Title:
PHTHALIMIDE DERIVATIVES OF NON-STEROIDAL ANTI-INFLAMMATORY COMPOUNDS AND/OR TNF-α MODULATORS, METHOD FOR PRODUCING SAME, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND USES THEREOF FOR THE TREATMENT OF INFLAMMATORY DISEASES
Document Type and Number:
WIPO Patent Application WO/2010/115252
Kind Code:
A1
Abstract:
The present invention relates to phthalimide derivatives of non-steroidal anti-inflammatory compounds and/or TNF-α modulators, to a method for producing these derivatives, to pharmaceutical compositions containing these derivatives, and to uses thereof, including the use for the treatment of inflammatory diseases, in particular those associated with chronic inflammatory conditions, such as rheumatoid arthritis, and inflammatory intestinal diseases (such as Crohn's disease), and to the use of these compositions as antipyretics, analgesics and platelet aggregation inhibitors.
Inventors:
SANTOS JEAN LEANDRO DOS SANTOS (BR)
VIZIOLI EDNIR DE OLIVEIRA (BR)
CHIN CHUNG MAN (BR)
MENEGON RENATO FARINA (BR)
BLAU LORENA (BR)
VIZIOLI EDNIR DE OLIVEIRA (BR)
CHIN CHUNG MAN (BR)
MENEGON RENATO FARINA (BR)
BLAU LORENA (BR)
Application Number:
PCT/BR2010/000099
Publication Date:
October 14, 2010
Filing Date:
April 07, 2010
Export Citation:
Assignee:
EMS SA (BR)
UNIV ESTADUAL PAULISTA JULIO D (BR)
SANTOS JEAN LEANDRO DOS SANTOS (BR)
VIZIOLI EDNIR DE OLIVEIRA (BR)
CHIN CHUNG MAN (BR)
MENEGON RENATO FARINA (BR)
BLAU LORENA (BR)
UNIV ESTADUAL PAULISTA JULIO D (BR)
SANTOS JEAN LEANDRO DOS SANTOS (BR)
VIZIOLI EDNIR DE OLIVEIRA (BR)
CHIN CHUNG MAN (BR)
MENEGON RENATO FARINA (BR)
BLAU LORENA (BR)
International Classes:
C07D209/48; A61K31/192; A61K31/196; A61K31/4035; A61K31/405; A61K31/60; A61K31/635; A61K31/655; A61P7/02; A61P29/00; C07C57/40; C07C65/10; C07C65/34; C07C209/28; C07C229/40; C07C229/42; C07C245/08; C07D209/28
Domestic Patent References:
| WO1998019649A2 | 1998-05-14 | |||
| WO2005039483A2 | 2005-05-06 |
Foreign References:
| CN101053662A | 2007-10-17 | |||
| BE772825A | 1972-01-17 | |||
| EP1485127A2 | 2004-12-15 | |||
| GB768821A | 1957-02-20 |
Other References:
BOURGUIGNON, J.: "Identical and Nonidentical Twin Drugs.", WERMUTH, C. G. THE PRACTICE OF MEDICINAL CHEMISTRY, vol. 15, no. PART I, pages 261 - 293
CENA, C. ET AL.: "Antiinflammatory, Gastrosparing and Antiplatelet Properties of New NO-Donor Esters of Aspirin", JOURNAL OF MEDICINAL CHEMISTRY, vol. 46, 2003, pages 747 - 754
ISHIZUMI, K. ET AL.: "Benzodiazepines. IX. Oxidation of N-Phthalimidoacetylindoles", CHEMICAL & PHARMACEUTICAL BULLETIN, vol. 21, no. 5, 1973, pages 1027 - 1030
BLOBAUM, A.L., MARNETT, L.J.: "Structural and functional basis of cyclooxygenase inhibition", J. MED. CHEM., vol. 50, no. 7, 2007, pages 1425 - 1441
RANG, H.P., DALE M.M., RITTER, J.M.: "Pharmacology", 2001, pages: 189
VANE, J.R.: "Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs", NATURE (LONDON) NEW BIOL., vol. 231, 1971, pages 232 - 235
HOWARD, P., DELAFONTAINE, P.: "Nonsteroidal Anti-Inflammatory Drugs and Cardiovascular Risk", JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, vol. 43, no. 4, 2004
KUJUBU, D. A., FLETCHER, B. S., VARNUM, B. C., LIM, R. W., HERSCHMAN, H. R.: "TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue", J. BIOL. CHEM., vol. 266, 1991, pages 12866 - 12872
SAPIRSTEIN A., SAITO H., TEXEL S.J., SAMAD T.A., O'LEARY E., BONVENTRE J.V.: "Cytosolic phospholipase A2alpha regulates induction of brain cyclooxygenase-2 in a mouse model of inflammation", AM J PHYSIOL REGUL INTEGR COMP PHYSIOL., vol. 288, no. 6, 2005, pages 1774 - 82
NARTEY, JL, REICHENBACH, S., STERCHI R., DIEPPE, P., EGGER, M.: "Risk of cardiovascular events and rofecoxib: cumulative meta-analysis", THE LANCET, vol. 364, no. 9450, 2004, pages 2021 - 2029
COLIN K. COMBS, DERRICK E. JOHNSON, J. COLLEEN KARLO, STEVEN B. CANNADY, GARY E. LANDRETH: "Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of B-Amyloidal-Stimulated proinflammatory Responses and Neurotoxicity by PPARg agonists", THE JOURNAL OF NEUROSCIENCE., vol. 20, no. 2, 2000, pages 558 - 567
BLASKO, I., STAMPFER-KOUNTCHEV, M., ROBATSCHER, P., VEERHUIS, R., EIKELENBOOM, P, GRUBECK-LOEBENSTEIN, B: "How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes", AGING CELL., 2004, pages 169 - 176
MCGEER PL, MCGEER EG: "Anti-inflammatory drugs in the fight against Alzheimer's disease", ANN NY ACAD SCI, vol. 777, 1996, pages 213 - 220
STEWART WF, KAWAS C., CORRADA M., METTER, EJ: "Risk of Alzheimer's disease and duration of NSAID use", NEUROLOGY, vol. 48, 1997, pages 626 - 632
STEEN, KSS, NURMOHAMED, MT, VISMAN, I., HEIJERMAN, M., BOERS, M., DIJKMANS, BAC, LEMS, WF: "Decreasing incidence of symptomatic gastrointestinal ulcers and ulcer complications in patients with rheumatoid arthritis", ANN RHEUM DIS., vol. 67, 2008, pages 256 - 259
ONG, CKS, LIRK, P., TAN, CH, SEYMOUR, RA: "An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs", CLINICAL MEDICINE & RESEARCH, vol. 5, no. 1, 2007, pages 19 - 34
WALLACE, J.L., KEENAN, C.M., GRANGER, D.N.: "Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophyl-dependent process", AM J PHYSIOL., vol. 259, no. 3, pages 462 - 467
ARMSTRONG, C.P, BLOWER, A.L.: "Non-steroidal anti-inflammatory drugs and life threatening Complications of peptic ulceration", GUT, vol. 28, no. 5, 1987, pages 527 - 532
ONG, C.K.S., LIRK, P., TAN, C.H., SEYMOUR, R.A.: "An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs", CLINICAL MEDICINE & RESEARCH, vol. 5, no. 1, 2007, pages 19 - 34
KRAYCHETE, D.C., CALASANS, M.T.A., VALENTE, C.M.L.: "Pro-inflammatory Cytokines and Pain", REV BRAS REUMATOL, vol. 46, no. 3, 2006, pages 199 - 206
ALEXANDRE-MOREIRA, M.S., TAKIYAC, C.M., ARRUDAD, L.B., PASCARELLIC, B., GOMESE, R.N., NETO, H.C.C.F., LIMA, L.M., BARREIRO, E.J.: "LASS Bio-468: a new achiral thalidomide analogue which modulates TNF-a and ? production and inhibits endotoxic shock and arthritis in an animal model", INTERNATIONAL IMMUNOPHARMACOLOGY, vol. 5, 2005, pages 485 - 494
KLOTZ, U., TEML, A., SCHWAB, M.: "Clinical Pharmacokinetics and Use of Infliximab", CLIN PHARMACOKINET, vol. 46, no. 8, 2007, pages 645 - 660
LIMA, L.M., FRAGA, C.A.M., BARREIRO, E.J.: "The rebirth of a drug: thalidomide", QUIM. NOVA., vol. 24, no. 5, 2001, pages 683 - 688
RANKIN, E.C., CHOY, E.H., KASSIMOS, D., KINGSLEY, G.H., SOPWITH, A.M., INSENBERG, D.A., PANAYI, G.S.: "The therapeutic effects of an engineered human anti-tumor necrosis factor alpha antibody CDP571 in rheumathoid arthritis", BR. J. RHEUMATOL., vol. 34, 1995, pages 334 - 342
RIBEIRO, R.A., VALE, M.L., FERRIERA, S.H, CUNHA, F.Q.: "Analgesic effect of thalidomide on inflammatory pain", EUR. J. PHARMACOL., vol. 391, 2000, pages 97 - 103
MIYACHI, H., OGASAWARA, A., AZUMA, A., HASHIMOTO, Y.: "Tumor necrosis factor-alpha production- inhibiting activity of phtalimide analogues on human leukemia THP-1 cells and a structure-activity relationship study", BIOORG. MED. CHEM., vol. 5, no. 11, 1997, pages 2095 - 2102
SURYAPRASAD, AG, PRINDIVILLE T.: "The biology of TNF blockade", AUTOIMMUNITY REVIEWS., vol. 2, 2003, pages 346 - 357
POPA, C., NETEA M.G., VAN RIEL P.L.C.M., VAN DER MEER J.W.M., STALENHOEF A.F.H.: "The role of TNF-a in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk", J. LIPID RES., vol. 48, 2007, pages 751 - 762
CLARK, A.I.: "How TNF was recognized as a key mechanism of disease", CYTOKINE & GROWTH FACTOR REVIEWS., vol. 18, 2007, pages 335 - 343
KODAMAA, S., DAVIS, M., FAUSTMAN, D. L.: "The therapeutic potential of tumor necrosis factor for autoimmune disease: a mechanistically based hypothesis", CELL. MOL. LIFE SCI., vol. 62, 2005, pages 1850 - 1862
AGGARWAL, B.B., SHISHODIA, S., ASHIKAWA, K., BHARTI, A.C.: "The Role of TNF and Its Family Members in Inflammation and Cancer: Lessons from Gene Deletion Current Drug Targets", INFLAMMATION & ALLERGY, vol. 1, 2002, pages 327 - 341
OCH, A.A., ZACHAROWSKI, K., BOEHM, 0., STEVENS, M., LIPFERT, P., GIESEN, H.J.V., WOLF, A., FREYNHAGEN, R.: "Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients", INFLAMMATION RESEARCH., vol. 56, 2007, pages 32 - 37
SCHENK, M., BOUCHON, A., SEIBOLD, F., MUELLER, C.: "TREM-1- expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases", J. CLIN. INVEST., vol. 117, 2007, pages 3097 - 3106
VALESINI, G., IANNUCCELLI, C., MAROCCHI, E., PASCOLI, L., SCALZI, V., DI FRANCO, M.: "Biological and clinical effects of anti-TNFa treatment", AUTOIMMUNITY REVIEWS., vol. 7, 2007, pages 35 - 41
WILLIAMS, R.O., PALEOLOG, E., FELDMANN, M.: "Cytokine inhibitors in rheumatoid arthritis and other autoimmune diseases", CURRENT OPINION IN PHARMACOLOGY., vol. 7, 2007, pages 412 - 417
WERMUTH, C.G.: "Selective optimization of side activities: another way for drug discovery", J MED CHEM., vol. 47, no. 6, 2004, pages 1303 - 1312
CENA, C., LOLLI, M.L., LAZZARATO, L., GUAITA, E., MORINI,G., CORUZZI, G., MCELROY, S.P., MEGSON, I.L., FRUTTERO, R., GASCO, A.: "Anti-inflammatory, Gastrosparing, and Antiplatelet Properties of New NO-Donor Esters of Aspirin", J. MED. CHEM., vol. 46, 2003, pages 747 - 754
BANDARAGE, U.K., CHEN, L, FANG, X., GARVEY, D.S., GLAVIN, A., JANERO, D.R., LETTS, L.G., MERCER, G.J., SAHA, J.K., SCHROEDER, J.D.: "Nitrosothiol Esters of Diclofenac: Synthesis and Pharmacological Characterization of the Gastrointestinal-Sparing Prodrugs", J. MED. CHEM., vol. 43, 2000, pages 4005 - 4016
COLLIER, H. 0. J., DINNEEN, L. C., JOHNSON, C.A., SCHNEIDER, C: "Abdominal constriction response and its suppression by analgesic drugs in the mouse", BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY, vol. 32, no. 2, 1968, pages 295 - 310
See also references of EP 2418200A4
CENA, C. ET AL.: "Antiinflammatory, Gastrosparing and Antiplatelet Properties of New NO-Donor Esters of Aspirin", JOURNAL OF MEDICINAL CHEMISTRY, vol. 46, 2003, pages 747 - 754
ISHIZUMI, K. ET AL.: "Benzodiazepines. IX. Oxidation of N-Phthalimidoacetylindoles", CHEMICAL & PHARMACEUTICAL BULLETIN, vol. 21, no. 5, 1973, pages 1027 - 1030
BLOBAUM, A.L., MARNETT, L.J.: "Structural and functional basis of cyclooxygenase inhibition", J. MED. CHEM., vol. 50, no. 7, 2007, pages 1425 - 1441
RANG, H.P., DALE M.M., RITTER, J.M.: "Pharmacology", 2001, pages: 189
VANE, J.R.: "Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs", NATURE (LONDON) NEW BIOL., vol. 231, 1971, pages 232 - 235
HOWARD, P., DELAFONTAINE, P.: "Nonsteroidal Anti-Inflammatory Drugs and Cardiovascular Risk", JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, vol. 43, no. 4, 2004
KUJUBU, D. A., FLETCHER, B. S., VARNUM, B. C., LIM, R. W., HERSCHMAN, H. R.: "TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue", J. BIOL. CHEM., vol. 266, 1991, pages 12866 - 12872
SAPIRSTEIN A., SAITO H., TEXEL S.J., SAMAD T.A., O'LEARY E., BONVENTRE J.V.: "Cytosolic phospholipase A2alpha regulates induction of brain cyclooxygenase-2 in a mouse model of inflammation", AM J PHYSIOL REGUL INTEGR COMP PHYSIOL., vol. 288, no. 6, 2005, pages 1774 - 82
NARTEY, JL, REICHENBACH, S., STERCHI R., DIEPPE, P., EGGER, M.: "Risk of cardiovascular events and rofecoxib: cumulative meta-analysis", THE LANCET, vol. 364, no. 9450, 2004, pages 2021 - 2029
COLIN K. COMBS, DERRICK E. JOHNSON, J. COLLEEN KARLO, STEVEN B. CANNADY, GARY E. LANDRETH: "Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of B-Amyloidal-Stimulated proinflammatory Responses and Neurotoxicity by PPARg agonists", THE JOURNAL OF NEUROSCIENCE., vol. 20, no. 2, 2000, pages 558 - 567
BLASKO, I., STAMPFER-KOUNTCHEV, M., ROBATSCHER, P., VEERHUIS, R., EIKELENBOOM, P, GRUBECK-LOEBENSTEIN, B: "How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes", AGING CELL., 2004, pages 169 - 176
MCGEER PL, MCGEER EG: "Anti-inflammatory drugs in the fight against Alzheimer's disease", ANN NY ACAD SCI, vol. 777, 1996, pages 213 - 220
STEWART WF, KAWAS C., CORRADA M., METTER, EJ: "Risk of Alzheimer's disease and duration of NSAID use", NEUROLOGY, vol. 48, 1997, pages 626 - 632
STEEN, KSS, NURMOHAMED, MT, VISMAN, I., HEIJERMAN, M., BOERS, M., DIJKMANS, BAC, LEMS, WF: "Decreasing incidence of symptomatic gastrointestinal ulcers and ulcer complications in patients with rheumatoid arthritis", ANN RHEUM DIS., vol. 67, 2008, pages 256 - 259
ONG, CKS, LIRK, P., TAN, CH, SEYMOUR, RA: "An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs", CLINICAL MEDICINE & RESEARCH, vol. 5, no. 1, 2007, pages 19 - 34
WALLACE, J.L., KEENAN, C.M., GRANGER, D.N.: "Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophyl-dependent process", AM J PHYSIOL., vol. 259, no. 3, pages 462 - 467
ARMSTRONG, C.P, BLOWER, A.L.: "Non-steroidal anti-inflammatory drugs and life threatening Complications of peptic ulceration", GUT, vol. 28, no. 5, 1987, pages 527 - 532
ONG, C.K.S., LIRK, P., TAN, C.H., SEYMOUR, R.A.: "An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs", CLINICAL MEDICINE & RESEARCH, vol. 5, no. 1, 2007, pages 19 - 34
KRAYCHETE, D.C., CALASANS, M.T.A., VALENTE, C.M.L.: "Pro-inflammatory Cytokines and Pain", REV BRAS REUMATOL, vol. 46, no. 3, 2006, pages 199 - 206
ALEXANDRE-MOREIRA, M.S., TAKIYAC, C.M., ARRUDAD, L.B., PASCARELLIC, B., GOMESE, R.N., NETO, H.C.C.F., LIMA, L.M., BARREIRO, E.J.: "LASS Bio-468: a new achiral thalidomide analogue which modulates TNF-a and ? production and inhibits endotoxic shock and arthritis in an animal model", INTERNATIONAL IMMUNOPHARMACOLOGY, vol. 5, 2005, pages 485 - 494
KLOTZ, U., TEML, A., SCHWAB, M.: "Clinical Pharmacokinetics and Use of Infliximab", CLIN PHARMACOKINET, vol. 46, no. 8, 2007, pages 645 - 660
LIMA, L.M., FRAGA, C.A.M., BARREIRO, E.J.: "The rebirth of a drug: thalidomide", QUIM. NOVA., vol. 24, no. 5, 2001, pages 683 - 688
RANKIN, E.C., CHOY, E.H., KASSIMOS, D., KINGSLEY, G.H., SOPWITH, A.M., INSENBERG, D.A., PANAYI, G.S.: "The therapeutic effects of an engineered human anti-tumor necrosis factor alpha antibody CDP571 in rheumathoid arthritis", BR. J. RHEUMATOL., vol. 34, 1995, pages 334 - 342
RIBEIRO, R.A., VALE, M.L., FERRIERA, S.H, CUNHA, F.Q.: "Analgesic effect of thalidomide on inflammatory pain", EUR. J. PHARMACOL., vol. 391, 2000, pages 97 - 103
MIYACHI, H., OGASAWARA, A., AZUMA, A., HASHIMOTO, Y.: "Tumor necrosis factor-alpha production- inhibiting activity of phtalimide analogues on human leukemia THP-1 cells and a structure-activity relationship study", BIOORG. MED. CHEM., vol. 5, no. 11, 1997, pages 2095 - 2102
SURYAPRASAD, AG, PRINDIVILLE T.: "The biology of TNF blockade", AUTOIMMUNITY REVIEWS., vol. 2, 2003, pages 346 - 357
POPA, C., NETEA M.G., VAN RIEL P.L.C.M., VAN DER MEER J.W.M., STALENHOEF A.F.H.: "The role of TNF-a in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk", J. LIPID RES., vol. 48, 2007, pages 751 - 762
CLARK, A.I.: "How TNF was recognized as a key mechanism of disease", CYTOKINE & GROWTH FACTOR REVIEWS., vol. 18, 2007, pages 335 - 343
KODAMAA, S., DAVIS, M., FAUSTMAN, D. L.: "The therapeutic potential of tumor necrosis factor for autoimmune disease: a mechanistically based hypothesis", CELL. MOL. LIFE SCI., vol. 62, 2005, pages 1850 - 1862
AGGARWAL, B.B., SHISHODIA, S., ASHIKAWA, K., BHARTI, A.C.: "The Role of TNF and Its Family Members in Inflammation and Cancer: Lessons from Gene Deletion Current Drug Targets", INFLAMMATION & ALLERGY, vol. 1, 2002, pages 327 - 341
OCH, A.A., ZACHAROWSKI, K., BOEHM, 0., STEVENS, M., LIPFERT, P., GIESEN, H.J.V., WOLF, A., FREYNHAGEN, R.: "Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients", INFLAMMATION RESEARCH., vol. 56, 2007, pages 32 - 37
SCHENK, M., BOUCHON, A., SEIBOLD, F., MUELLER, C.: "TREM-1- expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases", J. CLIN. INVEST., vol. 117, 2007, pages 3097 - 3106
VALESINI, G., IANNUCCELLI, C., MAROCCHI, E., PASCOLI, L., SCALZI, V., DI FRANCO, M.: "Biological and clinical effects of anti-TNFa treatment", AUTOIMMUNITY REVIEWS., vol. 7, 2007, pages 35 - 41
WILLIAMS, R.O., PALEOLOG, E., FELDMANN, M.: "Cytokine inhibitors in rheumatoid arthritis and other autoimmune diseases", CURRENT OPINION IN PHARMACOLOGY., vol. 7, 2007, pages 412 - 417
WERMUTH, C.G.: "Selective optimization of side activities: another way for drug discovery", J MED CHEM., vol. 47, no. 6, 2004, pages 1303 - 1312
CENA, C., LOLLI, M.L., LAZZARATO, L., GUAITA, E., MORINI,G., CORUZZI, G., MCELROY, S.P., MEGSON, I.L., FRUTTERO, R., GASCO, A.: "Anti-inflammatory, Gastrosparing, and Antiplatelet Properties of New NO-Donor Esters of Aspirin", J. MED. CHEM., vol. 46, 2003, pages 747 - 754
BANDARAGE, U.K., CHEN, L, FANG, X., GARVEY, D.S., GLAVIN, A., JANERO, D.R., LETTS, L.G., MERCER, G.J., SAHA, J.K., SCHROEDER, J.D.: "Nitrosothiol Esters of Diclofenac: Synthesis and Pharmacological Characterization of the Gastrointestinal-Sparing Prodrugs", J. MED. CHEM., vol. 43, 2000, pages 4005 - 4016
COLLIER, H. 0. J., DINNEEN, L. C., JOHNSON, C.A., SCHNEIDER, C: "Abdominal constriction response and its suppression by analgesic drugs in the mouse", BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY, vol. 32, no. 2, 1968, pages 295 - 310
See also references of EP 2418200A4
Attorney, Agent or Firm:
WEGMANN, Ana Cristina Almeida Müller (52Centro, -000 Rio de Janeiro - RJ, BR)
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