ZA200602214B - Inhibitors of phosphodiesterase type-IV - Google Patents

Inhibitors of phosphodiesterase type-IV Download PDF

Info

Publication number: ZA200602214B
Authority: ZA; South Africa
Prior art keywords: compound; formula; phenyl; methoxy; cyclopentyloxy
Prior art date: 2003-08-29

Application number

ZA200602214A

Other languages

English (en)

Inventor

Venkata P Palle

Balachandran Sarala

Salman Mohammad

Kakreja Gagan

Gupta Nidhi

Ray Abhijit

Sunanda G Dastidar

Original Assignee

Ranbaxy Lab Ltd

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.)

2003-08-29

Filing date

2006-03-16

Publication date

2007-04-25

2006-03-16 Application filed by Ranbaxy Lab Ltd filed Critical Ranbaxy Lab Ltd

2007-04-25 Publication of ZA200602214B publication Critical patent/ZA200602214B/en

Links

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
FNWCOKCDADLNRG-UHFFFAOYSA-N 3-(3-cyclopentyloxy-4-methoxyphenyl)-1-oxa-2,7-diazaspiro[4.4]non-2-ene Chemical compound COC1=CC=C(C=2CC3(CNCC3)ON=2)C=C1OC1CCCC1 FNWCOKCDADLNRG-UHFFFAOYSA-N 0.000 claims 1
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Classifications

- 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
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ZA200602214A 2003-08-29 2006-03-16 Inhibitors of phosphodiesterase type-IV ZA200602214B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US49894703P	2003-08-29	2003-08-29

Publications (1)

Publication Number	Publication Date
ZA200602214B true ZA200602214B (en)	2007-04-25

Family

ID=34272753

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200602214A ZA200602214B (en)	2003-08-29	2006-03-16	Inhibitors of phosphodiesterase type-IV

Country Status (11)

Country	Link
US (1)	US7825147B2 (es)
EP (1)	EP1663999A2 (es)
JP (1)	JP2007504123A (es)
AR (1)	AR045536A1 (es)
AU (1)	AU2004268847A1 (es)
BR (1)	BRPI0413330A (es)
CA (1)	CA2537185A1 (es)
NZ (1)	NZ545748A (es)
RU (1)	RU2387646C2 (es)
WO (1)	WO2005021515A2 (es)
ZA (1)	ZA200602214B (es)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AR045536A1 (es)	2003-08-29	2005-11-02	Ranbaxy Lab Ltd	Inhibidores de la fosfodiesterasa tipo -iv
WO2005051931A2 (en) *	2003-11-26	2005-06-09	Ranbaxy Laboratories Limited	Phosphodiesterase inhibitors
EP1751081A2 (en) *	2004-04-08	2007-02-14	Wyeth	Method for preparing 3-cyclopentyloxy-4-methoxybenzaldehyde
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.
DE102005044814A1 (de)	2005-05-19	2006-11-23	Grünenthal GmbH	Substituierte Sprio-Verbindungen und deren Verwendung zur Herstellung von Arzneimitteln
DE102005044813A1 (de) *	2005-05-19	2007-10-04	Grünenthal GmbH	Substituierte Spiro-Verbindungen und deren Verwendung zur Herstellung von Arzneimitteln
WO2007031838A1 (en)	2005-09-16	2007-03-22	Ranbaxy Laboratories Limited	Substituted pyrazolo [3,4-b] pyridines as phosphodiesterase inhibitors
US20100022571A1 (en)	2005-09-16	2010-01-28	Palle Venkata P	Substituted pyrazolo [3,4-b]pyridines as phosphodiesterase inhibitors
CA2626612A1 (en)	2005-10-19	2007-04-26	Ranbaxy Laboratories Limited	Pharmaceutical compositions of muscarinic receptor antagonists
WO2007045980A1 (en) *	2005-10-19	2007-04-26	Ranbaxy Laboratories Limited	Compositions of phosphodiesterase type iv inhibitors
EP1940810A2 (en) *	2005-10-19	2008-07-09	Ranbaxy Laboratories Limited	Inhibitors of phosphodiesterase type-iv
WO2008035315A2 (en) *	2006-09-22	2008-03-27	Ranbaxy Laboratories Limited	Inhibitors of phosphodiesterase type-iv
WO2008035316A2 (en) *	2006-09-22	2008-03-27	Ranbaxy Laboratories Limited	Phosphodiesterase inhibitors
CN103497185A (zh)	2007-03-14	2014-01-08	兰贝克赛实验室有限公司	用作磷酸二酯酶抑制剂的吡唑并(3,4-b)吡啶衍生物
EP2124943A1 (en) *	2007-03-14	2009-12-02	Ranbaxy Laboratories Limited	Pyrazolo [3, 4-b]pyridine derivatives as phosphodiesterase inhibitors
DK2148876T3 (da) *	2007-05-16	2012-01-16	Nycomed Gmbh	Pyrazolonderivater som PDE4-inhibitorer
US20100022590A1 (en) *	2008-01-17	2010-01-28	Biovitrum Ab (Publ.)	Novel compounds
US8809397B2 (en)	2010-05-27	2014-08-19	Targacept, Inc.	Nicotinic receptor non-competitive antagonists
CA2831704C (en)	2011-03-31	2019-10-01	Bayer Intellectual Property Gmbh	Herbicidally and fungicidally active 3-phenylisoxazoline-5-carboxamides and 3-phenylisoxazoline-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
EP2804603A1 (en)	2012-01-10	2014-11-26	President and Fellows of Harvard College	Beta-cell replication promoting compounds and methods of their use
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
US9585392B2 (en) *	2012-09-25	2017-03-07	Bayer Cropscience Ag	3-phenylisoxazolin derivatives with herbicidal action
EP2907806A1 (en) *	2014-02-14	2015-08-19	Universita Degli Studi Di Genova	New compounds as selective PDE4D inhibitors
CU20170166A7 (es)	2015-07-31	2018-03-13	Pfizer	Derivados de 1,1,1-trifluoro-3-hidroxipropan-2-il carbamato y derivados de 1, 1, 1-trifluoro-4-hidroxibutan-2-il carbamato como inhibidores de magl
RU2720203C1 (ru)	2017-01-20	2020-04-27	Пфайзер Инк.	1,1,1-трифтор-3-гидроксипропан-2-илкарбаматные производные как ингибиторы magl
RU2726631C1 (ru)	2017-01-23	2020-07-15	Пфайзер Инк.	Гетероциклические спиросоединения в качестве ингибиторов magl
PL3638666T3 (pl)	2017-06-13	2022-01-03	Bayer Aktiengesellschaft	Chwastobójczo skuteczne 3-fenyloizoksazolino-5-karboksyamidy amidów kwasu tetrahydro- i dihydrofuranokarboksylowego
BR112019026261B1 (pt)	2017-06-13	2023-12-19	Bayer Cropscience Aktiengesellschaft	3- fenilisoxazolina-5-carboxamidas e seus usos para controlar plantas indesejadas
WO2019034602A1 (de)	2017-08-17	2019-02-21	Bayer Aktiengesellschaft	Herbizid wirksame 3-phenyl-5-trifluormethylisoxazolin-5-carboxamide von cyclopentylcarbonsäuren und -estern
EA202091774A1 (ru)	2018-01-25	2020-12-07	Байер Акциенгезельшафт	Гербицидно-активные 3-фенилизоксазолин-5-карбоксамиды производных циклопентенилкарбоновой кислоты
EP3937637B1 (de)	2019-03-12	2023-04-19	Bayer Aktiengesellschaft	Herbizid wirksame 3-phenylisoxazolin-5-carboxamide von s-haltigen cyclopentenylcarbonsäureestern

Family Cites Families (72)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1047518A (en) *	1963-06-11	1966-11-02	Glaxo Lab Ltd	17ª-monoesters of 11,17,21-trihydroxy steroid compounds
NL128816C (es) *	1965-04-22
GB1159490A (en) *	1966-02-09	1969-07-23	Boots Pure Drug Co Ltd	Improvements in Acylated Steroids
GB1200886A (en) *	1966-09-23	1970-08-05	Allen & Hanburys Ltd	Phenylaminoethanol derivatives
US3937838A (en) *	1966-10-19	1976-02-10	Aktiebolaget Draco	Orally active bronchospasmolytic compounds and their preparation
US3639434A (en) *	1967-02-02	1972-02-01	Boots Pure Drug Co Ltd	17-acyloxysteroids and their manufacture
US3780177A (en) *	1967-06-16	1973-12-18	Warner Lambert Co	17-butyrate,21-ester derivatives of 6alpha,9alpha-difluoroprednisolone,compositions and use
CH540244A (de) *	1967-11-17	1973-08-15	Ciba Geigy Ag	Verfahren zur Herstellung neuer Halogenpregnadiene
GB1253831A (en) *	1968-01-19	1971-11-17	Glaxo Lab Ltd	9alpha,21-DIHALOPREGNANE COMPOUNDS
US3700681A (en) *	1971-02-16	1972-10-24	Pfizer	2-hydroxymethyl-3-hydroxy-6-(1-hydroxy-2-aminoethyl)pyridines
US3947478A (en) *	1972-01-12	1976-03-30	Akzona Incorporated	Alkylated 3,20-diketo-Δ4 -steroids of the pregnane series
US3994974A (en) *	1972-02-05	1976-11-30	Yamanouchi Pharmaceutical Co., Ltd.	α-Aminomethylbenzyl alcohol derivatives
SE378109B (es) *	1972-05-19	1975-08-18	Bofors Ab
US3992534A (en) *	1972-05-19	1976-11-16	Ab Bofors	Compositions and method of treating with component B of stereoisomeric mixtures of 2'-unsymmetrical 16,17-methylenedioxy steriods
SE378110B (es) *	1972-05-19	1975-08-18	Bofors Ab
FR2231374B1 (es) *	1973-05-30	1976-10-22	Jouveinal Sa
US4098803A (en) *	1973-05-30	1978-07-04	Jouveinal S.A.	Esters of 21-thiol-steroids hydrocortisone and cortisone
US4011258A (en) *	1973-06-21	1977-03-08	Aktiebolaget Draco	Orally active bronchospasmolytic compounds
ZA744259B (en) *	1973-08-17	1975-06-25	American Cyanamid Co	Topical steroid
US3980778A (en) *	1973-10-25	1976-09-14	The Upjohn Company	Anti-inflammatory steroid
NL7502252A (nl) *	1974-02-27	1975-08-29	Pierrel Spa	Werkwijze voor het bereiden van een geneesmid- del met anti-inflammatoire werking, gevormd ge- neesmiddel verkregen volgens deze werkwijze alsmede werkwijze voor het bereiden van in het geneesmiddel gebruikte nieuwe steroiden.
DE2655570A1 (de) *	1975-12-12	1977-06-16	Ciba Geigy Ag	Neue polyhalogensteroide und verfahren zu ihrer herstellung
US4076708A (en) *	1976-12-22	1978-02-28	Schering Corporation	Process for the preparation of 7α-halogeno-3-oxo-4-dehydro steroids and novel 7α-halogeno derivatives produced thereby
US4124707A (en) *	1976-12-22	1978-11-07	Schering Corporation	7α-Halogeno-3,20-dioxo-1,4-pregnadienes, methods for their manufacture, their use as anti-inflammatory agents, and pharmaceutical formulations useful therefor
US4081541A (en) *	1976-12-28	1978-03-28	Rorer Italiana S.P.A.	Steroid derivatives
US4115589A (en) *	1977-05-17	1978-09-19	The Upjohn Company	Compounds, compositions and method of use
DE2735110A1 (de) *	1977-08-04	1979-02-15	Hoechst Ag	Corticoid-17-alkylcarbonate und verfahren zu ihrer herstellung
JPS6040439B2 (ja) *	1978-03-29	1985-09-11	大正製薬株式会社	ヒドロコルチゾン誘導体
US4335121A (en) *	1980-02-15	1982-06-15	Glaxo Group Limited	Androstane carbothioates
CY1273A (en) *	1980-07-09	1985-03-08	Draco Ab	1-(dihydroxyphenyl)-2-amino-ethanol derivatives;preparation,compositions and intermediates
US4298604B1 (en) *	1980-10-06	1998-12-22	Schering Corp	Clotrimazole-betamethasone dipropionate combination
CY1359A (en) *	1981-02-02	1987-08-07	Schering Corp	Aromatic heterocyclic esters of steroids, their preparation and pharmaceutical compositions containing them
DE3133081A1 (de) *	1981-08-18	1983-03-10	Schering Ag, 1000 Berlin Und 4619 Bergkamen	Neue 6(alpha)-methylprednisolon-derivate, ihre herstellung und verwendung
US4472392A (en) *	1983-01-21	1984-09-18	The Upjohn Company	Sulfonate containing ester prodrugs of corticosteroids
ZW6584A1 (en) *	1983-04-18	1985-04-17	Glaxo Group Ltd	Phenethanolamine derivatives
CA1240708A (en) *	1983-11-15	1988-08-16	Johannes K. Minderhoud	Process for the preparation of hydrocarbons
CA1261835A (en) *	1984-08-20	1989-09-26	Masaaki Toda	(fused) benz(thio)amides
GB8607294D0 (en) *	1985-04-17	1986-04-30	Ici America Inc	Heterocyclic amide derivatives
US4826868A (en) *	1986-05-29	1989-05-02	Ortho Pharmaceutical Corporation	1,5-Diaryl-3-substituted pyrazoles pharmaceutical compositions and use
US4873259A (en) *	1987-06-10	1989-10-10	Abbott Laboratories	Indole, benzofuran, benzothiophene containing lipoxygenase inhibiting compounds
CA1326662C (en) *	1988-03-09	1994-02-01	Yutaka Mizushima	11.beta.,17.,21-trihydroxy-1,4-pregnadiene-3,20-dione 21-[(e,e)-3,7,11-trimethyl-2,6,10-dodecatrienoate]
US5278156A (en) *	1988-03-09	1994-01-11	Kuraray Co., Ltd.	11-beta, 17-alpha, 21-trihydroxy-1, 4-pregnadiene-3, 20 21-[(E-E)-3,7, 11-trimethyl-2,6,10-dodecatrienoate]
NZ232785A (en)	1989-03-15	1991-03-26	Janssen Pharmaceutica Nv	5-(1,2 benzisoxazol-, benzimidazol and benzisothiazol-3- yl)-1h-benzimadazol-2-yl carbamic acid ester derivatives preparatory processes, intermediates and anthelmintic compositions
NZ234883A (en)	1989-08-22	1995-01-27	Merck Frosst Canada Inc	Quinolin-2-ylmethoxy indole derivatives, preparation and pharmaceutical compositions thereof
CA2076012A1 (en) *	1990-02-14	1991-08-15	Yasuyuki Kato	Agent for inhibiting the formation of denatured ldl
GR1001529B (el) *	1990-09-07	1994-03-31	Elmuquimica Farm Sl	Μέ?οδος για την λήψη νέων 21-εστέρων της 16-17-ακετάλης της πρ να-1,4-διενο-3,20-διόνης.
PL165803B1 (pl) *	1990-09-10	1995-02-28	Schering Corp	Sposób wytwarzania nowego monohydratu 9a, 21-dichloro-16-a metylo-1,4-pregnadieno-11 ß , 17a-diolo-3,20-diono-17-(2’furanokarboksylanu) PL PL PL PL
US5565473A (en) *	1990-10-12	1996-10-15	Merck Frosst Canada, Inc.	Unsaturated hydroxyalkylquinoline acids as leukotriene antagonists
US6127353A (en) *	1991-09-06	2000-10-03	Schering Corporation	Mometasone furoate monohydrate, process for making same and pharmaceutical compositions
EP0542355A1 (en)	1991-11-15	1993-05-19	Merck Frosst Canada Inc.	Amorphous (Quinolin-2-ylmethoxy)indoles as leukotriene antagonists
US5254541A (en)	1991-11-15	1993-10-19	Merck Frosst Canada, Inc.	(Quinolin-2-ylmethoxy)indole/cyclodextrin complex
CA2165192C (en) *	1993-07-02	2001-04-24	Hermann Amschler	Fluoroalkoxy-substituted benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors
ATE187447T1 (de)	1993-11-26	1999-12-15	Pfizer	3-phenyl-2-isoxazoline derivate als entzündugshemmende mittel
WO1995014681A1 (en) *	1993-11-26	1995-06-01	Pfizer Inc.	Isoxazoline compounds as antiinflammatory agents
US5837699A (en) *	1994-01-27	1998-11-17	Schering Corporation	Use of mometasone furoate for treating upper airway passage diseases
NZ278667A (en) *	1994-03-09	2000-12-22	Pfizer	Use of isoxazoline derivatives to inhibit TNF production
TW438585B (en) *	1995-02-06	2001-06-07	Astra Ab	Pharmaceutical compositions for topical administration for prophylaxis and/or treatment of herpesvirus infections
US5710170A (en) *	1995-12-15	1998-01-20	Merck Frosst Canada, Inc.	Tri-aryl ethane derivatives as PDE IV inhibitors
US5976573A (en) *	1996-07-03	1999-11-02	Rorer Pharmaceutical Products Inc.	Aqueous-based pharmaceutical composition
US6207665B1 (en)	1997-06-12	2001-03-27	Schering Aktiengesellschaft	Piperazine derivatives and their use as anti-inflammatory agents
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
CN100355753C (zh)	2000-05-26	2007-12-19	辉瑞大药厂	用于制备具有治疗作用的莨菪烷衍生物的中间体
IL155092A0 (en)	2000-09-29	2003-10-31	Glaxo Group Ltd	Compounds useful in the treatment of inflammatory diseases
DE10050995A1 (de)	2000-10-14	2002-04-18	Boehringer Ingelheim Pharma	Neue Anticholinergika, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
US6642256B2 (en)	2000-12-21	2003-11-04	Warner-Lambert Company Llc	Piperidine derivatives as subtype selective N-Methyl-D-Aspartate antagonists
WO2002081447A1 (en)	2001-04-06	2002-10-17	Daewoong Pharmaceutical Co., Ltd.	3-cyclopentyloxy-4-methoxyphenyl-isothiazolinone derivatives and the use thereof
CA2450589C (en)	2001-06-08	2011-12-20	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
AR045536A1 (es)	2003-08-29	2005-11-02	Ranbaxy Lab Ltd	Inhibidores de la fosfodiesterasa tipo -iv
ES2370788T3 (es)	2005-02-07	2011-12-22	Aerocrine Ab	Controlar flujo de aliento exhalado durante análisis.
CA2626612A1 (en)	2005-10-19	2007-04-26	Ranbaxy Laboratories Limited	Pharmaceutical compositions of muscarinic receptor antagonists
WO2007045980A1 (en)	2005-10-19	2007-04-26	Ranbaxy Laboratories Limited	Compositions of phosphodiesterase type iv inhibitors

2004
- 2004-08-30 AR ARP040103114A patent/AR045536A1/es unknown
- 2004-08-30 RU RU2006109366/04A patent/RU2387646C2/ru not_active IP Right Cessation
- 2004-08-30 BR BRPI0413330-7A patent/BRPI0413330A/pt not_active Application Discontinuation
- 2004-08-30 US US10/930,569 patent/US7825147B2/en not_active Expired - Fee Related
- 2004-08-30 NZ NZ545748A patent/NZ545748A/en unknown
- 2004-08-30 JP JP2006524461A patent/JP2007504123A/ja not_active Withdrawn
- 2004-08-30 EP EP04769218A patent/EP1663999A2/en not_active Withdrawn
- 2004-08-30 CA CA002537185A patent/CA2537185A1/en not_active Abandoned
- 2004-08-30 AU AU2004268847A patent/AU2004268847A1/en not_active Abandoned
- 2004-08-30 WO PCT/IB2004/002804 patent/WO2005021515A2/en active Application Filing
2006
- 2006-03-16 ZA ZA200602214A patent/ZA200602214B/en unknown

Also Published As

Publication number	Publication date
RU2387646C2 (ru)	2010-04-27
WO2005021515A3 (en)	2005-08-25
RU2006109366A (ru)	2007-10-10
US7825147B2 (en)	2010-11-02
WO2005021515B1 (en)	2005-10-27
CA2537185A1 (en)	2005-03-10
WO2005021515A2 (en)	2005-03-10
NZ545748A (en)	2010-03-26
AU2004268847A1 (en)	2005-03-10
US20050075383A1 (en)	2005-04-07
JP2007504123A (ja)	2007-03-01
AR045536A1 (es)	2005-11-02
BRPI0413330A (pt)	2006-10-10
EP1663999A2 (en)	2006-06-07

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