DP2 receptor antagonists in development

Expert Opinion on Investigational Drugs

Volumn 19, Issue 8, 2010, Pages 947-961

  Norman, Peter ^a  

^a NORMAN CONSULTING   (United Kingdom)

Author keywords

Asthma; COPD; DP1 receptor; DP2 receptor; Inflammation; PGD2; TXA2

Indexed keywords

3 BENZYL 5 (6 CARBOXYHEXYL) 1 (2 CYCLOHEXYL 2 HYDROXYETHYLAMINO)HYDANTOIN; ACT 129968; ADC 3680; ADC 9971; AM 211; AM 461; AMG -853; AMG 009; AMG 853; AP 761; ARRY 060; ARRY 063; AZ 11805131; AZD 1981; AZD 5985; AZD 8075; LAROPIPRANT; OC 2417; OC 459; PLACEBO; PROSTAGLANDIN D2 RECEPTOR ANTAGONIST; PROSTAGLANDIN RECEPTOR BLOCKING AGENT; RAMATROBAN; S 555739; SAR 398171; SERATRODAST; TM 30089; UNCLASSIFIED DRUG; ANTIASTHMATIC AGENT; IMMUNOGLOBULIN RECEPTOR; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN D2; PROSTAGLANDIN D2 RECEPTOR; PROSTAGLANDIN RECEPTOR;

ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL ASSESSMENT; CLINICAL STUDY; CLINICAL TRIAL; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; DRUG TOLERABILITY; FORCED EXPIRATORY VOLUME; HUMAN; HUMAN TISSUE; IC 50; IN VIVO STUDY; LUNG BIOPSY; REVIEW; TREATMENT INDICATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; CLINICAL TRIAL (TOPIC); DRUG DESIGN; FEMALE; MALE; METABOLISM; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTI-ASTHMATIC AGENTS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ASTHMA; CLINICAL TRIALS AS TOPIC; DRUG DESIGN; FEMALE; HUMANS; MALE; MOLECULAR STRUCTURE; PROSTAGLANDIN D2; RECEPTORS, IMMUNOLOGIC; RECEPTORS, PROSTAGLANDIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77954725559     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.2010.500019     Document Type: Review

References (72)

1. Wenzel SE, Westcott JY, Smith HR, Larsen GL. Spectrum of prostanoid release after bronchoalveolar allergen challenge in atopic asthmatics and in control groups. An alteration in the ratio of bronchoconstrictive to bronchoprotective mediators. Am Rev Respir Dis 1989;139(2):450-7
2. Coleman RA, Smith WL, Narumiya S. International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 1994;46(2):205-29
3. Hirai H, Tanaka K, Yoshie O, et al. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med 2001;193(2):255-61
4. Sawyer N, Cauchon E, Chateauneuf A, et al. Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2. Br J Pharmacol 2002;137(8):1163-72
5. Mckenniff MG, Rodger IW, Norman P, Gardiner PJ. Characterisation of receptors mediating the contractile effects of prostanoids in guinea-pig and human airways. Eur J Pharmacol 1988;153(2-3):149-59
6. Mckenniff MG, Norman P, Cuthbert NJ, Gardiner PJ. BAY u3405, a potent and selective thromboxane A2 receptor antagonist on airway smooth muscle in vitro. Br J Pharmacol 1991;104(3):585-90
7. Magnussen H, Boerger S, Templin K, Baunack AR. Effects of a thromboxane-receptor antagonist, BAY u 3405, on prostaglandin D2-and exercise-induced bronchoconstriction. J Allergy Clin Immunol 1992;89(6):1119-26
8. Johnston SL, Smith S, Harrison J, et al. The effect of BAY u 3405, a thromboxane receptor antagonist, on prostaglandin D2-induced nasal blockage. J Allergy Clin Immunol 1993;91(4):903-9
9. Johnston SL, Freezer NJ, Ritter W, et al. Prostaglandin D2-induced bronchoconstriction is mediated only in part by the thromboxane prostanoid receptor. Eur Respir J 1995;8(3):411-15
10. Terada N, Yamakoshi T, Hasegawa M, et al. A. The effect of ramatroban (BAY u 3405), a thromboxane A2 receptor antagonist, on nasal cavity volume and minimum cross-sectional area and nasal mucosal hemodynamics after nasal mucosal allergen challenge in patients with perennial allergic rhinitis. Acta Otolaryngol Suppl 1998;537:32-7
11. Sugimoto H, Shichijo M, Iino T, et al. An orally bioavailable small molecule antagonist of CRTH2, ramatroban (BAY u3405), inhibits prostaglandin D2-induced eosinophil migration in vitro. J Pharmacol Exp Ther 2003;305(1):347-52
12. Hata AN, Lybrand TP, Marnett LJ, et al. Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. Mol Pharmacol 2005;67:640-7
13. Pettipher R, Hansel TT, Armer R. Antagonism of the prostaglandin D2 receptors DP1 and CRTH2 as an approach to treat allergic diseases. Nat Rev Drug Discov 2007;6(4):313-25
14. Pettipher R. The roles of the prostaglandin D(2) receptors DP(1) and CRTH2 in promoting allergic responses. Br J Pharmacol 2008;153(Suppl 1):S191-9
15. Philip G, van Adelsberg J, Loeys T, et al. Clinical studies of the DP1 antagonist laropiprant in asthma and allergic rhinitis. J Allergy Clin Immunol 2009;124(5):942-8
16. Birkinshaw TN, Teague SJ, Beech C, et al. Discovery of potent CRTh2 (DP2) receptor antagonists. Bioorg Med Chem Lett 2006;16(16):4287-90
17. AstraZeneca AB. Novel process for the preparation of substituted indoles. WO2006075139; 2006
18. AstraZeneca. One Month Dose Response Study of AZD1981 in asthma patients uncontrolled on inhaled steroids (OLIVE). NCT00758589
19. AstraZeneca. 14729-D9831C00002-1 Month Biopsy Study. NCT00766415
20. Sargnet C, Stinson S, Schmidt J, et al. The effect of a selective CRTh2 antagonist on tobacco smoke (TS) induced airway inflammation and remodelling in the mouse. Br J Pharmacol 2009;98. Available from: https://bps.conference- services.net/resources/344/1686/pdf/JB2009-0098.pdf
21. AstraZeneca AB. Novel compounds 951: a biphenyloxypropanoic acid as CRTH2 modulator and intermediates. WO2009004379
22. Oxagen plc. Available from: http://www. oxagen.co.uk/pdfs/CRTH2summary. pdf
23. Armer RE, Ashton MR, Boyd EA, et al. Indole-3-acetic acid antagonists of the prostaglandin D2 receptor CRTH2. J Med Chem 2005;48(20):6174-7
24. Oxagen Ltd. Microcrystalline (5-fluoro-2-methyl-3-quinolin-2-ylmethyl- indol-1-yl) acetic acid. WO2006092579; 2006
25. Stearns BA, Baccei C, Bain G, et al. Novel tricyclic antagonists of the prostaglandin D2 receptor DP2 with efficacy in a murine model of allergic rhinitis. Bioorg Med Chem Lett 2009;19(16):4647-51
26. Oxagen Ltd. Compounds having CRTH2 antagonist activity. WO2008012511; 2008
27. Pettipher R, Hansel TT. Antagonists of the prostaglandin D2 receptor CRTH2. Drug News Perspect 2008;21(6):317-322
28. Pettipher R. Role of CRTH2 in promoting Th2-mediated allergic responses New Drugs and Targets for Asthma and COPD, National Heart and Lung Institute, November 2008. Available from: (http://www.oxagen.co. uk/pdfs/ NHLI%20November%2020% 202008.pdf)
29. Oxagen Ltd. Novel CRTH2 antagonist shows potential in moderate persistent asthma: presented at ERS 18 September 2009. Available from: http://main.pslgroup.com/news/content.nsf/medicalnews/ 852576140048867A85257635005BC1C3?OpenDocument&id=&count=10
30. Oxagen OC000459 Dose Finding Study in patients with mild to moderate persistent asthma. NCT00890877
31. Fecher A, Pothier J, Gude M, et al. Novel Classes Of Crth2 Receptor Antagonists AFMC International Medicinal Chemistry Symposium 2008; XXth:September 02 (P227)
32. Actelion Pharmaceuticals Ltd. (3-Amino-1,2,3,4-tetrahydro-9h-carbazol-9- yl)-acetic acid derivatives. WO2008017989; 2008
33. Actelion Pharmaceuticals Ltd. Tetrahydropyridoindole derivatives. WO2005095397; 2009
34. Arimura A, Yasui K, Kishino J, et al. Prevention of allergic inflammation by a novel prostaglandin receptor antagonist, S-5751. J Pharmacol Exp Ther 2001;298(2):411-19
35. Arimura A. Discovery of a first-in-class drug, a prostaglandin D2 antagonist, for the treatment of allergic disease. In: Tamaki N, Kuge Y, editors, Molecular imaging for integrated medical therapy and drug development. Springer, Japan; 2010. p.281-7
36. Shionogi & Co., Ltd. Method for producing N-phenyl-N'- phenylsulfonylpiperazine derivative. WO-2008123349; 2008
37. Amira Pharmaceuticals, Inc. Antagonists of PGD2 receptors. WO2009061676; 2009
38. Amira Pharmaceuticals, Inc. Antagonists of prostaglandin D2 receptors. WO2009108720; 2009
39. Stebbins K, Broadhead AR, Baccei CS, et al. Pharmacological blockade of the DP2 receptor inhibits cigarette smoke-induced inflammation, mucus cell metaplasia and epithelial hyperplasia in the mouselLung. J Pharmacol Exp Ther 2010;332(3):764-75
40. Actimis Pharmaceuticals, Inc. Particulates of a CRTH2 antagonist. WO2008156780; 2008
41. Actimis Pharmaceuticals, Inc. Amine salts of a CRTH2 antagonist. WO2008156781; 2008
42. Actimis Pharmaceuticals, Inc. Pyrimidine derivatives useful for the treatment of diseases mediated by CRTH2. WO2004096777; 2004
43. Boehme SA, Franz-Bacon K, Chen EP, et al. A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation. Int Immunol 2009;21(1):81-93
44. Liu J, Fu Z, Wang Y, et al. Discovery and optimization of CRTH2 and DP dual antagonists. Bioorg Med Chem Lett 2009;19(22):6419-23
45. Amgen, Inc. Phenyl acetic acid derivatives as inflammation modulators. WO2009085177; 2009
46. Liu J, Wang Y, Sun Y, et al. Tetrahydroquinoline derivatives as CRTH2 antagonists. Bioorg Med Chem Lett 2009;19(24):6840-4
47. Ulven T, Kostenis E. Minor structural modifications convert the dual TP/CRTH2 antagonist ramatroban into a highly selective and potent CRTH2 antagonist. J Med Chem 2005;48(4):897-900
48. Mathiesen JM, Christopoulos A, Ulven T, et al. On the mechanism of interaction of potent surmountable and insurmountable antagonists with the prostaglandin D2 receptor CRTH2. Mol Pharmacol 2006;69(4):1441-53
49. Uller L, Mathiesen JM, Alenmyr L, et al. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation. Respir Res 2007;8:16
50. Grimstrup M, Rist O, Receveur JM, et al. Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2. Bioorg Med Chem Lett 2010;20(3):1181-5
51. Grimstrup M, Receveur JM, Rist O, et al. Exploration of SAR features by modifications of thiazoleacetic acids as CRTH2 antagonists. Bioorg Med Chem Lett 2010;20(5):1638-41
52. Argenta Discovery Ltd. Indolizine derivatives as ligands of the CRTH2 receptor. WO2007031747; 2007
53. Argenta Annual Report; 2008 sanofi-aventis. A new process for preparing 2-(3-{6-[2-(2,4-dichlorophenyl)-ethylamino]-2-methoxypyrimidin-4-yl}-phenyl) -2-methylpropionic acid. WO2009006086; 2009
54. Millennium Pharmaceuticals, Inc. PGD2 receptor antagonists for the treatment of inflammatory diseases. WO2006091674; 2006
55. Mimura H, Ikemura T, Kotera O, et al. Inhibitory effect of the 4-aminotetrahydroquinoline derivatives, selective chemoattractant receptor-homologous molecule expressed on T helper 2 cell antagonists, on eosinophil migration induced by prostaglandin D2. J Pharmacol Exp Ther 2005;314(1):244-51
56. Array Biopharma, Inc. 4-Heteroaryl-substituted phenoxyphenylacetic acid. WO2009061730; 2009
57. Eberhardt C, Wright D, Gomez A, et al. Identification and characterization of a potent and selective antagonist of the prostaglandin D2 receptor. Available from: http://www.arraybiopharma.com/-documents/Publication/ PubAttachment342.pdf
58. Shiraishi Y, Burgess LE, Takeda K, et al. PGD2 enhances and CRTH2 antagonism prevents early-and late-phase responses in allergic rhinitis. Available from: http://www.arraybiopharma.com/-documents/Publication/ PubAttachment345.pdf
59. Novartis AG. Use of pyrrolo[2,3-b] pyridines to prepare a medicament for treating pain. WO2007068418; 2007
60. Sandham DA, Aldcroft C, Baettig U, et al. 2-Cycloalkyl phenoxyacetic acid CRTh2 receptor antagonists. Bioorg Med Chem Lett 2007;17(15):4347-50
61. Sandham DA, Adcock C, Bala K, et al. 7-Azaindole-3-acetic acid derivatives: potent and selective CRTh2 receptor antagonists. Bioorg Med Chem Lett 2009;19(16):4794-8
62. Crosignani S, Page P, Missotten M, et al. Discovery of a new class of potent, selective, and orally bioavailable CRTH2 (DP2) receptor antagonists for the treatment of allergic inflammatory diseases. J Med Chem 2008;51(7):2227-43
63. Astellas Pharma, Inc. Carboxylic acid compound or salt thereof. WO2009096526; 2009
64. Abbott Laboratories. Thienopyrroles and pyrrolothiazoles as new therapeutic agents. WO2009102462; 2009
65. Ligand Pharmaceuticals, Inc. 2-Phenyl phenoxyacetic acids useful for treating inflammatory disorders. WO2009089192; 2009
66. Chemietek Llc. Heterocyclic compounds as CRTH2 receptor antagonists. WO2009049021; 2009
67. Icos Corp. Substituted phenyl acetic acids as DP-2 antagonists. WO2007143745; 2007
68. Merck Frosst Canada Ltd. Indole derivatives as CRTH2 receptor antagonists. WO2007019675; 2007
69. Tumey LN, Robarge MJ, Gleason E, et al. 3-Indolyl sultams as selective CRTh2 antagonists. Bioorg Med Chem Lett 2010;20(11):3287-90
70. Atherysys, Inc. Indole acetic acids exhibiting CRTH2 receptor antagonism and uses thereof. WO2006034419; 2006
71. Ly TW, Bacon KB. Small-molecule CRTH2 antagonists for the treatment of allergic inflammation: an overview. Expert Opin Investig Drugs 2005;14(7):769-73
72. Jones RL, Giembycz MA, Woodward DF. Prostanoid receptor antagonists: development strategies and therapeutic applications. Br J Pharmacol 2009;158(1):104-45