Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1

Expert Opinion on Therapeutic Patents

Volumn 27, Issue 2, 2017, Pages 127-143

  Kettle, Jason G ^a   Åstrand, Annika ^b   Catley, Matthew ^b   Grimster, Neil P ^a   Nilsson, Magnus ^b   Su, Qibin ^a   Woessner, Richard ^a  

^a ASTRAZENECA   (United Kingdom)

^b ASTRAZENECA R AND D   (Sweden)

Author keywords

JAK; JAK1 inhibitor; JAK2 inhibitor; JAK3 inhibitor; Janus kinase inhibitors; myelofibrosis; oncology; rheumatoid arthritis; ruxolitinib; tofacitinib; TYK2 inhibitor

Indexed keywords

5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; CEP 33779; EP 009; FILGOTINIB; IBRUTINIB; ITACITINIB; JANUS KINASE; JANUS KINASE INHIBITOR; RUXOLITINIB; TOFACITINIB; UNCLASSIFIED DRUG; UPADACITINIB; PROTEIN KINASE INHIBITOR;

ENZYME INHIBITION; HUMAN; NONHUMAN; ONCOLOGY; PATENT; REVIEW; ANIMAL; ANTAGONISTS AND INHIBITORS; DOSE RESPONSE; DRUG DESIGN; ENZYMOLOGY; INFLAMMATION; NEOPLASMS;

ANIMALS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; HUMANS; INFLAMMATION; JANUS KINASES; NEOPLASMS; PATENTS AS TOPIC; PROTEIN KINASE INHIBITORS;

EID: 85009250369     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1080/13543776.2017.1252753     Document Type: Review

References (96)

1. Vakil E, Tefferi A., BCR-ABL1-negative myeloproliferative neoplasms:a review of molecular biology, diagnosis, and treatment. Clin Lymphoma Myeloma Leuk. 2011;11(S1):S37–S45.
2. Kiu H, Nicholson SE. Biology and significance of the JAK/STAT signalling pathways. Growth Factors. 2012;30:88–106.
3. Schwartz DM, Bonelli M, Gadina M, et al. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016;12:25–36.• Recent review on receptor dependency of the different JAK isoforms.
4. Borden EC, Sen GC, Uze G, et al. Interferons at age 50:past, current and future impact on biomedicine. Nat Rev Drug Discov. 2007;6:975–990.
5. O’Shea JJ, Schwartz DM, Villarino AV, et al. The JAK-STAT pathway:impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311–328.•• Recent comprehensive review of JAK/STAT biology and leading inhibitors in development.
6. Clark JD, Flanagan ME, Telliez JB. Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases. J Med Chem. 2014;57:5023–5038.
7. Tan FH, Putoczki TL, Stylli SS, et al. The role of STAT3 signaling in mediating tumour resistance to cancer therapy. Curr Drug Targets. 2014;15:1341–1353.
8. Sansone P, Bromberg J. Targeting the interleukin-6/Jak/Stat pathway in human malignancies. J Clin Oncol. 2012;30:1005–1014.
9. Haura EB, Zheng Z, Song L, et al. Activated epidermal growth factor receptor–Stat-3 signaling promotes tumor survival in vivo in non-small cell lung cancer. Clin Cancer Res. 2005;11:8288–8294.
10. Lam LT, Wright G, Davis RE. Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-κB pathways in subtypes of diffuse large B-cell lymphoma. Blood. 2008;111:3701–3713.
11. Song JI, Grandis JR. STAT signaling in head and neck cancer. Oncogene. 2000;19:2489–2495.
12. Thomas SJ, Snowden JA, Zeidler MP, et al. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. Br J Cancer. 2015;113:365–371.
13. Yin Z, Zhang Y, Li Y, et al. Prognostic significance of STAT3 expression and its correlation with chemoresistance of non-small cell lung cancer cells. Acta Histochem. 2012;114:151–158.
14. Gao SP, Mark KG, Leslie K, et al. Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas. J Clin Invest. 2007;117:3846–3856.
15. Lee H-J, Zhuang G, Cao Y, et al. Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells. Cancer Cell. 2014;26:207–221.
16. O’Shea JJ, Holland SM, Staudt LM. JAKs and STATs in immunity, immunodeficiency, and cancer. N Engl J Med. 2013;368:161–170.
17. Ostojic A, Vrhovac R, Verstovsek S. Ruxolitinib for the treatment of myelofibrosis:its clinical potential. Ther Clin Risk Manag. 2012;8:95–103.• Clinical efficacy and safety findings for ruxolitinib in myelofibrosis.
18. Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells:role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2007;7:41–51.
19. Kortylewski M, Yu H. Role of Stat3 in suppressing anti-tumour immunity. Curr Op Immunol. 2008;20:228–233.
20. Avalle L, Pensa S, Regis G, et al. STAT1 and STAT3 in tumourigenesis:a matter of balance. Jakstat. 2012;1:65–72.• Overview of the competing roles of STAT1 and STAT3 in tumor growth vs. tumor immune surveillance.
21. Pensa S, Regis G, Boselli D, et al. STAT3 and STAT3 in tumourigenesis:two sides of the same coin? JAK-STAT pathway in disease. Landes Biosci. 2009.• In-depth review of the competing roles of STAT1 and STAT3 in the biology of tumor growth versus tumor immune surveillance, including control of gene expression and cytokine pathways.
22. Kortylewski M, Kujawski M, Wang T, et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumour immunity. Nat Med. 2005;11:1314–1321.
23. Niu G, Wright KL, Huang M, et al. Constitutive Stat3 activity up-regulates VEGF expression and tumour angiogenesis. Oncogene. 2002;21:2000–2008.
24. Integrity database:http://thomsonreuters.com/en/products-services/pharma-life-sciences/pharma-competitive-intelligence/cortellis-competitive-intelligence.html. cited 2015 Sep &Jan 2016.
25. SciFinder:http://www.cas.org/products/scifinder. cited 2015 Sep and 2016 Jan.
26. Kettle JG, Åstrand A, Catley M, et al. Inhibitors of JAK-family kinases:an update on the patent literature 2013-2015, part 2. Expert Opin Ther Pat. 2016. doi:10.1080/13543776.2017.1252754.
27. Dymock BW, See CS. Inhibitors of JAK2 and JAK3:an update on the patent literature 2010–2012. Expert Opin Ther Patents. 2013;23:449–501.
28. AbbVie Inc. JAK1selective inhibitor and uses thereof. WO2015061665. 2015
29. Abbott Laboratories. Novel tricyclic compounds. WO2011068881. 2011
30. AbbVie Inc. Tricyclic compounds useful as protein kinase inhibitors. WO2013043826. 2013
31. Almirall Prodesfarma SA, Pyridin-2(1H)-one derivatives as JAK inhibitors. WO2013017461. 2013
32. Ioannidis S, Lamb ML, Wang T, et al. Discovery of 5-chloro-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a novel inhibitor of the Jak/Stat pathway. J Med Chem. 2011;54:262–276.
33. Almirall Prodesfarma SA, Pyrazolopyrimidin-2-yl derivatives as JAK inhibitors. WO2015086693. 2015
34. Almirall Prodesfarma SA, Imidazolopyrimidin-2-yl derivatives as JAK inhibitors. WO2015091531. 2015
35. Array BioPharma Inc. 5,7-Substituted-imidazo[1,2-c]pyrimidines. WO2013055645. 2013
36. Arrien Pharmaceuticals LLC. 3,5-(Un)substituted-1H-pyrrolo[2,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine and 5H-pyrrolo[2-,3-b]pyrazine dual ITK and JAK3 kinase inhibitors. WO2014172513. 2014
37. Aurigene Discovery Technologies Ltd. Pyrimidine-2,4-diamine derivatives as kinase inhibitors. WO2014091265. 2014
38. Novartis. Pyrimidine derivatives. WO2006021454. 2006
39. BioCryst Pharmaceuticals Inc. Heterocyclic compounds as Janus kinase inhibitors. WO2013033093; 2013
40. Vertex Pharma. Tricyclic heteroaryl compounds useful as inhibitors of Janus kinase. WO2008079521. 2008
41. Wang T, Duffy JP, Wang J, et al. Janus kinase 2 inhibitors synthesis and characterization of a novel polycyclic azaindole. J Med Chem. 2009;52:7938–7941.
42. Hunt JT, Mitt T, Borzilleri R, et al. Discovery of the pyrrolo[2,1-f][1,2,4]triazine nucleus as a new kinase inhibitor template. J Med Chem. 2004;47:4054–4059.
43. Jin B. Novel compositions, uses and methods for their preparation. WO2015057695. 2015
44. Bristol-Myers Squibb Co. Imidazopyridazine JAK-3 inhibitors and their use for the treatment of inflammatory and autoimmune diseases. WO2014039595. 2014
45. Zydus Cadila Healthcare Ltd. N-Cyanomethylamides as inhibitors of Janus kinase. WO2015019365. 2015
46. Zydus Cadila Healthcare Ltd. Heterocyclic compounds. WO2013054351. 2013
47. Calitor Sciences Llc. Sunshine Lake Pharma Co Ltd. Substituted heteroaryl compounds and methods of use. WO2015094803. 2015
48. Calitor Sciences Llc. Sunshine Lake Pharma Co Ltd. Substituted heteroaryl compounds and methods of use. WO2015148867. 2015
49. Calitor Sciences Llc. Sunshine Lake Pharma Co Ltd. Substituted heteroaryl compounds and methods of use. WO2015073267. 2015
50. Genentech Inc. Pyrazolopyrimidine JAK inhibitor compounds and methods. WO2011003065. 2011
51. Vertex Pharmaceuticals Inc. Compounds useful as inhibitors of ATR kinase. WO2014143241. 2014
52. Infinity Pharmaceuticals Inc. Heterocyclic compounds and uses thereof. WO2015051244. 2015
53. Cellzome. Pyrazolo[4,3-c]pyridine derivatives as JAK inhibitors. WO2013017479. 2013
54. Cellzome. Pyrazolo[4,3-c]pyridine derivatives as JAK inhibitors. WO2013017480. 2013
55. Cellzome. Heterocyclyl pyrazolopyrimidine analogues as jak inhibitors. WO2011048082. 2011
56. Cellzome. Heterocyclyl pyrazolopyrimidine analogues as selective JAK inhibitors. WO2012022681. 2012
57. Cellzome. Pyrazolo[4,3-c]pyridine derivatives as kinase inhibitors. WO2013041605. 2013
58. Cellzome. Heterocyclyl pyrimidine analogues as JAK inhibitors. WO2013014162; 2013
59. Cellzome. Pyrimidine-2,4-diamine derivatives as kinase inhibitors. WO2013092854. 2013
60. Cellzome. Heterocyclyl pyrimidine analogs as TYK2 inhibitors. WO2013174895. 2013
61. Celon Pharma SP. Imidazo[1,2-b]pyridazin-6-amine derivatives as kinase JAK-2 inhibitors. WO2014020531. 2014
62. Celon Pharma SP. Pyrazolo[1,5-a]pyrimidine derivatives as kinase JAK-2 inhibitors. WO2015118434. 2015
63. Su Q, Ioannidis S, Chuaqui C, et al. Discovery of 1-methyl-1h-imidazole derivatives as potent jak2 inhibitors. J Med Chem. 2014;57:144–158.
64. AstraZeneca. Pyrazolyl-amino-substituted pyrimidines and their use for the treatment of cancer. WO2008132502. 2008
65. AstraZeneca. 5-aminopyrazol-3-yl-3h-imidazo [4,5-b] pyridine derivatives and their use for the treatment of cancer. WO2008129255. 2008
66. Cephalon Inc. Imidazo[4,5-b]pyridine derivatives as Alk and JAK modulators for the treatment of proliferative disorders. WO2013116291. 2013
67. Cephalon Inc. Treatment of multiple sclerosis with a 1,2,4-triazolo [1,5a] pyridine derivative. WO2015089153. 2015
68. Cephalon Inc. Preparation and uses of 1,2,4-triazolo[1,5a]pyridine derivatives. WO2010141796. 2010
69. Dugan BJ, Gingrich DE, Mesaros EF, et al. A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy:discovery of CEP-33779. J Med Chem. 2012;55:5243–5254.
70. CoNCERT Pharmaceuticals Inc. Deuterated pacritinib. WO2014159511. 2014
71. CoNCERT Pharmaceuticals Inc. Deuterated baricitinib. WO2014028756. 2014
72. CoNCERT Pharmaceuticals Inc. Deuterated derivatives of ruxolitinib. WO2013188783; 2013
73. Dana-Farber Cancer Institute, Inc. Janus kinase inhibitors and uses thereof. WO2015164614. 2015
74. Tan L, Akahane K, McNally R, et al. Development of selective covalent Janus kinase 3 inhibitors. J Med Chem. 2015;58:6589−6606.
75. Dana-Farber Cancer Institute, Inc. Hydrophobically tagged Janus kinase inhibitors and uses thereof. WO2015164604. 2015
76. Xie T, Lim SM, Westover KD, et al. Pharmacological targeting of the pseudokinase ​Her3. Nat Chem Biol. 2014;10:1006–1012.
77. Eli Lilly & Co. Lilly Industries Ltd. Inhibitor of JAK1 and JAK2. WO2013188184; 2013
78. Endo Health Solutions Inc. Endo Pharmaceuticals Solutions Inc. Individual. Pyrimido-pyridazinone compounds and use thereof. WO2013028818. 2013
79. EP Pharma Inc. Compositions and methods related to inhibitors of JAK kinase. WO2013148638. 2013
80. Stepkowski SM, Kao J, Wang M-E, et al. The Mannich base NC1153 promotes long-term allograft survival and spares the recipient from multiple toxicities. J Immunol. 2005;175:4236–4246.
81. Galapagos NV, Individual. Imidazo[4,5-c]pyridine derivatives useful for the treatment of degenerative and inflammatory diseases. WO2013117645. 2013
82. Galapagos NV, Imidazo [4,5-c] pyridine derivatives useful for the treatment of degenerative and inflammatory diseases. WO2013117649. 2013
83. Galapagos NV, Individual. Aminotriazolopyridine for use in the treatment of inflammation, and pharmaceutical compositions thereof. WO2013189771. 2013
84. Menet CJ, Fletcher SR, Van Lommen G, et al. Triazolopyridines as selective JAK1 inhibitors:from hit identification to GLPG0634. J Med Chem. 2014;57:9323−9342.
85. Galapagos NV, Benzimidazole derivatives and pharmaceutical compositions thereof for the treatment of inflammatory disorders. WO2015110378. 2015
86. Eli Lilly & Co. Hanmi Pharmaceutical Co Ltd. Triazolopyridine derivatives as a tyrosine kinase inhibitor. WO2013118986. 2013
87. Pan Z, Scheerens H, Li SJ, et al. Discovery of selective irreversible inhibitors for Bruton’s tyrosine kinase. ChemMedChem. 2007;2:58–61.
88. Eli Lilly & Co. Hanmi Pharmaceutical Co Ltd. Novel imidazopyridine derivatives as a tyrosine kinase inhibitor. WO2013100631. 2013
89. Beijing Hanmi Pharmaceutical Co Ltd. Compound inhibiting kinase activities of BTK and/or JAK3. WO2015039612. 2015
90. Beijing Hanmi Pharmaceutical Co Ltd. Compound inhibiting kinase activities of BTK and/or JAK3. WO2015039613. 2015
91. Incyte Corp. Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors. WO2013173720. 2013
92. Incyte Corp Individual. Cyclohexyl azetidine derivatives as JAK inhibitors. WO2013026025. 2013
93. Li J, Caulder E, Favata M, et al. Blockade of the IL-6/JAK/STAT3 signaling pathway inhibits pancreatic tumor cell growth in 3D spheroid cultures and in xenograft models. 106th Annu Meet Am Assoc Cancer Res (AACR) 2015(Apr 18-22, Philadelphia), Abst 779
94. Incyte Corp. Bipyrazole derivatives as JAK inhibitors. WO2014186706. 2014
95. Incyte Corp. Tricyclic fused thiophene derivatives as JAK inhibitors. WO2014071031. 2014
96. Incyte Corp. Processes of preparing a JAK1 inhibitor and new forms thereto. WO2015168246. 2015