OA10101A - Compounds useful for treating allergic and inflammatory diseases - Google Patents

Compounds useful for treating allergic and inflammatory diseases Download PDF

Info

Publication number: OA10101A
Authority: OA; OAPI
Prior art keywords: cyano; methoxyphenyl; cyclohexane; cyclopropylmethoxy; methyl
Prior art date: 1992-04-02

Application number

OA60565A

Other languages

English (en)

Inventor

Siegfried Benj Christensen Iv

Original Assignee

Smithkline Beecham Corp

Priority date (The priority date 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 date listed.)

1992-04-02

Filing date

1994-09-29

Publication date

1996-12-18

1994-09-29 Application filed by Smithkline Beecham Corp filed Critical Smithkline Beecham Corp

1996-12-18 Publication of OA10101A publication Critical patent/OA10101A/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 125
208000027866 inflammatory disease Diseases 0.000 title description 5
208000026935 allergic disease Diseases 0.000 title 1
230000000172 allergic effect Effects 0.000 title 1
-1 tetrahydrofuranyl,furanyl Chemical group 0.000 claims description 106
125000000217 alkyl group Chemical group 0.000 claims description 57
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
229910052739 hydrogen Inorganic materials 0.000 claims description 35
238000000034 method Methods 0.000 claims description 27
239000001257 hydrogen Substances 0.000 claims description 22
229910052799 carbon Inorganic materials 0.000 claims description 19
235000019000 fluorine Nutrition 0.000 claims description 19
125000001153 fluoro group Chemical group F* 0.000 claims description 16
229910052736 halogen Inorganic materials 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 10
229910052760 oxygen Inorganic materials 0.000 claims description 10
206010020751 Hypersensitivity Diseases 0.000 claims description 9
230000007815 allergy Effects 0.000 claims description 9
125000000335 thiazolyl group Chemical group 0.000 claims description 9
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
150000002431 hydrogen Chemical group 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
125000002971 oxazolyl group Chemical group 0.000 claims description 7
125000003226 pyrazolyl group Chemical group 0.000 claims description 7
125000001425 triazolyl group Chemical group 0.000 claims description 7
CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 6
125000005842 heteroatom Chemical group 0.000 claims description 6
UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 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
125000003831 tetrazolyl group Chemical group 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 5
NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
125000000623 heterocyclic group Chemical group 0.000 claims description 5
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000000168 pyrrolyl group Chemical group 0.000 claims description 5
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
239000007983 Tris buffer Substances 0.000 claims description 4
125000001246 bromo group Chemical group Br* 0.000 claims description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
150000003857 carboxamides Chemical class 0.000 claims description 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 3
125000000842 isoxazolyl group Chemical group 0.000 claims description 3
GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 claims description 3
125000002757 morpholinyl group Chemical group 0.000 claims description 3
125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
125000004193 piperazinyl group Chemical group 0.000 claims description 3
125000005592 polycycloalkyl group Polymers 0.000 claims description 3
150000003839 salts Chemical class 0.000 claims description 3
125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
125000001984 thiazolidinyl group Chemical group 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
ZEJDTJNXLFRPTR-UHFFFAOYSA-N 4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexene-1-carboxylic acid Chemical compound COC1=CC=C(C2(CC=C(CC2)C(O)=O)C#N)C=C1OC1CCCC1 ZEJDTJNXLFRPTR-UHFFFAOYSA-N 0.000 claims description 2
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
230000002757 inflammatory effect Effects 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
125000000160 oxazolidinyl group Chemical group 0.000 claims description 2
125000003386 piperidinyl group Chemical group 0.000 claims description 2
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
PNZXMIKHJXIPEK-UHFFFAOYSA-N cyclohexanecarboxamide Chemical compound NC(=O)C1CCCCC1 PNZXMIKHJXIPEK-UHFFFAOYSA-N 0.000 claims 1
125000005958 tetrahydrothienyl group Chemical group 0.000 claims 1
108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 47
238000011282 treatment Methods 0.000 abstract description 27
201000010099 disease Diseases 0.000 abstract description 23
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 23
230000005764 inhibitory process Effects 0.000 abstract description 15
238000004519 manufacturing process Methods 0.000 abstract description 12
230000001404 mediated effect Effects 0.000 abstract description 12
230000006433 tumor necrosis factor production Effects 0.000 abstract description 10
230000003197 catalytic effect Effects 0.000 abstract description 5
230000002255 enzymatic effect Effects 0.000 abstract description 4
102100040247 Tumor necrosis factor Human genes 0.000 abstract description 2
102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 abstract 1
108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
239000000203 mixture Substances 0.000 description 53
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
239000007787 solid Substances 0.000 description 46
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 45
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 42
239000000243 solution Substances 0.000 description 38
238000004458 analytical method Methods 0.000 description 37
238000003818 flash chromatography Methods 0.000 description 25
229940093499 ethyl acetate Drugs 0.000 description 24
235000019439 ethyl acetate Nutrition 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 21
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 21
229910052786 argon Inorganic materials 0.000 description 21
210000004027 cell Anatomy 0.000 description 20
238000000746 purification Methods 0.000 description 19
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 18
230000002401 inhibitory effect Effects 0.000 description 18
241000124008 Mammalia Species 0.000 description 17
238000006243 chemical reaction Methods 0.000 description 16
230000000694 effects Effects 0.000 description 16
241000725303 Human immunodeficiency virus Species 0.000 description 15
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
210000001616 monocyte Anatomy 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
210000001744 T-lymphocyte Anatomy 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
102000004127 Cytokines Human genes 0.000 description 10
108090000695 Cytokines Proteins 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
241000700605 Viruses Species 0.000 description 10
229910052740 iodine Inorganic materials 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
206010017533 Fungal infection Diseases 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
208000006673 asthma Diseases 0.000 description 9
229910052794 bromium Inorganic materials 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
239000003921 oil Substances 0.000 description 9
239000002904 solvent Substances 0.000 description 9
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 8
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 8
238000001727 in vivo Methods 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
241000282412 Homo Species 0.000 description 7
102000000589 Interleukin-1 Human genes 0.000 description 7
108010002352 Interleukin-1 Proteins 0.000 description 7
125000001188 haloalkyl group Chemical group 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
238000010992 reflux Methods 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
208000031888 Mycoses Diseases 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
206010040070 Septic Shock Diseases 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
238000009472 formulation Methods 0.000 description 6
208000015181 infectious disease Diseases 0.000 description 6
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238000010561 standard procedure Methods 0.000 description 6
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 5
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240000004808 Saccharomyces cerevisiae Species 0.000 description 5
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239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 5
235000011118 potassium hydroxide Nutrition 0.000 description 5
229940093932 potassium hydroxide Drugs 0.000 description 5
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 4
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YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
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BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
- 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
- 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
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C255/46—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/50—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/08—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of rings other than six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/30—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reactions not involving the formation of esterified sulfo groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
- C07C319/12—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols by reactions not involving the formation of mercapto groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Immunology (AREA)
Pulmonology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
External Artificial Organs (AREA)
Polysaccharides And Polysaccharide Derivatives (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

OA60565A 1992-04-02 1994-09-29 Compounds useful for treating allergic and inflammatory diseases OA10101A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US86203092A	1992-04-02	1992-04-02
US96876292A	1992-10-30	1992-10-30

Publications (1)

Publication Number	Publication Date
OA10101A true OA10101A (en)	1996-12-18

Family

ID=27127661

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA60565A OA10101A (en)	1992-04-02	1994-09-29	Compounds useful for treating allergic and inflammatory diseases

Country Status (16)

Country	Link
EP (3)	EP0919544B1 (fr)
JP (1)	JP2873090B2 (fr)
KR (1)	KR950700731A (fr)
AT (2)	ATE200980T1 (fr)
AU (2)	AU705566B2 (fr)
CY (2)	CY2331B1 (fr)
DE (2)	DE69332987T2 (fr)
DK (2)	DK0919544T3 (fr)
ES (2)	ES2197421T3 (fr)
MA (1)	MA22859A1 (fr)
MY (1)	MY109561A (fr)
OA (1)	OA10101A (fr)
PH (1)	PH31379A (fr)
PT (2)	PT919544E (fr)
RO (1)	RO115872B1 (fr)
RU (1)	RU2136656C1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2005187458A (ja) *	2003-12-04	2005-07-14	Santen Pharmaceut Co Ltd	シロミラストまたはその塩を有効成分とする掻痒治療剤
WO2005053672A1 (fr) *	2003-12-04	2005-06-16	Santen Pharmaceutical Co., Ltd.	Remede contre le prurit comportant du cilomilaste ou un sel de celui-ci comme principe actif
PT2359826E (pt) *	2006-07-05	2014-01-20	Takeda Gmbh	Combinação de um inibidor da hmg-coa redutase rosuvastatina e um inibidor da fosfodiesterase 4, tais como roflumilaste, óxido de n-roflumilaste, para o tratamento de doenças pulmonares inflamatórias

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1793383C3 (de) *	1968-09-10	1979-03-01	Knoll Ag, 6700 Ludwigshafen	4-Cyan-4-phenyl-aminocyclohexane und deren wasserlösliche Salze, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel
US4795757A (en) *	1984-09-04	1989-01-03	Rorer Pharmaceutical Corporation	Bisarylamines
DE3621581A1 (de) *	1986-06-27	1988-01-07	Merck Patent Gmbh	Polymerisierbare fluessigkristallmaterialien
US5096906A (en) *	1986-12-31	1992-03-17	University Of Virginia Alumni Patents Foundation	Method of inhibiting the activity of leukocyte derived cytokines
EP0633771A4 (en) *	1992-04-02	1995-02-22	Smithkline Beecham Corporation	Compounds.
WO1993019751A1 (fr) *	1992-04-02	1993-10-14	Smithkline Beecham Corporation	Composes utilisables dans le traitement des maladies inflammatoires et dans l'inhibition de la production du facteur de necrose tumorale
WO1993019747A1 (fr) *	1992-04-02	1993-10-14	Smithkline Beecham Corporation	Composes destines a traiter les maladies allergiques et inflammatoires

1993
- 1993-03-05 AT AT93907233T patent/ATE200980T1/de active
- 1993-03-05 DE DE69332987T patent/DE69332987T2/de not_active Expired - Lifetime
- 1993-03-05 PT PT98204466T patent/PT919544E/pt unknown
- 1993-03-05 DK DK98204466T patent/DK0919544T3/da active
- 1993-03-05 ES ES98204466T patent/ES2197421T3/es not_active Expired - Lifetime
- 1993-03-05 RU RU94045291A patent/RU2136656C1/ru active
- 1993-03-05 DE DE69330206T patent/DE69330206T2/de not_active Expired - Lifetime
- 1993-03-05 JP JP5517446A patent/JP2873090B2/ja not_active Expired - Lifetime
- 1993-03-05 EP EP98204466A patent/EP0919544B1/fr not_active Expired - Lifetime
- 1993-03-05 RO RO94-01601A patent/RO115872B1/ro unknown
- 1993-03-05 AT AT98204466T patent/ATE240290T1/de active
- 1993-03-05 EP EP03076446A patent/EP1420011A1/fr not_active Withdrawn
- 1993-03-05 EP EP03076447A patent/EP1380571A1/fr not_active Withdrawn
- 1993-03-05 DK DK93907233T patent/DK0633776T3/da active
- 1993-03-05 ES ES93907233T patent/ES2157923T3/es not_active Expired - Lifetime
- 1993-03-05 PT PT93907233T patent/PT633776E/pt unknown
- 1993-03-29 PH PH45956A patent/PH31379A/en unknown
- 1993-03-31 MY MYPI93000561A patent/MY109561A/en unknown
- 1993-04-01 MA MA23150A patent/MA22859A1/fr unknown
1994
- 1994-09-29 OA OA60565A patent/OA10101A/en unknown
- 1994-10-04 KR KR1019940703523A patent/KR950700731A/ko active Granted
1997
- 1997-08-08 AU AU33229/97A patent/AU705566B2/en not_active Expired
1999
- 1999-06-24 AU AU36759/99A patent/AU724115B2/en not_active Expired
2002
- 2002-11-05 CY CY0200061A patent/CY2331B1/xx unknown
2004
- 2004-08-27 CY CY0400066A patent/CY2474B1/xx unknown

Also Published As

Publication number	Publication date
RO115872B1 (ro)	2000-07-28
ES2197421T3 (es)	2004-01-01
PT633776E (pt)	2001-10-31
ATE200980T1 (de)	2001-05-15
CY2474B1 (en)	2005-06-03
DK0919544T3 (da)	2003-09-15
CY2331B1 (en)	2004-02-06
HK1012263A1 (en)	1999-07-30
AU724115B2 (en)	2000-09-14
DK0633776T3 (da)	2001-08-27
EP0919544B1 (fr)	2003-05-14
EP1380571A1 (fr)	2004-01-14
JPH07508508A (ja)	1995-09-21
JP2873090B2 (ja)	1999-03-24
PT919544E (pt)	2003-09-30
RU94045291A (ru)	1996-09-27
DE69332987T2 (de)	2004-05-19
ES2157923T3 (es)	2001-09-01
KR100344711B1 (fr)	2003-05-01
EP0919544A1 (fr)	1999-06-02
AU3322997A (en)	1997-10-23
PH31379A (en)	1998-10-29
RU2136656C1 (ru)	1999-09-10
HK1022467A1 (en)	2000-08-11
DE69330206D1 (de)	2001-06-13
EP1420011A1 (fr)	2004-05-19
ATE240290T1 (de)	2003-05-15
MA22859A1 (fr)	1993-12-31
DE69330206T2 (de)	2002-02-14
DE69332987D1 (de)	2003-06-18
MY109561A (en)	1997-02-28
AU705566B2 (en)	1999-05-27
AU3675999A (en)	1999-08-19
KR950700731A (ko)	1995-02-20

Publication	Publication Date	Title
AP516A (en)	1996-08-23	Pharmaceutical compositions containing novel compounds and their use in treating allergic and inflammatory diseases.
AU708544B2 (en)	1999-08-05	Compounds useful for treating allergic or inflammatory diseases
US6300372B1 (en)	2001-10-09	3-Cyano-3-(3,4-disubstituted) phenylcyclohexyl-1-carboxylates
EP0636026B1 (fr)	2001-12-05	Composes utilisables dans le traitement des maladies inflammatoires et dans l'inhibition de la production du facteur de necrose tumorale
WO1993019747A1 (fr)	1993-10-14	Composes destines a traiter les maladies allergiques et inflammatoires
WO1993019720A2 (fr)	1993-10-14	Composes
WO1995009623A1 (fr)	1995-04-13	Composes et compositions antiallergiques et anti-inflammatoires et leurs utilisations
WO1995009836A1 (fr)	1995-04-13	Composes et compositions de cyanocyclohexane et leurs utilisations
EP0722322A1 (fr)	1996-07-24	Composes, compositions et leur utilisation pour le traitement des allergies et de l'inflammation
EP0919544B1 (fr)	2003-05-14	Composés qui sont utiles pour la traitement des allergies et des malades de l'inflammation
WO1995009837A1 (fr)	1995-04-13	Composes cyano
HK1063180A (en)	2004-12-17	Compounds useful for treating allergic and inflammatory diseases
HK1067621A (en)	2005-04-15	Compounds useful for treating allergic and inflammatory diseases
HK1022467B (en)	2004-01-09	Compounds useful for treating allergic and inflammatory diseases
AU675640C (en)	1997-10-30	Compounds useful for treating allergic or inflammatory diseases
WO1996020156A1 (fr)	1996-07-04	Dimeres 3,3-(disubstitues)cyclohexane-1-carboxylate et leurs composes apparentes