The discovery of orally bioavailable tyrosine threonine kinase (TTK) inhibitors: 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides as anticancer agents

Journal of Medicinal Chemistry

Volumn 58, Issue 8, 2015, Pages 3366-3392

  Liu, Yong ^a   Lang, Yunhui ^a   Patel, Narendra Kumar ^a   Ng, Grace ^a   Laufer, Radoslaw ^a   Li, Sze Wan ^a   Edwards, Louise ^a   Forrest, Bryan ^a   Sampson, Peter B ^a   Feher, Miklos ^a   Ban, Fuqiang ^a   Awrey, Donald E ^a   Beletskaya, Irina ^a   Mao, Guodong ^a   Hodgson, Richard ^a   Plotnikova, Olga ^a   Qiu, Wei ^a   Chirgadze, Nickolay Y ^a   Mason, Jacqueline M ^a   Wei, Xin ^a   Lin, Dan Chi Chia ^a   Che, Yi ^a   Kiarash, Reza ^a   Madeira, Brian ^a   Fletcher, Graham C ^a   Mak, Tak W ^a   Bray, Mark R ^a   Pauls, Henry W ^a   more..

^a PRINCESS MARGARET HOSPITAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

3 [ 4 ( 3 OXA 8 AZABICYCLO[3.2.1]OCTAN 8 YL)PHENYL] N [CYCLOPENTYL(PYRIDIN 2 YL)METHYL] 1H INDAZOLE 5 CARBOXAMIDE; 3 [ 4 ( 3 OXA 8 AZABICYCLO[3.2.1]OCTAN 8 YL)PHENYL] N [CYCLOPROPYL(PYRIDIN 2 YL)METHYL] 1H INDAZOLE 5 CARBOXAMIDE; 3 [ 4 ( 4 HYDROXYPIPERIDIN 1 YL)PHENYL] N [( 1 MORPHOLINOCYCLOHEXYL)METHYL] 1H INDAZOLE 5 CARBOXAMIDE; 3 [ 4 ( 4 METHYLPIPERAZIN 1 YL)PHENYL] N [( 1 MORPHOLINOCYCLOHEXYL)METHYL] 1H INDAZOLE 5 CARBOXAMIDEI; 3 [[4 [(ENDO) 8 FORMYL 8 AZABICYCLO[3.2.1]OCTAN 3 YL]OXY]PHENYL] N ( 3 METHYL 1 (PYRIDIN 2 YL)BUTYL] 1H INDAZOLE 5 CARBOXAMIDE; ACETAMIDE DERIVATIVE; AMIDE; ANTINEOPLASTIC AGENT; IMATINIB; INDAZOLE DERIVATIVE; N [ 1 ( 2 CHLOROPHENYL) 2 METHYLPROPYL] 3 [ 4 [(ENDO) 3 HYDROXY 8 AZABICYCLO[3.2.1]OCGAN 8 YL]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [ 2 CYCLOPROPYL 1 (PYRIDIN 2 YL)ETHYL] 3 [4 [(ENDO) 3 HYDROXY 8 AZABICYCLO[3.2.1]OCTAN 8 YL]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [ CYCLOPROPYL(PYRIDIN 2 YL)METHYL] 3 [4 [(EXO) 3 HYDROXY 8 AZABICYCLO[3.2.1]OCTAN 8 YL]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOBUTYL(THIOPHEN 3 YL)METHYL] 3 [4 [[(ENDO) 8 FORMYL 8 AZABICYCLO[3.2.1]OCTAN 3 YL]OXY]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPENTYL(PYRIDIN 2 YL)METHYL] 3 [ 4 [(ENDO) 3 HYDROXY 8 AZABICYCLO[3.2.1]OCTAN 8 YL]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPENTYL(PYRIMIDIN 2 YL)METHYL] 3 [ 4 [(ENDO) 3 HYDROXY 8 AZABICYCLO[3.2.1]OCTAN 8 YL]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(PHENYL)METHYL] 3 ( 3-MORPHOLINOPHENYL) 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(PHENYL)METHYL] 3 ( 4 MORPHOLINOPHENYL) 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(PHENYL)METHYL] 3 [ 4 [( 1 METHYLPIPERIDIN 4YL)OXY]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(PHENYL)METHYL] 3 [ 4 [(ENDO) 3 HYDROXY 8 AZABICYCLO[3.2.1]OCTAN 8 YL]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(PHENYL)METHYL] 3 [4 [( 1 FORMYLPIPERIDIN 4 YL)OXY]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(PHENYL)METHYL] 3 [4 [(ENDO) 8 METHYL 8 AZABICYCLO[3.2.1]OCTAN 3 Y])PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(PHENYL)METHYL] 3 [4 [(EXO) 8 METHYL 8 AZABICYCLO[3.2.1]OCTAN 3 YL]OXY)PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(PHENYL)METHYL] 3 [4 [[ 1 [ 2 (DIMETHYLAMINO)ACETYL]PIPERIDIN 4 YL]OXY]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(PYRIDIN 2 YL)METHYL] 3 [ 4 [(ENDO) 3 HYDROXY 8 AZABICYCLO[3.2.1]OCTAN 8 YL]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(PYRIDIN 2 YL)METHYL] 3 [4 [( 1 FORMYLPIPERIDIN 4 YL)OXY]PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; N [CYCLOPROPYL(THIOPHEN 3 YL)METHYL] 3 [ 4 ( 4 HYDROXYPIPERIDIN 1 YL)PHENYL] 1H INDAZOLE 5 CARBOXAMIDE; PROTEIN TYROSINE KINASE INHIBITOR; SUNITINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; CELL CYCLE PROTEIN; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE; PROTEIN TYROSINE KINASE; TTK PROTEIN, HUMAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER INHIBITION; CELL CYCLE PROGRESSION; CELL DEATH; CHROMOSOME SEGREGATION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG POTENCY; DRUG SCREENING; DRUG STABILITY; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IC50; IN VIVO STUDY; INHIBITION CONSTANT; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MOUSE; NONHUMAN; ONE POT SYNTHESIS; PHYSICAL CHEMISTRY; PLASMA PROTEIN BINDING; PROTON NUCLEAR MAGNETIC RESONANCE; RACEMIC MIXTURE; RACEMIZATION; RAT; STEREOCHEMISTRY; X RAY; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; COLON; COLONIC NEOPLASMS; DRUG EFFECTS; ENZYMOLOGY; FEMALE; METABOLISM; NUDE MOUSE; ORAL DRUG ADMINISTRATION; PATHOLOGY; TUMOR CELL LINE; X RAY CRYSTALLOGRAPHY;

ADMINISTRATION, ORAL; ANIMALS; CELL CYCLE PROTEINS; CELL LINE, TUMOR; COLON; COLONIC NEOPLASMS; CRYSTALLOGRAPHY, X-RAY; FEMALE; HUMANS; INDAZOLES; MICE, NUDE; MODELS, MOLECULAR; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PROTEIN-TYROSINE KINASES;

EID: 84928490527     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm501740a     Document Type: Article

References (62)

1. Aarts, M.; Linardopoulos, S.; Turner, N. C. Tumour selective targeting of cell cycle kinases for cancer treatment Curr. Opin. Pharm. 2013, 13, 529-535
2. Foley, E. A.; Kapoor, T. M. Microtubule attachment and spindle assembly checkpoint signaling at the kinetochore Nature Rev. Mol. Cell Biol. 2013, 14, 25-37
3. Rajagopalan, H.; Lengauer, C. Progress Aneuploidy and cancer Nature 2004, 432, 338-341
4. Yang, Z.; Loncarek, J.; Khodjakov, A.; Rieder, C. L. Extra centrosomes and/or chromosomes prolong mitosis in human cells Nature Cell Biol. 2008, 10, 748-751
5. Duesberg, P.; Rausch, C.; Rasnick, D.; Hehlmann, R. Genetic instability of cancer cells is proportional to their degree of aneuploidy Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 13692-13695
6. Kops, G. J. P. L.; Foltz, D. R.; Cleveland, D. W. Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 8699-8704
7. Abrieu, A.; Magnaghi-Jaulin, L.; Kahana, J. A.; Peter, M.; Castro, A.; Vigneron, S.; Lorca, T.; Cleveland, D. W.; Labbe, J. C. Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint Cell 2001, 106, 83-93
8. Liu, X.; Winey, M. The Mps1 family of protein kinases Annu. Rev. Biochem. 2012, 81, 561-585
9. Mills, G. B.; Schmandt, R.; McGill, M.; Amendola, A.; Hill, M.; Jacobs, K.; May, C.; Rodricks, A. M.; Campbell, S.; Hogg, D. Expression of TTK, a novel human protein kinase, is associated with cell proliferation J. Biol. Chem. 1992, 267, 16000-16006
10. Yuan, B.; Xu, Y.; Woo, J.-H.; Wang, Y.; Bae, Y. K.; Yoon, D.-S.; Wersto, R. P.; Tully, E.; Wilsbach, K.; Gabrielson, E. Increased expression of mitotic checkpoint genes in breast cancer cells with chromosomal instability Clin. Cancer Res. 2006, 12, 405-410
11. Daniel, J.; Coulter, J.; Woo, J. H.; Wilsbach, K.; Gabrielson, E. High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 5384-5389
12. Kilpinen, S.; Ojala, K.; Kallioniemi, O. Analysis of kinase gene expression patterns across 5681 human tissue samples reveals functional genomic taxonomy of the kinome PLoS One 2010, 5, e15068
13. Landi, M. T.; Dracheva, T.; Rotunno, M.; Figueroa, J. D.; Liu, H.; Dasgupta, A.; Mann, F. E.; Fukuoka, J.; Hames, M.; Bergen, A. W.; Murphy, S. E.; Yang, P.; Pesatori, A. C.; Consonni, D.; Bertazzi, P. A.; Wacholder, S.; Shih, J. H.; Caporaso, N. E.; Jen, J. Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival PLoS One 2008, 3, e1651
14. Fisk, H. A.; Mattison, C. P.; Winey, M. Human Mps1 protein kinase is required for centrosome duplication and normal mitotic progression Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 14875-14880
15. Carter, S. L.; Eklund, A. C.; Kohane, I. S.; Harris, L. N.; Szallasi, Z. A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers Nature Genet. 2006, 38, 1043-1048
16. Salvatore, G.; Nappi, T. C.; Salerno, P.; Jiang, Y.; Garbi, C.; Ugolini, C.; Miccoli, P.; Basolo, F.; Castellone, M. D.; Cirafici, A. M.; Melillo, R. M.; Fusco, A.; Bittner, M. L.; Santoro, M. A cell proliferation and chromosomal instability signature in anaplastic thyroid carcinoma Cancer Res. 2007, 67, 10148-10158
17. Brough, R.; Frankum, J. R.; Sims, D.; Mackay, A.; Mendes-Pereira, A. M.; Bajrami, I.; Costa-Cabral, S.; Rafiq, R.; Ahmad, A. S.; Cerone, M. A.; Natrajan, R.; Sharpe, R.; Shiu, K. K.; Wetterskog, D.; Dedes, K. J.; Lambros, M. B.; Rawjee, T.; Linardopoulos, S.; Reis-Filho, J. S.; Turner, N. C.; Lord, C. J.; Ashworth, A. Functional viability profiles of breast cancer Cancer Discovery 2011, 1, 260-273
18. Gordon, D. J.; Resio, B.; Pellman, D. Causes and consequences of aneuploidy in cancer Nature Rev. Genet. 2012, 13, 189-203
19. de Sauvage, F.; Evangelista, M. Hedgehog kinases and their use in modulating hedgehog signaling. US Pat. Appl. US20070179091, 2007.
20. Nakamura, Y.; Daigo, Y.; Nakatsuru, S. TTK as a tumor marker and therapeutic target for lung cancer. PCT. Int. Appl. WO2008072777, 2008.
21. Leng, M.; Chan, D. W.; Luo, H.; Zhu, C.; Qin, J.; Wang, Y. MPS1-dependent mitotic BLM phosphorylation is important for chromosome stability Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 11485-11490
22. Wei, J. H.; Chou, Y. F.; Ou, Y. H.; Yeh, Y. H.; Tyan, S. W.; Sun, T. P.; Shen, C. Y.; Shieh, S. Y. TTK/Mps1 participates in the regulation of DNA damage checkpoint response by phosphorylating CHK2 on threonine 68 J. Biol. Chem. 2005, 280, 7748-7757
23. Nihira, K.; Taira, M.; Miki, Y.; Yoshida, K. TTK/Mps1 controls nuclear targeting of c-Abl by 14-3-3-coupled phosphorylation in response to oxidative stress Oncogene 2008, 27, 7285-7295
24. Mak, T. W. Targeting the Cell Cycle in Cancer: TTK (MPS1) and PLK4 as Novel Mitotic Targets, AACR 103rd Annual Meeting, Chicago, IL, April 1-5, 2012.
25. Laufer, R.; Ng, G.; Liu, Y.; Patel, N. K.; Edwards, L.; Lang, Y.; Li, S.-W.; Feher, M.; Awrey, D.; Leung, G.; Beletskaya, I.; Plotnikova, O.; Mason, J.; Hodgson, R.; Wei, X.; Mao, G.; Luo, X.; Huang, P.; Green, E.; Kiarash, R.; Lin, D. C.-C.; Harris-Brandts, M.; Nadeem, V.; Mak, T. W.; Pan, J. G.; Qui, W.; Chirgadze, N. Y.; Pauls, H. W. Discovery of inhibitors of the mitotic kinase TTK based on N -(3-(3-sulfamoylphenyl)-1 H -indazol-5-yl)-acetamides and carboxamides Bioorg. Med. Chem. 2014, 22, 4968-4997
26. Hewitt, L.; Tighe, A.; Santaguida, S.; White, A. M.; Jones, C. D.; Musacchio, A.; Green, S.; Taylor, S. S. Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex J. Cell. Biol. 2010, 190, 25-34
27. Santaguida, S.; Tighe, A.; D'Alise, A. M.; Taylor, S. S.; Musacchio, A. Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine J. Cell Biol. 2010, 190, 73-87
28. Kwiatkowski, N.; Jelluma, N.; Filippakopoulos, P.; Soundararajan, M.; Manak, M. S.; Kwon, M.; Choi, H. G.; Sim, T.; Deveraux, Q. L.; Rottmann, S.; Pellman, D.; Shah, J. V.; Kops, G. J.; Knapp, S.; Gray, N. S. Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function Nature Chem. Biol. 2010, 6, 359-368
29. Caldarelli, M.; Angiolini, M.; Disingrini, T.; Donati, D.; Guanci, M.; Nuvoloni, S.; Posteri, H.; Quartieri, F.; Silvagni, M.; Colombo, R. Synthesis and SAR of new pyrazolo[4,3- h ]quinazoline-3-carboxamide derivatives as potent and selective MPS1 kinase inhibitors Bioorg. Med. Chem. Lett. 2011, 21, 4507-4511
30. Estrada, A. A.; Liu, X.; Baker-Glenn, C.; Beresford, A.; Burdick, D. J.; Chambers, M.; Chan, B. K.; Chen, H.; Ding, X.; DiPasquale, A. G.; Dominguez, S. L.; Dotson, J.; Drummond, J.; Flagella, M.; Flynn, S.; Fuji, R.; Gill, A.; Gunzner-Toste, J.; Harris, S. F.; Heffron, T. P.; Kleinheinz, T.; Lee, D. W.; Le Pichon, C. E.; Lyssikatos, J. P.; Medhurst, A. D.; Moffat, J. G.; Mukund, S.; Nash, K.; Scearce-Levie, K.; Sheng, Z.; Shore, D. G.; Tran, T.; Trivedi, N.; Wang, S.; Zhang, S.; Zhang, X.; Zhao, G.; Zhu, H.; Sweeney, Z. K. Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors J. Med. Chem. 2012, 55, 9416-9433
31. Kusakabe, K.; Ide, N.; Daigo, Y.; Itoh, T.; Higashino, K.; Okano, Y.; Tadano, G.; Tachibana, Y.; Sato, Y.; Inoue, M.; Wada, T.; Iguchi, M.; Kanazawa, T.; Ishioka, Y.; Dohi, K.; Tagashira, S.; Kido, Y.; Sakamoto, S.; Yasuo, K.; Maeda, M.; Yamamoto, T.; Higaki, M.; Endoh, T.; Ueda, K.; Shiota, T.; Murai, H.; Nakamura, Y. Diaminopyridine-based potent and selective Mps1 kinase inhibitors binding to an unusual flipped-peptide conformation ACS Med. Chem. Lett. 2012, 3, 560-564
32. Naud, S.; Westwood, I. M.; Faisal, A.; Sheldrake, P.; Bavetsias, V.; Atrash, B.; Cheung, K.-M. J.; Liu, M.; Hayes, A.; Schmitt, J.; Wood, A.; Choi, V.; Boxall, K.; Mak, G.; Gurden, M.; Valenti, M.; de Haven Brandon, A.; Henley, A.; Baker, R.; McAndrew, C.; Matijssen, B.; Burke, R.; Hoelder, S.; Eccles, S. A.; Raynaud, F. I.; Linardopoulos, S.; van Montfort, R. L.; Blagg, J. Structure-based design of orally bioavailable 1 H -pyrrolo[3,2- c ]pyridine inhibitors of mitotic kinase monopolar spindle 1 (Mps1) J. Med. Chem. 2013, 56, 10045-10065
33. Kusakabe, K.-I.; Yoshida, H.; Nozu, K.; Hashizume, H.; Tadano, G.; Sato, J.; Tamura, Y.; Mitsuoka, Y. Fused imidazole derivative having TTK inhibitory action. PCT. Int. Appl. WO2011013729, 2011.
34. Jemaà, M.; Galluzzi, L.; Kepp, O.; Senovilla, L.; Brands, M.; Boemer, U.; Koppitz, M.; Lienau, P.; Prechtl, S.; Schulze, V.; Siemeister, G.; Wengner, A. M.; Mumberg, D.; Ziegelbauer, K.; Abrieu, A.; Castedo, M.; Vitale, I.; Kroemer, G. Characterization of novel MPS1 inhibitors with preclinical anticancer activity Cell Death Differ. 2013, 20, 1532-1545
35. Kusakabe, K.; Ide, N.; Daigo, Y.; Tachibana, Y.; Itoh, T.; Yamamoto, T.; Hashizume, H.; Hato, Y.; Higashino, K.; Okano, Y.; Sato, Y.; Inoue, M.; Iguchi, M.; Kanazawa, T.; Ishioka, Y.; Dohi, K.; Kido, Y.; Sakamoto, S.; Yasuo, K.; Maeda, M.; Higaki, M.; Ueda, K.; Yoshizawa, H.; Baba, Y.; Shiota, T.; Murai, H.; Nakamura, Y. Indazole-based potent and cell-active Mps1 kinase inhibitors: rational design from pan-kinase inhibitor anthrapyrazolone (SP600125) J. Med. Chem. 2013, 56, 4343-4356
36. Billingsley, K. L.; Buchwald, S. L. An improved system for the palladium-catalyzed borylation of aryl halides with pinacol borane J. Org. Chem. 2008, 73, 5589-5591
37. Ishiyama, T.; Murata, M.; Miyaura, N. Palladium(0)-catalyzed cross-coupling reaction of alkoxydiboron with haloarenes: a direct procedure for arylboronic esters J. Org. Chem. 1995, 60, 7508-7510
38. Jiang, D.; Fu, H.; Jiang, Y.; Zhao, Y. CuBr/ rac -BINOL-catalyzed N -arylations of aliphatic amines at room temperature J. Org. Chem. 2007, 72, 672-674
39. Sasse, A.; Ligneau, X.; Rouleau, A.; Elz, S.; Ganellin, C. R.; Arrang, J.-M.; Schwartz, J.-C.; Schunack, W.; Stark, H. Influence of bulky substituents on histamine H3 receptor agonist/antagonist properties J. Med. Chem. 2002, 45, 4000-4010
40. Gregg, B. T.; Golden, K. C.; Quinn, J. F.; Wang, H.-J.; Zhang, W.; Wang, R.; Wekesa, F.; Tymoshenko, D. O. Rapid, one-pot synthesis of α,α-disubstituted primary amines by the addition of Grignard reagents to nitriles under microwave heating conditions Tetrahedron Lett. 2009, 50, 3978-3981
41. Liu, G.; Cogan, D. A.; Ellman, J. A. Catalytic asymmetric synthesis of tert -butanesulfinamide. Application to the asymmetric synthesis of amines J. Am. Chem. Soc. 1997, 119, 9913-9914
42. Almansa, R.; Guijarro, D.; Yus, M. Synthesis of highly enantiomerically enriched amines by the diastereoselective addition of triorganozincates to N -(tert -butanesulfinyl)imines Tetrahedron: Asymmetry 2008, 19, 2484-2491
43. Jung, D.-I.; Song, J.-H.; Kim, Y.-H.; Lee, D.-H.; Song, H.-A.; Lee, Y.-G.; Park, Y.-M.; Choi, S.-K.; Hahn, J.-T.; Cho, S.-J. Synthesis of di-(N -tropinonyl)alkanes and di-(N -tropinonyl)benzenes Bull. Korean Chem. Soc. 2004, 25, 1932-1934
44. Kumar, D. V.; Hoarau, C.; Bursavich, M.; Slattum, P.; Gerrish, D.; Yager, K.; Saunders, M.; Shenderovich, M.; Roth, B. L.; McKinnon, R.; Chan, A.; Cimbora, D. M.; Bradford, C.; Reeves, L.; Patton, S.; Papac, D. I.; Williams, B. L.; Carlson, R. O. Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors Bioorg. Med. Chem. Lett. 2012, 22, 4377-4385
45. Warren, G. L.; Andrews, C. W.; Capelli, A.-M.; Clarke, B.; LaLonde, J.; Lambert, M. H.; Lindvall, M.; Nevins, N.; Semus, S. F.; Senger, S.; Tedesco, G.; Wall, I. D.; Woolven, J. M.; Peishoff, C. E.; Head, M. S. A critical assessment of docking programs and scoring functions J. Med. Chem. 2006, 49, 5912-5931
46. Feher, M.; Williams, C. I. Effect of input differences on the results of docking calculations J. Chem. Inf. Model. 2009, 49, 1704-1714
47. Feher, M.; Williams, C. I. Reducing docking score variations arising from input differences J. Chem. Inf. Model. 2010, 50, 1549-1560
48. Feher, M.; Williams, C. I. Numerical errors and chaotic behavior in docking simulations J. Chem. Inf. Model. 2012, 52, 724-738
49. Colombo, R.; Caldarelli, M.; Mennecozzi, M.; Giorgini, M. L.; Sola, F.; Cappella, P.; Perrera, C.; Re Depaolini, S.; Rusconi, L.; Cucchi, U.; Avanzi, N.; Bertrand, J. A.; Bossi, R. T.; Pesenti, E.; Galvani, A.; Isacchi, A.; Colotta, F.; Donati, D.; Moll, J. Targeting the mitotic checkpoint for cancer therapy with NMS-P715, an inhibitor of MPS1 kinase Cancer Res. 2010, 70, 10255-10264
50. Tardif, K. D.; Rogers, A.; Cassiano, J.; Roth, B. L.; Cimbora, D. M.; McKinnon, R.; Peterson, A.; Douce, T. B.; Robinson, R.; Dorweiler, I.; Davis, T.; Hess, M. A.; Ostanin, K.; Papac, D. I.; Baichwal, V.; McAlexander, I.; Willardsen, J. A.; Saunders, M.; Christophe, H.; Kumar, D. V.; Wettstein, D. A.; Carlson, R. O.; Williams, B. L. Characterization of the cellular and antitumor effects of MPI-0479605, a small-molecule inhibitor of the mitotic kinase (Mps1) Mol. Cancer Ther. 2011, 10, 2267-2275
51. MOE (Molecular Operating Environment), version 2012.10; Chemical Computing Group Inc.: 1010 Sherbrooke St. West, Suite 910, Montreal, Quebec, H3A 2R7, Canada, 2012.
52. Corina, version 3.2; Molecular Networks GmbH: Erlangen, Germany, 2006.
53. Schrödinger Suite 2012, Schrödinger, LLC: New York, 2012.
54. Glide, version 5.6; Schrödinger, LLC: New York, 2010.
55. Wang, W.; Yang, Y.; Gao, Y.; Xu, Q.; Wang, F.; Zhu, S.; Old, W.; Resing, K.; Ahn, M.; Lei, M.; Liu, X. Structural and mechanistic insights into Mps1 kinase activation J. Cell. Mol. Med. 2009, 13, 1679-1694
56. Laufer, R.; Forrest, B.; Li, S.-W.; Liu, Y.; Sampson, P.; Edwards, L.; Lang, Y.; Awrey, D. E.; Mao, G.; Plotnikova, O.; Leung, G.; Hodgson, R.; Beletskaya, I.; Mason, J. M.; Luo, X.; Wei, X.; Yao, Y.; Feher, M.; Ban, F.; Kiarash, R.; Green, E.; Mak, T. W.; Pan, G.; Pauls, H. W. The Discovery of PLK4 Inhibitors: (E)-3-((1 H -indazol-6-yl)methylene)indolin-2-ones as novel anti-proliferative agents J. Med. Chem. 2013, 56, 6069-6087
57. Kabsch, W. XDS Acta Crystallogr., Sect. D: Biol. Crystallogr. 2010, 66, 125-132
58. Adams, P.; Afonine, P.; Bunkoczi, G.; Chen, V. B.; Davis, I. W.; Echols, N.; Headd, J. J.; Hung, L.-W.; Kapral, G. J.; Grosse-Kunstleve, R. W.; McCoy, A. J.; Moriarty, N. W.; Oeffner, R.; Read, R. J.; Richardson, D. C.; Richardson, J. S.; Terwilliger, T. C.; Zwart, P. H. PHENIX: a comprehensive Python-based system for macromolecular structure solution Acta Crystallogr., Sect. D: Biol. Crystallogr. 2010, 66, 213-221
59. Emsley, P.; Lohkamp, B.; Scott, W. G.; Cowtan, K. Features and development of Coot Acta Crystallogr., Sect. D: Biol. Crystallogr. 2010, 46, 486-501
60. Bricogne, G.; Blanc, E.; Brandl, M.; Flensburg, C.; Keller, P.; Paciorek, W.; Roversi, P.; Sharff, A.; Smart, O. S.; Vonrhein, C.; Womack, T. O. Buster 2.10.0; Global Phasing Ltd: Cambridge, United Kingdom, 2011.
61. Usansky, J. I.; Desai, A.; Tang-Liu, D. PK functions for Microsoft Excel; http://www.pharmpk.com/soft.html (accessed March, 2015).
62. ACD/Structure Designer, version 12.01; Advanced Chemistry Development, Inc.: Toronto, ON, Canada, 2012.