CA2510807C - Inhibitors of tace - Google Patents
Inhibitors of tace Download PDFInfo
- Publication number
- CA2510807C CA2510807C CA2510807A CA2510807A CA2510807C CA 2510807 C CA2510807 C CA 2510807C CA 2510807 A CA2510807 A CA 2510807A CA 2510807 A CA2510807 A CA 2510807A CA 2510807 C CA2510807 C CA 2510807C
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- CA
- Canada
- Prior art keywords
- aliphatic
- cycloaliphatic
- ring
- substituents
- compound according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 title abstract description 9
- 239000003112 inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 239000000203 mixture Substances 0.000 claims abstract description 37
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 125000001931 aliphatic group Chemical group 0.000 claims description 120
- 229910052757 nitrogen Inorganic materials 0.000 claims description 57
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 46
- -1 1,2-methylenedioxy Chemical group 0.000 claims description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 229910052717 sulfur Inorganic materials 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000004306 triazinyl group Chemical group 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000001425 triazolyl group Chemical group 0.000 claims description 5
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
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- 239000003937 drug carrier Substances 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000005955 1H-indazolyl group Chemical group 0.000 claims description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 3
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- 206010040070 Septic Shock Diseases 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 3
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 3
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- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 claims description 3
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 claims description 3
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 claims description 3
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 2
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- 206010039705 Scleritis Diseases 0.000 claims description 2
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- 206010064390 Tumour invasion Diseases 0.000 claims description 2
- 208000025865 Ulcer Diseases 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 claims description 2
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- 230000000172 allergic effect Effects 0.000 claims description 2
- 230000007815 allergy Effects 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 230000033115 angiogenesis Effects 0.000 claims description 2
- 208000007474 aortic aneurysm Diseases 0.000 claims description 2
- 206010003246 arthritis Diseases 0.000 claims description 2
- 125000001769 aryl amino group Chemical group 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 208000010668 atopic eczema Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 230000009400 cancer invasion Effects 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- 230000019771 cognition Effects 0.000 claims description 2
- 208000010247 contact dermatitis Diseases 0.000 claims description 2
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- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
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- 230000001988 toxicity Effects 0.000 claims description 2
- 231100000419 toxicity Toxicity 0.000 claims description 2
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- 230000029663 wound healing Effects 0.000 claims description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 2
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 14
- 125000005842 heteroatom Chemical group 0.000 description 71
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 125000006413 ring segment Chemical group 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 125000003003 spiro group Chemical group 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 235000002639 sodium chloride Nutrition 0.000 description 12
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 11
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- 102100040247 Tumor necrosis factor Human genes 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 8
- 101000777461 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 17 Proteins 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
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- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
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- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
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| US44363903P | 2003-01-29 | 2003-01-29 | |
| US60/443,639 | 2003-01-29 | ||
| PCT/US2003/040512 WO2004056766A1 (en) | 2002-12-19 | 2003-12-19 | Inhibitors of tace |
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| CA2510807A1 CA2510807A1 (en) | 2004-07-08 |
| CA2510807C true CA2510807C (en) | 2011-11-22 |
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| JP (1) | JP4580866B2 (https=) |
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| US20020128476A1 (en) * | 1996-08-08 | 2002-09-12 | Smithkline Beecham Corporation | Inhibitors of cysteine protease |
| ATE443044T1 (de) * | 2002-12-19 | 2009-10-15 | Vertex Pharma | Tace inhibitoren |
| US7488745B2 (en) | 2004-07-16 | 2009-02-10 | Schering Corporation | Compounds for the treatment of inflammatory disorders |
| US7504424B2 (en) | 2004-07-16 | 2009-03-17 | Schering Corporation | Compounds for the treatment of inflammatory disorders |
| ATE478864T1 (de) | 2004-07-16 | 2010-09-15 | Schering Corp | Hydantoinderivate zur behandlung von entzündlichen erkrankungen |
| WO2007016597A2 (en) * | 2005-07-29 | 2007-02-08 | The Regents Of The University Of California | Targeting tnf-alpha converting enzyme (tace)-dependent growth factor shedding in cancer therapy |
| AR059036A1 (es) | 2006-01-17 | 2008-03-12 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
| TW201024304A (en) | 2008-09-24 | 2010-07-01 | Schering Corp | Compounds for the treatment of inflammatory disorders |
| EP2346857B1 (en) | 2008-09-24 | 2019-11-27 | Merck Sharp & Dohme Corp. | Compounds for the treatment of inflammatory disorders |
| EP2356111A1 (en) | 2008-11-10 | 2011-08-17 | Schering Corporation | Compounds for the treatment of inflammatory disorders |
| US8569336B2 (en) | 2008-11-10 | 2013-10-29 | Ling Tong | Compounds for the treatment of inflammatory disorders |
| DK2597084T3 (en) * | 2010-07-08 | 2016-08-15 | Kaken Pharma Co Ltd | N-HYDROXYFORMAMIDE DERIVATIVE AND MEDICINAL CONTAINING SAME |
| EP2617812B1 (en) | 2010-09-17 | 2019-03-20 | The University of Tokyo | Composition for maintaining platelet function |
| US12213970B2 (en) | 2018-10-29 | 2025-02-04 | Boehringer Ingelheim International Gmbh | Pyridinyl sulfonamide derivatives, pharmaceutical compositions and uses thereof |
| DK3873600T5 (da) | 2018-10-29 | 2024-03-18 | Boehringer Ingelheim Int | Pyridinylsulfonamidderivater, farmaceutiske sammensætninger og anvendelser deraf |
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| US3501489A (en) * | 1966-01-21 | 1970-03-17 | American Home Prod | 1-phenylsulfonyl-2-(2-thiazolin-2-yl-oxy and thiol) pyrrolidines |
| US5734081A (en) * | 1994-08-05 | 1998-03-31 | Warner-Lambert Company | Arylthio compounds |
| US6747027B1 (en) * | 1996-07-22 | 2004-06-08 | Pharmacia Corporation | Thiol sulfonamide metalloprotease inhibitors |
| BR9712792A (pt) * | 1996-08-28 | 1999-12-14 | Procter & Gamble | Inibidores de metaloprotease bidentada. |
| JPH11147876A (ja) * | 1997-09-12 | 1999-06-02 | Kanebo Ltd | テトラヒドロイソキノリン誘導体およびそれを有効成分とする薬剤 |
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| AR035313A1 (es) | 1999-01-27 | 2004-05-12 | Wyeth Corp | Inhibidores de tace acetilenicos de acido hidroxamico de sulfonamida a base de alfa-aminoacidos, composiciones farmaceuticas y el uso de los mismos para la manufactura de medicamentos. |
| US6313123B1 (en) | 1999-01-27 | 2001-11-06 | American Cyanamid Company | Acetylenic sulfonamide thiol tace inhibitors |
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- 2003-12-19 US US10/741,164 patent/US7485664B2/en not_active Expired - Fee Related
- 2003-12-19 CA CA2510807A patent/CA2510807C/en not_active Expired - Fee Related
- 2003-12-19 DE DE60329326T patent/DE60329326D1/de not_active Expired - Lifetime
- 2003-12-19 WO PCT/US2003/040512 patent/WO2004056766A1/en not_active Ceased
-
2008
- 2008-11-12 US US12/269,429 patent/US7919520B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004056766A1 (en) | 2004-07-08 |
| CA2510807A1 (en) | 2004-07-08 |
| US7919520B2 (en) | 2011-04-05 |
| US7485664B2 (en) | 2009-02-03 |
| EP1581488B1 (en) | 2009-09-16 |
| JP2006515319A (ja) | 2006-05-25 |
| US20090176782A1 (en) | 2009-07-09 |
| EP1581488A1 (en) | 2005-10-05 |
| DE60329326D1 (de) | 2009-10-29 |
| US20040186088A1 (en) | 2004-09-23 |
| AU2003297364A1 (en) | 2004-07-14 |
| ATE443044T1 (de) | 2009-10-15 |
| JP4580866B2 (ja) | 2010-11-17 |
| AU2003297364B2 (en) | 2009-07-09 |
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