BRPI0717058A2 - Composto, composição farmacêutica, método para tratar, prevenir, inibir ou suprimir uma condição inflamatória ou doença ou doenças do sistema nervoso central e método para a preparação de um composto - Google Patents
Composto, composição farmacêutica, método para tratar, prevenir, inibir ou suprimir uma condição inflamatória ou doença ou doenças do sistema nervoso central e método para a preparação de um composto Download PDFInfo
- Publication number
- BRPI0717058A2 BRPI0717058A2 BRPI0717058-0A2A BRPI0717058A BRPI0717058A2 BR PI0717058 A2 BRPI0717058 A2 BR PI0717058A2 BR PI0717058 A BRPI0717058 A BR PI0717058A BR PI0717058 A2 BRPI0717058 A2 BR PI0717058A2
- Authority
- BR
- Brazil
- Prior art keywords
- compound
- azaspiro
- dioxa
- difluoromethoxy
- formula
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 687
- 238000000034 method Methods 0.000 title description 59
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 6
- 239000008194 pharmaceutical composition Substances 0.000 title description 6
- 238000002360 preparation method Methods 0.000 title description 6
- 210000003169 central nervous system Anatomy 0.000 title description 5
- 201000010099 disease Diseases 0.000 title description 4
- 230000004968 inflammatory condition Effects 0.000 title description 3
- 230000002401 inhibitory effect Effects 0.000 title description 3
- -1 Ethyl [2- (difluoromethoxy) -5- (1,7-dioxa-2-azaspiro [4.4] non-2-en-3-yl) phenoxy] acetate Chemical class 0.000 claims description 117
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 96
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 42
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 28
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 8
- JGOJHHGLHYSJTJ-UHFFFAOYSA-N 3-[3-(4-chlorophenoxy)-4-(difluoromethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1=CC=C(Cl)C=C1 JGOJHHGLHYSJTJ-UHFFFAOYSA-N 0.000 claims description 3
- PCZCTKMVCGAKPV-UHFFFAOYSA-N 3-[3-cyclopentyloxy-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)(F)COC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1CCCC1 PCZCTKMVCGAKPV-UHFFFAOYSA-N 0.000 claims description 3
- SMKJDVMZHMINMF-UHFFFAOYSA-N 3-[4-(difluoromethoxy)-3-(2-morpholin-4-ylethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OCCN1CCOCC1 SMKJDVMZHMINMF-UHFFFAOYSA-N 0.000 claims description 3
- VEYQRTKVRVSCQS-UHFFFAOYSA-N 3-[4-(difluoromethoxy)-3-(4-fluorophenoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1=CC=C(F)C=C1 VEYQRTKVRVSCQS-UHFFFAOYSA-N 0.000 claims description 3
- YGOILRKBSICFDT-UHFFFAOYSA-N 3-[4-(difluoromethoxy)-3-[4-(trifluoromethoxy)phenoxy]phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1=CC=C(OC(F)(F)F)C=C1 YGOILRKBSICFDT-UHFFFAOYSA-N 0.000 claims description 3
- HEMYFIPNZQBKMN-UHFFFAOYSA-N 3-[4-(difluoromethoxy)-3-[4-(trifluoromethyl)phenoxy]phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1=CC=C(C(F)(F)F)C=C1 HEMYFIPNZQBKMN-UHFFFAOYSA-N 0.000 claims description 3
- PXFOEAYMJYVFQV-UHFFFAOYSA-N 7-[4-(difluoromethoxy)-3-methoxyphenyl]-2,5-dioxa-6-azaspiro[3.4]oct-6-ene Chemical compound C1=C(OC(F)F)C(OC)=CC(C=2CC3(COC3)ON=2)=C1 PXFOEAYMJYVFQV-UHFFFAOYSA-N 0.000 claims description 3
- YDZAHLCRNIVRAT-UHFFFAOYSA-N 3-[3-(cyclopentylmethoxy)-4-(difluoromethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OCC1CCCC1 YDZAHLCRNIVRAT-UHFFFAOYSA-N 0.000 claims description 2
- IUTNKHKTEXDLJQ-UHFFFAOYSA-N 5-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]pentanoic acid Chemical compound C1=C(OC(F)F)C(OCCCCC(=O)O)=CC(C=2CC3(COCC3)ON=2)=C1 IUTNKHKTEXDLJQ-UHFFFAOYSA-N 0.000 claims description 2
- ORABMQSVAJXFTQ-UHFFFAOYSA-N 2-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]-n-methylacetamide Chemical compound C1=C(OC(F)F)C(OCC(=O)NC)=CC(C=2CC3(COCC3)ON=2)=C1 ORABMQSVAJXFTQ-UHFFFAOYSA-N 0.000 claims 1
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims 1
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 claims 1
- CBEJRQJYGPDALT-UHFFFAOYSA-N n-cyclopropyl-2-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]acetamide Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OCC(=O)NC1CC1 CBEJRQJYGPDALT-UHFFFAOYSA-N 0.000 claims 1
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- 125000000217 alkyl group Chemical group 0.000 description 58
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- 238000006243 chemical reaction Methods 0.000 description 26
- 125000003118 aryl group Chemical group 0.000 description 25
- 230000015572 biosynthetic process Effects 0.000 description 25
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
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- 125000000304 alkynyl group Chemical group 0.000 description 24
- 125000001072 heteroaryl group Chemical group 0.000 description 24
- 125000001424 substituent group Chemical group 0.000 description 24
- 238000003786 synthesis reaction Methods 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
- 125000003342 alkenyl group Chemical group 0.000 description 23
- 229910052736 halogen Inorganic materials 0.000 description 23
- 150000002367 halogens Chemical class 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- 239000012453 solvate Substances 0.000 description 20
- 125000003545 alkoxy group Chemical group 0.000 description 19
- 125000002877 alkyl aryl group Chemical group 0.000 description 19
- 229910052739 hydrogen Inorganic materials 0.000 description 19
- 239000001257 hydrogen Substances 0.000 description 19
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 19
- 229910000027 potassium carbonate Inorganic materials 0.000 description 19
- 150000001204 N-oxides Chemical class 0.000 description 18
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- 239000003960 organic solvent Substances 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 229910052794 bromium Inorganic materials 0.000 description 17
- 229910052801 chlorine Inorganic materials 0.000 description 17
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 17
- 125000004093 cyano group Chemical group *C#N 0.000 description 16
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 16
- 150000002431 hydrogen Chemical class 0.000 description 16
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
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Classifications
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- 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
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
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- Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2097/DEL/2006 | 2006-09-22 | ||
| IN2097DE2006 | 2006-09-22 | ||
| PCT/IB2007/053854 WO2008035315A2 (en) | 2006-09-22 | 2007-09-22 | Inhibitors of phosphodiesterase type-iv |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0717058A2 true BRPI0717058A2 (pt) | 2013-10-15 |
Family
ID=39200943
Family Applications (1)
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| BRPI0717058-0A2A BRPI0717058A2 (pt) | 2006-09-22 | 2007-09-22 | Composto, composição farmacêutica, método para tratar, prevenir, inibir ou suprimir uma condição inflamatória ou doença ou doenças do sistema nervoso central e método para a preparação de um composto |
Country Status (11)
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| US (1) | US20110021473A1 (enExample) |
| EP (1) | EP2086948A2 (enExample) |
| JP (1) | JP2010504323A (enExample) |
| KR (1) | KR20090069309A (enExample) |
| CN (1) | CN101616901A (enExample) |
| AU (1) | AU2007298549A1 (enExample) |
| BR (1) | BRPI0717058A2 (enExample) |
| CA (1) | CA2664247A1 (enExample) |
| EA (1) | EA200900472A1 (enExample) |
| MX (1) | MX2009003100A (enExample) |
| WO (1) | WO2008035315A2 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006305620A1 (en) * | 2005-10-19 | 2007-04-26 | Ranbaxy Laboratories Limited | Compositions of phosphodiesterase type IV inhibitors |
| UA110241C2 (en) | 2011-03-31 | 2015-12-10 | Bayer Ip Gmbh | Herbicides and fungicides active phneylisoxazoline 3-5-carboxamide and 3- phneylisoxazoline -5-thioamides |
| KR101977920B1 (ko) | 2012-09-25 | 2019-05-13 | 바이엘 크롭사이언스 악티엔게젤샤프트 | 제초 작용을 가지는 3-페닐이속사졸린 유도체 |
| EP2907806A1 (en) * | 2014-02-14 | 2015-08-19 | Universita Degli Studi Di Genova | New compounds as selective PDE4D inhibitors |
| CN105085428B (zh) * | 2014-04-25 | 2019-03-22 | 广东东阳光药业有限公司 | 芳杂环类衍生物及其在药物上的应用 |
| CN110770232B (zh) | 2017-06-13 | 2023-08-15 | 拜耳公司 | 除草活性的四氢和二氢呋喃羧酸和酯的3-苯基异噁唑啉-5-甲酰胺 |
| EP3638666B1 (de) | 2017-06-13 | 2021-07-21 | Bayer Aktiengesellschaft | Herbizid wirksame 3-phenylisoxazolin-5-carboxamide von tetrahydro- und dihydrofurancarbonsäureamiden |
| US20200369630A1 (en) | 2017-08-17 | 2020-11-26 | Bayer Aktiengesellschaft | Herbicidally active 3-phenyl-5-trifluoromethylisoxazoline-5-carboxamides of cyclopentylcarboxylic acids and esters |
| EA202091774A1 (ru) | 2018-01-25 | 2020-12-07 | Байер Акциенгезельшафт | Гербицидно-активные 3-фенилизоксазолин-5-карбоксамиды производных циклопентенилкарбоновой кислоты |
| CN108976107B (zh) * | 2018-08-23 | 2021-03-23 | 南方医科大学 | 3-芳基-4-烷氧基苄胺衍生物及其制备方法和应用 |
| CA3133025A1 (en) | 2019-03-12 | 2020-09-17 | Bayer Aktiengesellschaft | Herbicidally active 3-phenylisoxazoline-5-carboxamides of s-containing cyclopentenyl carboxylic acid esters |
Family Cites Families (58)
| 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 (enExample) * | 1965-04-22 | |||
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| 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 |
| 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 |
| SE378109B (enExample) * | 1972-05-19 | 1975-08-18 | Bofors Ab | |
| SE378110B (enExample) * | 1972-05-19 | 1975-08-18 | Bofors Ab | |
| US4098804A (en) * | 1973-05-30 | 1978-07-04 | Jouveinal S.A. | Esters of 21-thiol prednisone and prednisolone |
| FR2231374B1 (enExample) * | 1973-05-30 | 1976-10-22 | Jouveinal Sa | |
| 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 |
| 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 |
| 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 |
| ZA81976B (en) * | 1980-02-15 | 1982-07-28 | Glaxo Group Ltd | Androstane carbothioates |
| EP0043807B1 (en) * | 1980-07-09 | 1984-05-30 | Aktiebolaget Draco | 1-(dihydroxyphenyl)-2-amino-ethanol derivatives; preparation, compositions and intermediates |
| US4298604B1 (en) * | 1980-10-06 | 1998-12-22 | Schering Corp | Clotrimazole-betamethasone dipropionate combination |
| ATE8790T1 (de) * | 1981-02-02 | 1984-08-15 | Schering Corporation | Aromatische heterocyclische steroidester, verfahren zu ihrer herstellung und pharmazeutische zusammensetzungen, die sie enthalten. |
| 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 |
| US4783259A (en) * | 1986-07-07 | 1988-11-08 | Wade Charles E | Helical coil filter element |
| 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] |
| 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] |
| 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. |
| WO1992004365A1 (en) * | 1990-09-10 | 1992-03-19 | Schering Corporation | Mometasone furoate monohydrate, process for making same and pharmaceutical compositions |
| 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 |
| US5225202A (en) * | 1991-09-30 | 1993-07-06 | E. R. Squibb & Sons, Inc. | Enteric coated pharmaceutical compositions |
| DE69422061T2 (de) * | 1993-11-26 | 2000-03-30 | Pfizer, Inc. | 3-phenyl-2-isoxazoline derivate als entzündugshemmende mittel |
| US5837699A (en) * | 1994-01-27 | 1998-11-17 | Schering Corporation | Use of mometasone furoate for treating upper airway passage diseases |
| TW438585B (en) * | 1995-02-06 | 2001-06-07 | Astra Ab | Pharmaceutical compositions for topical administration for prophylaxis and/or treatment of herpesvirus infections |
| US5976573A (en) * | 1996-07-03 | 1999-11-02 | Rorer Pharmaceutical Products Inc. | Aqueous-based pharmaceutical composition |
| US7122207B2 (en) * | 1998-05-22 | 2006-10-17 | Bristol-Myers Squibb Company | High drug load acid labile pharmaceutical composition |
| US6727272B1 (en) * | 2002-07-15 | 2004-04-27 | Unitech Pharmaceuticals, Inc. | Leflunomide analogs for treating rheumatoid arthritis |
| RU2387646C2 (ru) * | 2003-08-29 | 2010-04-27 | Рэнбакси Лабораториз Лимитед | Ингибиторы фосфодиэстеразы типа-iv |
| 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 |
| AR055395A1 (es) * | 2005-08-26 | 2007-08-22 | Vertex Pharma | Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c |
| AU2006305620A1 (en) * | 2005-10-19 | 2007-04-26 | Ranbaxy Laboratories Limited | Compositions of phosphodiesterase type IV inhibitors |
| EP1948164A1 (en) * | 2005-10-19 | 2008-07-30 | Ranbaxy Laboratories, Ltd. | Pharmaceutical compositions of muscarinic receptor antagonists |
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2007
- 2007-09-22 KR KR1020097008110A patent/KR20090069309A/ko not_active Withdrawn
- 2007-09-22 EA EA200900472A patent/EA200900472A1/ru unknown
- 2007-09-22 WO PCT/IB2007/053854 patent/WO2008035315A2/en not_active Ceased
- 2007-09-22 MX MX2009003100A patent/MX2009003100A/es not_active Application Discontinuation
- 2007-09-22 AU AU2007298549A patent/AU2007298549A1/en not_active Abandoned
- 2007-09-22 EP EP07826506A patent/EP2086948A2/en not_active Withdrawn
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- 2007-09-22 CA CA002664247A patent/CA2664247A1/en not_active Abandoned
- 2007-09-22 US US12/442,257 patent/US20110021473A1/en not_active Abandoned
- 2007-09-22 CN CN200780043485A patent/CN101616901A/zh active Pending
- 2007-09-22 BR BRPI0717058-0A2A patent/BRPI0717058A2/pt not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EA200900472A1 (ru) | 2009-10-30 |
| WO2008035315A9 (en) | 2008-10-23 |
| WO2008035315A2 (en) | 2008-03-27 |
| WO2008035315A3 (en) | 2008-12-04 |
| CA2664247A1 (en) | 2008-03-27 |
| AU2007298549A1 (en) | 2008-03-27 |
| MX2009003100A (es) | 2009-05-11 |
| JP2010504323A (ja) | 2010-02-12 |
| US20110021473A1 (en) | 2011-01-27 |
| EP2086948A2 (en) | 2009-08-12 |
| KR20090069309A (ko) | 2009-06-30 |
| CN101616901A (zh) | 2009-12-30 |
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| Date | Code | Title | Description |
|---|---|---|---|
| B11A | Dismissal acc. art.33 of ipl - examination not requested within 36 months of filing | ||
| B11Y | Definitive dismissal - extension of time limit for request of examination expired [chapter 11.1.1 patent gazette] |