ZA200305382B - Tricyclic lactam and sultam derivatives and their use as histone deacetylase inhibitors. - Google Patents
Tricyclic lactam and sultam derivatives and their use as histone deacetylase inhibitors. Download PDFInfo
- Publication number
- ZA200305382B ZA200305382B ZA200305382A ZA200305382A ZA200305382B ZA 200305382 B ZA200305382 B ZA 200305382B ZA 200305382 A ZA200305382 A ZA 200305382A ZA 200305382 A ZA200305382 A ZA 200305382A ZA 200305382 B ZA200305382 B ZA 200305382B
- Authority
- ZA
- South Africa
- Prior art keywords
- naphtho
- dioxo
- isothiazol
- group
- acid hydroxyamide
- Prior art date
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- 150000003951 lactams Chemical class 0.000 title description 16
- 239000003276 histone deacetylase inhibitor Substances 0.000 title description 4
- 229940121372 histone deacetylase inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 47
- -1 8-(1,1-dioxo-2H-naphtho[1,8-cd]isothiazol-2-yl)-octanoic acid Chemical compound 0.000 claims description 28
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 102000003964 Histone deacetylase Human genes 0.000 claims description 8
- 108090000353 Histone deacetylase Proteins 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 5
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 239000003112 inhibitor Substances 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 230000004663 cell proliferation Effects 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- OOVWSANATRFYQN-UHFFFAOYSA-N 7-(2,2-dioxo-2lambda6-thia-3-azatricyclo[6.3.1.04,12]dodeca-1(11),4,6,8(12),9-pentaen-3-yl)-N-hydroxy-3-methylheptanamide Chemical compound C1=CC(S(N2CCCCC(C)CC(=O)NO)(=O)=O)=C3C2=CC=CC3=C1 OOVWSANATRFYQN-UHFFFAOYSA-N 0.000 claims description 2
- FGLFOXXJBKOZPL-UHFFFAOYSA-N N-hydroxy-7-(7-methyl-2,2-dioxo-2lambda6-thia-3-azatricyclo[6.3.1.04,12]dodeca-1(11),4(12),5,7,9-pentaen-3-yl)heptanamide Chemical compound ONC(=O)CCCCCCN1S(=O)(=O)C2=CC=CC3=C2C1=CC=C3C FGLFOXXJBKOZPL-UHFFFAOYSA-N 0.000 claims description 2
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- OSNAWTYXIMEYMA-UHFFFAOYSA-N CC(CCCN(C1=C(C2=CC=C3)C3=CC=C1)S2(=O)=O)CCC(NO)=O.CC(CCCC(NO)=O)CCN(C1=C(C2=CC=C3)C3=CC=C1)S2(=O)=O.NO Chemical compound CC(CCCN(C1=C(C2=CC=C3)C3=CC=C1)S2(=O)=O)CCC(NO)=O.CC(CCCC(NO)=O)CCN(C1=C(C2=CC=C3)C3=CC=C1)S2(=O)=O.NO OSNAWTYXIMEYMA-UHFFFAOYSA-N 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
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- 238000006243 chemical reaction Methods 0.000 description 26
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- 239000002585 base Substances 0.000 description 12
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- 241001465754 Metazoa Species 0.000 description 8
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- 239000002904 solvent Substances 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
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- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 6
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
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- 239000003480 eluent Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- GPYLCFQEKPUWLD-UHFFFAOYSA-N 1h-benzo[cd]indol-2-one Chemical compound C1=CC(C(=O)N2)=C3C2=CC=CC3=C1 GPYLCFQEKPUWLD-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 108010033040 Histones Proteins 0.000 description 4
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- 230000006907 apoptotic process Effects 0.000 description 4
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- 230000009467 reduction Effects 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
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- 102000006947 Histones Human genes 0.000 description 3
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
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- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- HOBYPSNNFBRLIX-UHFFFAOYSA-N 1,8-naphthosultam Chemical compound C1=CC(S(=O)(=O)N2)=C3C2=CC=CC3=C1 HOBYPSNNFBRLIX-UHFFFAOYSA-N 0.000 description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/90—Benzo [c, d] indoles; Hydrogenated benzo [c, d] indoles
- C07D209/92—Naphthostyrils
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
- Indole Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01101873 | 2001-01-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200305382B true ZA200305382B (en) | 2004-10-11 |
Family
ID=8176314
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200305382A ZA200305382B (en) | 2001-01-27 | 2003-07-11 | Tricyclic lactam and sultam derivatives and their use as histone deacetylase inhibitors. |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US7091229B2 (ko) |
| EP (1) | EP1358168B1 (ko) |
| JP (1) | JP3961955B2 (ko) |
| KR (1) | KR100628013B1 (ko) |
| CN (1) | CN1216047C (ko) |
| AR (1) | AR035417A1 (ko) |
| AT (1) | ATE301644T1 (ko) |
| AU (1) | AU2002246053B2 (ko) |
| BR (1) | BR0206738A (ko) |
| CA (1) | CA2432196C (ko) |
| DE (1) | DE60205454T2 (ko) |
| ES (1) | ES2248531T3 (ko) |
| MX (1) | MXPA03006422A (ko) |
| WO (1) | WO2002062773A1 (ko) |
| ZA (1) | ZA200305382B (ko) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0226855D0 (en) | 2002-11-18 | 2002-12-24 | Queen Mary & Westfield College | Histone deacetylase inhibitors |
| EP1608628A2 (en) * | 2003-03-17 | 2005-12-28 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| EP1713460A2 (en) * | 2003-12-10 | 2006-10-25 | Wisconsin Alumni Research Foundation | Fk228 analogs and their use as hdac-inhibitors |
| US20050137234A1 (en) * | 2003-12-19 | 2005-06-23 | Syrrx, Inc. | Histone deacetylase inhibitors |
| US20050159470A1 (en) * | 2003-12-19 | 2005-07-21 | Syrrx, Inc. | Histone deacetylase inhibitors |
| WO2006016680A1 (en) * | 2004-08-09 | 2006-02-16 | Astellas Pharma Inc. | Hydroxyamide compounds having activity as inhibitors of histone deacetylase (hdac) |
| JP2008524246A (ja) * | 2004-12-16 | 2008-07-10 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼ阻害剤 |
| US20100087328A1 (en) * | 2005-03-01 | 2010-04-08 | The Regents Of The University Of Michigan | Brm expression and related diagnostics |
| US7604939B2 (en) * | 2005-03-01 | 2009-10-20 | The Regents Of The University Of Michigan | Methods of identifying active BRM expression-promoting HDAC inhibitors |
| WO2006122319A2 (en) * | 2005-05-11 | 2006-11-16 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| EA200800321A1 (ru) * | 2005-07-14 | 2008-06-30 | Такеда Сан Диего, Инк. | Ингибиторы гистондеацетилазы |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
| JP2009506069A (ja) | 2005-08-26 | 2009-02-12 | ブレインセルス，インコーポレイティド | ムスカリン性受容体調節による神経発生 |
| CA2625153A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| US20070112017A1 (en) | 2005-10-31 | 2007-05-17 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| EP1976835A2 (en) * | 2006-01-13 | 2008-10-08 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| EP2377531A2 (en) | 2006-05-09 | 2011-10-19 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| US7678808B2 (en) | 2006-05-09 | 2010-03-16 | Braincells, Inc. | 5 HT receptor mediated neurogenesis |
| ES2288803B1 (es) * | 2006-07-07 | 2008-12-16 | Universidad De Granada | Derivados de benzo(d)isotiazoles como inhibidores de las histonas desacetilasas. |
| WO2008030651A1 (en) | 2006-09-08 | 2008-03-13 | Braincells, Inc. | Combinations containing a 4-acylaminopyridine derivative |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| GB0620823D0 (en) | 2006-10-19 | 2006-11-29 | Univ London | Histone deacetylase inhibitors |
| TWI519508B (zh) * | 2007-06-12 | 2016-02-01 | Achaogen Inc | 抗菌劑 |
| WO2009002941A1 (en) * | 2007-06-22 | 2008-12-31 | Board Of Regents, The University Of Texas System | Composition and method for the treatment of diseases affected by histone deacetylase inhibitors |
| US20100261710A1 (en) * | 2007-08-21 | 2010-10-14 | Arqule, Inc. | HDAC Inhibitors |
| WO2009067808A1 (en) * | 2007-11-27 | 2009-06-04 | Ottawa Health Research Institute | Amplification of cancer-specific oncolytic viral infection by histone deacetylase inhibitors |
| EP2231596A4 (en) * | 2007-12-14 | 2012-06-06 | Univ Georgetown | INHIBITORS OF HISTONATE ACETYLASE |
| WO2010011700A2 (en) | 2008-07-23 | 2010-01-28 | The Brigham And Women's Hospital, Inc. | Treatment of cancers characterized by chromosomal rearrangement of the nut gene |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| EP2414359A1 (en) * | 2009-03-31 | 2012-02-08 | ArQule, Inc. | Peri-fused pyrazolo-pyrimidine compounds |
| WO2015058106A1 (en) * | 2013-10-18 | 2015-04-23 | The General Hospital Corporation | Imaging histone deacetylases with a radiotracer using positron emission tomography |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6143791A (en) * | 1994-02-03 | 2000-11-07 | Cambridge Neuroscience, Inc. | Therapeutic guanidines |
| AUPO721997A0 (en) * | 1997-06-06 | 1997-07-03 | Queensland Institute Of Medical Research, The | Anticancer compounds |
| ES2238778T3 (es) * | 1997-12-25 | 2005-09-01 | Meiji Seika Kaisha, Ltd. | Derivados de tetrahidrobenzoindol. |
| US6271222B1 (en) * | 1998-05-28 | 2001-08-07 | Merck & Co., Inc. | Penem antibacterial compounds, compositions and methods of treatment |
| US6221859B1 (en) * | 1999-08-27 | 2001-04-24 | Merck & Co., Inc. | Carbapenem antibacterial compositions and methods of the treatment |
-
2002
- 2002-01-14 AR ARP020100106A patent/AR035417A1/es unknown
- 2002-01-24 MX MXPA03006422A patent/MXPA03006422A/es active IP Right Grant
- 2002-01-24 BR BR0206738-2A patent/BR0206738A/pt not_active IP Right Cessation
- 2002-01-24 US US10/470,121 patent/US7091229B2/en not_active Expired - Fee Related
- 2002-01-24 DE DE60205454T patent/DE60205454T2/de not_active Expired - Fee Related
- 2002-01-24 KR KR1020037009854A patent/KR100628013B1/ko not_active IP Right Cessation
- 2002-01-24 JP JP2002562728A patent/JP3961955B2/ja not_active Expired - Fee Related
- 2002-01-24 EP EP02714107A patent/EP1358168B1/en not_active Expired - Lifetime
- 2002-01-24 WO PCT/EP2002/000705 patent/WO2002062773A1/en active IP Right Grant
- 2002-01-24 CA CA002432196A patent/CA2432196C/en not_active Expired - Fee Related
- 2002-01-24 ES ES02714107T patent/ES2248531T3/es not_active Expired - Lifetime
- 2002-01-24 AU AU2002246053A patent/AU2002246053B2/en not_active Ceased
- 2002-01-24 CN CN028039793A patent/CN1216047C/zh not_active Expired - Fee Related
- 2002-01-24 AT AT02714107T patent/ATE301644T1/de not_active IP Right Cessation
-
2003
- 2003-07-11 ZA ZA200305382A patent/ZA200305382B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002062773A1 (en) | 2002-08-15 |
| AR035417A1 (es) | 2004-05-26 |
| DE60205454D1 (de) | 2005-09-15 |
| DE60205454T2 (de) | 2006-03-30 |
| JP2004517956A (ja) | 2004-06-17 |
| CA2432196C (en) | 2007-11-27 |
| ATE301644T1 (de) | 2005-08-15 |
| JP3961955B2 (ja) | 2007-08-22 |
| BR0206738A (pt) | 2004-02-03 |
| MXPA03006422A (es) | 2003-10-15 |
| KR20030072607A (ko) | 2003-09-15 |
| US7091229B2 (en) | 2006-08-15 |
| CA2432196A1 (en) | 2002-08-15 |
| US20040077698A1 (en) | 2004-04-22 |
| KR100628013B1 (ko) | 2006-09-26 |
| EP1358168A1 (en) | 2003-11-05 |
| CN1216047C (zh) | 2005-08-24 |
| CN1487925A (zh) | 2004-04-07 |
| AU2002246053B2 (en) | 2005-02-17 |
| ES2248531T3 (es) | 2006-03-16 |
| EP1358168B1 (en) | 2005-08-10 |
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