WO2018069210A1 - Tétrahydrofuro [3,4-c] isoquinolines en tant qu'inhibiteurs de pde4 - Google Patents
Tétrahydrofuro [3,4-c] isoquinolines en tant qu'inhibiteurs de pde4 Download PDFInfo
- Publication number
- WO2018069210A1 WO2018069210A1 PCT/EP2017/075602 EP2017075602W WO2018069210A1 WO 2018069210 A1 WO2018069210 A1 WO 2018069210A1 EP 2017075602 W EP2017075602 W EP 2017075602W WO 2018069210 A1 WO2018069210 A1 WO 2018069210A1
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- WIPO (PCT)
- Prior art keywords
- compound
- disease
- formula
- ethoxy
- methoxy
- Prior art date
Links
- 0 *c(*(*)c1)cc2c1C(c1cc(*C(I)=O)ccc1)=*[C@@]1[C@@]2COC1 Chemical compound *c(*(*)c1)cc2c1C(c1cc(*C(I)=O)ccc1)=*[C@@]1[C@@]2COC1 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Definitions
- R4 and R5 are methyl, and R6 and R7, together with the nitrogen atom to which both are bonded form a pyrrolidin-1-yl, piperidin-1-yl, azepan-1-yl, morpholin-4-yl,
- the invention relates to a compound of formula 1 , wherein
- the compounds of formula 4 are saponified to give the benzoic acid derivatives of formula 3, which then can be activated prior to the reaction with compounds of formula R3-H for example by forming an acid halide or acid anhydride.
- Compounds of formula 1 finally then can be obtained from the activated compounds of formula 2 by reaction with compounds of formula R3-H, in which R3 has the meanings given above.
- the compounds according to the invention are isolated and purified in a manner known per se, e.g. by distilling off the solvent in vacuo and recrystallizing the residue obtained from a suitable solvent or subjecting it to one of the customary purification methods, such as column chromatography on a suitable support material.
- the invention preferably relates to a method of treating or preventing dermatological diseases, such as, but not limited to, psoriasis or atopic dermatitis (eczema) comprising administering to a patient in need thereof a therapeutically effective amount of at least one of the compounds of the invention.
- dermatological diseases such as, but not limited to, psoriasis or atopic dermatitis (eczema) comprising administering to a patient in need thereof a therapeutically effective amount of at least one of the compounds of the invention.
- the invention furthermore relates to a pharmaceutical composition according to the invention inhibiting the type 4 phosphodiesterase, especially for the treatment or prophylaxis of diseases alleviated by inhibition of type 4 phosphodiesterase, in particular for the treatment or prophylaxis of the diseases exemplified above.
- a pharmaceutical composition for oral administration being a tablet may comprise one or more pharmaceutically acceptable auxiliaries (for example, carriers and/or excipients) suitable for preparing tablet formulations.
- the carrier may, for example, be or include lactose, cellulose or mannitol.
- the tablet may also or instead contain one or more pharmaceutically acceptable excipients, for example, a binding agent, a lubricant and/or a tablet disintegrant.
- compositions according to the invention can be administered such that the dose of the compound of the invention is in the range customary for type 4 phosphodiesterase inhibitors.
- This amphiphilic lipid sub-layer layer includes (O-acyl)-omega-hydroxy fatty acids (OAHFAs) and free fatty acids (VLC-FFAs, longer than C28) which are synthesized by elongation of very long chain fatty acids-4 (ELOVL4) enzyme [5].
- OAHFAs O-acyl-omega-hydroxy fatty acids
- VLC-FFAs free fatty acids
- the OAHFAs and the VLC-FFAs are recently found as major amphiphilic lipids in meibum of human and animals [6].
- the ratio of OAHFA in meibum is lower in dry eye patients than that of normal subjects.
- the extent of OAHFA reduction depends on the severi- ty of dry eye [7].
Abstract
La présente invention concerne des composés de formule 1, dans laquelle, R1, R2 et R3 ont les significations indiquées dans la description, ces composés sont de nouveaux inhibiteurs efficaces de phosphodiestérase de type 4.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662406172P | 2016-10-10 | 2016-10-10 | |
US62/406,172 | 2016-10-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2018069210A1 true WO2018069210A1 (fr) | 2018-04-19 |
Family
ID=60043199
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2017/075602 WO2018069210A1 (fr) | 2016-10-10 | 2017-10-09 | Tétrahydrofuro [3,4-c] isoquinolines en tant qu'inhibiteurs de pde4 |
Country Status (1)
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WO (1) | WO2018069210A1 (fr) |
Citations (22)
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EP0372777A2 (fr) | 1988-12-06 | 1990-06-13 | Riker Laboratories, Inc. | Formulations d'aérosols à usage médical |
EP0407028A2 (fr) | 1989-05-31 | 1991-01-09 | FISONS plc | Formule médicamenteuse et appareil d'inhalation |
WO1991004011A1 (fr) | 1989-09-20 | 1991-04-04 | Riker Laboratories, Inc. | Formulations aerosols medicinales |
WO1991011495A1 (fr) | 1990-02-03 | 1991-08-08 | Boehringer Ingelheim Kg | Nouveaux melanges de gaz propulseurs et leur utilisation dans des preparations medicamenteuses |
WO1991011173A1 (fr) | 1990-02-02 | 1991-08-08 | Fisons Plc | Compositions d'agents propulseurs |
WO1991014422A1 (fr) | 1990-03-23 | 1991-10-03 | Minnesota Mining And Manufacturing Company | Emploi de fluorotensioactifs solubles dans la preparation de formulations d'aerosols doseurs |
EP0505321A2 (fr) | 1991-03-21 | 1992-09-23 | Ciba-Geigy Ag | Inhalateur |
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EP0553298A1 (fr) | 1990-10-18 | 1993-08-04 | Minnesota Mining & Mfg | Formulation d'aerosol contenant du beclomethasone 17,21 dipropionate. |
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US6302331B1 (en) | 1999-04-23 | 2001-10-16 | Battelle Pulmonary Therapeutics, Inc. | Directionally controlled EHD aerosol sprayer |
WO2002030394A2 (fr) | 2000-10-09 | 2002-04-18 | 3M Innovative Properties Company | Formulations medicinales en aerosol |
US6397838B1 (en) | 1998-12-23 | 2002-06-04 | Battelle Pulmonary Therapeutics, Inc. | Pulmonary aerosol delivery device and method |
WO2002066476A1 (fr) | 2001-02-21 | 2002-08-29 | Altana Pharma Ag | 6-phenylbenzonaphtyridines |
US6454193B1 (en) | 1999-04-23 | 2002-09-24 | Battellepharma, Inc. | High mass transfer electrosprayer |
WO2004018431A2 (fr) | 2002-08-17 | 2004-03-04 | Altana Pharma Ag | Nouvelles phenanthridines |
WO2004018465A2 (fr) | 2002-08-17 | 2004-03-04 | Altana Pharma Ag | Nouvelles benzonaphtyridines |
WO2005077906A1 (fr) | 2004-02-18 | 2005-08-25 | Altana Pharma Ag | Nouveaux hydroxy-6-phenylphenenthridines a substitution guanidinyle efficaces en tant qu'inhibiteurs de la phosphodiesterase (pde) 4 |
WO2006027345A2 (fr) * | 2004-09-08 | 2006-03-16 | Altana Pharma Ag | Nouveaux derives 3-thia-10-aza-phenanthrene |
-
2017
- 2017-10-09 WO PCT/EP2017/075602 patent/WO2018069210A1/fr active Application Filing
Patent Citations (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0372777A2 (fr) | 1988-12-06 | 1990-06-13 | Riker Laboratories, Inc. | Formulations d'aérosols à usage médical |
EP0407028A2 (fr) | 1989-05-31 | 1991-01-09 | FISONS plc | Formule médicamenteuse et appareil d'inhalation |
WO1991004011A1 (fr) | 1989-09-20 | 1991-04-04 | Riker Laboratories, Inc. | Formulations aerosols medicinales |
WO1991011173A1 (fr) | 1990-02-02 | 1991-08-08 | Fisons Plc | Compositions d'agents propulseurs |
WO1991011495A1 (fr) | 1990-02-03 | 1991-08-08 | Boehringer Ingelheim Kg | Nouveaux melanges de gaz propulseurs et leur utilisation dans des preparations medicamenteuses |
WO1991014422A1 (fr) | 1990-03-23 | 1991-10-03 | Minnesota Mining And Manufacturing Company | Emploi de fluorotensioactifs solubles dans la preparation de formulations d'aerosols doseurs |
EP0553298A1 (fr) | 1990-10-18 | 1993-08-04 | Minnesota Mining & Mfg | Formulation d'aerosol contenant du beclomethasone 17,21 dipropionate. |
EP0505321A2 (fr) | 1991-03-21 | 1992-09-23 | Ciba-Geigy Ag | Inhalateur |
WO1993011743A1 (fr) | 1991-12-12 | 1993-06-24 | Glaxo Group Limited | Medicaments |
EP0650410A1 (fr) | 1992-06-30 | 1995-05-03 | FISONS plc | Procede de production de compositions pour medicaments |
EP0691865A1 (fr) | 1993-03-31 | 1996-01-17 | Fisons Plc | Dispositif d'inhalation |
EP0725725A1 (fr) | 1993-10-08 | 1996-08-14 | Fisons Plc | Procede de production de formulations medicamenteuses |
WO2000007567A1 (fr) | 1998-08-04 | 2000-02-17 | Jago Research Ag | Formulations d'aerosol a usage medical |
US6397838B1 (en) | 1998-12-23 | 2002-06-04 | Battelle Pulmonary Therapeutics, Inc. | Pulmonary aerosol delivery device and method |
US6302331B1 (en) | 1999-04-23 | 2001-10-16 | Battelle Pulmonary Therapeutics, Inc. | Directionally controlled EHD aerosol sprayer |
US6454193B1 (en) | 1999-04-23 | 2002-09-24 | Battellepharma, Inc. | High mass transfer electrosprayer |
WO2002030394A2 (fr) | 2000-10-09 | 2002-04-18 | 3M Innovative Properties Company | Formulations medicinales en aerosol |
WO2002066476A1 (fr) | 2001-02-21 | 2002-08-29 | Altana Pharma Ag | 6-phenylbenzonaphtyridines |
WO2004018431A2 (fr) | 2002-08-17 | 2004-03-04 | Altana Pharma Ag | Nouvelles phenanthridines |
WO2004018465A2 (fr) | 2002-08-17 | 2004-03-04 | Altana Pharma Ag | Nouvelles benzonaphtyridines |
WO2005077906A1 (fr) | 2004-02-18 | 2005-08-25 | Altana Pharma Ag | Nouveaux hydroxy-6-phenylphenenthridines a substitution guanidinyle efficaces en tant qu'inhibiteurs de la phosphodiesterase (pde) 4 |
WO2006027345A2 (fr) * | 2004-09-08 | 2006-03-16 | Altana Pharma Ag | Nouveaux derives 3-thia-10-aza-phenanthrene |
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