Inhibitors of anaplastic lymphoma kinase: A patent review

Expert Opinion on Therapeutic Patents

Volumn 20, Issue 12, 2010, Pages 1653-1681

  Milkiewicz, Karen L ^a   Ott, Gregory R ^a  

^a CEPHALON INC   (United States)

Author keywords

ALK; cancer; IGF receptor; IGF 1R; receptor tyrosine kinase; small molecule kinase inhibitor

Indexed keywords

2 [5 CHLORO 2 (2 METHOXY 4 MORPHOLINOANILINO) 4 PYRIMIDINYLAMINO] N METHYLBENZAMIDE; 3 [1 (2,6 DICHLORO 3 FLUOROPHENYL)ETHOXY] 5 [1 (4 PIPERIDINYL) 1H PYRAZOL 4 YL] 2 PYRIDINYLAMINE; ANAPLASTIC LYMPHOMA KINASE; ANAPLASTIC LYMPHOMA KINASE INHIBITOR; AP 26113; BMS 536924; BMS 695735; CARBOLINE DERIVATIVE; ENZYME INHIBITOR; GSK 1838705; IMIDAZOLE DERIVATIVE; IMIDAZOQUINOLINE DERIVATIVE; INDAZOLE DERIVATIVE; ISOQUINOLINE DERIVATIVE; NAPHTHALENE DERIVATIVE; NMS E628; PYRAZOLONE DERIVATIVE; TAE 684; THIAZOLE DERIVATIVE; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; CLINICAL TRIAL; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; HUMAN; LUNG NON SMALL CELL CANCER; NONHUMAN; PATENT; REVIEW; STRUCTURE ANALYSIS;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOPLASMS; PATENTS AS TOPIC; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES;

EID: 78649248299     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543776.2010.527332     Document Type: Review

References (85)

1. Rottgers S, Gombert M, Teigler-Schlegel A, et al. ALK fusion genes in children with atypical myeloproliferative disease. Leukemia 2010;24:1197-200
2. Palmer RH, Vernersson E, Grabbe C, et al. Anaplastic lymphoma kinase: signaling in development and disease. Biochem J 2009;420(3):345-61
3. Chiarle R, Voena C, Ambrogio C, et al. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nature Reviews Cancer 2008;8(1):11-23
4. Mano H. Non-solid oncogenes in solid tumors: EML4-ALK fusion genes in lung cancer. Cancer Sci 2008;99(12):2349-55
5. Mosse YP, Wood A, Maris JM. Inhibition of ALK signaling for cancer therapy. Clin Cancer Res 2009;15(18):5609-14
6. Lee CC, Jia Y, Li N, et al. Crystal structure of the anaplastic lymphoma kinase (ALK) catalytic domain Biochem J 2010;430(3):425-37
7. Bossi RT, Saccardo MB, Ardini E, et al. Crystal structures of anaplastic lymphoma kinase in complex with ATP competitive inhibitors. Biochemistry 2010;49(32):6813-25
8. Cheng M, Ott GR. Anaplastic lymphoma kinase as a therapeutic target in anaplastic large cell lymphoma, non-small cell lung cancer and neuroblastoma. Anticancer Agents Med Chem 2010;10(3):236-49
9. Webb TR, Slavish J, George RE, et al. Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy. Expert Rev Anticancer Ther 2009;9(3):331-56
10. Chiarle R, Martinengo C, Mastini C, et al. The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination. Nat Med 2008;14(6):676-80
11. Mastini C, Martinengo C, Inghirami G, et al. Anaplastic lymphoma kinase: an oncogene for tumor vaccination. J Mol Med 2009;87(7):669-77
12. Chiarle R, Inghirami G, Forni G. Anaplastic lymphoma kinase (alk) as oncoantigen for lymphoma vaccination. EP2042191; 2009
13. Inghirami G, Chiarle R. Alk protein tyrosine kinase fused with nucleophosmin and siRNA against ALK gene expression for treating lymphoma. WO2004096142; 2004
14. Esbatech. Antibodies binding to the extracellular domain of the receptor tyrosine kinase ALK. WO2007124610; 2007
15. Esbatech. Anti-anaplastic lymphoma kinase antibodies suitable for treating metastatic cancers or tumors. WO2008131575; 2008
16. Medimmune. Anti-anaplstic lymphoma kinase antibodies, antagonists and agonists for diagnosis and treatment of cancer. WO2007059300; 2007
17. Phase 2, Open-Label Single Arm Study of the efficacy and safety of PF-02341066 in patients with non-small cell lung cancer harboring A translocation or inversion event involving the anaplastic lymphoma kinase (ALK) Gene, NCT00932451. Available from: www.clinicaltrials.gov, 2010
18. Phase 3, Randomized, Open-Label Study of the efficacy and safety of PF-02341066 versus standard of care chemotherapy (Pemetrexed Or Docetaxel) in patients with non-small lung cancer harboring A translocation or inversion event involving the anaplastic lymphoma kinase (ALK) Gene Locus, NCT00932893. Available from: www.clinicaltrials.gov, 2010
19. Phase 1B Open-Label Study of the safety and clinical activity of crizotinib (pf-02341066) in tumors with genetic events involving the anaplastic lymphoma (LKA) Gene Locus, NCT01121588. Available from: www.clinicaltrials.gov, 2010
20. Phase 1 Safety, Pharmacokinetic And Pharmacodynamic Study of pf-02341066, a c-met/hgfr selective tyrosine kinase inhibitor, administered orally to patients with advanced cancer, NCT00585195. Available from: www.clinicaltrials. gov, 2010
21. A Phase I/II Study of PF-02341066, an oral small molecule inhibitor of anaplastic lymphoma kinase (alk) and c-met, in children with relapsed/refractory solid tumors, primary cns tumors, and anaplastic large cell lymphoma, NCT00939770. Available from: www.clinicaltrials.gov, 2010
22. Christensen JG, Zou HY, Arango ME, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther 2007;6(12,Pt. 1):3314-22
23. Sugen. Preparation of aminoheteroaryl compounds as protein kinase inhibitors. PCT Int Appl WO2004076412; 2004
24. Pfizer. Preparation of aminoheteroaryl compounds as c-Met tyrosine kinase inhibitors. PCT Int Appl WO2006021886; 2006
25. Xcovery, Inc. Substituted pyridazine carboxamide compounds as kinase inhibitor compounds. WO2009154769; 2009
26. Cephalon, Inc. Preparation of pyridopyrazine derivatives as ALK and c-Met inhibitors. WO2007130468; 2007
27. Milkiewicz KL, Weinberg LR, Albom MS, et al. Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase. Bioorg Med Chem 2010;18(12):4351-62
28. Ariad. Pyrazinopyrazine derivatives as kinase inhibitors and their preparation, pharmaceutical compositions and use in the treatment of cancer. WO2010056311; 2010
29. Ariad. Azaindole derivatives as kinase inhibitors. WO2010068292; 2010
30. OSI pharmaceuticals Substituted pyrrolo [2,3-b]pyridines and pyrrolo[2,3-b] pyrazines as inhibitors of c-Met and RON tyrosine kinase receptor and their preparation, pharmaceutical compositions and use in the treatment of cancer. WO2010059771; 2010
31. To the best of our knowledge, the earliest patents in the DAP class targeting ATP pockets were ATP-ase inhibitors (a) SmithKline Beecham. Preparation of diaminopyrimidines as gastric acid secretion inhibitors. WO9118887. 1991
32. The earliest kinase specific patent: (b) Celltech Therapeutics Limited. Preparation of substituted 2-anilinopyrimidines as protein kinase inhibitors. WO9719065; 1997
33. Novartis. Preparation of novel 2,4-di(phenylamino)pyrimidines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders. WO2004080980; 2004
34. Galkin AV, Melnick JS, Kim S, et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci USA 2007;104(1):270-5
35. Novartis. Preparation of 2,4-di (phenylamino)pyrimidines useful in the treatment of proliferative disorders. WO2005026130; 2005
36. Novartis. Preparation of 2,4-pyrimidinediamines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders. WO2005016894; 2005
37. Novartis. Preparation of 2,4-di[(hetero) arylamino]pyrimidine derivatives as ZAP-70 and/or SYK inhibitors. WO2005026158; 2005
38. Novartis. Preparation of pyrimidine compounds as FAK and/or ALK inhibitors. WO2006021457; 2006
39. Novartis. Preparation of N,N¢-diarylpyrimidinediamine for use as protein kinase inhibitors. WO2008073687; 2008
40. Novartis. Preparation of pyrimidine compounds as IGF-1 receptor and anaplastic lymphoma kinase inhibitors to treat proliferative disorders. WO2009158431; 2009
41. Novartis. Pyrimidine derivatives as IGF-1R and ALK inhibitors and their preparation, pharmaceutical compositions and use in the treatment of diseases. WO2009032668; 2009
42. Novartis. Preparation of substituted 2-(phenylamino)pyrimidin-4-amine as IGF-1 receptor and anaplastic lymphoma kinase inhibitors for treating proliferative disorders. WO2010002655; 2010
43. Cephalon, Inc. Preparation of fused bicyclic derivatives of 2,4-diaminopyrimidine as ALK and c-Met kinase inhibitors. WO2008051547; 2008
44. Ott GR, Tripathy R, Cheng M, et al. Discovery of a potent inhibitor of anaplastic lymphoma kinase with in vivo antitumour activity. ACS Med Chem Lett 2010; DOI: 10.1021/ml100158s
45. Quail MR, Lu L, Ghose AK, et al. In vitro Activity and in vivo Efficacy of a Benzazepinone ALK Inhibitor in EML4-ALK Positive and Negative Non-Small Cell Lung Cancer Cells (Abstract 3735). Proc Am Assoc Cancer Res 2009
46. Lu L, Quail MR, Jones M, et al. In vitro activity and in vivo efficacy of a Benzazepinone ALk inhbitor on human neuroblastoma-derived cell lines(Abstract 3736). Proc Am Assoc Cancer Res 2009
47. Ariad. Preparation of phosphorus derivatives as kinase inhibitors. WO2009143389; 2009
48. Rivera VM, Anjum R, Wang F, et al. Efficacy and pharmacodynamic analysis of AP26113, a potent and selective orally active inhibitor of anaplastic lymphoma kinase (Abstract 3623) (ALK). Proc Am Assoc Cancer Res 2010
49. Zhang S, Wang F, Keats J, et al. AP26113, a potent ALK inhibitor, overcomes mutations in EML4-ALK that confer resistance to PF-02341066 (Abstract LB-298) (PF1066). Proc Am Assoc Cancer Res 2010
50. Novartis. Preparation of 2-(Het) arylamino-6-aminopyridine derivatives and fused forms thereof as kinase inhibitors for treating hyperproliferative and angiogenesis disorders WO2009032703; 2009
51. Novartis. Preparation of triazine and pyrimidine derivatives as kinase inhibitors. WO2009126514; 2009
52. Novartis. Preparation of pyrimidine derivatives as protein kinase inhibitors for treating proliferative disorders, immune disorders, and infections. WO2009126515; 2009
53. GlaxoSmithKline. Preparation of 2-[[2-(phenylamino)-1H-pyrrolo[2,3-d] pyrimidin-4-yl]amino]benzamide derivatives as inhibitors of IGF-1R and IR receptor tyrosine kinase and ALK kinase for treating cancer WO2009020990; 2009
54. GlaxoSmithKline. Preparation of pyrrolopyrimidine derivatives for use as IGF-1R inhibitors. WO2010045451; 2010
55. Chamberlain SD, Redman AM, Wilson JW, et al. Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d] pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity. Bioorg Med Chem Lett 2009;19(2):360-4
56. Chamberlain SD, Redman AM, Patnaik S, et al. Optimization of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d] pyrimidine inhibitors of IGF-1R: elimination of an acid-mediated decomposition pathway. Bioorg Med Chem Lett 2009;19(2):373-7
57. Chamberlain SD, Wilson JW, Deanda F, et al. Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase. Bioorg Med Chem Lett 2009;19(2):469-73
58. Sabbatini P, Korenchuk S, Rowand JL, et al. GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther 2009;8(10):2811-20
59. Astellas Pharma. Preparation of di (arylamino)aryl derivatives as inhibitors of kinase activity of EML4-ALK fusion protein and EGFR variant protein. WO2009008371; 2009
60. Astellas Pharma. Di(arylamino)aryl Compound. US2010/0099658; 2010
61. Astellas Pharma. Di(arylamino)aryl Compound. US2010/0099658; 2010
62. Janssen Pharmaceutica. Preparation of cyclic peptides and analogs thereof containing pyrimidines for treating hyperproliferative disorders. PCT Int Appl WO2006061415; 2006
63. Incyte. Macrocyclic compounds as kinase inhibitors and their preparation, pharmaceutical compositions and their use in the treatment of JAK/ALK-associated diseases. WO2009132202; 2009
64. Li R, Xue L, Zhu T, et al. Design and Synthesis of 5-Aryl-pyridone- carboxamides as Inhibitors of Anaplastic Lymphoma Kinase. J Med Chem 2006;49(3):1006-15
65. Chembridge and St. Jude's Children's Research hospital. Tricyclic compound derivatives useful in the treatment of neoplastic diseases, inflammatory disorders and immunomodulatory disorders. WO2008021369; 2008
66. Chembridge and St. Jude's Children's Research hospital Preparation of imidazo [4,5-f]isoindole derivatives as tyrosine kinase inhibitors. WO2009117097; 2009
67. Wittman M, Carboni J, Attar R, et al. Discovery of a 1H-Benzoimidazol-2- yl-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor i receptor kinase with in vivo antitumor activity. J Med Chem 2005;48(18):5639-43
68. Velaparthi U, Wittman M, Liu P, et al. Discovery and evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl) piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl) pyridin-2(1H)-one (BMS-695735), an orally efficacious inhibitor of insulin-like growth factor-1 receptor kinase with broad spectrum in vivo antitumor activity. J Med Chem 2008;51(19):5897-900
69. AstraZeneca. Preparation of tricyclyl 2,4-diamino-1,3,5-triazine derivatives as JAK inhibitors. WO2009150462; 2009
70. Bristol-Myers Squibb. Triazine derivatives as tyrosine kinase inhibitors and their preparation, pharmaceutical compositions and use in the treatment of cancer. WO2009015254; 2009
71. Exelixis. Preparation of pyrazolo[3,4-c] isoquinoline derivatives as anaplastic lymphoma kinase modulators. WO2005009389; 2005
72. Leahy JW, Lewis GL, Nuss JM, et al. Preparation of thiazoles and analogs as anaplastic lymphoma kinase modulators. WO2005097765; 2007
73. Universita Degli Studi di Milan, Universite de Geneve, and Universite Claue Bernard Lyon. Preparation of heterocyclylthiazolylbenzene derivatives and analogs for use as antiproliferative agents. Universita Degli Studi di Milano-Bicocca, Italy; Universite de Geneve; Universite Claude Bernard Lyon WO2009121535; 2009
74. Universita Degli Studi di Milan, Universite de Geneve, and Universite Claue Bernard Lyon. Preparation of 9H-pyrido[2,3-b]indoles as inhibitors of oncogenic protein kinases useful in the treatment of cancer. WO2010025872; 2010
75. Nerviano Medical Sciences. Indazole derivatives as kinase inhibitors for the treatment of cancer and their preparation. WO2008074749; 2008
76. Nerviano Medical Sciences. Preparation of substituted indazole derivatives for use as kinase inhibitors WO2009013126; 2009
77. Nerviano Medical Sciences. Carbamoyl derivatives of bicyclic carbonylamino-pyrazoles as prodrugs for the treatment of cancer and their preparation. WO2009138440; 2009
78. Nerviano Medical Sciences. Preparation of substituted indazole derivatives active as kinase inhibitors for treating cancer, cell proliferative disorders, and other diseases. WO2010069966; 2010
79. Aridini E, Menichincheri M, De Ponti C, et al. A highly potent and selective and orally available ALK inhibitor with demonstrated anti-tumor efficacy in ALK dependent lymphoma and non small cell lung cancer models (Abstract 3737). Proc Am Assoc Cancer Res 2009
80. Novartis. Preparation of imidazoquinoline derivatives as protein kinase inhibitors. WO2005054237; 2005
81. Novartis. Preparation of substituted fused naphthyridines as protein kinase inhibitors. WO2007134259; 2007
82. Cephalon, Inc. Preparation of heterocyclylpyrazolinones as protein kinase inhibitors. WO2001032653; 2001
83. McHugh RJ, Tripathy R, Angeles T, et al. Design and synthesis of pyrazolone-based anaplastic lymphoma kinase (ALK) inhibitors. Abstracts of Papers, 235th ACS National Meeting; New Orleans, LA, United States; 2008
84. Quail MR, Lu L, Wan W, et al. PI3K/Akt/mTOR activity is a major determinant for the sensitivity of NPM-ALK (+) Anaplastic large cell lymphoma cells to ALK inhibition (Abstract # 2503). Proc Am Assoc Cancer Res 2010
85. Lin E, Li L, Guan Y, et al. Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers. Mol Cancer Res 2009;7(9):1466-76