TWI320784B - Organic compounds - Google Patents
Organic compounds Download PDFInfo
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- TWI320784B TWI320784B TW091132476A TW91132476A TWI320784B TW I320784 B TWI320784 B TW I320784B TW 091132476 A TW091132476 A TW 091132476A TW 91132476 A TW91132476 A TW 91132476A TW I320784 B TWI320784 B TW I320784B
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- phenyl
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- 150000002894 organic compounds Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 89
- 150000003839 salts Chemical group 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 38
- -1 cyano, carboxyl Chemical group 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 230000002757 inflammatory effect Effects 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims description 15
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 230000000414 obstructive effect Effects 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 208000023504 respiratory system disease Diseases 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 claims description 3
- 238000003776 cleavage reaction Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 230000007017 scission Effects 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- 239000002689 soil Substances 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 230000002222 downregulating effect Effects 0.000 claims 1
- 239000008267 milk Substances 0.000 claims 1
- 210000004080 milk Anatomy 0.000 claims 1
- 235000013336 milk Nutrition 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- 239000000203 mixture Substances 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000003795 chemical substances by application Substances 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
- 208000006673 asthma Diseases 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 201000010099 disease Diseases 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 239000010410 layer Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 206010006895 Cachexia Diseases 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- 206010006451 bronchitis Diseases 0.000 description 9
- 108010044467 Isoenzymes Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 102100040247 Tumor necrosis factor Human genes 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 5
- 229940126062 Compound A Drugs 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- 239000005864 Sulphur Substances 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 230000000172 allergic effect Effects 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 208000010668 atopic eczema Diseases 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 239000003018 immunosuppressive agent Substances 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 229940124630 bronchodilator Drugs 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
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- 239000000843 powder Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
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- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001098805 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4A Proteins 0.000 description 3
- 101000988424 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4B Proteins 0.000 description 3
- 101000988419 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4D Proteins 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
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- 125000004448 alkyl carbonyl group Chemical group 0.000 description 3
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- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
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- 229940124589 immunosuppressive drug Drugs 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
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- 229910052757 nitrogen Inorganic materials 0.000 description 3
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- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
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- RCRNXDJXXKPOTE-LURJTMIESA-N (2s)-2-amino-4-tert-butylsulfanylbutanoic acid Chemical compound CC(C)(C)SCC[C@H](N)C(O)=O RCRNXDJXXKPOTE-LURJTMIESA-N 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
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- A61P9/00—Drugs for disorders of the cardiovascular system
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- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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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
- A61P9/12—Antihypertensives
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| GB0209882A GB0209882D0 (en) | 2002-04-30 | 2002-04-30 | Organic compounds |
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| TWI320784B true TWI320784B (en) | 2010-02-21 |
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| JP2010504933A (ja) | 2006-09-29 | 2010-02-18 | ノバルティス アーゲー | Ｐｉ３ｋ脂質キナーゼ阻害剤としてのピラゾロピリミジン |
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| ES2320954B1 (es) * | 2007-03-02 | 2010-03-16 | Laboratorio Almirall S.A. | Nuevo procedimiento de preparacion de 3-metil-4-fenilisoxazolo (3,4-d)iridazin-7(6h)-ona. |
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| BRPI0820669A2 (pt) | 2007-12-10 | 2020-08-04 | Novartis Ag | compostos orgânicos |
| JP5584138B2 (ja) | 2008-01-11 | 2014-09-03 | ノバルティス アーゲー | キナーゼ阻害剤としてのピリミジン類 |
| US8268834B2 (en) | 2008-03-19 | 2012-09-18 | Novartis Ag | Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme |
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| ES2396023T3 (es) | 2009-01-29 | 2013-02-18 | Novartis Ag | Bencimidazoles sustituidos para el tratamiento de astrocitomas |
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| BR112012003262A8 (pt) | 2009-08-12 | 2016-05-17 | Novartis Ag | compostos de hidrazona heterocíclica e seus usos para tratar câncer e inflamação |
| UA111579C2 (uk) | 2009-08-17 | 2016-05-25 | Інтеллікіне Ллк | ГЕТЕРОЦИКЛІЧНІ ПОХІДНІ 2-АМІНОБЕНЗО[d]ОКСАЗОЛУ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ НА ЇХ ОСНОВІ ТА ЇХ ЗАСТОСУВАННЯ ДЛЯ ЛІКУВАННЯ ЗАХВОРЮВАННЯ, ПОВ'АНОГО З РІ3-КІНАЗОЮ |
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| US20110082145A1 (en) * | 2009-10-01 | 2011-04-07 | Alcon Research, Ltd. | Olopatadine compositions and uses thereof |
| AU2010310449A1 (en) | 2009-10-22 | 2012-05-03 | Vertex Pharmaceuticals Incorporated | Compositions for treatment of cystic fibrosis and other chronic diseases |
| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| BR112013000946B1 (pt) | 2010-07-14 | 2020-09-08 | Novartis Ag | Compostos heterocíclicos agonistas de receptor de ip, seus usos, composição e combinação farmacêuticas |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| WO2012107500A1 (en) | 2011-02-10 | 2012-08-16 | Novartis Ag | [1, 2, 4] triazolo [4, 3 -b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| WO2012116237A2 (en) | 2011-02-23 | 2012-08-30 | Intellikine, Llc | Heterocyclic compounds and uses thereof |
| BR112013021638A2 (pt) | 2011-02-25 | 2016-08-02 | Irm Llc | "compostos inibidores de trk, seu uso e composições que os compreendem" |
| TW201311149A (zh) * | 2011-06-24 | 2013-03-16 | Ishihara Sangyo Kaisha | 有害生物防治劑 |
| US8883819B2 (en) | 2011-09-01 | 2014-11-11 | Irm Llc | Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension |
| UY34329A (es) | 2011-09-15 | 2013-04-30 | Novartis Ag | Compuestos de triazolopiridina |
| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| JP6165733B2 (ja) | 2011-09-16 | 2017-07-19 | ノバルティス アーゲー | Ｎ−置換ヘテロシクリルカルボキサミド類 |
| WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
| CN103946221B (zh) | 2011-09-16 | 2016-08-03 | 诺华股份有限公司 | 用于治疗囊性纤维化的杂环化合物 |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| US9174994B2 (en) | 2011-11-23 | 2015-11-03 | Intellikine, Llc | Enhanced treatment regimens using mTor inhibitors |
| AR089698A1 (es) | 2012-01-13 | 2014-09-10 | Novartis Ag | Compuestos heterociclicos antagonistas del receptor ip |
| US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
| MX371119B (es) | 2012-04-03 | 2020-01-17 | Novartis Ag | Productos de combinacion con los inhibidores de cinasa de tirosina y su uso. |
| CN103969300B (zh) * | 2013-01-24 | 2016-08-17 | 湖北大学 | 一种识别cgg三核苷酸重复序列的双功能电活性探针、探针的制备及试剂盒 |
| ES2637719T3 (es) | 2013-02-13 | 2017-10-16 | Novartis Ag | Compuestos heterocíclicos agonistas del receptor IP |
| MD20150071A2 (ro) | 2013-02-19 | 2016-02-29 | Pfizer Inc. | Compuşi azabenzimidazolici ca inhibitori ai PDE4 izoenzimelor pentru tratamentul tulburărilor SNC şi altor afecţiuni |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| AU2014241430B2 (en) | 2013-03-14 | 2018-04-26 | Dart Neuroscience (Cayman) Ltd. | Substituted pyridine and pyrazine compounds as PDE4 inhibitors |
| HK1219421A1 (zh) | 2013-03-15 | 2017-04-07 | 因特利凯有限责任公司 | 激酶抑制剂的组合及其用途 |
| GB201305668D0 (en) | 2013-03-28 | 2013-05-15 | Glaxosmithkline Ip Dev Ltd | Avs6 Integrin Antagonists |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途 |
| KR20160145780A (ko) | 2014-04-24 | 2016-12-20 | 노파르티스 아게 | 포스파티딜이노시톨 3-키나제 억제제로서의 아미노 피리딘 유도체 |
| CA2945212A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Amino pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| AU2014391610B2 (en) | 2014-04-24 | 2018-01-25 | Novartis Ag | Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| WO2016012896A1 (en) | 2014-07-24 | 2016-01-28 | Pfizer Inc. | Pyrazolopyrimidine compounds |
| WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
| US10195208B2 (en) | 2014-07-31 | 2019-02-05 | Novartis Ag | Combination therapy |
| EA031201B1 (ru) | 2014-08-06 | 2018-11-30 | Пфайзер Инк. | Соединения имидазопиридазина |
| GB201417002D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| GB201417094D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| CN106146491B (zh) * | 2015-03-27 | 2017-12-12 | 沈阳三生制药有限责任公司 | 被芳基或杂芳基取代的5‑羟基‑1,7‑萘啶化合物、其制备方法及其制药用途 |
| GB201604680D0 (en) | 2016-03-21 | 2016-05-04 | Glaxosmithkline Ip Dev Ltd | Chemical Compounds |
| CA3124670A1 (en) | 2018-12-28 | 2020-07-02 | Regeneron Pharmaceuticals, Inc. | Treatment of respiratory disorders with arachidonate 15-lipoxygenase (alox15) inhibitors |
| US20200383960A1 (en) | 2019-06-10 | 2020-12-10 | Novartis Ag | Pyridine and Pyrazine derivative for the Treatment of CF, COPD, and Bronchiectasis |
| CN110339192A (zh) * | 2019-08-22 | 2019-10-18 | 吉林大学 | 一种掌叶防己碱用于治疗急性肺损伤的实验方法 |
| KR20220052934A (ko) | 2019-08-28 | 2022-04-28 | 노파르티스 아게 | 치환 1,3-페닐 헤테로아릴 유도체 및 질환 치료에서의 이의 용도 |
| EP3805206B1 (en) * | 2019-10-08 | 2026-08-05 | Novaled GmbH | Compound and an organic semiconducting layer, an organic electronic device, a display device and a lighting device comprising the same |
| TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗ｔｓｌｐ抗體治療炎性或阻塞性氣道疾病之方法 |
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| GB8800397D0 (en) * | 1988-01-08 | 1988-02-10 | Sandoz Ltd | Improvements in/relating to organic compounds |
| IE903911A1 (en) * | 1989-11-20 | 1991-05-22 | Ici Plc | Diazine derivatives |
| US5466697A (en) * | 1994-07-13 | 1995-11-14 | Syntex (U.S.A.) Inc. | 8-phenyl-1,6-naphthyridin-5-ones |
| GB9622386D0 (en) * | 1996-10-28 | 1997-01-08 | Sandoz Ltd | Organic compounds |
| RU2174123C2 (ru) * | 1996-10-28 | 2001-09-27 | Новартис Аг | Производные 8-арил-1,7-нафтиридина и фармацевтическая композиция, обладающая противовоспалительной активностью |
| WO1999018077A1 (en) | 1997-10-02 | 1999-04-15 | Eisai Co., Ltd. | Fused pyridine derivatives |
| JP2002114684A (ja) | 2000-10-03 | 2002-04-16 | Eisai Co Ltd | 尿路疾患治療剤 |
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