IE53001B1 - Mannich-base hydroxamic acid prodrugs for the improved bioavailability of non-steroidal anti-inflammatory agents, a process for their preparation and a pharmaceutical composition containing them - Google Patents
Mannich-base hydroxamic acid prodrugs for the improved bioavailability of non-steroidal anti-inflammatory agents, a process for their preparation and a pharmaceutical composition containing themInfo
- Publication number
- IE53001B1 IE53001B1 IE899/81A IE89981A IE53001B1 IE 53001 B1 IE53001 B1 IE 53001B1 IE 899/81 A IE899/81 A IE 899/81A IE 89981 A IE89981 A IE 89981A IE 53001 B1 IE53001 B1 IE 53001B1
- Authority
- IE
- Ireland
- Prior art keywords
- methyl
- acid
- acetohydroxamic acid
- chlorobenzoyl
- alkyl
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims abstract description 20
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 title claims abstract description 15
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title claims description 12
- 238000000034 method Methods 0.000 title claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 239000000651 prodrug Substances 0.000 title abstract description 11
- 229940002612 prodrug Drugs 0.000 title abstract description 11
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 title description 10
- -1 cyano, carbamyl Chemical group 0.000 claims abstract description 57
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 20
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 20
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 18
- 125000003118 aryl group Chemical group 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 150000002391 heterocyclic compounds Chemical class 0.000 claims abstract description 8
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 7
- 229940121363 anti-inflammatory agent Drugs 0.000 claims abstract description 7
- 125000002252 acyl group Chemical group 0.000 claims abstract description 6
- 125000005024 alkenyl aryl group Chemical group 0.000 claims abstract description 6
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 6
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 claims abstract description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 4
- 125000005025 alkynylaryl group Chemical group 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 3
- 125000002541 furyl group Chemical group 0.000 claims abstract description 3
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
- 229960001171 acetohydroxamic acid Drugs 0.000 claims description 62
- RRUDCFGSUDOHDG-UHFFFAOYSA-N acetohydroxamic acid Chemical compound CC(O)=NO RRUDCFGSUDOHDG-UHFFFAOYSA-N 0.000 claims description 60
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 229960000905 indomethacin Drugs 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 11
- 241001465754 Metazoa Species 0.000 claims description 8
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 8
- 229960002009 naproxen Drugs 0.000 claims description 8
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 8
- 230000003637 steroidlike Effects 0.000 claims description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 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
- 150000003462 sulfoxides Chemical class 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- 229960000894 sulindac Drugs 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 150000001204 N-oxides Chemical class 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- RJMIEHBSYVWVIN-LLVKDONJSA-N (2r)-2-[4-(3-oxo-1h-isoindol-2-yl)phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1N1C(=O)C2=CC=CC=C2C1 RJMIEHBSYVWVIN-LLVKDONJSA-N 0.000 claims description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 4
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 4
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 4
- 229960001680 ibuprofen Drugs 0.000 claims description 4
- 229960004187 indoprofen Drugs 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 229960001017 tolmetin Drugs 0.000 claims description 4
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 claims description 4
- APBSKHYXXKHJFK-UHFFFAOYSA-N 2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CSC(C=2C=CC(Cl)=CC=2)=N1 APBSKHYXXKHJFK-UHFFFAOYSA-N 0.000 claims description 3
- YTRMTPPVNRALON-UHFFFAOYSA-N 2-phenyl-4-quinolinecarboxylic acid Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=CC=C1 YTRMTPPVNRALON-UHFFFAOYSA-N 0.000 claims description 3
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 229950005608 bucloxic acid Drugs 0.000 claims description 3
- IJTPQQVCKPZIMV-UHFFFAOYSA-N bucloxic acid Chemical compound ClC1=CC(C(=O)CCC(=O)O)=CC=C1C1CCCCC1 IJTPQQVCKPZIMV-UHFFFAOYSA-N 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 229960002468 cinchophen Drugs 0.000 claims description 3
- 229950011171 cinmetacin Drugs 0.000 claims description 3
- NKPPORKKCMYYTO-DHZHZOJOSA-N cinmetacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)\C=C\C1=CC=CC=C1 NKPPORKKCMYYTO-DHZHZOJOSA-N 0.000 claims description 3
- 229960001209 clonixin Drugs 0.000 claims description 3
- CLOMYZFHNHFSIQ-UHFFFAOYSA-N clonixin Chemical compound CC1=C(Cl)C=CC=C1NC1=NC=CC=C1C(O)=O CLOMYZFHNHFSIQ-UHFFFAOYSA-N 0.000 claims description 3
- KPHWPUGNDIVLNH-UHFFFAOYSA-M diclofenac sodium Chemical compound [Na+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KPHWPUGNDIVLNH-UHFFFAOYSA-M 0.000 claims description 3
- 229950006236 fenclofenac Drugs 0.000 claims description 3
- IDKAXRLETRCXKS-UHFFFAOYSA-N fenclofenac Chemical compound OC(=O)CC1=CC=CC=C1OC1=CC=C(Cl)C=C1Cl IDKAXRLETRCXKS-UHFFFAOYSA-N 0.000 claims description 3
- 229950011481 fenclozic acid Drugs 0.000 claims description 3
- 229960004369 flufenamic acid Drugs 0.000 claims description 3
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 claims description 3
- 229960002390 flurbiprofen Drugs 0.000 claims description 3
- 229950009183 ibufenac Drugs 0.000 claims description 3
- CYWFCPPBTWOZSF-UHFFFAOYSA-N ibufenac Chemical compound CC(C)CC1=CC=C(CC(O)=O)C=C1 CYWFCPPBTWOZSF-UHFFFAOYSA-N 0.000 claims description 3
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 3
- 229960000991 ketoprofen Drugs 0.000 claims description 3
- 229960003803 meclofenamic acid Drugs 0.000 claims description 3
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 claims description 3
- 229940063674 voltaren Drugs 0.000 claims description 3
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 229960000616 diflunisal Drugs 0.000 claims description 2
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 229960003464 mefenamic acid Drugs 0.000 claims description 2
- 229960000851 pirprofen Drugs 0.000 claims description 2
- PIDSZXPFGCURGN-UHFFFAOYSA-N pirprofen Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N1CC=CC1 PIDSZXPFGCURGN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004543 purin-7-yl group Chemical group N1=CN=C2N=CN(C2=C1)* 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims 2
- 230000002757 inflammatory effect Effects 0.000 claims 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
- 150000001735 carboxylic acids Chemical group 0.000 claims 1
- CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
- 150000002462 imidazolines Chemical class 0.000 claims 1
- 150000003219 pyrazolines Chemical class 0.000 claims 1
- 150000003236 pyrrolines Chemical class 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 230000000699 topical effect Effects 0.000 abstract description 13
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 10
- 239000012528 membrane Substances 0.000 abstract description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 6
- 230000002496 gastric effect Effects 0.000 abstract description 3
- 125000002843 carboxylic acid group Chemical group 0.000 abstract 1
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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- 235000002639 sodium chloride Nutrition 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
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- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
- C07D209/28—1-(4-Chlorobenzoyl)-2-methyl-indolyl-3-acetic acid, substituted in position 5 by an oxygen or nitrogen atom; Esters thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14352080A | 1980-04-24 | 1980-04-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE810899L IE810899L (en) | 1981-10-24 |
| IE53001B1 true IE53001B1 (en) | 1988-05-11 |
Family
ID=22504442
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE899/81A IE53001B1 (en) | 1980-04-24 | 1981-04-22 | Mannich-base hydroxamic acid prodrugs for the improved bioavailability of non-steroidal anti-inflammatory agents, a process for their preparation and a pharmaceutical composition containing them |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0039051B1 (enExample) |
| JP (1) | JPS56167643A (enExample) |
| AT (1) | ATE14423T1 (enExample) |
| DE (1) | DE3171467D1 (enExample) |
| DK (1) | DK156717C (enExample) |
| ES (1) | ES501573A0 (enExample) |
| GR (1) | GR74496B (enExample) |
| IE (1) | IE53001B1 (enExample) |
| PT (1) | PT72878B (enExample) |
Families Citing this family (196)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4943587A (en) * | 1988-05-19 | 1990-07-24 | Warner-Lambert Company | Hydroxamate derivatives of selected nonsteroidal antiinflammatory acyl residues and their use for cyclooxygenase and 5-lipoxygenase inhibition |
| US5112868A (en) * | 1988-05-19 | 1992-05-12 | Warner-Lambert Company | Hydroxamate derivatives of selected nonsteroidal antiinflammatory acyl residues having cyclooxygenase and 5-lipoxygenase inhibition |
| US5068251A (en) * | 1988-12-16 | 1991-11-26 | Abbott Laboratories | Lipoxygenase inhibiting compounds |
| US5212189A (en) * | 1991-12-17 | 1993-05-18 | Warner-Lambert Company | Thiadiazole or oxadiazole analogs of fenamic acids containing substituted hydroxamate side chains as antiinflammatory agents |
| US6096753A (en) | 1996-12-05 | 2000-08-01 | Amgen Inc. | Substituted pyrimidinone and pyridone compounds and methods of use |
| US6410729B1 (en) | 1996-12-05 | 2002-06-25 | Amgen Inc. | Substituted pyrimidine compounds and methods of use |
| US6022884A (en) | 1997-11-07 | 2000-02-08 | Amgen Inc. | Substituted pyridine compounds and methods of use |
| US6335329B1 (en) | 1997-12-19 | 2002-01-01 | Amgen Inc. | Carboxylic acid substituted heterocycles, derivatives thereof and methods of use |
| US6107291A (en) * | 1997-12-19 | 2000-08-22 | Amgen Inc. | Azepine or larger medium ring derivatives and methods of use |
| US6174901B1 (en) | 1998-12-18 | 2001-01-16 | Amgen Inc. | Substituted pyridine and pyridazine compounds and methods of use |
| US6187777B1 (en) | 1998-02-06 | 2001-02-13 | Amgen Inc. | Compounds and methods which modulate feeding behavior and related diseases |
| US6514964B1 (en) | 1999-09-27 | 2003-02-04 | Amgen Inc. | Fused cycloheptane and fused azacycloheptane compounds and their methods of use |
| US6849639B2 (en) | 1999-12-14 | 2005-02-01 | Amgen Inc. | Integrin inhibitors and their methods of use |
| US6429223B1 (en) * | 2000-06-23 | 2002-08-06 | Medinox, Inc. | Modified forms of pharmacologically active agents and uses therefor |
| US6921762B2 (en) | 2001-11-16 | 2005-07-26 | Amgen Inc. | Substituted indolizine-like compounds and methods of use |
| JP2005531574A (ja) | 2002-05-22 | 2005-10-20 | アムジエン・インコーポレーテツド | 痛みの治療にバニロイド受容体リガンドとして使用するためのアミノ−ピリジン、−ピリジンおよびピリダジン誘導体 |
| US7176322B2 (en) | 2002-05-23 | 2007-02-13 | Amgen Inc. | Calcium receptor modulating agents |
| US6908935B2 (en) | 2002-05-23 | 2005-06-21 | Amgen Inc. | Calcium receptor modulating agents |
| TW200410945A (en) | 2002-08-08 | 2004-07-01 | Amgen Inc | Vanilloid receptor ligands and their use in treatments" |
| US7504396B2 (en) | 2003-06-24 | 2009-03-17 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
| US7442698B2 (en) | 2003-07-24 | 2008-10-28 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
| US7582631B2 (en) | 2004-01-14 | 2009-09-01 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
| US7429616B2 (en) | 2005-07-15 | 2008-09-30 | Board Of Regents, University Of Texas System | Synthesis and complete stereochemical assignment of psymberin/irciniastatin for use as antitumor compounds |
| US7754717B2 (en) | 2005-08-15 | 2010-07-13 | Amgen Inc. | Bis-aryl amide compounds and methods of use |
| GT200600381A (es) | 2005-08-25 | 2007-03-28 | Compuestos organicos | |
| US8232427B2 (en) | 2006-03-29 | 2012-07-31 | Novartis Ag | Selective hydroxamate based MMP inhibitors |
| CA2787343C (en) | 2006-06-26 | 2016-08-02 | Amgen Inc. | Compositions comprising modified lcat and uses thereof |
| AU2007272830B2 (en) | 2006-07-14 | 2011-07-28 | Amgen Inc. | Alkyne-substituted pyridone compounds and methods of use |
| EP2079724B1 (en) | 2006-07-20 | 2010-05-26 | Amgen Inc. | Substituted pyridone compounds and methods of use |
| CA2657258A1 (en) | 2006-07-20 | 2008-01-24 | Novartis Ag | Amino-piperidine derivatives as cetp inhibitors |
| CA2658190C (en) | 2006-07-20 | 2013-01-29 | Amgen Inc. | Di-amino-substituted heterocyclic compounds and methods of use |
| HRP20160350T1 (hr) | 2007-03-23 | 2016-05-06 | Amgen Inc. | Heterociklički spojevi i njihove uporabe |
| PL2207775T3 (pl) | 2007-11-05 | 2012-08-31 | Novartis Ag | Pochodne 4-benzyloamino-1-karboksyacylo-piperydyny jako inhibitory CETP użyteczne do leczenia chorób, takich jak hiperlipidemia lub stwardnienie tętnic |
| AU2008333272B2 (en) | 2007-12-03 | 2012-03-29 | Novartis Ag | 1,2-disubstituted-4-benzylamino-pyrrolidine derivatives as CETP inhibitors useful for the treatment of diseases such as hyperli pidemia or arteriosclerosis |
| ES2524259T3 (es) | 2008-03-24 | 2014-12-04 | Novartis Ag | Inhibidores de metaloproteinasa de matriz a base de arilsulfonamida |
| CA2746307C (en) | 2008-12-17 | 2013-11-19 | Amgen Inc. | Aminopyridine and carboxypyridine compounds as phosphodiesterase 10 inhibitors |
| WO2010085968A1 (en) | 2008-12-30 | 2010-08-05 | European Molecular Biology Laboratory (Embl) | Toluidine sulfonamides and their use as hif-inhibitors |
| WO2010075869A1 (en) | 2008-12-30 | 2010-07-08 | European Molecular Biology Laboratory (Embl) | Toluidine sulfonamides and their use |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| US20110182850A1 (en) | 2009-04-10 | 2011-07-28 | Trixi Brandl | Organic compounds and their uses |
| ES2459468T3 (es) | 2009-05-15 | 2014-05-09 | Novartis Ag | Arilpiridinas como inhibidores de aldosterona sintasa |
| CA2763565A1 (en) | 2009-05-28 | 2010-12-02 | Novartis Ag | Substituted aminobutyric derivatives as neprilysin inhibitors |
| PL2435409T3 (pl) | 2009-05-28 | 2015-01-30 | Novartis Ag | Podstawione pochodne aminopropionowe jako inhibitory neprylizyny |
| CN102625799A (zh) | 2009-06-25 | 2012-08-01 | 安姆根有限公司 | 杂环化合物及其用途 |
| EP2445902A2 (en) | 2009-06-25 | 2012-05-02 | Amgen, Inc | Heterocyclic compounds and their uses as inhibitors of pi3k activity |
| CA2781865A1 (en) | 2009-06-25 | 2010-12-29 | Amgen Inc. | Polycyclic derivatives of pyridine and their use in the treatment of (inter alia) rheumatoid arthritis and similar diseases |
| JP2012531435A (ja) | 2009-06-25 | 2012-12-10 | アムジエン・インコーポレーテツド | ＰＩ３Ｋ阻害剤としての４Ｈ−ピリド［１，２−ａ］ピリミジン−４−オン誘導体 |
| UY32799A (es) | 2009-07-24 | 2011-02-28 | Novartis Ag | Derivados de oxazina y su uso en el tratamiento de trastornos neurológicos |
| EA201200321A1 (ru) | 2009-08-26 | 2012-09-28 | Новартис Аг | Тетразамещенные гетероарильные соединения и их применение в качестве модуляторов mdm2 и/или mdm4 |
| MX2012002591A (es) | 2009-09-03 | 2012-04-02 | Allergan Inc | Compuestos como moduladores de tirosina cinasas. |
| US9340555B2 (en) | 2009-09-03 | 2016-05-17 | Allergan, Inc. | Compounds as tyrosine kinase modulators |
| AU2010291206A1 (en) | 2009-09-04 | 2012-02-23 | Novartis Ag | Bipyridines useful for the treatment of proliferative diseases |
| KR20120049940A (ko) | 2009-09-04 | 2012-05-17 | 노파르티스 아게 | 키나제 억제제로서의 헤테로아릴 화합물 |
| MX2012002758A (es) | 2009-09-04 | 2012-04-19 | Novartis Ag | Pirazinil-piridinas utiles para el tratamiento de enfermedades proliferativas. |
| AR078770A1 (es) | 2009-10-27 | 2011-11-30 | Elara Pharmaceuticals Gmbh | Derivados de dihidrobenzo oxacinas y tiazinas, composiciones farmaceuticas que los contienen y uso de los mismos para el tratamiento de enfermedades inflamatorias e hiperproliferativas. |
| EP2993169B1 (en) | 2009-11-17 | 2017-12-20 | Novartis AG | Aryl-pyridine derivatives as aldosterone synthase inhibitors |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| EP2507234B1 (en) | 2009-11-30 | 2014-03-12 | Novartis AG | Imidazole derivatives as aldosterone synthase inhibitors |
| US8633313B2 (en) | 2009-12-18 | 2014-01-21 | Amgen Inc. | Heterocyclic compounds and their uses |
| WO2011073316A1 (en) | 2009-12-18 | 2011-06-23 | Novartis Ag | 4-aryl-butane-1,3-diamides |
| US8530648B2 (en) | 2009-12-21 | 2013-09-10 | Novartis Ag | Diaza-spiro[5.5]undecanes |
| ES2460915T3 (es) | 2009-12-21 | 2014-05-16 | Novartis Ag | Piridinas fusionadas con heteroarilo disustituido |
| US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
| AR080056A1 (es) | 2010-02-01 | 2012-03-07 | Novartis Ag | Derivados de ciclohexil-amida como antagonistas de los receptores de crf |
| CN102762572A (zh) | 2010-02-01 | 2012-10-31 | 诺瓦提斯公司 | 作为CRF-1受体拮抗剂的吡唑并[5,1b]*唑衍生物 |
| EP2531490B1 (en) | 2010-02-02 | 2014-10-15 | Novartis AG | Cyclohexyl amide derivatives as crf receptor antagonists |
| US8791100B2 (en) | 2010-02-02 | 2014-07-29 | Novartis Ag | Aryl benzylamine compounds |
| UY33226A (es) | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina deuterada como inhibidores de la cdk4/6 |
| UY33227A (es) | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina como inhibidores de la cdk4/6 |
| UY33304A (es) | 2010-04-02 | 2011-10-31 | Amgen Inc | Compuestos heterocíclicos y sus usos |
| AR082453A1 (es) | 2010-04-21 | 2012-12-12 | Novartis Ag | Compuestos de furopiridina, composiciones farmaceuticas que los contienen y usos de los mismos |
| CN103221404B (zh) | 2010-05-13 | 2015-12-16 | 安姆根有限公司 | 可用作pde10抑制剂的不饱和氮杂环化合物 |
| EP2569302A1 (en) | 2010-05-13 | 2013-03-20 | Amgen, Inc | Heteroaryloxyheterocyclyl compounds as pde10 inhibitors |
| US8952037B2 (en) | 2010-05-13 | 2015-02-10 | Amgen Inc. | Heteroaryloxycarbocyclyl compounds as PDE10 inhibitors |
| CA2800578A1 (en) | 2010-05-13 | 2011-11-17 | Amgen Inc. | Nitrogen-heterocyclic compounds as phosphodiesterase 10 inhibitors |
| JP2013532149A (ja) | 2010-06-17 | 2013-08-15 | ノバルティス アーゲー | ピペリジニル置換１，３−ジヒドロ−ベンゾイミダゾール−２−イリデンアミン誘導体 |
| CN102947274A (zh) | 2010-06-17 | 2013-02-27 | 诺瓦提斯公司 | 联苯基取代的1,3-二氢-苯并咪唑-2-亚基胺衍生物 |
| UY33469A (es) | 2010-06-29 | 2012-01-31 | Irm Llc Y Novartis Ag | Composiciones y metodos para modular la via de señalizacion de wnt |
| JP2013530239A (ja) | 2010-06-30 | 2013-07-25 | アムジエン・インコーポレーテツド | Ｐｉ３ｋ阻害剤としてのキノリン |
| EP2588471A1 (en) | 2010-06-30 | 2013-05-08 | Amgen Inc. | Heterocyclic compounds and their use as inhibitors of pi3k activity |
| AU2011271462A1 (en) | 2010-06-30 | 2013-01-10 | Amgen Inc. | Nitrogen containing heterocyclic compounds as PIK3 -delta inhibitors |
| MX2012015135A (es) | 2010-07-01 | 2013-05-06 | Amgen Inc | Compuestos heterociclicos y su uso como inhibidores de la actividad pi3k. |
| JP2013530236A (ja) | 2010-07-01 | 2013-07-25 | アムジエン・インコーポレーテツド | Ｐｉ３ｋ活性の阻害剤としての複素環式化合物およびその用途 |
| JP2013533884A (ja) | 2010-07-02 | 2013-08-29 | アムジエン・インコーポレーテツド | Ｐｉ３ｋ活性阻害剤としての複素環化合物およびそれらの使用 |
| UA112517C2 (uk) | 2010-07-06 | 2016-09-26 | Новартіс Аг | Тетрагідропіридопіримідинові похідні |
| CN102666507B (zh) | 2010-07-13 | 2014-09-17 | 诺华股份有限公司 | 噁嗪衍生物及其在治疗神经病症中的用途 |
| BR112013000946B1 (pt) | 2010-07-14 | 2020-09-08 | Novartis Ag | Compostos heterocíclicos agonistas de receptor de ip, seus usos, composição e combinação farmacêuticas |
| EA201300160A1 (ru) | 2010-07-22 | 2013-06-28 | Новартис Аг | 2,3,5-тризамещенные тиофены и их применение |
| US9290485B2 (en) | 2010-08-04 | 2016-03-22 | Novartis Ag | N-((6-amino-pyridin-3-yl)methyl)-heteroaryl-carboxamides |
| DK2616465T3 (da) | 2010-09-13 | 2016-02-01 | Novartis Ag | Triazin-oxadiazoler |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| EP3181566A1 (en) | 2010-09-20 | 2017-06-21 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
| US20120101110A1 (en) | 2010-10-26 | 2012-04-26 | Sangamesh Badiger | Diaza-spiro[5.5]undecanes |
| US20140031355A1 (en) | 2010-11-04 | 2014-01-30 | Amgen Inc. | Heterocyclic compounds and their uses |
| US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
| US8993631B2 (en) | 2010-11-16 | 2015-03-31 | Novartis Ag | Method of treating contrast-induced nephropathy |
| US8877815B2 (en) | 2010-11-16 | 2014-11-04 | Novartis Ag | Substituted carbamoylcycloalkyl acetic acid derivatives as NEP |
| WO2012068343A1 (en) | 2010-11-17 | 2012-05-24 | Amgen Inc. | Quinoline derivatives as pik3 inhibitors |
| JP2014500277A (ja) | 2010-12-09 | 2014-01-09 | アムジエン・インコーポレーテツド | Ｐｉｍ阻害剤としての二環式化合物 |
| JP2014500319A (ja) | 2010-12-20 | 2014-01-09 | アイアールエム・リミテッド・ライアビリティ・カンパニー | ファルネソイドｘ受容体を調節するための組成物および方法 |
| WO2012087520A1 (en) | 2010-12-20 | 2012-06-28 | Irm Llc | Compositions and methods for modulating farnesoid x receptors |
| CU24152B1 (es) | 2010-12-20 | 2016-02-29 | Irm Llc | 1,2 oxazol-8-azabiciclo[3,2,1]octano 8 il como moduladores de fxr |
| MX2013007261A (es) | 2010-12-23 | 2013-11-04 | Amgen Inc | Compuestos heterociclicos y sus usos. |
| CN103402996B (zh) | 2011-01-04 | 2015-02-11 | 诺瓦提斯公司 | 可用于治疗年龄相关性黄斑变性(amd)的吲哚化合物或其类似物 |
| EA201391033A1 (ru) | 2011-01-13 | 2014-01-30 | Новартис Аг | Ингибиторы bace-2 для лечения метаболических расстройств |
| WO2012101064A1 (en) | 2011-01-28 | 2012-08-02 | Novartis Ag | N-acyl pyrimidine biaryl compounds as protein kinase inhibitors |
| WO2012101065A2 (en) | 2011-01-28 | 2012-08-02 | Novartis Ag | Pyrimidine biaryl amine compounds and their uses |
| WO2012101063A1 (en) | 2011-01-28 | 2012-08-02 | Novartis Ag | N-acyl pyridine biaryl compounds and their uses |
| WO2012101066A1 (en) | 2011-01-28 | 2012-08-02 | Novartis Ag | Pyridine biaryl amine compounds and their uses |
| GB201103578D0 (en) | 2011-03-02 | 2011-04-13 | Sabrepharm Ltd | Dipyridinium derivatives |
| WO2012129338A1 (en) | 2011-03-22 | 2012-09-27 | Amgen Inc. | Azole compounds as pim inhibitors |
| WO2012130306A1 (en) | 2011-03-30 | 2012-10-04 | Elara Pharmaceuticals Gmbh | Bicyclic 2,3-dihyrdobenzazine compounds for use in therapy |
| WO2012130314A1 (en) | 2011-03-31 | 2012-10-04 | Elara Pharmaceuticals Gmbh | Composition comprising docetaxel |
| JP2014509616A (ja) | 2011-03-31 | 2014-04-21 | エーエムベーエルエーエム テクノロジー トランスファー ゲーエムベーハー | 治療用イミダゾ［１，２−ａ］ピリジン化合物 |
| WO2012138648A1 (en) | 2011-04-06 | 2012-10-11 | Irm Llc | Compositions and methods for modulating lpa receptors |
| JP2014516941A (ja) | 2011-04-29 | 2014-07-17 | アムジェン インコーポレイテッド | Ｐｉｍ阻害剤としての二環式ピリダジン化合物 |
| AP2013007331A0 (en) | 2011-06-24 | 2013-12-31 | Amgen Inc | TRPM8 antagonists and their use in treatments |
| EP2723718A1 (en) | 2011-06-24 | 2014-04-30 | Amgen Inc. | Trpm8 antagonists and their use in treatments |
| US8846656B2 (en) | 2011-07-22 | 2014-09-30 | Novartis Ag | Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators |
| WO2013057711A1 (en) | 2011-10-21 | 2013-04-25 | Novartis Ag | Quinazoline derivatives as pi3k modulators |
| AR089698A1 (es) | 2012-01-13 | 2014-09-10 | Novartis Ag | Compuestos heterociclicos antagonistas del receptor ip |
| WO2013105058A1 (en) | 2012-01-13 | 2013-07-18 | Novartis Ag | 7,8- dihydropyrido [3, 4 - b] pyrazines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders |
| US9115129B2 (en) | 2012-01-13 | 2015-08-25 | Novartis Ag | Substituted pyrido[2,3-B]pyrazines as IP receptor agonists |
| EP2802583A1 (en) | 2012-01-13 | 2014-11-19 | Novartis AG | Fused piperidines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders |
| EP2802582A1 (en) | 2012-01-13 | 2014-11-19 | Novartis AG | Fused dihydropyrido [2,3 -b]pyrazines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders |
| WO2013130660A1 (en) | 2012-02-28 | 2013-09-06 | Amgen Inc. | Amides as pim inhibitors |
| TW201348231A (zh) | 2012-02-29 | 2013-12-01 | Amgen Inc | 雜雙環化合物 |
| EP2828262A4 (en) | 2012-03-19 | 2015-09-23 | Forum Pharmaceuticals Inc | IMIDAZOTRIAZINONVERBINDUNGEN |
| WO2013152150A1 (en) | 2012-04-04 | 2013-10-10 | Amgen Inc. | Heterocyclic compounds and their uses |
| SG11201406973PA (en) | 2012-05-04 | 2014-12-30 | Novartis Ag | Complement pathway modulators and uses thereof |
| US20150152083A1 (en) | 2012-06-06 | 2015-06-04 | Irm Llc, A Delaware Limited Liability Company | Compounds and Compositions for Modulating EGFR Activity |
| JO3300B1 (ar) | 2012-06-06 | 2018-09-16 | Novartis Ag | مركبات وتركيبات لتعديل نشاط egfr |
| AR091436A1 (es) | 2012-06-14 | 2015-02-04 | Amgen Inc | Compuestos de azetidina y piperidina utiles como inhibidores de pde10 |
| CA2877526A1 (en) | 2012-06-20 | 2013-12-27 | Novartis Ag | Complement pathway modulators and uses thereof |
| CN104640855B (zh) | 2012-06-28 | 2017-08-29 | 诺华股份有限公司 | 补体途经调节剂及其用途 |
| JP6209605B2 (ja) | 2012-06-28 | 2017-10-04 | ノバルティス アーゲー | ピロリジン誘導体、および補体経路調節因子としてのその使用 |
| CN104619698B (zh) | 2012-06-28 | 2016-08-31 | 诺华股份有限公司 | 吡咯烷衍生物及其作为补体途径调节剂的用途 |
| EP2867229B1 (en) | 2012-06-28 | 2017-07-26 | Novartis AG | Pyrrolidine derivatives and their use as complement pathway modulators |
| WO2014002051A2 (en) | 2012-06-28 | 2014-01-03 | Novartis Ag | Complement pathway modulators and uses thereof |
| US20150191462A1 (en) | 2012-06-28 | 2015-07-09 | Novartis Ag | Pyrrolidine derivatives and their use as complement pathway modulators |
| US9550755B2 (en) | 2012-07-12 | 2017-01-24 | Novartis Ag | Complement pathway modulators and uses thereof |
| WO2014022752A1 (en) | 2012-08-03 | 2014-02-06 | Amgen Inc. | Macrocycles as pim inhibitors |
| WO2014023329A1 (en) | 2012-08-06 | 2014-02-13 | Life And Brain Gmbh | Niclosamide and its derivatives for use in the treatment of solid tumors |
| WO2014041125A1 (en) | 2012-09-13 | 2014-03-20 | Baden-Württemberg Stiftung Gmbh | Specific inhibitors of protein p21 as therapeutic agents |
| ES2637719T3 (es) | 2013-02-13 | 2017-10-16 | Novartis Ag | Compuestos heterocíclicos agonistas del receptor IP |
| SG11201506018PA (en) | 2013-02-14 | 2015-08-28 | Novartis Ag | Substituted bisphenyl butanoic phosphonic acid derivatives as nep (neutral endopeptidase) inhibitors |
| US20150018376A1 (en) | 2013-05-17 | 2015-01-15 | Novartis Ag | Pyrimidin-4-yl)oxy)-1h-indole-1-carboxamide derivatives and use thereof |
| US20160178610A1 (en) | 2013-08-07 | 2016-06-23 | Friedrich Miescher Institute For Biomedical Research | New screening method for the treatment Friedreich's ataxia |
| EP2924026A1 (en) | 2014-03-28 | 2015-09-30 | Novartis Tiergesundheit AG | Aminosulfonylmethylcyclohexanes as JAK inhibitors |
| WO2016088082A1 (en) | 2014-12-05 | 2016-06-09 | Novartis Ag | Amidomethyl-biaryl derivatives complement factor d inhibitors and uses thereof |
| CN107531686B (zh) | 2015-03-24 | 2021-07-09 | 亥姆霍兹感染研究中心有限责任公司 | 铜绿假单胞菌LecB的抑制剂 |
| US10351576B2 (en) | 2015-04-30 | 2019-07-16 | Novartis Ag | Fused tricyclic pyrazole derivatives useful for farnesoid X receptors |
| MX2018001989A (es) | 2015-08-19 | 2018-06-19 | Vivus Inc | Formulaciones farmaceuticas. |
| CN105418480B (zh) * | 2015-11-16 | 2019-05-10 | 青岛大学 | 2-(1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1氢-吲哚-3-基)-n-羟基乙酰胺的制备和应用 |
| MY197595A (en) | 2015-12-18 | 2023-06-27 | Amgen Inc | Alkyl dihydroquinoline sulfonamide compounds |
| WO2017106872A1 (en) | 2015-12-18 | 2017-06-22 | Amgen Inc | Alkynyl dihydroquinoline sulfonamide compounds |
| CN110290808B (zh) | 2017-02-10 | 2023-07-11 | 诺华股份有限公司 | 1-(4-氨基-5-溴-6-(1h-吡唑-1-基)嘧啶-2-基)-1h-吡唑-4-醇及其在治疗癌症中的用途 |
| WO2018229194A1 (en) | 2017-06-14 | 2018-12-20 | European Molecular Biology Laboratory | Benzofuran ureas or carbamates and heteroaromatic analogues thereof for use in therapy |
| JP2020523363A (ja) | 2017-06-14 | 2020-08-06 | ヨーロピアン モレキュラー バイオロジー ラボラトリーＥｕｒｏｐｅａｎ Ｍｏｌｅｃｕｌａｒ Ｂｉｏｌｏｇｙ Ｌａｂｏｒａｔｏｒｙ | 治療への使用のための二環式複素芳香族アミド化合物 |
| JP2020523379A (ja) | 2017-06-14 | 2020-08-06 | ヨーロピアン モレキュラー バイオロジー ラボラトリーＥｕｒｏｐｅａｎ Ｍｏｌｅｃｕｌａｒ Ｂｉｏｌｏｇｙ Ｌａｂｏｒａｔｏｒｙ | 治療への使用のためのベンゾフランアミドおよびそれらの複素芳香族アナログ |
| CN111032654A (zh) | 2017-06-14 | 2020-04-17 | 欧洲分子生物学实验室 | 用于疗法的双环杂芳族脲或氨基甲酸酯化合物 |
| WO2019154859A1 (en) | 2018-02-06 | 2019-08-15 | Universität Heidelberg | Fap inhibitor |
| PH12020551205A1 (en) | 2018-02-06 | 2021-04-19 | Univ Heidelberg | Fap inhibitors |
| UY38072A (es) | 2018-02-07 | 2019-10-01 | Novartis Ag | Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos |
| GB201811825D0 (en) | 2018-07-19 | 2018-09-05 | Benevolentai Bio Ltd | Organic compounds |
| GB201813791D0 (en) | 2018-08-23 | 2018-10-10 | Benevolental Bio Ltd | Organic compounds |
| MA54550A (fr) | 2018-12-20 | 2022-03-30 | Amgen Inc | Inhibiteurs de kif18a |
| IL283639B2 (en) | 2018-12-20 | 2024-06-01 | Amgen Inc | Kif18a inhibitors |
| AU2019404576B2 (en) | 2018-12-20 | 2025-07-17 | Amgen Inc. | Heteroaryl amides useful as KIF18A inhibitors |
| AU2019401495B2 (en) | 2018-12-20 | 2025-06-26 | Amgen Inc. | Heteroaryl amides useful as KIF18A inhibitors |
| JP7699100B2 (ja) | 2019-08-02 | 2025-06-26 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤 |
| US20220289724A1 (en) | 2019-08-02 | 2022-09-15 | Amgen Inc. | Kif18a inhibitors |
| MX428368B (es) | 2019-08-02 | 2025-11-13 | Amgen Inc | Inhibidores de kif18a |
| AU2020325115B2 (en) | 2019-08-02 | 2026-03-12 | Amgen Inc. | Pyridine derivatives as KIF18A inhibitors |
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| AU2021209418A1 (en) | 2020-01-22 | 2022-07-21 | Benevolentai Bio Limited | Topical pharmaceutical compositions comprising imidazo[1,2-b]pyridazine compounds |
| IL294688A (en) | 2020-01-22 | 2022-09-01 | Benevolentai Bio Ltd | Pharmaceutical compositions and their uses |
| JP2023521802A (ja) | 2020-04-14 | 2023-05-25 | アムジエン・インコーポレーテツド | 新生物疾患の処置のためのｋｉｆ１８ａ阻害剤 |
| WO2021234181A1 (en) | 2020-05-22 | 2021-11-25 | Universität Heidelberg | Use of fap inhibitor in a method of diagnosis |
| JP7880201B2 (ja) | 2020-06-10 | 2026-06-25 | アムジエン・インコーポレーテツド | シクロプロピルジヒドロキノリンスルホンアミド化合物 |
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| EP4204087A1 (en) | 2020-08-26 | 2023-07-05 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft | Inhibitors of no production |
| TW202237095A (zh) | 2020-12-03 | 2022-10-01 | 德商艾斯巴赫生物有限公司 | Ａｌｃ１抑制劑及與ｐａｒｐｉ之協同性 |
| EP4262878A1 (en) | 2020-12-17 | 2023-10-25 | Trustees Of Tufts College | Fap-activated radiotheranostics, and uses related thereto |
| CN118891042A (zh) | 2021-10-29 | 2024-11-01 | 艾斯巴赫生物有限公司 | 与新型变构结合位点结合的病毒解旋酶抑制剂 |
| WO2023161427A1 (en) | 2022-02-24 | 2023-08-31 | Eisbach Bio Gmbh | Viral combination therapy |
| CN119365198A (zh) | 2022-05-02 | 2025-01-24 | 艾斯巴赫生物有限公司 | ALC1抑制剂的用途和与PARPi的协同作用 |
| WO2024022332A1 (en) | 2022-07-26 | 2024-02-01 | Shanghai Sinotau Biotech. Co., Ltd | Fap inhibitors |
| WO2025012460A1 (en) | 2023-07-12 | 2025-01-16 | HMNC Holding GmbH | Deuterated 1,3 dihydro -2h-indole-2-one derivatives |
| EP4590664A1 (en) | 2023-09-12 | 2025-07-30 | Shanghai Sinotau Biotech. Co., Ltd | Inhibitors of prostate specific membrane antigen and use thereof |
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| AU2024366320A1 (en) | 2023-10-25 | 2026-04-16 | Eisbach Bio Gmbh | Alc1 inhibitors for use in treating cancer by potentiating the effects of several classes of approved cancer drugs |
| CN122070131A (zh) | 2023-10-25 | 2026-05-19 | 艾斯巴赫生物有限公司 | 在同源重组缺陷型（hrd）癌症的治疗中使用的作为alc1抑制剂的吡啶并噻吩并嘧啶衍生物 |
| WO2025093706A1 (en) | 2023-10-31 | 2025-05-08 | Eisbach Bio Gmbh | Alc1 inhibitors alc1i-1 and alc1i-2 for use in treating pancreatic cancer by potentiating the effect of irinotecan |
| WO2025252850A1 (en) | 2024-06-06 | 2025-12-11 | Helmholtz-Zentrum für Infektionsforschung GmbH | Thiourea based derivatives are novel antimicrobials against a. baumannii |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1081993A (en) * | 1963-04-17 | 1967-09-06 | Ici Ltd | Difluoramino compounds |
| US3336194A (en) * | 1963-04-30 | 1967-08-15 | Merck & Co Inc | Indolyl acid amides |
| US3417096A (en) * | 1965-07-01 | 1968-12-17 | Bristol Myers Co | Certain 5(1-benzoyl-3-indolylmethyl) tetrazoles |
| IT1036004B (it) * | 1968-05-21 | 1979-10-30 | Abc Ist Biolog Chem Spa | Acidt 3 indolil adetoidrossamici |
| NO134946C (enExample) * | 1970-09-09 | 1977-01-12 | Ciba Geigy Ag | |
| US4206220A (en) * | 1978-07-13 | 1980-06-03 | Interx Research Corporation | Prodrugs for the improved delivery of non-steroidal anti-inflammatory agents |
-
1981
- 1981-04-16 PT PT72878A patent/PT72878B/pt not_active IP Right Cessation
- 1981-04-21 GR GR64756A patent/GR74496B/el unknown
- 1981-04-22 IE IE899/81A patent/IE53001B1/en not_active IP Right Cessation
- 1981-04-23 JP JP6073181A patent/JPS56167643A/ja active Granted
- 1981-04-23 ES ES501573A patent/ES501573A0/es active Granted
- 1981-04-23 AT AT81103066T patent/ATE14423T1/de not_active IP Right Cessation
- 1981-04-23 DK DK182081A patent/DK156717C/da not_active IP Right Cessation
- 1981-04-23 EP EP81103066A patent/EP0039051B1/en not_active Expired
- 1981-04-23 DE DE8181103066T patent/DE3171467D1/de not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| EP0039051A2 (en) | 1981-11-04 |
| ATE14423T1 (de) | 1985-08-15 |
| JPS56167643A (en) | 1981-12-23 |
| ES8207508A1 (es) | 1982-09-16 |
| EP0039051B1 (en) | 1985-07-24 |
| EP0039051A3 (en) | 1982-05-26 |
| ES501573A0 (es) | 1982-09-16 |
| PT72878A (en) | 1981-05-01 |
| IE810899L (en) | 1981-10-24 |
| PT72878B (en) | 1983-03-29 |
| GR74496B (enExample) | 1984-06-28 |
| DE3171467D1 (en) | 1985-08-29 |
| DK156717B (da) | 1989-09-25 |
| DK182081A (da) | 1981-10-25 |
| DK156717C (da) | 1990-02-19 |
| JPH04982B2 (enExample) | 1992-01-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |