JP2007502844A - カテプシンｓの阻害剤 - Google Patents
カテプシンｓの阻害剤 Download PDFInfo
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- JP2007502844A JP2007502844A JP2006524107A JP2006524107A JP2007502844A JP 2007502844 A JP2007502844 A JP 2007502844A JP 2006524107 A JP2006524107 A JP 2006524107A JP 2006524107 A JP2006524107 A JP 2006524107A JP 2007502844 A JP2007502844 A JP 2007502844A
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- Prior art keywords
- group
- substituted
- member selected
- alkyl
- cathepsin
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- 150000001875 compounds Chemical class 0.000 claims abstract description 147
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- 230000005764 inhibitory process Effects 0.000 claims abstract description 59
- 238000000034 method Methods 0.000 claims abstract description 54
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- 108010084457 Cathepsins Proteins 0.000 claims abstract description 36
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 71
- -1 benzoimidazolyl Chemical group 0.000 claims description 62
- 229910052717 sulfur Inorganic materials 0.000 claims description 61
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 55
- 229910052760 oxygen Inorganic materials 0.000 claims description 55
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
- 125000000623 heterocyclic group Chemical group 0.000 claims description 44
- 229910052799 carbon Inorganic materials 0.000 claims description 41
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 33
- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 229910052731 fluorine Inorganic materials 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
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- 241000124008 Mammalia Species 0.000 claims description 18
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 14
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- 239000000758 substrate Substances 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
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- 239000000047 product Substances 0.000 description 18
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
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- 238000002360 preparation method Methods 0.000 description 11
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- 239000000741 silica gel Substances 0.000 description 10
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- 102000004172 Cathepsin L Human genes 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 229910052736 halogen Inorganic materials 0.000 description 8
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- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
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Images
Classifications
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- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
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- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
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| US49685803P | 2003-08-20 | 2003-08-20 | |
| US10/922,362 US7256207B2 (en) | 2003-08-20 | 2004-08-18 | Inhibitors of cathepsin S |
| PCT/US2004/027316 WO2005018568A2 (en) | 2003-08-20 | 2004-08-19 | Inhibitors of cathepsin s |
Publications (2)
| Publication Number | Publication Date |
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| JP2007502844A true JP2007502844A (ja) | 2007-02-15 |
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| EP (1) | EP1658274A4 (enExample) |
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| AU (1) | AU2004266151B2 (enExample) |
| BR (1) | BRPI0413755A (enExample) |
| CA (1) | CA2534489A1 (enExample) |
| MX (1) | MXPA06001888A (enExample) |
| WO (1) | WO2005018568A2 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013513569A (ja) * | 2009-12-11 | 2013-04-22 | エフ．ホフマン−ラ ロシュ アーゲー | Ａｍｐｋモジュレーターとして有用なスピロインドール−シクロプロパンインドリノン |
| JP2022518054A (ja) * | 2019-01-22 | 2022-03-11 | アドヴェリオ・ファーマ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | ４－（２，２，３，３－テトラフルオロプロピル）モルホリンを製造する方法 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7256207B2 (en) * | 2003-08-20 | 2007-08-14 | Irm Llc | Inhibitors of cathepsin S |
| TWI389897B (zh) | 2005-02-22 | 2013-03-21 | Chugai Pharmaceutical Co Ltd | 1- (2H) -isoquinolinone derivatives |
| US7751835B2 (en) * | 2005-10-04 | 2010-07-06 | Airvana, Inc. | Non-circular paging areas |
| GB2476823B (en) | 2010-01-11 | 2012-05-02 | Subsea 7 Contracting Uk Ltd | Improvements relating to abandonment and recovery of pipelines |
| EP3946332A1 (en) | 2019-04-05 | 2022-02-09 | Université de Bretagne Occidentale | Protease-activated receptor-2 inhibitors for the treatment of sensory neuropathy induced by a marine neurotoxic poisoning |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001068591A1 (en) * | 2000-03-16 | 2001-09-20 | F. Hoffmann-La Roche Ag | Carboxylic acid derivatives as ip antagonists |
| WO2002070517A2 (en) * | 2001-03-02 | 2002-09-12 | Merck Frosst Canada & Co. | Cathepsin cysteine protease inhibitors |
| WO2003031437A1 (en) * | 2001-10-09 | 2003-04-17 | Smithkline Beecham Corporation | Propylcarbamate derivatives as inhibitors of serine and cysteine proteases |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4499295A (en) | 1983-05-09 | 1985-02-12 | G. D. Searle & Co. | Protease inhibitors |
| US5374623A (en) | 1992-08-20 | 1994-12-20 | Prototek, Inc. | Cysteine protease inhibitors effective for in vivo use |
| DE69406083T2 (de) | 1993-04-28 | 1998-02-26 | Ihara Chemical Ind Co | Aminosäureamide, bakterizide für gartenbau und landwirtschaft sowie herstellungverfahren |
| US5648514A (en) | 1994-12-29 | 1997-07-15 | Allergan | Substituted acetylenes having retinoid-like biological activity |
| US5691368A (en) | 1995-01-11 | 1997-11-25 | Hoechst Marion Roussel, Inc. | Substituted oxazolidine calpain and/or cathepsin B inhibitors |
| US5849711A (en) | 1995-06-06 | 1998-12-15 | Athena Neurosciences, Inc. | Cathepsin and methods and compositions for inhibition thereof |
| TW438591B (en) | 1995-06-07 | 2001-06-07 | Arris Pharm Corp | Reversible cysteine protease inhibitors |
| AU1118097A (en) | 1995-10-30 | 1997-05-22 | Smithkline Beecham Corporation | Protease inhibitors |
| EA199700087A1 (ru) | 1995-10-30 | 1998-04-30 | Смитклайн Бичам Корпорейшн | Способ ингибирования катепсина к |
| DE19610784A1 (de) * | 1996-03-19 | 1997-09-25 | Hoechst Ag | Fluoralkyl- und Fluoralkoxysubstituierte heterocyclische Bradykinin-Antagonisten, Verfahren zu ihrer Herstellung und ihre Verwendung |
| US5840733A (en) | 1996-07-01 | 1998-11-24 | Redcell, Canada, Inc. | Methods and compositions for producing novel conjugates of thrombin inhibitors and endogenous carriers resulting in anti-thrombins with extended lifetimes |
| US5916887A (en) | 1996-09-23 | 1999-06-29 | National Research Council Of Canada | 4-substituted-3-(2-amino-2-cycloalkyl methyl)-acetamido azetidin-2-one derivatives as cysteine proteinase regulators |
| US6004933A (en) | 1997-04-25 | 1999-12-21 | Cortech Inc. | Cysteine protease inhibitors |
| CN1255162A (zh) | 1997-05-08 | 2000-05-31 | 史密丝克莱恩比彻姆公司 | 蛋白酶抑制剂 |
| GB9723407D0 (en) | 1997-11-05 | 1998-01-07 | Ciba Geigy Ag | Organic compounds |
| GB9903548D0 (en) | 1999-02-16 | 1999-04-07 | Novartis Ag | Organic compounds |
| US6395897B1 (en) | 1999-03-02 | 2002-05-28 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nitrile compounds useful as reversible inhibitors of #9 cathepsin 5 |
| EP1178958B1 (en) | 1999-03-15 | 2004-02-18 | Axys Pharmaceuticals, Inc. | N-cyanomethyl amides as protease inhibitors |
| US6313117B1 (en) * | 1999-07-30 | 2001-11-06 | Boehringer Ingelheim Pharmaceuticals, Inc. | Succinate derivative compounds useful as cysteine protease inhibitors |
| WO2001019816A1 (en) | 1999-09-13 | 2001-03-22 | Boehringer Ingelheim Pharmaceuticals, Inc. | Novel spiroheterocyclic compounds useful as reversible inhibitors of cysteine proteases |
| US6420364B1 (en) | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
| MXPA03001421A (es) | 2000-08-14 | 2004-01-26 | Johnson & Johnson | Pirazoles sustituidos. |
| BRPI0113286B8 (pt) | 2000-08-14 | 2021-05-25 | Johnson & Johnson | pirazóis substituídos e composição farmacêutica compreendendo os mesmos. |
| ATE324372T1 (de) | 2000-08-14 | 2006-05-15 | Ortho Mcneil Pharm Inc | Substituierte pyrazole |
| IL156577A0 (en) | 2000-12-22 | 2004-01-04 | Axys Pharm Inc | Selective cathepsin s inhibitors and pharmaceutical compositions containing the same |
| JP4365094B2 (ja) | 2001-03-02 | 2009-11-18 | メルク フロスト カナダ リミテツド | カテプシンシステインプロテアーゼ阻害薬 |
| WO2002070519A1 (en) | 2001-03-05 | 2002-09-12 | Axys Pharmaceuticals, Inc. | Monobactams as cathepsin k inhibitors |
| US20050107616A1 (en) | 2001-08-03 | 2005-05-19 | David Gene Barrett | Alpha-ketoamide derivatives as cathepsin k inhibitors |
| US20030144234A1 (en) | 2001-08-30 | 2003-07-31 | Buxton Francis Paul | Methods for the treatment of chronic pain and compositions therefor |
| WO2004000838A1 (en) | 2002-06-24 | 2003-12-31 | Axys Pharmaceuticals, Inc. | Peptidic compounds as cysteine protease inhibitors |
| US7256207B2 (en) * | 2003-08-20 | 2007-08-14 | Irm Llc | Inhibitors of cathepsin S |
-
2004
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- 2004-08-19 BR BRPI0413755-8A patent/BRPI0413755A/pt not_active IP Right Cessation
- 2004-08-19 JP JP2006524107A patent/JP2007502844A/ja active Pending
- 2004-08-19 EP EP04781915A patent/EP1658274A4/en not_active Withdrawn
- 2004-08-19 CA CA002534489A patent/CA2534489A1/en not_active Abandoned
- 2004-08-19 AU AU2004266151A patent/AU2004266151B2/en not_active Ceased
- 2004-08-19 WO PCT/US2004/027316 patent/WO2005018568A2/en not_active Ceased
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2007
- 2007-07-13 US US11/777,879 patent/US7507755B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001068591A1 (en) * | 2000-03-16 | 2001-09-20 | F. Hoffmann-La Roche Ag | Carboxylic acid derivatives as ip antagonists |
| WO2002070517A2 (en) * | 2001-03-02 | 2002-09-12 | Merck Frosst Canada & Co. | Cathepsin cysteine protease inhibitors |
| WO2003031437A1 (en) * | 2001-10-09 | 2003-04-17 | Smithkline Beecham Corporation | Propylcarbamate derivatives as inhibitors of serine and cysteine proteases |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013513569A (ja) * | 2009-12-11 | 2013-04-22 | エフ．ホフマン−ラ ロシュ アーゲー | Ａｍｐｋモジュレーターとして有用なスピロインドール−シクロプロパンインドリノン |
| JP2022518054A (ja) * | 2019-01-22 | 2022-03-11 | アドヴェリオ・ファーマ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | ４－（２，２，３，３－テトラフルオロプロピル）モルホリンを製造する方法 |
| JP7471306B2 (ja) | 2019-01-22 | 2024-04-19 | アドヴェリオ・ファーマ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | ４－（２，２，３，３－テトラフルオロプロピル）モルホリンを製造する方法 |
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| AU2004266151B2 (en) | 2007-08-02 |
| AU2004266151A1 (en) | 2005-03-03 |
| US7507755B2 (en) | 2009-03-24 |
| CA2534489A1 (en) | 2005-03-03 |
| US7256207B2 (en) | 2007-08-14 |
| US20070259873A1 (en) | 2007-11-08 |
| US20050107368A1 (en) | 2005-05-19 |
| WO2005018568A2 (en) | 2005-03-03 |
| WO2005018568A3 (en) | 2005-09-09 |
| EP1658274A2 (en) | 2006-05-24 |
| MXPA06001888A (es) | 2006-05-31 |
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| BRPI0413755A (pt) | 2006-10-31 |
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