Structure-Based Design and Synthesis of 3-Amino-1,5-dihydro-4H-pyrazolopyridin-4-one Derivatives as Tyrosine Kinase 2 Inhibitors

Journal of Medicinal Chemistry

Volumn 59, Issue 2, 2016, Pages 733-749

  Yogo, Takatoshi ^a   Nagamiya, Hiroyuki ^a   Seto, Masaki ^a   Sasaki, Satoshi ^a   Shih Chung, Huang ^a   Ohba, Yusuke ^a,d   Tokunaga, Norihito ^a   Lee, Gil Nam ^b,e   Rhim, Chul Yun ^b,e   Yoon, Cheol Hwan ^b,e   Cho, Suk Young ^b,f   Skene, Robert ^c   Yamamoto, Syunsuke ^a   Satou, Yousuke ^a   Kuno, Masako ^a   Miyazaki, Takahiro ^a   Nakagawa, Hideyuki ^a   Okabe, Atsutoshi ^a   Marui, Shogo ^a   Aso, Kazuyoshi ^a   Yoshida, Masato ^a   more..

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

^b Chemizon   (South Korea)

^c Takeda San Diego Inc   (United States)

^d JAPAN TOBACCO INC   (Japan)

^e CMG Pharmaceutical CoLtd   (South Korea)

^f WUXI APPTEC   (China)

Author keywords

[No Author keywords available]

Indexed keywords

1 METHYL 3 PYRAZOLYL DERIVATIVE; 3 AMINO 1,5 DIHYDRO 4H PYRAZOLOPYRIDIN 4 ONE DERIVATIVE; 3 AMINO 5 (3 METHYLBUTAN 2 YL) 7 [1 METHYL 5 (MORPHOLIN 4 YL) 1H PYRAZOL 3 YL] 1,5 DIHYDRO 4H PYRAZOLOL[4,3 C]PYRIDIN 4 ONE; 3 AMINO 5 (3 METHYLBUTAN 2 YL) 7 [1 METHYL 5 (TETRAHYDRO 2H PYRAN 4 YL) 1H PYRAZOL 3 YL] 1,5 DIHYDRO 4H PYRAZOLO[4,3 C]PYRIDIN 4 ONE; 3 AMINO 5 (3 METHYLBUTAN 2 YL) 7 [5 (MORPHOLIN 4 YL)PYRIDIN 2 YL] 1,5 DIHYDRO 4H PYRAZOLO[4,3 C]PYRIDIN 4 ONE; 3 AMINO 7 [5 (2 HYDROXYPROPAN 2 YL) 1 METHYL 1H PYRAZOL 3 YL] 5 (3 METHYLBUTAN 2 YL) 1H PYRAZOLO[4,3 C]PYRIDIN 4(5H)ONE; ALPHA INTERFERON; AMINOINDAZOLE DERIVATIVE; BARICITINIB; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INDAZOLE DERIVATIVE; INTERLEUKIN 21; INTERLEUKIN 22; INTERLEUKIN 23; INTERLEUKIN 6; JANUS KINASE; JANUS KINASE 1; JANUS KINASE 2; JANUS KINASE 2 INHIBITOR; JANUS KINASE 3; JANUS KINASE INHIBITOR; PROTEIN KINASE TYK2; PROTEIN KINASE TYK2 INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; PYRAZOLINE DERIVATIVE; STAT1 PROTEIN; STAT3 PROTEIN; STAT4 PROTEIN; STAT5 PROTEIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; INTERLEUKIN DERIVATIVE; INTERLEUKIN-22; PROTEIN KINASE INHIBITOR; TYK2 PROTEIN, HUMAN;

ANEMIA; ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CHEMICAL MODIFICATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CYTOKINE PRODUCTION; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME INHIBITION ASSAY; HEMOGLOBIN BLOOD LEVEL; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IC50; MALE; MAXIMUM PLASMA CONCENTRATION; MEAN RESIDENCE TIME; MOLECULAR DOCKING; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PHARMACODYNAMICS; RAT; REACTION OPTIMIZATION; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; STRUCTURE BASED DRUG DESIGN; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CHEMICAL STRUCTURE; DOSE RESPONSE; DRUG EFFECTS; ENZYMOLOGY; JURKAT CELL LINE; LEWIS RAT; MONOCYTE; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ANIMALS; CRYSTALLOGRAPHY, X-RAY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INTERLEUKIN-23; INTERLEUKINS; JANUS KINASE 2; JURKAT CELLS; MALE; MODELS, MOLECULAR; MONOCYTES; PROTEIN KINASE INHIBITORS; RATS; RATS, INBRED LEW; STRUCTURE-ACTIVITY RELATIONSHIP; TYK2 KINASE;

EID: 84970935850     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b01857     Document Type: Article

References (47)

1. Shuai, K.; Liu, B. Regulation of JAK-STAT Signalling in the Immune System Nat. Rev. Immunol. 2003, 3, 900-911 10.1038/nri1226
2. Ghoreschi, K.; Laurence, A.; ÓShea, J. J. Janus Kinases in Immune Cell Signalling Immunol. Rev. 2009, 228, 273-287 10.1111/j.1600-065X.2008.00754.x
3. Aringer, M.; Cheng, A.; Nelson, J. W.; Chen, M.; Sudarshan, C.; Zhou, Y. J.; ÓShea, J. J. Janus kinases and their role in growth and disease Life Sci. 1999, 64, 2173-2186 10.1016/S0024-3205(98)00538-4
4. Schindler, C. W. Series introduction. JAK-STAT signaling in human disease J. Clin. Invest. 2002, 109, 1133-1137 10.1172/JCI0215644
5. Tan, K. W.; Griffiths, C. E. Novel systemic therapies for the treatment of psoriasis Expert Opin. Pharmacother. 2015, 1-14 10.1517/14656566.2016.1109636
6. Mahmood, T.; Zaghi, D.; Menter, A. Emerging oral drugs for psoriasis Expert Opin. Emerging Drugs 2015, 20, 209-20 10.1517/14728214.2015.1010509
7. Weger, W. Current status and new developments in the treatment of psoriasis and psoriatic arthritis with biological agents Br. J. Pharmacol. 2010, 160, 810-820 10.1111/j.1476-5381.2010.00702.x
8. Schafer, J. A.; Kjesbo, N. K.; Gleason, P. P. Formulary review of 2 new biologic agents: tocilizumab for rheumatoid arthritis and ustekinumab for plaque psoriasis J. Manag. Care Pharm. 2010, 16, 402-416
9. Laws, P. M.; Young, H. S. Update of the management of chronic psoriasis: new approaches and emerging treatment options Clin., Cosmet. Invest. Dermatol. 2010, 3, 25-37 10.2147/CCID.S6497
10. Johnsson, H. J.; McInnes, I. B. Interleukin-12 and interleukin-23 inhibition in psoriatic arthritis Clin. Exp. Rheumatol. 2015, 33, S115-8
11. Scanlon, J. V.; Exter, B. P.; Steinberg, M.; Jarvis, C. I. Ustekinumab: treatment of adult moderate-to-severe chronic plaque psoriasis Ann. Pharmacother. 2009, 43, 1456-1465 10.1345/aph.1M151
12. Elliott, M.; Benson, J.; Blank, M.; Brodmerkel, C.; Baker, D.; Sharples, K. R.; Szapary, P. Ustekinumab: lessons learned from targeting interleukin-12/23p40 in immune-mediated diseases Ann. N. Y. Acad. Sci. 2009, 1182, 97-110 10.1111/j.1749-6632.2009.05070.x
13. Leonardi, C. L.; Kimball, A. B.; Papp, K. A.; Yeilding, N.; Guzzo, C.; Wang, Y.; Dooley, L. T.; Gordon, K. B. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1) Lancet 2008, 371, 1665-1674 10.1016/S0140-6736(08)60725-4
14. Papp, K. A.; Langley, R. G.; Lebwohl, M.; Krueger, G. G.; Szapary, P.; Yeilding, N.; Guzzo, C.; Hsu, M.-C.; Wang, Y.; Li, S.; Dooley, L. T.; Reich, K. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2) Lancet 2008, 371, 1675-1684 10.1016/S0140-6736(08)60726-6
15. Griffiths, C. E. M.; Strober, B. E.; Kerkhof, P. V. D.; Ho, V.; Fidelus, G. R.; Yeilding, N.; Guzzo, C.; Xia, Y.; Zhou, B.; Li, S.; Dooley, L. T.; Goldstein, N. H.; Menter, A. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis N. Engl. J. Med. 2010, 362, 118-128 10.1056/NEJMoa0810652
16. Krueger, G. G.; Langley, R. G.; Leonardi, C.; Yeilding, N.; Guzzo, C.; Wang, Y.; Dooley, L. T. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis N. Engl. J. Med. 2007, 356, 580-592 10.1056/NEJMoa062382
17. Lopez-Ferrer, A.; Vilarrasa, E.; Puig, L. Secukinumab (AIN457) for the treatment of psoriasis Expert Rev. Clin. Immunol. 2015, 11, 1177-88 10.1586/1744666X.2015.1095092
18. Griffiths, C. E.; Reich, K.; Lebwohl, M.; van de Kerkhof, P.; Paul, C.; Menter, A.; Cameron, G. S.; Erickson, J.; Zhang, L.; Secrest, R. J.; Ball, S.; Braun, D. K.; Osuntokun, O. O.; Heffernan, M. P.; Nickoloff, B. J.; Papp, K. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials Lancet 2015, 386, 541-51 10.1016/S0140-6736(15)60125-8
19. Strange, A.; Capon, F.; Spencer, C. C.; Knight, J.; Weale, M. E.; Allen, M. H.; Barton, A.; Band, G.; Bellenguez, C.; Bergboer, J. G.; Blackwell, J. M.; Bramon, E.; Bumpstead, S. J.; Casas, J. P.; Cork, M. J.; Corvin, A.; Deloukas, P.; Dilthey, A.; Duncanson, A.; Edkins, S.; Estivill, X.; Fitzgerald, O.; Freeman, C.; Giardina, E.; Gray, E.; Hofer, A.; Hüffmeier, U.; Hunt, S. E.; Irvine, A. D.; Jankowski, J.; Kirby, B.; Langford, C.; Lascorz, J.; Leman, J.; Leslie, S.; Mallbris, L.; Markus, H. S.; Mathew, C. G.; McLean, W. H.; McManus, R.; Mössner, R.; Moutsianas, L.; Naluai, A. T.; Nestle, F. O.; Novelli, G.; Onoufriadis, A.; Palmer, C. N.; Perricone, C.; Pirinen, M.; Plomin, R.; Potter, S. C.; Pujol, R. M.; Rautanen, A.; Riveira-Munoz, E.; Ryan, A. W.; Salmhofer, W.; Samuelsson, L.; Sawcer, S. J.; Schalkwijk, J.; Smith, C. H.; Stahle, M.; Su, Z.; Tazi-Ahnini, R.; Traupe, H.; Viswanathan, A. C.; Warren, R. B.; Weger, W.; Wolk, K.; Wood, N.; Worthington, J.; Young, H. S.; Zeeuwen, P. L.; Hayday, A.; Burden, A. D.; Griffiths, C. E.; Kere, J.; Reis, A.; McVean, G.; Evans, D. M.; Brown, M. A.; Barker, J. N.; Peltonen, L.; Donnelly, P.; Trembath, R. C. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1 Nat. Genet. 2010, 42, 985-990 10.1038/ng.694
20. Tsoi, L. C.; Spain, S. L.; Knight, J.; Ellinghaus, E.; Stuart, P. E.; Capon, F.; Ding, J.; Li, Y.; Tejasvi, T.; Gudjonsson, J. E.; Kang, H. M.; Allen, M. H.; McManus, R.; Novelli, G.; Samuelsson, L.; Schalkwijk, J.; Stahle, M.; Burden, A. D.; Smith, C. H.; Cork, M. J.; Estivill, X.; Bowcock, A. M.; Krueger, G. G.; Weger, W.; Worthington, J.; Tazi-Ahnini, R.; Nestle, F. O.; Hayday, A.; Hoffmann, P.; Winkelmann, J.; Wijmenga, C.; Langford, C.; Edkins, S.; Andrews, R.; Blackburn, H.; Strange, A.; Band, G.; Pearson, R. D.; Vukcevic, D.; Spencer, C. C.; Deloukas, P.; Mrowietz, U.; Schreiber, S.; Weidinger, S.; Koks, S.; Kingo, K.; Esko, T.; Metspalu, A.; Lim, H. W.; Voorhees, J. J.; Weichenthal, M.; Wichmann, H. E.; Chandran, V.; Rosen, C. F.; Rahman, P.; Gladman, D. D.; Griffiths, C. E.; Reis, A.; Kere, J.; Collaborative Association Study of Psoriasis (CASP); Genetic Analysis of Psoriasis Consortium; Psoriasis Association Genetics Extension; Wellcome Trust Case Control Consortium 2.; Nair, R. P.; Franke, A.; Barker, J. N.; Abecasis, G. R.; Elder, J. T.; Trembath, R. C. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity Nat. Genet. 2012, 44, 1341-1348 10.1038/ng.2467
21. Franke, A.; McGovern, D. P.; Barrett, J. C.; Wang, K.; Radford-Smith, G. L.; Ahmad, T.; Lees, C. W.; Balschun, T.; Lee, J.; Roberts, R.; Anderson, C. A.; Bis, J. C.; Bumpstead, S.; Ellinghaus, D.; Festen, E. M.; Georges, M.; Green, T.; Haritunians, T.; Jostins, L.; Latiano, A.; Mathew, C. G.; Montgomery, G. W.; Prescott, N. J.; Raychaudhuri, S.; Rotter, J. I.; Schumm, P.; Sharma, Y.; Simms, L. A.; Taylor, K. D.; Whiteman, D.; Wijmenga, C.; Baldassano, R. N.; Barclay, M.; Bayless, T. M.; Brand, S.; Büning, C.; Cohen, A.; Colombel, J. F.; Cottone, M.; Stronati, L.; Denson, T.; De Vos, M.; DInca, R.; Dubinsky, M.; Edwards, C.; Florin, T.; Franchimont, D.; Gearry, R.; Glas, J.; Van Gossum, A.; Guthery, S. L.; Halfvarson, J.; Verspaget, H. W.; Hugot, J. P.; Karban, A.; Laukens, D.; Lawrance, I.; Lemann, M.; Levine, A.; Libioulle, C.; Louis, E.; Mowat, C.; Newman, W.; Panés, J.; Phillips, A.; Proctor, D. D.; Regueiro, M.; Russell, R.; Rutgeerts, P.; Sanderson, J.; Sans, M.; Seibold, F.; Steinhart, A. H.; Stokkers, P. C.; Torkvist, L.; Kullak-Ublick, G.; Wilson, D.; Walters, T.; Targan, S. R.; Brant, S. R.; Rioux, J. D.; DAmato, M.; Weersma, R. K.; Kugathasan, S.; Griffiths, A. M.; Mansfield, J. C.; Vermeire, S.; Duerr, R. H.; Silverberg, M. S.; Satsangi, J.; Schreiber, S.; Cho, J. H.; Annese, V.; Hakonarson, H.; Daly, M. J.; Parkes, M. Genome-wide meta-analysis increases to 71 the number of confirmed Crohńs disease susceptibility loci Nat. Genet. 2010, 42, 1118-1125 10.1038/ng.717
22. Bahlo, M.; Booth, D. R.; Broadley, S. A.; Brown, M. A.; Foote, S. J.; Griffiths, L. R.; Kilpatrick, T. J.; Lechner-Scott, J.; Moscato, P.; Perreau, V. M.; Rubio, J. P.; Scott, R. J.; Stankovich, J.; Stewart, G. J.; Taylor, B. V.; Wiley, J.; Brown, M. A.; Booth, D. R.; Clarke, G.; Cox, M. B.; Csurhes, P. A.; Danoy, P.; Drysdale, K.; Field, J.; Foote, S. J.; Greer, J. M.; Griffiths, L. R.; Guru, P.; Hadler, J.; McMorran, B. J.; Jensen, C. J.; Johnson, L. J.; McCallum, R.; Merriman, M.; Merriman, T.; Pryce, K.; Scott, R. J.; Stewart, G. J.; Tajouri, L.; Wilkins, E. J.; Rubio, J. P.; Bahlo, M.; Brown, M. A.; Browning, B. L.; Browning, S. R.; Perera, D.; Rubio, J. P.; Stankovich, J.; Broadley, S.; Butzkueven, H.; Carroll, W. M.; Chapman, C.; Kermode, A. G.; Marriott, M.; Mason, D.; Heard, R. N.; Pender, M. P.; Slee, M.; Tubridy, N.; Lechner-Scott, J.; Taylor, B. V.; Willoughby, E.; Kilpatrick, T. J. Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20 Nat. Genet. 2009, 41, 824-828 10.1038/ng.396
23. Ban, M.; Goris, A.; Lorentzen, A. R.; Baker, A.; Mihalova, T.; Ingram, G.; Booth, D. R.; Heard, R. N.; Stewart, G. J.; Bogaert, E.; Dubois, B.; Harbo, H. F.; Celius, E. G.; Spurkland, A.; Strange, R.; Hawkins, C.; Robertson, N. P.; Dudbridge, F.; Wason, J.; De Jager, P. L.; Hafler, D.; Rioux, J. D.; Ivinson, A. J.; McCauley, J. L.; Pericak-Vance, M.; Oksenberg, J. R.; Hauser, S. L.; Sexton, D.; Haines, J.; Sawcer, S. Wellcome Trust Case-Control Consortium (WTCCC).; Compston A. Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor Eur. J. Hum. Genet. 2009, 17, 1309-1313 10.1038/ejhg.2009.41
24. Suarez-Gestal, M.; Calaza, M.; Endreffy, E.; Pullmann, R.; Ordi-Ros, J.; Sebastiani, G. D.; Ruzickova, S.; Jose Santos, M.; Papasteriades, C.; Marchini, M.; Skopouli, F. N.; Suarez, A.; Blanco, F. J.; DAlfonso, S.; Bijl, M.; Carreira, P.; Witte, T.; Migliaresi, S.; Gomez-Reino, J. J.; Gonzalez, A. European Consortium of SLE DNA Collections. Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study Arthritis Res. Ther. 2009, 11, R69 10.1186/ar2698
25. Cunninghame Graham, D. S.; Morris, D. L.; Bhangale, T. R.; Criswell, L. A.; Syvänen, A. C.; Rönnblom, L.; Behrens, T. W.; Graham, R. R.; Vyse, T. J. Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus PLoS Genet. 2011, 7, e1002341 10.1371/journal.pgen.1002341
26. Parganas, E.; Wang, D.; Stravopodis, D.; Topham, D. J.; Marine, J. C.; Teglund, S.; Vanin, E. F.; Bodner, S.; Colamonici, O. R.; vanDeursen, J. M.; Grosveld, G.; Ihle, J. N. Jak2 is essential for signaling through a variety of cytokine receptors Cell 1998, 93, 385-395 10.1016/S0092-8674(00)81167-8
27. Frenzel, K.; Wallace, T. A.; McDoom, I.; Xiao, H. D.; Capecchi, M. R.; Bernstein, K. E.; Sayeski, P. P. A functional Jak2 tyrosine kinase domain is essential for mouse development Exp. Cell Res. 2006, 312, 2735-2744 10.1016/j.yexcr.2006.05.004
28. Neubauer, H.; Cumano, A.; Muller, M.; Wu, H.; Huffstadt, U.; Pfeffer, K. Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis Cell 1998, 93, 397-409 10.1016/S0092-8674(00)81168-X
29. Fleischmann, R.; Cutolo, M.; Genovese, M. C.; Lee, E. B.; Kanik, K. S.; Sadis, S.; Connell, C. A.; Gruben, D.; Krishnaswami, S.; Wallenstein, G.; Wilkinson, B. E.; Zwillich, S. H. Phase 2B doseranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to DMARDs Arthritis Rheum. 2012, 64, 617-629 10.1002/art.33383
30. Kremer, J. M.; Cohen, S.; Wilkinson, B. E.; Connell, C. A.; French, J. L.; Gomez-Reino, J.; Gruben, D.; Kanik, K. S.; Krishnaswami, S.; Pascual-Ramos, V.; Wallenstein, G.; Zwillich, S. H. A phase 2B dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate alone Arthritis Rheum. 2012, 64, 970-981 10.1002/art.33419
31. Verstovsek, S.; Kantarjian, H.; Mesa, R. A.; Pardanani, A. D.; Cortes-Franco, J.; Thomas, D. A.; Estrov, Z.; Fridman, J. S.; Bradley, E. C.; Erickson-Viitanen, S.; Vaddi, K.; Levy, R.; Tefferi, A. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis N. Engl. J. Med. 2010, 363, 1117-1127 10.1056/NEJMoa1002028
32. Keystone, E. C.; Taylor, P. C.; Drescher, E.; Schlichting, D. E.; Beattie, S. D.; Berclaz, P. Y.; Lee, C. H.; Fidelus-Gort, R. K.; Luchi, M. E.; Rooney, T. P.; Macias, W. L.; Genovese, M. C. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate Ann. Rheum. Dis. 2015, 74, 333-40 10.1136/annrheumdis-2014-206478
33. Bachelez, H.; van de Kerkhof, P. C.; Strohal, R.; Kubanov, A.; Valenzuela, F.; Lee, J. H.; Yakusevich, V.; Chimenti, S.; Papacharalambous, J.; Proulx, J.; Gupta, P.; Tan, H.; Tawadrous, M.; Valdez, H.; Wolk, R. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial Lancet 2015, 386, 552-61 10.1016/S0140-6736(14)62113-9
34. Papp, K. A.; Menter, M. A.; Abe, M.; Elewski, B.; Feldman, S. R.; Gottlieb, A. B.; Langley, R.; Luger, T.; Thaci, D.; Buonanno, M.; Gupta, P.; Proulx, J.; Lan, S.; Wolk, R. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials Br. J. Dermatol. 2015, 173, 949-61 10.1111/bjd.14018
35. Hsu, L.; Armstrong, A. W. JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis J. Immunol. Res. 2014, 2014, 283617 10.1155/2014/283617
36. Kwatra, S. G.; Dabade, T. S.; Gustafson, C. J.; Feldman, S. R. JAK inhibitors in psoriasis: a promising new treatment modality J. Drugs Dermatol.: JDD 2012, 11, 913-8
37. Norman, P. Selective JAK1 inhibitor and selective Tyk2 inhibitor patents Expert Opin. Ther. Pat. 2012, 22, 1233-1249 10.1517/13543776.2012.723693
38. Liang, J.; Tsui, V.; Van Abbema, A.; Bao, L.; Barrett, K.; Beresini, M.; Berezhkovskiy, L.; Blair, W. S.; Chang, C.; Driscoll, J.; Eigenbrot, C.; Ghilardi, N.; Gibbons, P.; Halladay, J.; Johnson, A.; Kohli, P. B.; Lai, Y.; Liimatta, M.; Mantik, P.; Menghrajani, K.; Murray, J.; Sambrone, A.; Xiao, Y.; Shia, S.; Shin, Y.; Smith, J.; Sohn, S.; Stanley, M.; Ultsch, M.; Zhang, B.; Wu, L. C.; Magnuson, S. Lead identification of novel and selective TYK2 inhibitors Eur. J. Med. Chem. 2013, 67, 175-87 10.1016/j.ejmech.2013.03.070
39. Liang, J.; van Abbema, A.; Balazs, M.; Barrett, K.; Berezhkovsky, L.; Blair, W.; Chang, C.; Delarosa, D.; DeVoss, J.; Driscoll, J.; Eigenbrot, C.; Ghilardi, N.; Gibbons, P.; Halladay, J.; Johnson, A.; Kohli, P. B.; Lai, Y.; Liu, Y.; Lyssikatos, J.; Mantik, P.; Menghrajani, K.; Murray, J.; Peng, I.; Sambrone, A.; Shia, S.; Shin, Y.; Smith, J.; Sohn, S.; Tsui, V.; Ultsch, M.; Wu, L. C.; Xiao, Y.; Yang, W.; Young, J.; Zhang, B.; Zhu, B. Y.; Magnuson, S. Lead optimization of a 4-aminopyridine benzamide scaffold to identify potent, selective, and orally bioavailable TYK2 inhibitors J. Med. Chem. 2013, 56, 4521-36 10.1021/jm400266t
40. Jang, W. D.; Kim, J. T.; Son, H. Y.; Park, S. Y.; Cho, Y. S.; Koo, T. S.; Lee, H.; Kang, N. S. Discovery of Tyk2 inhibitors via the virtual site-directed fragment-based drug design Bioorg. Med. Chem. Lett. 2015, 25, 3947-52 10.1016/j.bmcl.2015.07.037
41. Smith, G. F. Designing drugs to avoid toxicity Prog. Med. Chem. 2011, 50, 1-47 10.1016/B978-0-12-381290-2.00001-X
42. Chrencik, J. E.; Patny, A.; Leung, I. K.; Korniski, B.; Emmons, T. L.; Hall, T.; Weinberg, R. A.; Gormley, J. A.; Williams, J. M.; Day, J. E.; Hirsch, J. L.; Kiefer, J. R.; Leone, J. W.; Fischer, H. D.; Sommers, C. D.; Huang, H. C.; Jacobsen, E. J.; Tenbrink, R. E.; Tomasselli, A. G.; Benson, T. E. Structural and thermodynamic characterization of the TYK2 and JAK3 kinase domains in complex with CP-690550 and CMP-6 J. Mol. Biol. 2010, 400, 413-433 10.1016/j.jmb.2010.05.020
43. ÓSullivan, L. A.; Liongue, C.; Lewis, R. S.; Stephenson, S. E.; Ward, A. C. Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease Mol. Immunol. 2007, 44, 2497-2506 10.1016/j.molimm.2006.11.025
44. Fridman, J. S.; Scherle, P. A.; Collins, R.; Burn, T. C.; Li, Y.; Li, J.; Covington, M. B.; Thomas, B.; Collier, P.; Favata, M. F.; Wen, X.; Shi, J.; McGee, R.; Haley, P. J.; Shepard, S.; Rodgers, J. D.; Yeleswaram, S.; Hollis, G.; Newton, R. C.; Metcalf, B.; Friedman, S. M.; Vaddi, K. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050 J. Immunol. 2010, 184, 5298-307 10.4049/jimmunol.0902819
45. Sohn, S. J.; Barrett, K.; Van Abbema, A.; Chang, C.; Kohli, P. B.; Kanda, H.; Smith, J.; Lai, Y.; Zhou, A.; Zhang, B.; Yang, W.; Williams, K.; Macleod, C.; Hurley, C. A.; Kulagowski, J. J.; Lewin-Koh, N.; Dengler, H. S.; Johnson, A. R.; Ghilardi, N.; Zak, M.; Liang, J.; Blair, W. S.; Magnuson, S.; Wu, L. C. A restricted role for TYK2 catalytic activity in human cytokine responses revealed by novel TYK2-selective inhibitors J. Immunol. 2013, 191, 2205-16 10.4049/jimmunol.1202859
46. Zhang, R.; Zhang, D.; Guo, Y.; Zhou, G.; Jiang, Z.; Dong, D. Vilsmeier reaction of enaminones: efficient synthesis of halogenated pyridin-2(1H)-ones J. Org. Chem. 2008, 73, 9504-9507 10.1021/jo801959j
47. 2B adenosine receptor antagonists J. Med. Chem. 2012, 55, 797-811 10.1021/jm201292w