Title:
2,4,6,7-TETRAHYDRO-PYRAZOLO[4,3-D]PYRIMIDIN-5-ONE DERIVATIVES AND RELATED COMPOUNDS AS C5A RECEPTOR MODULATORS FOR TREATING VASCULITIS AND INFLAMMATORY DISEASES
Document Type and Number:
WIPO Patent Application WO/2019/137927
Kind Code:
A1
Abstract:
The present invention relates to derivatives of formula (I) wherein Ring A, X, Y, Z, RA, R1, R2, R3 and R4 are The present invention discloses derivatives of formula (I), wherein Ring A, X, Y, Z, RA, R1, R2, R3 and R4 are as described in the description, and in particular e.g. 2,4,6,7-tetrahydro-pyrazolo[4,3- d]pyrimidin-5-one derivatives and related compounds, their preparation, pharmaceutically acceptable salts thereof, their use as pharmaceuticals, pharmaceutical compositions containing one or more compounds of formula (I), and especially their use as C5a receptor modulators for treating e.g. vasculitis and inflammatory diseases.
Inventors:
FROIDEVAUX SYLVIE (CH)
HUBLER FRANCIS (CH)
MURPHY MARK (CH)
RENNEBERG DORTE (CH)
STAMM SIMON (CH)
HUBLER FRANCIS (CH)
MURPHY MARK (CH)
RENNEBERG DORTE (CH)
STAMM SIMON (CH)
Application Number:
PCT/EP2019/050372
Publication Date:
July 18, 2019
Filing Date:
January 09, 2019
Export Citation:
Assignee:
IDORSIA PHARMACEUTICALS LTD (CH)
International Classes:
C07D487/04; A61K31/519; A61P9/00; A61P9/10; A61P9/14
Domestic Patent References:
| WO2006042102A2 | 2006-04-20 | |||
| WO2014134426A1 | 2014-09-04 | |||
| WO2015033299A1 | 2015-03-12 | |||
| WO2015044900A1 | 2015-04-02 | |||
| WO2015034820A1 | 2015-03-12 |
Other References:
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RICKLIN, D. ET AL., NAT IMMUNOL, vol. 11, no. 9, 2010, pages 785 - 797
CHARLES J. ET AL., SEMIN NEPHROL, vol. 33, no. 6, 2013, pages 557 - 564
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KALLENBERG, C. G.; P. HEERINGA, MOL IMMUNOL, vol. 68, no. 1, 2015, pages 53 - 56
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HOWARD, R. J. ET AL., ARCH SURG, vol. 123, no. 12, 1988, pages 1496 - 1501
KIRKLIN, J. K. ET AL., J THORAC CARDIOVASC SURG, vol. 86, no. 6, 1983, pages 845 - 857
CRADDOCK, P. R. ET AL., J CLIN INVEST, vol. 60, no. 1, 1977, pages 260 - 264
CRADDOCK, P. R. ET AL., N ENGL J MED, vol. 296, no. 14, 1977, pages 769 - 774
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WONG EK; KAVANAGH D, TRANSL RES, vol. 165, no. 2, 2015, pages 306 - 20
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DE HOOG, V. C. ET AL., CARDIOVASC RES, vol. 103, no. 4, 2014, pages 521 - 529
BLESS, N. M. ET AL., AM J PHYSIOL, vol. 276, no. 1, 1999, pages L57 - 63
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HEIDEMAN, M.; T. E. HUGLI, J TRAUMA, vol. 24, no. 12, 1984, pages 1038 - 1043
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STEVENS, J. H. ET AL., J CLIN INVEST, vol. 77, no. 6, 1986, pages 1812 - 1816
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MULLIGAN, M. S. ET AL., J CLIN INVEST, vol. 98, no. 2, 1996, pages 503 - 512
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HOESEL, L. M. ET AL., J IMMUNOL, vol. 178, no. 12, 2007, pages 7902 - 7910
YUAN, G. ET AL., CHIN MED J (ENGL, vol. 116, no. 9, 2003, pages 1408 - 1412
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LI, L. ET AL., METABOLISM, vol. 64, no. 5, 2015, pages 597 - 610
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ZHANG ET AL., CLIN J AM SOC NEPHROL, vol. 9, 2014, pages 1876 - 1882
STAAB, E. B. ET AL., INT IMMUNOPHARMACOL, vol. 21, no. 2, 2014, pages 293 - 300
HEIMBACH, L. ET AL., J BIOL CHEM, vol. 286, no. 17, 2011, pages 15003 - 15009
GAMMON, W. R., IMMUNOL SER, vol. 46, 1989, pages 509 - 525
CAO, Q. ET AL., AM J PHYSIOL CELL PHYSIOL, vol. 302, no. 12, 2012, pages C1731 - 1740
JOHSWICH, K. ET AL., INFLAMM BOWEL DIS, vol. 15, no. 12, 2009, pages 1812 - 1823
WOODRUFF, T. M. ET AL., J IMMUNOL, vol. 171, no. 10, 2003, pages 5514 - 5520
JAIN, U. ET AL., BR J PHARMACOL, vol. 168, no. 2, 2013, pages 488 - 501
O'BARR, S. A. ET AL., J IMMUNOL, vol. 166, no. 6, 2001, pages 4154 - 4162
GASQUE, P. ET AL., AM J PATHOL, vol. 150, no. 1, 1997, pages 31 - 41
MANTOVANI, S. ET AL., J NEUROIMMUNOL, vol. 276, no. 1-2, 2014, pages 213 - 218
HUMAYUN, S. ET AL., J NEUROIMMUNOL, vol. 210, no. 1-2, 2009, pages 52 - 62
WOODRUFF, T. M. ET AL., J IMMUNOL, vol. 181, no. 12, 2008, pages 8727 - 8734
FONSECA, M. I. ET AL., J NEUROINFLAMMATION, vol. 10, 2013, pages 25
AGER, R. R. ET AL., J NEUROCHEM, vol. 113, no. 2, 2010, pages 389 - 401
WANG, X. J. ET AL., NEUROCHEM INT, vol. 50, no. 1, 2007, pages 39 - 50
SINGHRAO ET AL., EXPERIMENTAL NEUROLOGY, vol. 159, 1999, pages 362 - 376
HARTUNG, H. P. ET AL., NEUROLOGY, vol. 37, no. 6, 1987, pages 1006 - 1009
WAKERLEY, B. R.; N. YUKI, EXPERT REV NEUROTHER, vol. 15, no. 8, 2015, pages 847 - 849
HALSTEAD, S. K. ET AL., BRAIN, vol. 131, 2008, pages 1197 - 1208
BASTA, M.; D. R. BRANCH, CLIN EXP IMMUNOL, vol. 178, no. 1, 2014, pages 87 - 88
ZWIRNER, J. ET AL., MOL IMMUNOL, vol. 36, no. 13-14, 1999, pages 877 - 884
JACOB, A.; B. HACK ET AL., J NEUROIMMUNOL, vol. 221, no. 1-2, 2010, pages 46 - 52
LAWLEY, T. J. ET AL., J IMMUNOL, vol. 123, no. 3, 1979, pages 1382 - 1387
KARSTEN, C. M.; J. KOHL, IMMUNOBIOLOGY, vol. 217, no. 11, 2012, pages 1067 - 1079
STRACHAN, A. J. ET AL., J IMMUNOL, vol. 164, no. 12, 2000, pages 6560 - 6565
KOHL, J.; J. E. GESSNER, MOL IMMUNOL, vol. 36, no. 13-14, 1999, pages 893 - 903
BAUMANN, U. ET AL., J IMMUNOL, vol. 164, no. 2, 2000, pages 1065 - 1070
JOSE, P. J. ET AL., ANN RHEUM DIS, vol. 49, no. 10, 1990, pages 747 - 752
GRANT, E. P. ET AL., J EXP MED, vol. 196, no. 11, 2002, pages 1461 - 1471
PORCEL, J. M. ET AL., CLIN IMMUNOL IMMUNOPATHOL, vol. 74, no. 3, 1995, pages 283 - 288
PAWARIA, S. ET AL., J IMMUNOL, vol. 193, no. 7, 2014, pages 3288 - 3295
LIU, L. ET AL., J CLIN IMMUNOL, vol. 34, no. 2, 2014, pages 224 - 232
FIEBIGER, E. ET AL., J CLIN INVEST, vol. 101, no. 1, 1998, pages 243 - 251
SPROTT, H. ET AL., J RHEUMATOL, vol. 27, no. 2, 2000, pages 402 - 404
MA, R. ET AL., J CLIN IMMUNOL, vol. 33, no. 1, 2013, pages 172 - 178
SONG, D. ET AL., AM J REPROD IMMUNOL, vol. 74, no. 4, 2015, pages 345 - 356
DAVIN, J. C.; N. C. VAN DE KAR, THER ADV HEMATOL, vol. 6, no. 4, 2015, pages 171 - 185
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DANG, L. ET AL., MOL MED REP, vol. 11, no. 6, 2015, pages 4183 - 4189
KAPLAN, A. P., J ALLERGY CLIN IMMUNOL, vol. 114, no. 3, 2004, pages 465 - 474
YAN, S. ET AL., J DERMATOL SCI, vol. 76, no. 3, 2014, pages 240 - 245
DIANI, M.; G. ALTOMARE; E. REALI, AUTOIMMUN REV, vol. 14, no. 4, 2015, pages 286 - 292
NATAF, S. ET AL., J IMMUNOL, vol. 162, no. 7, 1999, pages 4018 - 4023
TSUJI, R. F. ET AL., J IMMUNOL, vol. 165, no. 3, 2000, pages 1588 - 1598
WERFEL, T. ET AL., ARCH DERMATOL RES, vol. 289, no. 2, 1997, pages 83 - 86
MROWIETZ, U. ET AL., EXP DERMATOL, vol. 10, no. 4, 2001, pages 238 - 245
HOWELL ET AL., J. CLIN. INVEST., vol. 121, no. 4, 2011, pages 1429 - 1444
ZAH H. ET AL., ONCOIMMUNOLOGY, vol. 6, no. 10, 2017, pages e1349587
WANG Y. ET AL., CANCER DISCOVERY, vol. 6, no. 9, 2016, pages 1022 - 1035
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T.W. GREENE; P.G.M. WUTS: "Protective Groups in Organic Synthesis", 1999, WILEY-INTERSCIENCE
GUO, R. F.; P. A. WARD, ANNU REV IMMUNOL, vol. 23, 2005, pages 821 - 852
N.S. MERLE ET AL.: "Complement System Part II: Role in Immunity", FRONT IMMUNOL, vol. 6, 2015, pages 257
KENNETH MURPHY: "Janeway's Immunobiology", 2012, GARLAND SCIENCE, pages: 48 - 72
RICKLIN, D. ET AL., NAT IMMUNOL, vol. 11, no. 9, 2010, pages 785 - 797
CHARLES J. ET AL., SEMIN NEPHROL, vol. 33, no. 6, 2013, pages 557 - 564
"Vasculitis", 2008, OXFORD UNIVERSITY PRESS, pages: 47 - 53
HUANG, Y. M. ET AL., ARTHRITIS RHEUMATOL, vol. 67, no. 10, 2015, pages 2780 - 2790
KALLENBERG, C. G.; P. HEERINGA, MOL IMMUNOL, vol. 68, no. 1, 2015, pages 53 - 56
XIAO, H. ET AL., J AM SOC NEPHROL, vol. 25, no. 2, 2014, pages 225 - 231
HOWARD, R. J. ET AL., ARCH SURG, vol. 123, no. 12, 1988, pages 1496 - 1501
KIRKLIN, J. K. ET AL., J THORAC CARDIOVASC SURG, vol. 86, no. 6, 1983, pages 845 - 857
CRADDOCK, P. R. ET AL., J CLIN INVEST, vol. 60, no. 1, 1977, pages 260 - 264
CRADDOCK, P. R. ET AL., N ENGL J MED, vol. 296, no. 14, 1977, pages 769 - 774
ZECHER, D. ET AL., ARTERIOSCLER THROMB VASC BIOL, vol. 34, no. 2, 2014, pages 313 - 320
WONG EK; KAVANAGH D, TRANSL RES, vol. 165, no. 2, 2015, pages 306 - 20
WEISMAN, H. F., T. ET AL., SCIENCE, vol. 249, no. 4965, 1990, pages 146 - 151
DE HOOG, V. C. ET AL., CARDIOVASC RES, vol. 103, no. 4, 2014, pages 521 - 529
BLESS, N. M. ET AL., AM J PHYSIOL, vol. 276, no. 1, 1999, pages L57 - 63
AMSTERDAM, E. A. ET AL., AM J PHYSIOL, vol. 268, no. 1, 1995, pages H448 - 457
RILEY, R. D. ET AL., J THORAC CARDIOVASC SURG, vol. 120, no. 2, 2000, pages 350 - 358
FARRAR, C. A.; S. H. SACKS, CURR OPIN ORGAN TRANSPLANT, vol. 19, no. 1, 2014, pages 8 - 13
MUELLER, M. ET AL., IMMUNOBIOLOGY, vol. 218, no. 9, 2013, pages 1131 - 1138
DISTELMAIER, K. ET AL., THROMB HAEMOST, vol. 102, no. 3, 2009, pages 564 - 572
MAVROIDIS, M. ET AL., BASIC RES CARDIOL, vol. 110, no. 3, 2015, pages 27
PANDEY ET AL., NATURE, vol. 543, 2017, pages 108 - 112
SARMA, J. V.; P. A. WARD, CELL HEALTH CYTOSKELET, vol. 4, 2012, pages 73 - 82
CZERMAK, B. J. ET AL., J LEUKOC BIOL, vol. 64, no. 1, 1998, pages 40 - 48
TOFUKUJI, M. ET AL., J THORAC CARDIOVASC SURG, vol. 116, no. 6, 1998, pages 1060 - 1068
HAMMERSCHMIDT, D. E. ET AL., LANCET, vol. 1, no. 8175, 1980, pages 947 - 949
MARC, M. M. ET AL., AM J RESPIR CELL MOL BIOL, vol. 31, no. 2, 2004, pages 216 - 219
HUBER-LANG, M. ET AL.: "Role of C5a in multiorgan failure during sepsis", J IMMUNOL, vol. 166, no. 2, 2001, pages 1193 - 1199
HEIDEMAN, M.; T. E. HUGLI, J TRAUMA, vol. 24, no. 12, 1984, pages 1038 - 1043
SMEDEGARD, G. ET AL., AM J PATHOL, vol. 135, no. 3, 1989, pages 489 - 497
UNNEWEHR, H. ET AL., J IMMUNOL, vol. 190, no. 8, 2013, pages 4215 - 4225
HOPKEN, U. ET AL., EUR J IMMUNOL, vol. 26, no. 5, 1996, pages 1103 - 1109
STEVENS, J. H. ET AL., J CLIN INVEST, vol. 77, no. 6, 1986, pages 1812 - 1816
CZERMAK, B. J. ET AL., NAT MED, vol. 5, no. 7, 1999, pages 788 - 792
GUO, R. F. ET AL., J CLIN INVEST, vol. 106, no. 10, 2000, pages 1271 - 1280
MULLIGAN, M. S. ET AL., J CLIN INVEST, vol. 98, no. 2, 1996, pages 503 - 512
BOZIC, C. R. ET AL., SCIENCE, vol. 273, no. 5282, 1996, pages 1722 - 1725
HOESEL, L. M. ET AL., J IMMUNOL, vol. 178, no. 12, 2007, pages 7902 - 7910
YUAN, G. ET AL., CHIN MED J (ENGL, vol. 116, no. 9, 2003, pages 1408 - 1412
PANDEY, M. K., CURR ALLERGY ASTHMA REP, vol. 13, no. 6, 2013, pages 596 - 606
LI, L. ET AL., METABOLISM, vol. 64, no. 5, 2015, pages 597 - 610
CHENG, L. ET AL., INVEST OPHTHALMOL VIS SCI, vol. 54, no. 13, 2013, pages 8191 - 8198
BAO, L. ET AL., EUR J IMMUNOL, vol. 35, no. 8, 2005, pages 2496 - 2506
ZHANG ET AL., CLIN J AM SOC NEPHROL, vol. 9, 2014, pages 1876 - 1882
STAAB, E. B. ET AL., INT IMMUNOPHARMACOL, vol. 21, no. 2, 2014, pages 293 - 300
HEIMBACH, L. ET AL., J BIOL CHEM, vol. 286, no. 17, 2011, pages 15003 - 15009
GAMMON, W. R., IMMUNOL SER, vol. 46, 1989, pages 509 - 525
CAO, Q. ET AL., AM J PHYSIOL CELL PHYSIOL, vol. 302, no. 12, 2012, pages C1731 - 1740
JOHSWICH, K. ET AL., INFLAMM BOWEL DIS, vol. 15, no. 12, 2009, pages 1812 - 1823
WOODRUFF, T. M. ET AL., J IMMUNOL, vol. 171, no. 10, 2003, pages 5514 - 5520
JAIN, U. ET AL., BR J PHARMACOL, vol. 168, no. 2, 2013, pages 488 - 501
O'BARR, S. A. ET AL., J IMMUNOL, vol. 166, no. 6, 2001, pages 4154 - 4162
GASQUE, P. ET AL., AM J PATHOL, vol. 150, no. 1, 1997, pages 31 - 41
MANTOVANI, S. ET AL., J NEUROIMMUNOL, vol. 276, no. 1-2, 2014, pages 213 - 218
HUMAYUN, S. ET AL., J NEUROIMMUNOL, vol. 210, no. 1-2, 2009, pages 52 - 62
WOODRUFF, T. M. ET AL., J IMMUNOL, vol. 181, no. 12, 2008, pages 8727 - 8734
FONSECA, M. I. ET AL., J NEUROINFLAMMATION, vol. 10, 2013, pages 25
AGER, R. R. ET AL., J NEUROCHEM, vol. 113, no. 2, 2010, pages 389 - 401
WANG, X. J. ET AL., NEUROCHEM INT, vol. 50, no. 1, 2007, pages 39 - 50
SINGHRAO ET AL., EXPERIMENTAL NEUROLOGY, vol. 159, 1999, pages 362 - 376
HARTUNG, H. P. ET AL., NEUROLOGY, vol. 37, no. 6, 1987, pages 1006 - 1009
WAKERLEY, B. R.; N. YUKI, EXPERT REV NEUROTHER, vol. 15, no. 8, 2015, pages 847 - 849
HALSTEAD, S. K. ET AL., BRAIN, vol. 131, 2008, pages 1197 - 1208
BASTA, M.; D. R. BRANCH, CLIN EXP IMMUNOL, vol. 178, no. 1, 2014, pages 87 - 88
ZWIRNER, J. ET AL., MOL IMMUNOL, vol. 36, no. 13-14, 1999, pages 877 - 884
JACOB, A.; B. HACK ET AL., J NEUROIMMUNOL, vol. 221, no. 1-2, 2010, pages 46 - 52
LAWLEY, T. J. ET AL., J IMMUNOL, vol. 123, no. 3, 1979, pages 1382 - 1387
KARSTEN, C. M.; J. KOHL, IMMUNOBIOLOGY, vol. 217, no. 11, 2012, pages 1067 - 1079
STRACHAN, A. J. ET AL., J IMMUNOL, vol. 164, no. 12, 2000, pages 6560 - 6565
KOHL, J.; J. E. GESSNER, MOL IMMUNOL, vol. 36, no. 13-14, 1999, pages 893 - 903
BAUMANN, U. ET AL., J IMMUNOL, vol. 164, no. 2, 2000, pages 1065 - 1070
JOSE, P. J. ET AL., ANN RHEUM DIS, vol. 49, no. 10, 1990, pages 747 - 752
GRANT, E. P. ET AL., J EXP MED, vol. 196, no. 11, 2002, pages 1461 - 1471
PORCEL, J. M. ET AL., CLIN IMMUNOL IMMUNOPATHOL, vol. 74, no. 3, 1995, pages 283 - 288
PAWARIA, S. ET AL., J IMMUNOL, vol. 193, no. 7, 2014, pages 3288 - 3295
LIU, L. ET AL., J CLIN IMMUNOL, vol. 34, no. 2, 2014, pages 224 - 232
FIEBIGER, E. ET AL., J CLIN INVEST, vol. 101, no. 1, 1998, pages 243 - 251
SPROTT, H. ET AL., J RHEUMATOL, vol. 27, no. 2, 2000, pages 402 - 404
MA, R. ET AL., J CLIN IMMUNOL, vol. 33, no. 1, 2013, pages 172 - 178
SONG, D. ET AL., AM J REPROD IMMUNOL, vol. 74, no. 4, 2015, pages 345 - 356
DAVIN, J. C.; N. C. VAN DE KAR, THER ADV HEMATOL, vol. 6, no. 4, 2015, pages 171 - 185
NEUBER, K., R. ET AL., IMMUNOLOGY, vol. 73, no. 1, 1991, pages 83 - 87
DANG, L. ET AL., MOL MED REP, vol. 11, no. 6, 2015, pages 4183 - 4189
KAPLAN, A. P., J ALLERGY CLIN IMMUNOL, vol. 114, no. 3, 2004, pages 465 - 474
YAN, S. ET AL., J DERMATOL SCI, vol. 76, no. 3, 2014, pages 240 - 245
DIANI, M.; G. ALTOMARE; E. REALI, AUTOIMMUN REV, vol. 14, no. 4, 2015, pages 286 - 292
NATAF, S. ET AL., J IMMUNOL, vol. 162, no. 7, 1999, pages 4018 - 4023
TSUJI, R. F. ET AL., J IMMUNOL, vol. 165, no. 3, 2000, pages 1588 - 1598
WERFEL, T. ET AL., ARCH DERMATOL RES, vol. 289, no. 2, 1997, pages 83 - 86
MROWIETZ, U. ET AL., EXP DERMATOL, vol. 10, no. 4, 2001, pages 238 - 245
HOWELL ET AL., J. CLIN. INVEST., vol. 121, no. 4, 2011, pages 1429 - 1444
ZAH H. ET AL., ONCOIMMUNOLOGY, vol. 6, no. 10, 2017, pages e1349587
WANG Y. ET AL., CANCER DISCOVERY, vol. 6, no. 9, 2016, pages 1022 - 1035
REMINGTON: "The Science and Practice of Pharmacy", 2005, LIPPINCOTT WILLIAMS & WILKINS, article "Pharmaceutical Manufacturing"
T.W. GREENE; P.G.M. WUTS: "Protective Groups in Organic Synthesis", 1999, WILEY-INTERSCIENCE
Attorney, Agent or Firm:
VELKER, Jörg (CH)
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