ZA200602214B - Inhibitors of phosphodiesterase type-IV - Google Patents
Inhibitors of phosphodiesterase type-IV Download PDFInfo
- Publication number
- ZA200602214B ZA200602214B ZA200602214A ZA200602214A ZA200602214B ZA 200602214 B ZA200602214 B ZA 200602214B ZA 200602214 A ZA200602214 A ZA 200602214A ZA 200602214 A ZA200602214 A ZA 200602214A ZA 200602214 B ZA200602214 B ZA 200602214B
- Authority
- ZA
- South Africa
- Prior art keywords
- compound
- formula
- phenyl
- methoxy
- cyclopentyloxy
- Prior art date
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- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title description 12
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title description 12
- 239000003112 inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 279
- 238000000034 method Methods 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 125000000304 alkynyl group Chemical group 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 20
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 17
- -1 cyano, hydroxy Chemical group 0.000 claims description 17
- 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 16
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 16
- 150000002431 hydrogen Chemical group 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 16
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 150000001204 N-oxides Chemical class 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 9
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 9
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 9
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 230000003301 hydrolyzing effect Effects 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 6
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 5
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 5
- 206010069698 Langerhans' cell histiocytosis Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 5
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 5
- 201000010105 allergic rhinitis Diseases 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims description 5
- 208000003401 eosinophilic granuloma Diseases 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 230000035939 shock Effects 0.000 claims description 5
- 208000030507 AIDS Diseases 0.000 claims description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 206010006451 bronchitis Diseases 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- AUWZMLVTZUFEFV-UHFFFAOYSA-N 1-[3-(3-cyclopentyloxy-4-methoxyphenyl)-5-methyl-1,2-oxazolidine-3-carbonyl]pyrrolidine-2-carboxylic acid Chemical compound COC1=CC=C(C2(NOC(C)C2)C(=O)N2C(CCC2)C(O)=O)C=C1OC1CCCC1 AUWZMLVTZUFEFV-UHFFFAOYSA-N 0.000 claims description 2
- ZRMSLZYPULVJIU-UHFFFAOYSA-N 1-[3-(3-cyclopentyloxy-4-methoxyphenyl)-5-methyl-4h-1,2-oxazole-5-carbonyl]-n,n-diethylpyrrolidine-2-carboxamide Chemical compound CCN(CC)C(=O)C1CCCN1C(=O)C1(C)ON=C(C=2C=C(OC3CCCC3)C(OC)=CC=2)C1 ZRMSLZYPULVJIU-UHFFFAOYSA-N 0.000 claims description 2
- BPQKSFCSTIHMHB-UHFFFAOYSA-N 1-[3-(3-cyclopentyloxy-4-methoxyphenyl)-5-methyl-4h-1,2-oxazole-5-carbonyl]-n-methylpyrrolidine-2-carboxamide Chemical compound CNC(=O)C1CCCN1C(=O)C1(C)ON=C(C=2C=C(OC3CCCC3)C(OC)=CC=2)C1 BPQKSFCSTIHMHB-UHFFFAOYSA-N 0.000 claims description 2
- LLSRLLPHUVVLQJ-UHFFFAOYSA-N 1-cycloheptyldiazepane Chemical compound C1CCCCCC1N1NCCCCC1 LLSRLLPHUVVLQJ-UHFFFAOYSA-N 0.000 claims description 2
- VHWWDFRTGWBMNT-UHFFFAOYSA-N 2-[3-(3-cyclopentyloxy-4-methoxyphenyl)-5-(piperidine-1-carbonyl)-4h-1,2-oxazol-5-yl]-1-piperidin-1-ylethanone Chemical compound COC1=CC=C(C=2CC(CC(=O)N3CCCCC3)(ON=2)C(=O)N2CCCCC2)C=C1OC1CCCC1 VHWWDFRTGWBMNT-UHFFFAOYSA-N 0.000 claims description 2
- VUXVGGWYFVRDPE-UHFFFAOYSA-N 3-(3-cyclopentyloxy-4-methoxyphenyl)-1,7-dioxa-2-azaspiro[4.4]non-2-en-6-one Chemical compound COC1=CC=C(C=2CC3(C(OCC3)=O)ON=2)C=C1OC1CCCC1 VUXVGGWYFVRDPE-UHFFFAOYSA-N 0.000 claims description 2
- WFFZGYRTVIPBFN-UHFFFAOYSA-N 3h-indene-1,2-dione Chemical compound C1=CC=C2C(=O)C(=O)CC2=C1 WFFZGYRTVIPBFN-UHFFFAOYSA-N 0.000 claims description 2
- IFBCLNZONJOJSI-UHFFFAOYSA-N [3-(3-cyclopentyloxy-4-methoxyphenyl)-5-methyl-4h-1,2-oxazol-5-yl]-(4-hydroxypiperidin-1-yl)methanone Chemical compound COC1=CC=C(C=2CC(C)(ON=2)C(=O)N2CCC(O)CC2)C=C1OC1CCCC1 IFBCLNZONJOJSI-UHFFFAOYSA-N 0.000 claims description 2
- VPLCUPMGRLTSDT-UHFFFAOYSA-N [3-(3-cyclopentyloxy-4-methoxyphenyl)-5-methyl-4h-1,2-oxazol-5-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound COC1=CC=C(C=2CC(C)(ON=2)C(=O)N2CCN(C)CC2)C=C1OC1CCCC1 VPLCUPMGRLTSDT-UHFFFAOYSA-N 0.000 claims description 2
- YUWWQYSDBLFNBZ-UHFFFAOYSA-N [3-(3-cyclopentyloxy-4-methoxyphenyl)-5-methyl-4h-1,2-oxazol-5-yl]-[2-(hydroxymethyl)pyrrolidin-1-yl]methanone Chemical compound COC1=CC=C(C=2CC(C)(ON=2)C(=O)N2C(CCC2)CO)C=C1OC1CCCC1 YUWWQYSDBLFNBZ-UHFFFAOYSA-N 0.000 claims description 2
- GIUGBRCETALQDF-UHFFFAOYSA-N [3-(3-cyclopentyloxy-4-methoxyphenyl)-5-methyl-4h-1,2-oxazol-5-yl]-pyrrolidin-1-ylmethanone Chemical compound COC1=CC=C(C=2CC(C)(ON=2)C(=O)N2CCCC2)C=C1OC1CCCC1 GIUGBRCETALQDF-UHFFFAOYSA-N 0.000 claims description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 230000004968 inflammatory condition Effects 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- QREIFHORJQHKSO-UHFFFAOYSA-N tert-butyl 4-[3-(3-cyclopentyloxy-4-methoxyphenyl)-5-methyl-4h-1,2-oxazole-5-carbonyl]piperazine-1-carboxylate Chemical compound COC1=CC=C(C=2CC(C)(ON=2)C(=O)N2CCN(CC2)C(=O)OC(C)(C)C)C=C1OC1CCCC1 QREIFHORJQHKSO-UHFFFAOYSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 22
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 9
- 239000003795 chemical substances by application Substances 0.000 claims 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 6
- 238000006243 chemical reaction Methods 0.000 claims 6
- 239000012351 deprotecting agent Substances 0.000 claims 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 5
- 238000005822 methylenation reaction Methods 0.000 claims 5
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims 4
- 241001465754 Metazoa Species 0.000 claims 4
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims 4
- 238000006264 debenzylation reaction Methods 0.000 claims 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims 4
- 239000007800 oxidant agent Substances 0.000 claims 4
- 230000003647 oxidation Effects 0.000 claims 4
- 238000007254 oxidation reaction Methods 0.000 claims 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 claims 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 3
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims 2
- 239000003810 Jones reagent Substances 0.000 claims 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical group OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical group [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims 2
- 239000003054 catalyst Substances 0.000 claims 2
- 239000003638 chemical reducing agent Substances 0.000 claims 2
- 229940043279 diisopropylamine Drugs 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 150000007530 organic bases Chemical class 0.000 claims 2
- 239000003444 phase transfer catalyst Substances 0.000 claims 2
- 239000012286 potassium permanganate Substances 0.000 claims 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 claims 2
- ADZJWYULTMTLQZ-UHFFFAOYSA-N tritylphosphane;hydrobromide Chemical compound [Br-].C=1C=CC=CC=1C(C=1C=CC=CC=1)([PH3+])C1=CC=CC=C1 ADZJWYULTMTLQZ-UHFFFAOYSA-N 0.000 claims 2
- IZYFBZDLXRHRLF-UHFFFAOYSA-N tritylphosphane;hydroiodide Chemical compound [I-].C=1C=CC=CC=1C(C=1C=CC=CC=1)([PH3+])C1=CC=CC=C1 IZYFBZDLXRHRLF-UHFFFAOYSA-N 0.000 claims 2
- JBJVUYQWNWDIQP-UHFFFAOYSA-N (4-benzylpiperidin-1-yl)-[3-(3-cyclopentyloxy-4-methoxyphenyl)-5-methyl-4h-1,2-oxazol-5-yl]methanone Chemical compound COC1=CC=C(C=2CC(C)(ON=2)C(=O)N2CCC(CC=3C=CC=CC=3)CC2)C=C1OC1CCCC1 JBJVUYQWNWDIQP-UHFFFAOYSA-N 0.000 claims 1
- XCAUWZOZIULRIG-UHFFFAOYSA-N (5-benzyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-[3-(3-cyclopentyloxy-4-methoxyphenyl)-5-methyl-4h-1,2-oxazol-5-yl]methanone Chemical compound COC1=CC=C(C=2CC(C)(ON=2)C(=O)N2C3CC(N(C3)CC=3C=CC=CC=3)C2)C=C1OC1CCCC1 XCAUWZOZIULRIG-UHFFFAOYSA-N 0.000 claims 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims 1
- VWHSSVFVRWQQPH-UHFFFAOYSA-N 2-[3-(3-cyclopentyloxy-4-methoxyphenyl)-1-oxa-2-azaspiro[4.5]dec-2-en-8-yl]isoindole-1,3-dione Chemical compound COC1=CC=C(C=2CC3(ON=2)CCC(CC3)N2C(C3=CC=CC=C3C2=O)=O)C=C1OC1CCCC1 VWHSSVFVRWQQPH-UHFFFAOYSA-N 0.000 claims 1
- BQIMXUOULCAYQO-UHFFFAOYSA-N 2-[3-(3-cyclopentyloxy-4-methoxyphenyl)-5-[2-(hydroxymethyl)piperidine-1-carbonyl]-4h-1,2-oxazol-5-yl]-1-[4-(hydroxymethyl)piperidin-1-yl]ethanone Chemical compound COC1=CC=C(C=2CC(CC(=O)N3CCC(CO)CC3)(ON=2)C(=O)N2C(CCCC2)CO)C=C1OC1CCCC1 BQIMXUOULCAYQO-UHFFFAOYSA-N 0.000 claims 1
- HEHXGIANRHJMRY-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound C1=C(OC)C(OC)=CC=C1C(C1)=NOC11COCC1 HEHXGIANRHJMRY-UHFFFAOYSA-N 0.000 claims 1
- WKJBMVPIBBHFQI-UHFFFAOYSA-N 3-(3-cyclohexyloxy-4-methoxyphenyl)-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound COC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1CCCCC1 WKJBMVPIBBHFQI-UHFFFAOYSA-N 0.000 claims 1
- DPVJZWJFXGRGJO-UHFFFAOYSA-N 3-(3-cyclopentyloxy-4-methoxyphenyl)-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound COC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1CCCC1 DPVJZWJFXGRGJO-UHFFFAOYSA-N 0.000 claims 1
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- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
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- A—HUMAN NECESSITIES
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- 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]
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- A—HUMAN NECESSITIES
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- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/10—Spiro-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Dermatology (AREA)
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- Communicable Diseases (AREA)
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- Pain & Pain Management (AREA)
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- Otolaryngology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| US49894703P | 2003-08-29 | 2003-08-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200602214B true ZA200602214B (en) | 2007-04-25 |
Family
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Family Applications (1)
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| ZA200602214A ZA200602214B (en) | 2003-08-29 | 2006-03-16 | Inhibitors of phosphodiesterase type-IV |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US7825147B2 (fr) |
| EP (1) | EP1663999A2 (fr) |
| JP (1) | JP2007504123A (fr) |
| AR (1) | AR045536A1 (fr) |
| AU (1) | AU2004268847A1 (fr) |
| BR (1) | BRPI0413330A (fr) |
| CA (1) | CA2537185A1 (fr) |
| NZ (1) | NZ545748A (fr) |
| RU (1) | RU2387646C2 (fr) |
| WO (1) | WO2005021515A2 (fr) |
| ZA (1) | ZA200602214B (fr) |
Families Citing this family (33)
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| EP1663999A2 (fr) | 2003-08-29 | 2006-06-07 | Ranbaxy Laboratories, Ltd. | Inhibiteurs de la phosphodiesterase de type iv |
| EP1694655A2 (fr) * | 2003-11-26 | 2006-08-30 | Ranbaxy Laboratories Limited | Inhibiteurs de la phosphodiesterase |
| MXPA06011697A (es) * | 2004-04-08 | 2006-12-14 | Wyeth Corp | Metodo para preparar 3-ciclopentiloxi-4-metoxibenzaldehido. |
| US20080009535A1 (en) * | 2004-08-30 | 2008-01-10 | Sarala Balachandran | Inhibitors of phosphodiesterase type-IV |
| ES2370788T3 (es) * | 2005-02-07 | 2011-12-22 | Aerocrine Ab | Controlar flujo de aliento exhalado durante análisis. |
| DE102005044813A1 (de) | 2005-05-19 | 2007-10-04 | Grünenthal GmbH | Substituierte Spiro-Verbindungen und deren Verwendung zur Herstellung von Arzneimitteln |
| DE102005044814A1 (de) * | 2005-05-19 | 2006-11-23 | Grünenthal GmbH | Substituierte Sprio-Verbindungen und deren Verwendung zur Herstellung von Arzneimitteln |
| WO2007031977A2 (fr) | 2005-09-16 | 2007-03-22 | Ranbaxy Laboratories Limited | Inhibiteurs de la phosphodiesterase |
| US7915286B2 (en) | 2005-09-16 | 2011-03-29 | Ranbaxy Laboratories Limited | Substituted pyrazolo [3,4-b] pyridines as phosphodiesterase inhibitors |
| EP1940810A2 (fr) * | 2005-10-19 | 2008-07-09 | Ranbaxy Laboratories Limited | Inhibiteurs de phosphodiesterase de type-iv |
| CA2626628A1 (fr) * | 2005-10-19 | 2007-04-26 | Ranbaxy Laboratories Limited | Compositions d'inhibiteurs de la phosphodiesterase de type iv |
| AU2006305619A1 (en) | 2005-10-19 | 2007-04-26 | Ranbaxy Laboratories Limited | Pharmaceutical compositions of muscarinic receptor antagonists |
| WO2008035316A2 (fr) * | 2006-09-22 | 2008-03-27 | Ranbaxy Laboratories Limited | Inhibiteurs de phosphodiestérase |
| US20110021473A1 (en) * | 2006-09-22 | 2011-01-27 | Ranbaxy Laboratories Limited | Inhibitors of phosphodiesterase type-iv |
| EP2124943A1 (fr) * | 2007-03-14 | 2009-12-02 | Ranbaxy Laboratories Limited | Dérivés de pyrazolo[3,4-b]pyridine comme inhibiteurs de phosphodiestérases |
| AU2008224541B2 (en) * | 2007-03-14 | 2013-08-22 | Sun Pharmaceutical Industries Limited | Pyrazolo (3, 4-b) pyridine derivatives as phosphodiesterase inhibitors |
| RS52074B (en) * | 2007-05-16 | 2012-06-30 | Nycomed Gmbh | PIRAZOLONE DERIVATED AS PDE4 INHIBITORS |
| US20100022590A1 (en) * | 2008-01-17 | 2010-01-28 | Biovitrum Ab (Publ.) | Novel compounds |
| EP2576496B1 (fr) | 2010-05-27 | 2017-03-08 | Catalyst Biosciences, Inc. | Récepteurs nicotiniques utiles comme antagonistes non compétitifs |
| DK2691379T3 (en) | 2011-03-31 | 2017-02-13 | Bayer Ip Gmbh | HERBICID AND FUNGICID ACTIVE 3-PHENYLISOXAZOLINE-5-CARBOXAMIDES AND 3-PHENYLISOXAZOLIN-5-THIOAMIDES |
| RU2461547C1 (ru) * | 2011-05-20 | 2012-09-20 | Государственное образовательное учреждение высшего профессионального образования Волгоградский государственный технический университет (ВолгГТУ) | Способ получения адамант-1-илсодержащих эфиров 3-r-4,5-дигидроизоксазол-5-карбоновых кислот |
| WO2013106547A1 (fr) | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Composés promoteurs de réplication des cellules bêta et leurs procédés d'utilisation |
| CN103467260A (zh) * | 2012-06-08 | 2013-12-25 | 上海医药工业研究院 | 一种3-羟基-4-二氟甲氧基苯甲醛的制备方法 |
| CN104812739B (zh) | 2012-09-25 | 2017-12-12 | 拜尔农作物科学股份公司 | 具有除草作用的3‑苯基异噁唑啉衍生物 |
| EP2907806A1 (fr) | 2014-02-14 | 2015-08-19 | Universita Degli Studi Di Genova | Nouveux composés comme inhibiteurs sélectifs de PDE4D |
| EA035823B1 (ru) | 2015-07-31 | 2020-08-17 | Пфайзер Инк. | 1,1,1-трифтор-3-гидроксипропан-2-ил карбаматные производные и 1,1,1-трифтор-4-гидроксибутан-2-ил карбаматные производные в качестве ингибиторов magl |
| CA3050625C (fr) | 2017-01-20 | 2021-07-20 | Pfizer Inc. | Derives de 1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate utilises comme inhibiteurs de la magl |
| MX2019008690A (es) | 2017-01-23 | 2019-09-18 | Pfizer | Compuestos espiro heterociclicos como inhibidores de magl. |
| MX2019014981A (es) | 2017-06-13 | 2020-02-24 | Bayer Ag | 3-fenilisoxazolin-5-carboxamidas de tetrahidro- y dihidrofurancarboxamidas con efecto herbicida. |
| SI3638665T1 (sl) | 2017-06-13 | 2021-11-30 | Bayer Aktiengesellschaft | Herbicidni 3-fenilizoksazolin-5-karboksamidi tetrahidro in dihidrofuran karboksilnih kislin in estrov |
| EP3668845B1 (fr) | 2017-08-17 | 2024-06-26 | Bayer Aktiengesellschaft | Herbicides efficaces de 3-phénylisoxazolin-5-carboxamide des acides et des esters carboniques cyclopentyles |
| CA3089286A1 (fr) | 2018-01-25 | 2019-08-01 | Bayer Aktiengesellschaft | 3-phenyl-isoxazoline-5-carboxamides de derives d'acide cyclopentenyl-carboxylique a action herbicide |
| EP3937637B1 (fr) | 2019-03-12 | 2023-04-19 | Bayer Aktiengesellschaft | 3-phénylisoxazolino-5-carboxamides des ester d'acide carboxylique de cyclopentényle contenant du s à action herbicide |
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| JPH1171319A (ja) * | 1997-08-29 | 1999-03-16 | Asahi Glass Co Ltd | （ジフルオロメトキシ）ベンズアルデヒド化合物の製造方法 |
| ES2311126T3 (es) | 2000-05-26 | 2009-02-01 | Pfizer Inc. | Derivados de triazolil tropano como moduladores de ccr5. |
| CN1478084A (zh) | 2000-09-29 | 2004-02-25 | 用于治疗炎性疾病的化合物 | |
| DE10050995A1 (de) | 2000-10-14 | 2002-04-18 | Boehringer Ingelheim Pharma | Neue Anticholinergika, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| JP2004516295A (ja) * | 2000-12-21 | 2004-06-03 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | サブタイプ選択的なｎ−メチル−ｄ−アスパラギン酸拮抗薬としてのピペリジン誘導体 |
| WO2002081447A1 (fr) | 2001-04-06 | 2002-10-17 | Daewoong Pharmaceutical Co., Ltd. | Derives de 3-cyclopentyloxy-4-methoxyphenyl-isothiazolinone et utilisation de ces derives |
| AU2002314944B2 (en) | 2001-06-08 | 2008-03-06 | Cytokine Pharmasciences, Inc. | Isoxazoline compounds having MIF antagonist activity |
| US7183321B2 (en) | 2001-12-17 | 2007-02-27 | Bristol-Myers Squibb Company | Antidiabetic formulation and method |
| EP1663999A2 (fr) | 2003-08-29 | 2006-06-07 | Ranbaxy Laboratories, Ltd. | Inhibiteurs de la phosphodiesterase de type iv |
| ES2370788T3 (es) | 2005-02-07 | 2011-12-22 | Aerocrine Ab | Controlar flujo de aliento exhalado durante análisis. |
| CA2626628A1 (fr) | 2005-10-19 | 2007-04-26 | Ranbaxy Laboratories Limited | Compositions d'inhibiteurs de la phosphodiesterase de type iv |
| AU2006305619A1 (en) | 2005-10-19 | 2007-04-26 | Ranbaxy Laboratories Limited | Pharmaceutical compositions of muscarinic receptor antagonists |
-
2004
- 2004-08-30 EP EP04769218A patent/EP1663999A2/fr not_active Withdrawn
- 2004-08-30 JP JP2006524461A patent/JP2007504123A/ja not_active Withdrawn
- 2004-08-30 CA CA002537185A patent/CA2537185A1/fr not_active Abandoned
- 2004-08-30 WO PCT/IB2004/002804 patent/WO2005021515A2/fr active Application Filing
- 2004-08-30 RU RU2006109366/04A patent/RU2387646C2/ru not_active IP Right Cessation
- 2004-08-30 NZ NZ545748A patent/NZ545748A/en unknown
- 2004-08-30 BR BRPI0413330-7A patent/BRPI0413330A/pt not_active Application Discontinuation
- 2004-08-30 AU AU2004268847A patent/AU2004268847A1/en not_active Abandoned
- 2004-08-30 US US10/930,569 patent/US7825147B2/en not_active Expired - Fee Related
- 2004-08-30 AR ARP040103114A patent/AR045536A1/es unknown
-
2006
- 2006-03-16 ZA ZA200602214A patent/ZA200602214B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007504123A (ja) | 2007-03-01 |
| US7825147B2 (en) | 2010-11-02 |
| NZ545748A (en) | 2010-03-26 |
| RU2387646C2 (ru) | 2010-04-27 |
| EP1663999A2 (fr) | 2006-06-07 |
| AU2004268847A1 (en) | 2005-03-10 |
| AR045536A1 (es) | 2005-11-02 |
| WO2005021515A2 (fr) | 2005-03-10 |
| CA2537185A1 (fr) | 2005-03-10 |
| WO2005021515B1 (fr) | 2005-10-27 |
| WO2005021515A3 (fr) | 2005-08-25 |
| US20050075383A1 (en) | 2005-04-07 |
| BRPI0413330A (pt) | 2006-10-10 |
| RU2006109366A (ru) | 2007-10-10 |
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