Inhibition of FcεRI-mediated activation of mast cells by 2,3,4- trihydropyrimidino[2,1-α]isoquinolines

Journal of Medicinal Chemistry

Volumn 41, Issue 7, 1998, Pages 1050-1059

  Scholz, Dieter ^a   Schmidt, Hannelore ^a   Prieschl, Eva E ^a   Csonga, Robert ^a   Scheirer, Winfried ^a   Weber, Virginia ^a   Lembachner, Anna ^a   Seidl, Gunther ^a   Werner, Gudrun ^a   Mayer, Peter ^a   Baumruker, Thomas ^a  

^a Novartis Forschungsinstitut GmbH   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

2,3,4 TRIHYDROPYRIMIDINO[2,1A]ISOQUINOLINE DERIVATIVE; 6 [4 (TRIMETHYLSILYL)PHENYL] 3,4 DIHYDRO 2H PYRIMIDO[2,1A]ISOQUINOLINE; 7 BUTYL 6 (4 PHENETHYLPHENYL) 3,4 DIHYDRO 2H [2,1A]ISOQUINOLINE; BETA N ACETYLHEXOSAMINIDASE; FC RECEPTOR; IMMUNOGLOBULIN E; INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 6; KETAMINE; LEUKOTRIENE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; XYLAZINE; CYTOKINE; ISOQUINOLINE DERIVATIVE; PYRIMIDINE DERIVATIVE;

ALLERGIC ASTHMA; ALLERGIC CONJUNCTIVITIS; ALLERGIC RHINITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARACHIDONIC ACID METABOLISM; ARTICLE; CELL ACTIVATION; CONTROLLED STUDY; DRUG DETERMINATION; DRUG SYNTHESIS; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; HUMAN; HUMAN CELL; IMMEDIATE TYPE HYPERSENSITIVITY; INTRADERMAL DRUG ADMINISTRATION; MAST CELL; MAST CELL DEGRANULATION; MOUSE; NONHUMAN; REPORTER GENE; SKIN ANAPHYLAXIS; URTICARIA; ANIMAL; CELL LINE; DRUG EFFECT; METABOLISM; SYNTHESIS;

ANIMALS; CELL LINE; CYTOKINES; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; GENES, REPORTER; ISOQUINOLINES; LEUKOTRIENES; MAST CELLS; MICE; PYRIMIDINES;

EID: 15444361105     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9706628     Document Type: Article

References (30)

1. Mygind, N.; Dahl, R.; Pedersen, S. In Essential Allergy, 2nd ed.; Mygind, N., Ed.; Blackwell Science Ltd.: Oxford, 1996; pp 3-433.
2. Burd, P. R.; Rogers, H. W.; Gordon, J. R.; Martin, C. A.; Jayaraman, S.; Wilson, S. D.; Dvorak, A. M.; Galli, S. J.; Dorf, M. E. Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines. J. Exp. Med. 1989, 770, 245-257.
3. Lewis, R. A.; Austen, K. F.; Soberman, R. J. Leukotrienes and other products of the 5-lipoxygenase pathway -biochemistry and relation to pathobiology in human diseases. N. Engl. J. Med. 1990, 323, 645-655.
4. Kulmburg, P. A.; Huber, N. E.; Scheer, B. J.; Wrann, M.; Baumruker, T. Immunoglobulin E plus antigen challenge induces a novel intercrine/chemokine in mouse mast cells. J. Exp. Med. 1992, 176, 1773-1778.
5. Corne, J.; Djukanovic, R.; Thomas, L.; Warner, J.; Botta, L.; Grandordy, B.; Gygax, D.; Heusser, C.; Patalano, F.; Richardson, W.; Kilchherr, E.; Staehelin, T.; Davis, F.; Gordon, W.; Sun, L.; Liou, R.; Wang, G.; Chang, T. W.; Holgate, S. The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics. J. Clin. Invest. 1997, 99, 879-887.
6. Emmel, E. A.; Verweij, C. L.; Durand, D. B.; Higgins, K. M.; Lacy, E.; Crabtree, G. R. Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell Activation. Science 1989, 246, 1617-1620.
7. Schreiber, S. L.; Crabtree, G. R. The mechanism of action of cyclosporin A and FK506. Immunol. Today 1992, 13, 136-142.
8. Jarmin, D. I.; Kulmburg, P. A.; Huber, N. E.; Baumann, G.; Prieschl-Strassmayr, E. E.; Baumruker, T. A transcription factor with AP3-like binding specificity mediates gene regulation after an allergic triggering with IgE and antigen in mouse mast cells. J. Immunol. 1994, 153, 5720-5729.
9. Prieschl, E. E.; Pendl, G. G.; Elbe, A.; Serfling, E.; Harrer, N. E.; Stingl, G.; Baumruker, T. Induction of the TNFα promoter in the murine dendritic cell line DC18 and the murine mast cell line CPU is differently regulated. J. Immunol. 1996, 157, 2645-2653.
10. Galli, S. J. New insights into "the riddle of the mast cells": microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab. Invest. 1990, 62, 5-33.
11. Houlihan, W. J.; Cheon, S. H.; Parrino, V. A.; Handley, D. A.; Larson, D. A. Structural modification of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinoline platelet activating factor receptor antagonists. J. Med. Chem. 1993, 36 (6), 3098-3102.
12. Brombacher, F.; Schafer, T.; Weissenstein, U.; Tschopp, C.; Andersen, E.; Burki, K.; Baumann, G. IL-2 promoter-driven lacZ expression as a monitoring tool for IL-2 expression in primary T cells of transgenic mice. Int. Immunol. 1994, 6, 189-197.
13. Prieschl, E. E.; Novotny, V.; Csonga, R.; Jaksche, D.; Elbe-Bürger, A.; Thumb, W.; Auer, M.; Stingl, G.; Baumruker, T. Unpublished results.
14. Fruman, D. A.; Wood, M. A.; Gjertson, C. K.; Katz, H. R.; Burakoff, S. J.; Bierer, B. E. FK506 binding protein 12 mediates sensitivity to both FK506 and rapamycin in murine mast cells. Eur. J. Immunol. 1995, 25, 563-571.
15. Pendl, G. G.; Prieschl, E. E.; Harrer, N. E.; Baumruker, T. Effects of phosphatidylinositol-3-kinase inhibitors on degranulation and gene induction of allergically triggered mouse mast cells. Int. Arch. Allergy Immunol. 1997, 112, 392-399.
16. ras links FcεRI to NF-AT family member in mast cells. The AP3-like factor in this cell type is an NF-AT family member. J. Immunol 1995, 155, 4963-4970.
17. Csonga, R.; Prieschl, E. E.; Baumruker, T. Common and distinct signaling pathways mediate the induction of TNFα and IL-5 in IgE plas antigen stimulated mast cells. J. Immunol. 1998, in press.
18. Paolini, R.; Jouvin, M. H.; Kinet, J. P. Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engagement and disengagement. Nature 1991, 353, 855-858.
19. Lin, S.; Cicala, C.; Scharenberg, A. M.; Kinet, J. P. The Fc (epsilon) RI beta subunit functions as an amplifier of Fc (epsilon) RI gamma-mediated cell activation signals. Cell 1996, 85, 985-995.
20. Scharenberg, A. M.; Lin, S.; Cuenod, B.; Yamamura, H.; Kinet, J. P. Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering. EMBO J. 1995, 14, 3385-3394.
21. Jouvin, M. E.; Adamczewski, M.; Numerof, R.; Letourneur, O.; Valle, A.; Kinet, J. Differential control of the tyrosine kinases lyn and syk by two signaling chains of the high affinity immunoglobulin E receptor. J. Biol. Chem. 1994, 269, 5918-5925.
22. Jabril Cuenod, B.; Zhang, C.; Scharenberg, A. M.; Paolini, R.; Numerof, R.; Beaven, M. A.; Kinet, J. P. Syk-dependent phosphorylation of She. A potential link between FcepsilonRI and ' the Ras/mitogen-activated protein kinase signaling pathway through SOS and Grb2. J. Biol. Chem. 1996, 271, 16268-16272.
23. Shiue, L.; Green, J.; Green, O. M.; Karas, J. L.; Morgenstern, J. P.; Ram, M. K.; Taylor, M. K.; Zoller, M. J.; Zydowsky, L. D.; Bolen, J. B.; Brugge, J. S. Interaction of p72syk with the gamma and beta subunits of the high-affinity receptor for immunoglobulin E, Fc epsilon RI. Mol. Cell Biol 1995, 15, 272-281.
24. Millard, P. J.; Ryand, T. A.; Webb, W. W.; Fewtrell, C. Immunoglobulin E receptor cross-linking induces oscillations in intracellular free ionized calcium in individual tumor mast cells. J. Biol. Chem. 1989, 264, 19730-19739.
25. Matthews, G.; Neher, E.; Penner, R. Second messenger-activated calcium influx in rat peritonel mast cells. J. Physiol 1989, 418, 105-130.
26. Choi, O. H.; Kim, J. H,; Kinet, J. P. Calcium mobilization via sphingosine kinase in signaling by the Fc epsilon RI antigen receptor. Nature 1996, 380, 634-636.
27. Johannes, F. J.; Prestle, J.; Eis, S.; Oberhagemann, P.; Pfizenmaier, K. PKCμ is a novel, atypical member of the protein kinase C family. J. Biol. Chem. 1994, 269, 6140-6148.
28. Houlihan, W. J.; Munder, P. G.; Handley, D. A.; Cheon, S. H.; Parriono, V. A. Antitumor activity of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinolines. J. Med. Chem. 1995, 38, 234-240 and citations therein.
29. Houlihan, W. J.; Parrino, V. A. Directed lithiation of 2-phenyland 2-(o-methylphenyl)imidazole. J. Org. Chem. 1982,47, 5177-5180.
30. Houlihan, W. J.; Gogerty, J. H.; Parrino, V. A.; Ryan, E. Antidepressant activity of 5-aryl-2,3,5,6-tetrahydroimidazo[2,1-a]isoquinolin-5-ols. J. Med. Chem. 1983, 26, 765-768.