CA2727069A1 - Thiophene or thiazole derivatives and their use as pi3k inhibitors - Google Patents
Thiophene or thiazole derivatives and their use as pi3k inhibitors Download PDFInfo
- Publication number
- CA2727069A1 CA2727069A1 CA2727069A CA2727069A CA2727069A1 CA 2727069 A1 CA2727069 A1 CA 2727069A1 CA 2727069 A CA2727069 A CA 2727069A CA 2727069 A CA2727069 A CA 2727069A CA 2727069 A1 CA2727069 A1 CA 2727069A1
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- Prior art keywords
- membered
- optionally substituted
- nitrogen
- sulfur
- oxygen
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- 229930192474 thiophene Natural products 0.000 title description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 title 2
- 239000012828 PI3K inhibitor Substances 0.000 title 1
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 title 1
- 150000007979 thiazole derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 175
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 13
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 12
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 12
- 230000002062 proliferating effect Effects 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims description 111
- 229910052757 nitrogen Inorganic materials 0.000 claims description 105
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 98
- 239000000203 mixture Substances 0.000 claims description 89
- 125000005842 heteroatom Chemical group 0.000 claims description 77
- 229910052717 sulfur Inorganic materials 0.000 claims description 77
- 229910052760 oxygen Inorganic materials 0.000 claims description 76
- 239000011593 sulfur Chemical group 0.000 claims description 76
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 75
- 239000001301 oxygen Chemical group 0.000 claims description 75
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 73
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 70
- 125000000623 heterocyclic group Chemical group 0.000 claims description 59
- 125000001931 aliphatic group Chemical group 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 34
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 33
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 30
- 125000001424 substituent group Chemical group 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000002947 alkylene group Chemical group 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 230000000694 effects Effects 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
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 206010002198 Anaphylactic reaction Diseases 0.000 claims description 3
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 3
- 208000006029 Cardiomegaly Diseases 0.000 claims description 3
- 208000032612 Glial tumor Diseases 0.000 claims description 3
- 206010018338 Glioma Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 206010020751 Hypersensitivity Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 208000038016 acute inflammation Diseases 0.000 claims description 3
- 230000006022 acute inflammation Effects 0.000 claims description 3
- 230000007815 allergy Effects 0.000 claims description 3
- 230000036783 anaphylactic response Effects 0.000 claims description 3
- 208000003455 anaphylaxis Diseases 0.000 claims description 3
- 230000005784 autoimmunity Effects 0.000 claims description 3
- 208000037976 chronic inflammation Diseases 0.000 claims description 3
- 230000006020 chronic inflammation Effects 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 claims 1
- 108091007960 PI3Ks Proteins 0.000 abstract description 37
- 239000003112 inhibitor Substances 0.000 abstract description 10
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 abstract 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 142
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 92
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 73
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 71
- 235000019253 formic acid Nutrition 0.000 description 71
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
- 239000000243 solution Substances 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- -1 ATR Proteins 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 37
- 102000038030 PI3Ks Human genes 0.000 description 36
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
- 239000011541 reaction mixture Substances 0.000 description 31
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 230000015572 biosynthetic process Effects 0.000 description 30
- 238000012552 review Methods 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- 125000003118 aryl group Chemical group 0.000 description 26
- 238000003786 synthesis reaction Methods 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- 235000002639 sodium chloride Nutrition 0.000 description 25
- 125000001072 heteroaryl group Chemical group 0.000 description 24
- 206010028980 Neoplasm Diseases 0.000 description 23
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- 201000011510 cancer Diseases 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- 239000002904 solvent Substances 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- VTHCULBLEKIUTL-UHFFFAOYSA-N thiophene-3-carbonitrile Chemical compound N#CC1=[C]SC=C1 VTHCULBLEKIUTL-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- 229940093499 ethyl acetate Drugs 0.000 description 17
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 16
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 229910052786 argon Inorganic materials 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 238000007876 drug discovery Methods 0.000 description 14
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- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
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- 125000004429 atom Chemical group 0.000 description 12
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 10
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13248408P | 2008-06-19 | 2008-06-19 | |
| US61/132,484 | 2008-06-19 | ||
| PCT/US2009/003607 WO2009154741A1 (en) | 2008-06-19 | 2009-06-17 | Thiophene or thiazole derivatives and their use as pi3k inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2727069A1 true CA2727069A1 (en) | 2009-12-23 |
Family
ID=41010579
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2727069A Abandoned CA2727069A1 (en) | 2008-06-19 | 2009-06-17 | Thiophene or thiazole derivatives and their use as pi3k inhibitors |
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|---|---|
| US (3) | US8183240B2 (enExample) |
| EP (1) | EP2313399B1 (enExample) |
| JP (1) | JP5596026B2 (enExample) |
| KR (1) | KR20110018451A (enExample) |
| CN (1) | CN102066365A (enExample) |
| AU (1) | AU2009260782B2 (enExample) |
| BR (1) | BRPI0914223A2 (enExample) |
| CA (1) | CA2727069A1 (enExample) |
| CL (1) | CL2010001474A1 (enExample) |
| CO (1) | CO6331431A2 (enExample) |
| CR (1) | CR20110032A (enExample) |
| EA (1) | EA201170052A1 (enExample) |
| ES (1) | ES2491522T3 (enExample) |
| GE (1) | GEP20125650B (enExample) |
| IL (1) | IL210055A0 (enExample) |
| MA (1) | MA32468B1 (enExample) |
| MX (1) | MX2010014125A (enExample) |
| NZ (1) | NZ589844A (enExample) |
| UA (1) | UA106206C2 (enExample) |
| WO (1) | WO2009154741A1 (enExample) |
| ZA (1) | ZA201008875B (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009094224A1 (en) | 2008-01-25 | 2009-07-30 | Millennium Pharmaceuticals, Inc. | Thiophenes and their use as phosphatidylinositol 3-kinase (pi3k) inhibitors |
| AU2009260782B2 (en) * | 2008-06-19 | 2014-12-11 | Millennium Pharmaceuticals, Inc. | Thiophene or thiazole derivatives and their use as PI3K inhibitors |
| US9139589B2 (en) | 2009-01-30 | 2015-09-22 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| US9090601B2 (en) | 2009-01-30 | 2015-07-28 | Millennium Pharmaceuticals, Inc. | Thiazole derivatives |
| US8796314B2 (en) | 2009-01-30 | 2014-08-05 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| EP2603216A4 (en) * | 2010-08-11 | 2013-12-18 | Millennium Pharm Inc | HETEROARYLE AND USES THEREOF |
| WO2012021611A1 (en) * | 2010-08-11 | 2012-02-16 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| TW201217365A (en) | 2010-08-11 | 2012-05-01 | Millennium Pharm Inc | Heteroaryls and uses thereof |
| JP5726635B2 (ja) | 2010-08-25 | 2015-06-03 | 株式会社Ｎｔｔドコモ | マルチモードフロントエンド回路 |
| UY33671A (es) | 2010-10-13 | 2012-04-30 | Millenium Pharmaceuticals Inc | Heteroarilos y sus usos |
| CN102503930B (zh) * | 2011-10-28 | 2014-07-02 | 浙江大学 | 3,4,5,-三取代氨基噻吩类化合物及其制备和用途 |
| DK2790705T3 (en) | 2011-12-15 | 2018-03-12 | Novartis Ag | Use of inhibitors of the activity or function of PI3K |
| WO2013096642A1 (en) * | 2011-12-23 | 2013-06-27 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| IN2014DN06898A (enExample) | 2012-03-14 | 2015-05-15 | Salk Inst For Biological Studi | |
| JP6576326B2 (ja) | 2013-03-14 | 2019-09-18 | ソーク インスティテュート フォー バイオロジカル スタディーズ | 腫瘍溶解性アデノウイルス組成物 |
| EP2968537A1 (en) | 2013-03-15 | 2016-01-20 | Genentech, Inc. | Methods of treating cancer and preventing cancer drug resistance |
| CA2939048A1 (en) * | 2014-02-14 | 2015-08-20 | The University Of British Columbia | Human androgen receptor dna-binding domain (dbd) compounds as therapeutics and methods for their use |
| JP7054527B2 (ja) | 2016-02-23 | 2022-04-14 | ソーク インスティテュート フォー バイオロジカル スタディーズ | アデノウイルスの複製動態を測定するための高スループットアッセイ |
| KR20220163505A (ko) | 2016-02-23 | 2022-12-09 | 솔크 인스티튜트 포 바이올로지칼 스터디즈 | 바이러스 동역학에 미치는 영향 최소화를 위한 치료용 아데노바이러스의 외인성 유전자 발현 |
| JP2019536468A (ja) | 2016-12-12 | 2019-12-19 | ソーク インスティテュート フォー バイオロジカル スタディーズ | 腫瘍を標的にする合成アデノウイルスおよびその使用 |
| AU2019251356B2 (en) | 2018-04-09 | 2025-06-12 | Salk Institute For Biological Studies | Oncolytic adenovirus compositions with enhanced replication properties |
| WO2020261144A1 (en) * | 2019-06-28 | 2020-12-30 | Pfizer Inc. | 5-(thiophen-2-yl)-1h-tetrazole derivatives as bckdk inhibitors useful for treating various diseases |
| CN110759900B (zh) * | 2019-10-25 | 2021-07-30 | 沈阳药科大学 | 噻吩类化合物的制备方法和用途 |
| AU2020406139A1 (en) | 2019-12-20 | 2022-06-30 | Bayer Aktiengesellschaft | Substituted thiophene carboxamides, thiophene carboxylic acids and derivatives thereof |
| CN113527281B (zh) * | 2020-04-20 | 2023-12-22 | 昆山彭济凯丰生物科技有限公司 | 杂环化合物及其制备方法和应用 |
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| DD275870A1 (de) | 1988-09-27 | 1990-02-07 | Univ Leipzig | Verfahren zur herstellung von in 5-position verschiedenartig substituierten 3-aminothiophen-4-carbonitrilen |
| WO2006078287A2 (en) | 2004-05-06 | 2006-07-27 | Plexxikon, Inc. | Pde4b inhibitors and uses therefor |
| GB0508472D0 (en) * | 2005-04-26 | 2005-06-01 | Glaxo Group Ltd | Compounds |
| BRPI0710874A2 (pt) | 2006-04-26 | 2012-02-14 | Hoffmann La Roche | compostos de tienopirimidina, processos de produção dos referidos compostos, composições farmacêuticas contendo os mesmos, kit, produto, e usos dos compostos |
| US20090076009A1 (en) * | 2006-05-03 | 2009-03-19 | Arnould Jean-Claude Retired | Thiazole derivatives and their use as anti-tumour agents |
| MX2009002046A (es) * | 2006-08-24 | 2009-03-06 | Astrazeneca Ab | Derivados de morfolino pirimidina utiles en el tratamiento de trastornos proliferativos. |
| CA2704711C (en) * | 2007-09-24 | 2016-07-05 | Genentech, Inc. | Thiazolopyrimidine p13k inhibitor compounds and methods of use |
| WO2009094224A1 (en) * | 2008-01-25 | 2009-07-30 | Millennium Pharmaceuticals, Inc. | Thiophenes and their use as phosphatidylinositol 3-kinase (pi3k) inhibitors |
| AU2009260782B2 (en) * | 2008-06-19 | 2014-12-11 | Millennium Pharmaceuticals, Inc. | Thiophene or thiazole derivatives and their use as PI3K inhibitors |
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- 2009-06-17 GE GEAP200912065A patent/GEP20125650B/en unknown
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- 2009-06-17 US US12/456,455 patent/US8183240B2/en active Active
- 2009-06-17 UA UAA201100563A patent/UA106206C2/ru unknown
- 2009-06-17 EA EA201170052A patent/EA201170052A1/ru unknown
- 2009-06-17 WO PCT/US2009/003607 patent/WO2009154741A1/en not_active Ceased
- 2009-06-17 NZ NZ589844A patent/NZ589844A/xx not_active IP Right Cessation
- 2009-06-17 EP EP09767054.1A patent/EP2313399B1/en active Active
- 2009-06-17 CA CA2727069A patent/CA2727069A1/en not_active Abandoned
- 2009-06-17 KR KR1020117001175A patent/KR20110018451A/ko not_active Ceased
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|---|---|
| US8183240B2 (en) | 2012-05-22 |
| JP2011524904A (ja) | 2011-09-08 |
| CO6331431A2 (es) | 2011-10-20 |
| EP2313399B1 (en) | 2014-05-28 |
| EP2313399A1 (en) | 2011-04-27 |
| US20120202812A1 (en) | 2012-08-09 |
| US8440664B2 (en) | 2013-05-14 |
| JP5596026B2 (ja) | 2014-09-24 |
| CL2010001474A1 (es) | 2011-04-29 |
| ES2491522T3 (es) | 2014-09-08 |
| UA106206C2 (ru) | 2014-08-11 |
| MX2010014125A (es) | 2011-02-24 |
| ZA201008875B (en) | 2012-02-29 |
| WO2009154741A1 (en) | 2009-12-23 |
| KR20110018451A (ko) | 2011-02-23 |
| NZ589844A (en) | 2012-11-30 |
| WO2009154741A8 (en) | 2010-03-25 |
| AU2009260782A1 (en) | 2009-12-23 |
| IL210055A0 (en) | 2011-02-28 |
| AU2009260782B2 (en) | 2014-12-11 |
| CN102066365A (zh) | 2011-05-18 |
| US20130217689A1 (en) | 2013-08-22 |
| CR20110032A (es) | 2011-03-14 |
| MA32468B1 (fr) | 2011-07-03 |
| GEP20125650B (en) | 2012-09-25 |
| BRPI0914223A2 (pt) | 2019-09-24 |
| EA201170052A1 (ru) | 2011-06-30 |
| US20100075951A1 (en) | 2010-03-25 |
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