Design, synthesis, and biological evaluation of 3-(1-aryl-1 h -indol-5-yl)propanoic acids as new indole-based cytosolic phospholipase a2α inhibitors

Journal of Medicinal Chemistry

Volumn 57, Issue 17, 2014, Pages 7244-7262

  Tomoo, Toshiyuki ^a   Nakatsuka, Takashi ^a   Katayama, Toyoko ^b   Hayashi, Yasuhiro ^c   Fujieda, Yusuke ^d   Terakawa, Maki ^e   Nagahira, Kazuhiro ^e  

^a Faculty of Pharmaceutical Chemistry   (Japan)

^b RandD Administration   (Japan)

^c Exploratory Technology   (Japan)

^d Discovery Technology   (Finland)

^e DAIICHI SANKYO CO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

3 [1 (4 PHENOXYPHENYL) 3 (2 PHENYLETHYL) 1H INDOL 5 YL]PROPANOIC ACID TROMETHAMINE SALT; ANTIASTHMATIC AGENT; ANTIINFLAMMATORY AGENT; CYTOSOLIC PHOSPHOLIPASE A2; CYTOSOLIC PHOSPHOLIPASE A2ALPHA INHIBITOR; DEXAMETHASONE; INDOLE DERIVATIVE; OVALBUMIN; PHENYL GROUP; PHORBOL 13 ACETATE 12 MYRISTATE; PHOSPHOLIPASE A2 GROUP IV; PROPIONIC ACID; PROPIONIC ACID DERIVATIVE; UNCLASSIFIED DRUG; 3-(1-(4-PHENOXYPHENYL)-3-(2-PHENYLETHYL)-1H-INDOL-5-YL)PROPANOIC ACID; ENZYME INHIBITOR; INDOLE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; ASTHMA; BIOLOGICAL ACTIVITY; CELL ASSAY; CONTROLLED STUDY; DOG; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; EAR EDEMA; ENZYME ASSAY; ENZYME INHIBITION; FEMALE; GUINEA PIG; HAPLORHINI; HUMAN; IC50; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CHEMICAL MODEL; CHEMICAL STRUCTURE; CHEMICALLY INDUCED; CHEMISTRY; CYTOSOL; EDEMA; ENZYMOLOGY; METABOLIC CLEARANCE RATE; METABOLISM; SYNTHESIS; U937 CELL LINE;

ANIMALS; AREA UNDER CURVE; ASTHMA; CYTOSOL; DOGS; DRUG DESIGN; EDEMA; ENZYME INHIBITORS; FEMALE; GROUP IV PHOSPHOLIPASES A2; GUINEA PIGS; HAPLORHINI; HUMANS; INDOLES; MALE; METABOLIC CLEARANCE RATE; MICE; MICE, INBRED C57BL; MODELS, CHEMICAL; MOLECULAR STRUCTURE; OVALBUMIN; PROPIONATES; STRUCTURE-ACTIVITY RELATIONSHIP; TETRADECANOYLPHORBOL ACETATE; U937 CELLS;

EID: 84921457246     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500494y     Document Type: Article

References (83)

1. 2enzymes: classification and characterization Biochim. Biophys. Acta 2000, 1488, 1-19
2. 2enzymes: physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention Chem. Rev. 2011, 111, 6130-6185
3. 2+-dependent translocation domain with homology to PKC and GAP Cell 1991, 65, 1043-1051
4. 2J. Biol. Chem. 1991, 266, 14850-14853
5. 2enzymes on product-containing vesicles: application to the determination of substrate preferences Biochemistry 1993, 32, 5949-5958
6. 2with membrane in the macrophage cell line RAW 264.7 J. Biol. Chem. 1990, 265, 5409-5413
7. 2is a 100-kDa protein in human monoblast U937 cells J. Biol. Chem. 1991, 266, 5268-5272
8. 2is phosphorylated and activated by MAP kinase Cell 1993, 72, 269-278
9. 2C2 domain for interfacial activity J. Biol. Chem. 2003, 278, 23842-23850
10. 2via a novel site in the C2 domain J. Biol. Chem. 2007, 282, 20467-20474
11. Buczynski, M. W.; Dumlao, D. S.; Dennis, E. A. Thematic review series: proteomics. An integrated omics analysis of eicosanoid biology J. Lipid Res. 2009, 50, 1015-1038
12. Rouzer, C. A.; Marnett, L. J. Cyclooxygenases: structural and functional insights J. Lipid Res. 2009, 50, S29-S34
13. 2activity regulates the synthesis of platelet-activating factor in granulocytic HL-60 cells J. Biol. Chem. 1990, 265, 12363-12371
14. Theodorou, V.; Fioramonti, J.; Junien, J. L.; Bueno, L. Anaphylactic colonic hypersecretion in cow's milk sensitized guinea-pigs depends upon release of Interleukin-1, prostaglandins and mast cell degranulation Aliment. Pharmacol. Ther. 1994, 8, 301-307
15. Peters-Golden, M.; Henderson, W. R., Jr. The role of leukotrienes in allergic rhinitis Ann. Allergy Asthma Immunol. 2005, 94, 609-618
16. Hozawa, S.; Haruta, Y.; Ishioka, S.; Yamakido, M. Effects of a PAF antagonist, Y-24180, on bronchial hyperresponsiveness in patients with asthma Am. J. Respir. Crit. Care Med. 1995, 152, 1198-1202
17. Nagai, H. Prostaglandin as a target molecule for pharmacotherapy of allergic inflammatory diseases Allergol. Int. 2008, 57, 187-196
18. Nagase, T.; Ishii, S.; Kume, K.; Uozumi, N.; Izumi, T.; Ouchi, Y.; Shimizu, T. Platelet-activating factor mediates acid-induced lung injury in genetically engineered mice J. Clin. Invest. 1999, 104, 1071-1076
19. Rolin, S.; Masereel, B.; Dogne, J.-M. Prostanoids as pharmacological targets in COPD and asthma Eur. J. Pharmacol. 2006, 533, 89-100
20. 2plays a key role in the pathogenesis of multiple sclerosis-like disease Neuron 2004, 41, 323-335
21. 2superfamily in experimental autoimmune encephalomyelitis Brain 2009, 132, 1221-1235
22. Kihara, Y.; Ishii, S.; Kita, Y.; Toda, A.; Shimada, A.; Shimizu, T. Dual phase regulation of experimental allergic encephalomyelitis by platelet-activating factor J. Exp. Med. 2005, 202, 853-863
23. Hikiji, H.; Ishii, S.; Shindou, H.; Takato, T.; Shimizu, T. Absence of platelet-activating factor receptor protects mice from osteoporosis following ovariectomy J. Clin. Invest. 2004, 114, 85-93
24. 2in allergic response and parturition Nature 1997, 390, 618-622
25. 2α-deficient mice are resistant to collagen-induced arthritis J. Exp. Med. 2003, 197, 1297-1302
26. 2Nat. Immunol. 2000, 1, 42-46
27. 2in bleomycin-induced pulmonary fibrosis Nat. Med. 2002, 8, 480-484
28. Miyaura, C.; Inada, M.; Matsumoto, C.; Ohshiba, T.; Uozumi, N.; Shimizu, T.; Ito, A. An essential role of cytosolic phospholipase A2α in prostaglandin E2-mediated bone resorption associated with inflammation J. Exp. Med. 2003, 197, 1303-1310
29. 2α-deficient mice are resistant to experimental autoimmune encephalomyelitis J. Exp. Med. 2005, 202, 841-851
30. 2Nature 1997, 390, 622-625
31. 2-associated production of MMP-9 in macrophages and formation of atherosclerotic lesions Biol. Pharm. Bull. 2008, 31, 363-368
32. 2participates in the progression of hepatic fibrosis FASEB J. 2012, 26, 4111-4121
33. 2: biochemical properties and physiological roles IUBMB Life 2006, 58, 328-333
34. 2as a target for drug design Drugs Future 2000, 25, 823-832
35. 2inhibitors in inflammation Expert Opin. Ther. Patents 2001, 11, 1123-1136
36. 2inhibitors as potential therapeutic agents for the treatment of inflammatory diseases Expert Opin. Ther. Patents 2010, 20, 1-18
37. 2inhibitors for the treatment of inflammatory diseases: a patent review Expert Opin. Ther. Patents 2013, 23, 333-344
38. 2J. Am. Chem. Soc. 1996, 118, 5519-5525
39. 2: structure-function studies with vesicle, micelle, and membrane assays Biochim. Biophys. Acta 1999, 1420, 45-56
40. 2Biochemistry 1993, 32, 5935-5940
41. 2that acts at the lipid/water interface and possesses anti-inflammatory activity in skin inflammation models J. Pharmacol. Exp. Ther. 2001, 298, 376-385
42. 2J. Med. Chem. 2000, 43, 1041-1044
43. 2. Part 2: synthesis of potent and crystallized 4-triphenylmethylthio derivative 'pyrrophenone' Bioorg. Med. Chem. Lett. 2001, 11, 587-590
44. 2α, pyrrophenone Biochem. J. 2002, 363, 727-735
45. 2: variation of the substituents in positions 1, 3, and 5 J. Med. Chem. 1997, 40, 3381-3392
46. 2-mediated arachidonic acid release by several indole-2-carboxylic acids and 3-(pyrrol-2-yl)propionic acids in bovine and in human platelets Arch. Pharm. (Weinheim, Ger.) 2000, 333, 312-314
47. 2J. Med. Chem. 1997, 40, 2694-2705
48. 2Bioorg. Med. Chem. Lett. 2001, 11, 2569-2572
49. 2α J. Med. Chem. 2007, 50, 1380-1400
50. 2α inhibitors: discovery and in vitro and in vivo characterization of 4-{3-[5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1-(diphenylmethyl)-1 H -indol-3-yl]propyl}benzoic acid, efipladib J. Med. Chem. 2008, 51, 3388-3413
51. 2by novel 2-oxoamides in vitro, in cells, and in vivo J. Med. Chem. 2004, 47, 3615-3628
52. 2release J. Pharmacol. Exp. Ther. 2006, 316, 466-475
53. 2activity and cellular arachidonate release based on dipeptides and pseudodipeptides Bioorg. Med. Chem. 2009, 17, 4833-4843
54. 2based on a 1,3-disubstituted propan-2-one skeleton J. Med. Chem. 2002, 45, 1348-1362
55. 2α with reduced lipophilicity: synthesis, biological activity, metabolic stability, solubility, bioavailability, and topical in vivo activity J. Med. Chem. 2010, 53, 5165-5178
56. 2. PCT Int. Appl. WO 2006/128142, 2006.
57. Lamothe, J.; Lee, K.; Schelling, S.; Stedman, N.; Leach, M.; McKew, J.; Clark, J.; Nickerson-Nutter, C.; Hegen, M. Sa.29. Efficacy of giripladib, a novel inhibitor of cytosolic phospholipase A2α, in two different mouse models of rheumatoid arthritis Clin. Immunol 2008, 127 (Suppl) S89-S90
58. 2α inhibitors: substrate mimetics Bioorg. Med. Chem. Lett. 2003, 13, 4501-4504
59. 2α: effect of substituents in position 3 of the indole scaffold on inhibitory potency, metabolic stability, solubility, and bioavailability J. Med. Chem. 2010, 53, 8298-8308
60. Nagao, Y.; Hirata, T.; Goto, S.; Sano, S.; Kakehi, A.; Iizuka, K.; Shiro, M. Intramolecular nonbonded S···O interaction recognized in (acylimino)thiadiazoline derivatives as angiotensin II receptor antagonists and related compounds J. Am. Chem. Soc. 1998, 120, 3104-3110
61. Unangst, P. C.; Connor, D. T.; Stabler, S. R.; Weikert, R. J. Synthesis of novel 1-phenyl-1 H -indole-2-carboxylic acids. I. Utilization of Ullmann and Dieckmann reactions for the preparation of 3-hydroxy, 3-alkoxy, and 3-alkyl derivatives J. Heterocycl. Chem. 1987, 24, 811-815
62. Unangst, P. C.; Connor, D. T.; Stabler, S. R. Synthesis of novel 1-phenyl-1 H -indole-2-carboxylic acids. II. Preparation of 3-dialkylamino, 3-alkylthio, 3-alkylsulfinyl, and 3-alkylsulfonyl derivatives J. Heterocycl. Chem. 1987, 24, 817-820
63. Ketcha, D. M.; Gribble, G. W. A convenient synthesis of 3-acylindoles via Friedel Crafts acylation of 1-(phenylsulfonyl)indole. A new route to pyridocarbazole-5,11-quinones and ellipticine J. Org. Chem. 1985, 50, 5451-5457
64. Comins, D. L.; Stroud, E. D. Synthesis of 3-substituted indoles via N-acylindolium ions Tetrahedron Lett. 1986, 27, 1869-1872
65. 1Dreceptors Eur. J. Med. Chem. 1997, 32, 129-134
66. Huang, M. A simple modification of the Wolff-Kishner reduction J. Am. Chem. Soc. 1946, 68, 2487-2488
67. Demko, Z. P.; Sharpless, K. B. Preparation of 5-substituted 1 H -tetrazoles from nitriles in water J. Org. Chem. 2001, 66, 7945-7950
68. Boivin, J.; El Kaim, L.; Zard, S. Z. A new and efficient synthesis of trifluoromethyl ketones from carboxylic acids. part I Tetrahedron 1995, 51, 2573-2584
69. Kikugawa, Y.; Miyake, Y.; Kawase, M. Methoxylation of bromo-1,2,3,4-tetrahydrocarbazoles. Oxidation and subsequent rearrangement of 1,2,3,4-tetrahydrocarbazoles to spiro-(cyclopentane-1,2′-indolin)-3′-ones Chem. Pharm. Bull. 1981, 29, 1231-1236
70. Schmidt, U.; Lieberknecht, A.; Griesser, H.; Talbiersky, J. Synthesis of peptide alkaloids. 5. New method for synthesis of ansa peptides. Amino acids and peptides. 34 J. Org. Chem. 1982, 47, 3261-3264
71. Katritzky, A. R.; Suzuki, K.; Singh, S. K.; He, H.-Y. Regiospecific C-acylation of pyrroles and indoles using N -acylbenzotriazoles J. Org. Chem. 2003, 68, 5720-5723
72. 2) bond formation: N -Arylation of aromatic and unsaturated nitrogen and the reductive elimination chemistry of palladium azolyl and methyleneamido complexes J. Am. Chem. Soc. 1998, 120, 827-828
73. Old, D. W.; Harris, M. C.; Buchwald, S. L. Efficient palladium-catalyzed N -arylation of indoles Org. Lett. 2000, 2, 1403-1406
74. 2J. Biol. Chem. 1994, 269, 23250-23254
75. 2reveals a novel topology and catalytic mechanism Cell 1999, 97, 349-360
76. 2determined by molecular dynamics and deuterium exchange mass spectrometry J. Am. Chem. Soc. 2009, 131, 8083-8091
77. Griffiths, R. J.; Wood, B. E.; Li, S.; Blackham, A. Pharmacological modification of 12- O -tetradecanoylphorbol-13-acetate induced inflammation and epidermal cell proliferation in mouse skin Agents Actions 1988, 25, 344-351
78. Qian, C.; Hwang, S.-B.; Libertine-Garahan, L.; Eckman, J. B.; Cai, X.; Scannell, R. T.; Yeh, C. G. Anti-inflammatory activities of LDP-392, a dual PAF receptor antagonist and 5-lipoxygenase inhibitor Pharmacol. Res. 2001, 44, 213-220
79. Pepys, J.; Hutchcroft, B. J. Bronchial provocation tests in etiologic diagnosis and analysis of asthma Am. Rev. Respir. Dis. 1975, 112, 829-859
80. Orehek, J.; Gayrard, P.; Smith, A. P.; Grimaud, C.; Charpin, J. Airway response to carbachol in normal and asthmatic subjects: distinction between bronchial sensitivity and reactivity Am. Rev. Respir. Dis. 1977, 115, 937-943
81. 2, cyclooxygenases, and terminal prostanoid synthases in different phases of prostanoid biosynthesis in rat peritoneal macrophages J. Immunol. 1998, 160, 2974-2982
82. Dole, V. P.; Meinertz, H. Microdetermination of long-chain fatty acids in plasma and tissues J. Biol. Chem. 1960, 235, 2595-2599
83. 2inhibitor: A new class of anti-inflammatory drugs, SPI J. Pharmacol. Exp. Ther. 1999, 288, 1117-1124