, I.;
Leclerc, S.; Meijer, L.; Monge, A. Pyrazolo[3,4-b]quinoxalines.
A New Class of Cyclin-Dependent Kinases Inhibitors. Bioorg.
Med. Chem. Lett. 2002, 10, 2177-2184.
(43) Furet, P.; Meyer, T.; Strauss, A.; Raccuglia, S.; Rondeau, J.-M.
Structure-Based Design and Protein X-ray Analysis of a Protein
Kinase Inhibitor. Bioorg. Med. Chem. Lett. 2002, 12, 221-224.
(44) Davis, S. T.; Benson, B. G.; Bramson, H. N.; Chapman, D. E.;
Dickerson, S. H.; Dold, K. M.; Eberwein, D. J.; Edelstein, M.;
Frye, S. V.; Gampe, R. T., Jr.; Griffin, R. J.; Harris, P. A.; Hassell,
A. M.; Holmes, W. D.; Hunter, R. N.; Knick, V. B.; Lackey, K.;
Lovejoy, B.; Luzzio, M. J.; Murray, D.; Parker, P.; Rocque, W.
J.; Shewchuk, L.; Veal, J. M.; Walker, D. H.; Kuyper, L. F.
Prevention of Chemotherapy-Induced Alopecia in Rats by CDK
Inhibitors. Science 2001, 291, 134-137.
(45) Sielecki, T. M.; Johnson, T. L.; Liu, J.; Muckelbauer, J. K.;
Grafstrom, R. H.; Cox, S.; Boylan, J.; Burton, C. R.; Chen, H.;
Smallwood, A.; Chang, C.-H.; Boisclair, M.; Benfield, P. A.;
Trainor, G. L.; Seitz, S. P. Quinazolines as Cyclin Dependent
Kinase Inhibitors. Bioorg. Med. Chem. Lett. 2001, 11, 1157-
1160.
(46) Furet, P.; Meyer, T.; Mittl, P.; Fretz, H. Identification of cyclin-
dependent kinase 1 inhibitors of a new chemical type by
structure-based design and database searching. J. Comput.-
Aided Mol. Des. 2001, 15, 489-495.
(47) Sasaki, S.; Hashimoto, T.; Obana, N.; Yasuda, H.; Uehara, Y.;
Maeda, M. Design of New Inhibitors for CDC2 Kinase Based on
a Multiple Pseudosubstrate Structure. Bioorg. Med. Chem. Lett.
1998, 8, 1019-1022.