CA2824925A1 - Quinazolinone inhibitors of dynein - Google Patents
Quinazolinone inhibitors of dynein Download PDFInfo
- Publication number
- CA2824925A1 CA2824925A1 CA2824925A CA2824925A CA2824925A1 CA 2824925 A1 CA2824925 A1 CA 2824925A1 CA 2824925 A CA2824925 A CA 2824925A CA 2824925 A CA2824925 A CA 2824925A CA 2824925 A1 CA2824925 A1 CA 2824925A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- hydrogen
- chosen
- halogen
- alkylamino
- 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.)
- Abandoned
Links
- 102000013035 dynein heavy chain Human genes 0.000 title claims description 23
- 108060002430 dynein heavy chain Proteins 0.000 title claims description 23
- 239000003112 inhibitor Substances 0.000 title description 14
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical compound C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 82
- -1 cyano, nitro, acetyl Chemical group 0.000 claims abstract description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
- 239000001257 hydrogen Substances 0.000 claims abstract description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 11
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 6
- 210000004027 cell Anatomy 0.000 claims description 66
- 210000004081 cilia Anatomy 0.000 claims description 34
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 24
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 239000004215 Carbon black (E152) Substances 0.000 claims description 15
- 229930195733 hydrocarbon Natural products 0.000 claims description 15
- 150000002430 hydrocarbons Chemical class 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000004442 acylamino group Chemical group 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 238000000338 in vitro Methods 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
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- 206010028980 Neoplasm Diseases 0.000 claims description 6
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
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- 125000001624 naphthyl group Chemical group 0.000 claims description 3
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- 125000002541 furyl group Chemical group 0.000 claims description 2
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- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 8
- 150000002431 hydrogen Chemical class 0.000 claims 6
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 42
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- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
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- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
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- 239000008273 gelatin Substances 0.000 description 1
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- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
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- 239000001963 growth medium Substances 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
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- 229930014626 natural product Natural products 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
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- LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
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- FFJLRVBPVWKFTA-UHFFFAOYSA-N purealin Natural products C1=C(Br)C(OC)=C(Br)C(O)C11ON=C(C(=O)NCCCOC=2C(=CC(CC(=NO)C(=O)NCCC=3NC(N)=NC=3)=CC=2Br)Br)C1 FFJLRVBPVWKFTA-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
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- 230000000979 retarding effect Effects 0.000 description 1
- 230000007441 retrograde transport Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
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- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 229940083575 sodium dodecyl sulfate Drugs 0.000 description 1
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- 229910052717 sulfur Inorganic materials 0.000 description 1
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- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
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- 108091006106 transcriptional activators Proteins 0.000 description 1
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- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161434545P | 2011-01-20 | 2011-01-20 | |
| US61/434,545 | 2011-01-20 | ||
| PCT/US2012/021639 WO2012099916A1 (en) | 2011-01-20 | 2012-01-18 | Quinazolinone inhibitors of dynein |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2824925A1 true CA2824925A1 (en) | 2012-07-26 |
Family
ID=45774309
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2824925A Abandoned CA2824925A1 (en) | 2011-01-20 | 2012-01-18 | Quinazolinone inhibitors of dynein |
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| Country | Link |
|---|---|
| US (1) | US9145376B2 (enExample) |
| EP (1) | EP2665712A1 (enExample) |
| JP (1) | JP2014506565A (enExample) |
| AU (1) | AU2012207393A1 (enExample) |
| CA (1) | CA2824925A1 (enExample) |
| IL (1) | IL227490A0 (enExample) |
| WO (1) | WO2012099916A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102015221969A1 (de) * | 2015-11-09 | 2017-05-11 | Technische Universität Dresden | Verfahren zur automatisierten Detektion einer Aktivität von Wirkstoffen in einer Lösung |
| KR102672900B1 (ko) * | 2016-09-01 | 2024-06-10 | (주)아모레퍼시픽 | 2,4-디클로로-a-(3,4-디하이드로-4-옥소-2(1H)-퀴나졸리닐리덴)-β-옥소-벤젠프로판니트릴을 포함하는 멜라닌 증진용 조성물 |
| US11192893B2 (en) | 2017-05-18 | 2021-12-07 | The Rockefeller University | Pyrazoloquinazolinone antitumor agents |
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| JPH0995485A (ja) * | 1995-03-16 | 1997-04-08 | Takeda Chem Ind Ltd | 複素環化合物、その製造法および剤 |
| US20050080138A1 (en) * | 1999-09-16 | 2005-04-14 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
| AU2003225668A1 (en) * | 2002-03-01 | 2003-09-16 | Pintex Pharmaceutical, Inc. | Pin1-modulating compounds and methods of use thereof |
| US20060052345A1 (en) * | 2002-11-04 | 2006-03-09 | Nps Pharmaceuticals, Inc. | Quinazolinone compounds as calcilytics |
| EP2177189B1 (en) | 2003-02-12 | 2015-11-04 | The Procter and Gamble Company | Absorbent core for an absorbent article |
| WO2007124171A2 (en) * | 2006-04-20 | 2007-11-01 | Massachusetts Institute Of Technology | Compositions and methods for treating trinucleotide repeat disorders |
| AR062200A1 (es) * | 2006-08-04 | 2008-10-22 | Aeterna Zentaris Gmbh | Derivados de antraceno y su uso para el tratamiento de emfermedades tumorales bengnas y malingnas |
| US8686102B2 (en) | 2007-11-02 | 2014-04-01 | Momentive Performance Materials Inc. | Textiles treated with copolymers of epoxy compounds and amino silanes having enhanced wet-strength |
| US20090118421A1 (en) | 2007-11-02 | 2009-05-07 | Momentive Performance Materials Inc. | Copolymer of epoxy compounds and amino silanes |
| US8119640B2 (en) | 2008-02-12 | 2012-02-21 | The Board Of Trustees Of The Leland Stanford Junior University | Hedgehog pathway antagonists methods of use |
| EP2376495A4 (en) * | 2008-12-08 | 2012-10-31 | Vm Pharma Llc | COMPOSITIONS OF PROTEIN RECEPTOR TYROSINE KINASE INHIBITORS |
-
2012
- 2012-01-18 CA CA2824925A patent/CA2824925A1/en not_active Abandoned
- 2012-01-18 EP EP12706722.1A patent/EP2665712A1/en not_active Withdrawn
- 2012-01-18 AU AU2012207393A patent/AU2012207393A1/en not_active Abandoned
- 2012-01-18 WO PCT/US2012/021639 patent/WO2012099916A1/en not_active Ceased
- 2012-01-18 US US13/980,527 patent/US9145376B2/en not_active Expired - Fee Related
- 2012-01-18 JP JP2013550547A patent/JP2014506565A/ja active Pending
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2013
- 2013-07-15 IL IL227490A patent/IL227490A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2012207393A1 (en) | 2013-08-08 |
| US9145376B2 (en) | 2015-09-29 |
| EP2665712A1 (en) | 2013-11-27 |
| IL227490A0 (en) | 2013-09-30 |
| US20130296349A1 (en) | 2013-11-07 |
| WO2012099916A1 (en) | 2012-07-26 |
| JP2014506565A (ja) | 2014-03-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20180118 |