AU729495B2 - Phosphodiesterase 4-inhibiting diazepinoindolones - Google Patents
Phosphodiesterase 4-inhibiting diazepinoindolones Download PDFInfo
- Publication number
- AU729495B2 AU729495B2 AU77652/98A AU7765298A AU729495B2 AU 729495 B2 AU729495 B2 AU 729495B2 AU 77652/98 A AU77652/98 A AU 77652/98A AU 7765298 A AU7765298 A AU 7765298A AU 729495 B2 AU729495 B2 AU 729495B2
- Authority
- AU
- Australia
- Prior art keywords
- oxo
- methyl
- phenyl
- diazepino
- dihydro
- 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.)
- Ceased
Links
- ZWOMUDQWODQGQH-UHFFFAOYSA-N 1H-pyrrolo[2,3-g][1,2]benzodiazepin-2-one Chemical class C1=CC2=NN=CC=CC2=C2C1=CC(=O)N2 ZWOMUDQWODQGQH-UHFFFAOYSA-N 0.000 title claims description 19
- MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 title abstract 2
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 title abstract 2
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 title abstract 2
- 230000002401 inhibitory effect Effects 0.000 title description 6
- 238000000034 method Methods 0.000 claims abstract description 145
- 150000001875 compounds Chemical class 0.000 claims abstract description 120
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 206010065687 Bone loss Diseases 0.000 claims abstract description 6
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- 231100000753 hepatic injury Toxicity 0.000 claims abstract description 6
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- 230000036303 septic shock Effects 0.000 claims abstract description 6
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 5
- 206010067125 Liver injury Diseases 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 230000008569 process Effects 0.000 claims description 119
- 239000000203 mixture Substances 0.000 claims description 102
- 239000000543 intermediate Substances 0.000 claims description 75
- KCKIKSJECTZLJA-UHFFFAOYSA-N indol-4-one Chemical compound O=C1C=CC=C2N=CC=C12 KCKIKSJECTZLJA-UHFFFAOYSA-N 0.000 claims description 56
- 239000002253 acid Substances 0.000 claims description 48
- -1 5 -Methoxy-2-methyl-4-oxo-4H-quinazolin-3yl Chemical group 0.000 claims description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 43
- 239000000460 chlorine Substances 0.000 claims description 41
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- 239000001257 hydrogen Substances 0.000 claims description 36
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- 150000002431 hydrogen Chemical class 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 22
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- 239000002609 medium Substances 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 13
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 150000001408 amides Chemical class 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 9
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- 229910052799 carbon Inorganic materials 0.000 claims description 8
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- HDPNBNXLBDFELL-UHFFFAOYSA-N 1,1,1-trimethoxyethane Chemical compound COC(C)(OC)OC HDPNBNXLBDFELL-UHFFFAOYSA-N 0.000 claims description 7
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- SDOFMBGMRVAJNF-SLPGGIOYSA-N (2r,3r,4r,5s)-6-aminohexane-1,2,3,4,5-pentol Chemical compound NC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO SDOFMBGMRVAJNF-SLPGGIOYSA-N 0.000 claims description 4
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- 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 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
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- IVKNUIVDQMARCO-UHFFFAOYSA-N oxazin-4-one Chemical compound O=C1C=CON=C1 IVKNUIVDQMARCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 4
- 239000000376 reactant Substances 0.000 claims description 4
- 229910052979 sodium sulfide Inorganic materials 0.000 claims description 4
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 claims description 4
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- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 3H-quinazolinyl-4-one Natural products C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
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- UPPVFNJVXPOKDU-UHFFFAOYSA-N 3-amino-1H-pyrrolo[2,3-g][1,2]benzodiazepin-2-one Chemical compound C1=CC2=NN=CC=CC2=C2C1=C(N)C(=O)N2 UPPVFNJVXPOKDU-UHFFFAOYSA-N 0.000 claims description 2
- UPZQLUGOLBVHKF-UHFFFAOYSA-N 6-amino-11-(2-methyl-4-oxoquinazolin-3-yl)-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound CC1=NC2=CC=CC=C2C(=O)N1C(C(N1CCC=2C=C(N)C=C3C1=2)=O)N=C3C1=CC=CC=C1 UPZQLUGOLBVHKF-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
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- 229960000310 isoleucine Drugs 0.000 description 1
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- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000011268 leukocyte chemotaxis Effects 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000012254 magnesium hydroxide Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 235000006109 methionine Nutrition 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- CEKCJQBZVNIMLD-UHFFFAOYSA-N methyl 2-amino-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C=C1N CEKCJQBZVNIMLD-UHFFFAOYSA-N 0.000 description 1
- OKWYFKAOYCWMLJ-UHFFFAOYSA-N methyl 2-methyl-3-(6-methyl-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl)-4-oxoquinazoline-7-carboxylate Chemical compound C=1C(C(=O)OC)=CC=C(C2=O)C=1N=C(C)N2C(C(N1CCC=2C=C(C)C=C3C1=2)=O)N=C3C1=CC=CC=C1 OKWYFKAOYCWMLJ-UHFFFAOYSA-N 0.000 description 1
- UTBCRHAMJFMIIR-UHFFFAOYSA-N methyl 3-chloro-3-oxopropanoate Chemical compound COC(=O)CC(Cl)=O UTBCRHAMJFMIIR-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- OAOSXODRWGDDCV-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine;4-methylbenzenesulfonic acid Chemical compound CN(C)C1=CC=NC=C1.CC1=CC=C(S(O)(=O)=O)C=C1 OAOSXODRWGDDCV-UHFFFAOYSA-N 0.000 description 1
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 206010036784 proctocolitis Diseases 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- BSYFXFLGOGQHFU-UHFFFAOYSA-N pyrrolo[2,3-g][1,2]benzodiazepine Chemical class N1=NC=CC=C2C3=NC=CC3=CC=C21 BSYFXFLGOGQHFU-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-M succinate(1-) Chemical compound OC(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-M 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/06—Peri-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9705422A FR2762841B1 (fr) | 1997-04-30 | 1997-04-30 | Diazepino-indolones inhibitrices de phosphodiesterases iv |
| FR97/05422 | 1997-04-30 | ||
| PCT/EP1998/002827 WO1998049169A1 (en) | 1997-04-30 | 1998-04-30 | Phosphodiesterase 4-inhibiting diazepinoindolones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU7765298A AU7765298A (en) | 1998-11-24 |
| AU729495B2 true AU729495B2 (en) | 2001-02-01 |
Family
ID=9506517
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU77652/98A Ceased AU729495B2 (en) | 1997-04-30 | 1998-04-30 | Phosphodiesterase 4-inhibiting diazepinoindolones |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US6239130B1 (https=) |
| EP (1) | EP0980374B1 (https=) |
| JP (1) | JP2001522367A (https=) |
| KR (1) | KR20010020386A (https=) |
| AT (1) | ATE232534T1 (https=) |
| AU (1) | AU729495B2 (https=) |
| BR (1) | BR9809429A (https=) |
| CA (1) | CA2278217A1 (https=) |
| DE (1) | DE69811360T2 (https=) |
| DK (1) | DK0980374T3 (https=) |
| ES (1) | ES2190083T3 (https=) |
| FR (1) | FR2762841B1 (https=) |
| HR (1) | HRP980231B1 (https=) |
| MX (1) | MXPA99006979A (https=) |
| NZ (1) | NZ337589A (https=) |
| WO (1) | WO1998049169A1 (https=) |
| ZA (1) | ZA983704B (https=) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2795731B1 (fr) * | 1999-07-02 | 2001-09-07 | Warner Lambert Co | PROCEDE DE PREPARATION DE [1,4] DIAZEPINO [6,7,1-hi] INDOL-4-ONES SUBSTITUEES |
| MXPA02008627A (es) * | 2000-03-03 | 2003-02-24 | Pfizer Prod Inc | Derivados de eteres de pirazol como agentes antiinflamatorios/analgesicos. |
| EP1161949A1 (en) | 2000-06-09 | 2001-12-12 | Warner-Lambert Company | Use od diazepinoindoles for the treatment of chronic obstructive pulmonary disease |
| EP1188438A1 (en) * | 2000-09-15 | 2002-03-20 | Warner-Lambert Company | Pharmaceutical composition for preventing or treating a disease associated with an excess of Il-12 production |
| EP1199074A1 (en) * | 2000-09-15 | 2002-04-24 | Warner-Lambert Company | Pharmaceutical composition for preventing or treating a disease associated with an excess of il-12 production |
| EP1389468A4 (en) * | 2001-05-23 | 2007-01-10 | Tanabe Seiyaku Co | COMPOSITIONS FOR PROMOTING BONE FRACTURE HEALING |
| CN1537018A (zh) | 2001-05-23 | 2004-10-13 | 田边制药株式会社 | 一种用于软骨疾病再生治疗的组合物 |
| AU2002317377A1 (en) * | 2001-07-20 | 2003-03-03 | Cancer Research Technology Limited | Biphenyl apurinic/apyrimidinic site endonuclease inhibitors to treat cancer |
| MY140561A (en) | 2002-02-20 | 2009-12-31 | Nycomed Gmbh | Dosage form containing pde 4 inhibitor as active ingredient |
| US20050187278A1 (en) * | 2003-08-28 | 2005-08-25 | Pharmacia Corporation | Treatment or prevention of vascular disorders with Cox-2 inhibitors in combination with cyclic AMP-specific phosphodiesterase inhibitors |
| WO2006073413A1 (en) * | 2004-02-20 | 2006-07-13 | The Board Of Trustees Of The University Of Illinois | Blood pressure reduction in salt-sensitive |
| MXPA06012279A (es) * | 2004-04-23 | 2007-01-31 | Celgene Corp | Metodos de uso y composiciones que comprenden moduladores de pde4 para el tratamiento y manejo de la hipertension pulmonar. |
| JP2008536888A (ja) * | 2005-04-19 | 2008-09-11 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | 肺高血圧症の治療のためのロフルミラスト |
| EP2079739A2 (en) * | 2006-10-04 | 2009-07-22 | Pfizer Products Inc. | Pyrido[4,3-d]pyrimidin-4(3h)-one derivatives as calcium receptor antagonists |
| KR20100014565A (ko) * | 2007-04-11 | 2010-02-10 | 알콘 리서치, 리미티드 | 알레르기성 비염 및 알레르기성 결막염을 치료하기 위한 ｔｎｆａ의 억제제 및 항히스타민의 용도 |
| US20090182035A1 (en) * | 2007-04-11 | 2009-07-16 | Alcon Research, Ltd. | Use of a combination of olopatadine and cilomilast to treat non-infectious rhinitis and allergic conjunctivitis |
| EP2170306A1 (en) * | 2007-06-26 | 2010-04-07 | Lexicon Pharmaceuticals, Inc. | Methods of treating serotonin-mediated diseases and disorders |
| CN102548536A (zh) * | 2009-10-01 | 2012-07-04 | 爱尔康研究有限公司 | 奥洛他定组合物及其用途 |
| WO2020139830A2 (en) | 2018-12-28 | 2020-07-02 | Regeneron Pharmaceuticals, Inc. | Treatment of respiratory disorders with arachidonate15-lipoxygenase (alox15) inhibitors |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2725719B1 (fr) * | 1994-10-14 | 1996-12-06 | Jouveinal Inst Rech | Diazepino-indoles inhibiteurs de phosphodiesterases iv |
-
1997
- 1997-04-30 FR FR9705422A patent/FR2762841B1/fr not_active Expired - Fee Related
-
1998
- 1998-04-29 HR HR980231A patent/HRP980231B1/xx not_active IP Right Cessation
- 1998-04-30 JP JP54662498A patent/JP2001522367A/ja not_active Abandoned
- 1998-04-30 EP EP98925598A patent/EP0980374B1/en not_active Expired - Lifetime
- 1998-04-30 DK DK98925598T patent/DK0980374T3/da active
- 1998-04-30 ZA ZA9803704A patent/ZA983704B/xx unknown
- 1998-04-30 AT AT98925598T patent/ATE232534T1/de not_active IP Right Cessation
- 1998-04-30 DE DE69811360T patent/DE69811360T2/de not_active Expired - Fee Related
- 1998-04-30 AU AU77652/98A patent/AU729495B2/en not_active Ceased
- 1998-04-30 US US09/380,883 patent/US6239130B1/en not_active Expired - Fee Related
- 1998-04-30 MX MXPA99006979A patent/MXPA99006979A/es unknown
- 1998-04-30 ES ES98925598T patent/ES2190083T3/es not_active Expired - Lifetime
- 1998-04-30 NZ NZ337589A patent/NZ337589A/xx unknown
- 1998-04-30 BR BR9809429-7A patent/BR9809429A/pt not_active IP Right Cessation
- 1998-04-30 WO PCT/EP1998/002827 patent/WO1998049169A1/en not_active Ceased
- 1998-04-30 CA CA002278217A patent/CA2278217A1/en not_active Abandoned
- 1998-04-30 KR KR1019997010008A patent/KR20010020386A/ko not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| FR2762841B1 (fr) | 1999-07-02 |
| EP0980374B1 (en) | 2003-02-12 |
| CA2278217A1 (en) | 1998-11-05 |
| US6239130B1 (en) | 2001-05-29 |
| DE69811360D1 (de) | 2003-03-20 |
| FR2762841A1 (fr) | 1998-11-06 |
| EP0980374A1 (en) | 2000-02-23 |
| DE69811360T2 (de) | 2003-10-09 |
| DK0980374T3 (da) | 2003-05-05 |
| ES2190083T3 (es) | 2003-07-16 |
| WO1998049169A1 (en) | 1998-11-05 |
| NZ337589A (en) | 2000-10-27 |
| AU7765298A (en) | 1998-11-24 |
| JP2001522367A (ja) | 2001-11-13 |
| HRP980231B1 (en) | 2002-06-30 |
| KR20010020386A (ko) | 2001-03-15 |
| BR9809429A (pt) | 2000-06-13 |
| ZA983704B (en) | 1999-10-25 |
| HRP980231A2 (en) | 2000-04-30 |
| MXPA99006979A (es) | 2005-04-19 |
| ATE232534T1 (de) | 2003-02-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |