HRP20090509T1 - 5-substituted quinoline and isoquinoline derivatives, a method for the production thereof and their use as antiphlogistics - Google Patents

5-substituted quinoline and isoquinoline derivatives, a method for the production thereof and their use as antiphlogistics Download PDF

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HRP20090509T1
HRP20090509T1 HR20090509T HRP20090509T HRP20090509T1 HR P20090509 T1 HRP20090509 T1 HR P20090509T1 HR 20090509 T HR20090509 T HR 20090509T HR P20090509 T HRP20090509 T HR P20090509T HR P20090509 T1 HRP20090509 T1 HR P20090509T1
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Jaroch Stefan
Rehwinkel Hartmut
Sch�cke Heike
Schmees Norbert
Skuballa Werner
Schneider Matthias
H�bner Jan
Petrov Orlin
Dinter Christian
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Bayer Schering Pharma Aktiengesellschaft
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Abstract

Spojevi opće formule (IIa) ili (IIb) gdjeR1 i R2 neovisno jedan o drugome označavaju vodikov atom, C1-3 alkilnu skupinu, halogen, cijano-, C1-3 alkoksi-, ili hidroksilnu skupinu, kao i njihove racemate ili odijeljene stereoizomere te njihove fiziološki pogodne soli. Patent sadrži još 21 patentni zahtjev.Compounds of general formula (IIa) or (IIb) wherein R1 and R2 independently of one another denote a hydrogen atom, a C1-3 alkyl group, a halogen, a cyano-, C1-3 alkoxy-, or hydroxyl group, as well as their racemates or separated stereoisomers, and their physiologically acceptable salts. The patent contains another 21 patent claims.

Claims (22)

1. Spojevi opće formule (IIa) ili (IIb) [image] gdje R1 i R2 neovisno jedan o drugome označavaju vodikov atom, C1-3 alkilnu skupinu, halogen, cijano-, C1-3 alkoksi-, ili hidroksilnu skupinu, kao i njihove racemate ili odijeljene stereoizomere te njihove fiziološki pogodne soli.1. Compounds of general formula (IIa) or (IIb) [image] where R1 and R2 independently of each other denote a hydrogen atom, a C1-3 alkyl group, a halogen, a cyano-, a C1-3 alkoxy-, or a hydroxyl group, as well as their racemates or separated stereoisomers and their physiologically suitable salts. 2. Spojevi opće formule (IIa) ili (IIb) prema zahtjevu 1, gdje su R1 i R2 neovisno jedan o drugome vodikov atom, klorov atom, metilna ili hidroksilna skupina.2. Compounds of the general formula (IIa) or (IIb) according to claim 1, where R1 and R2 are independently of each other a hydrogen atom, a chlorine atom, a methyl or a hydroxyl group. 3. Spoj prema zahtjevu 1, naime 5-[4-(5-fluor-2,3-dihidrobenzofuran-7-il)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]-2-metilkinolin, 5-[4-(5-fluor-2,3-dihidrobenzofuran-7-il)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]-1-metilkinolin, 5-[4-(5-fluor-2,3-dihidrobenzofuran-7-il)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]izokinol-1(2H)-on, 5-[4-(5-fluor-2,3-dihidrobenzofuran-7-il)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]-2,6-dimetilkinolin, 5-[4-(5-fluor-2,3-dihidrobenzofuran-7-il)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]-6-klor-2-metilkinolin, 5-[4-(5-fluor-2,3-dihidrobenzofuran-7-il)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]izokinolin, 5-[4-(5-fluor-2,3-dihidrobenzofuran-7-il)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]kinolin, 5-[4-(2,3-dihidro-5-fluor-7-benzofuranil)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]kinolin-2[1H]-on, 6-fluor-5-[4-(5-fluor-2,3-dihidrobenzofuran-7-il)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]-2-metilkinolin, 8-fluor-5-[4-(5-fluor-2,3-dihidrobenzofuran-7-il)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]-2-metilkinolin ili 5-[4-(5-fluor-2,3-dihidrobenzofuran-7-il)-2-hidroksi-4-metil-2-trifluormetil-pentilamino]-2-metilizokinol-1(2H)-on.3. The compound according to claim 1, namely 5-[4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]-2-methylquinoline, 5-[4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]-1-methylquinoline, 5-[4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]isoquinol-1(2H)-one, 5-[4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]-2,6-dimethylquinoline, 5-[4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]-6-chloro-2-methylquinoline, 5-[4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]isoquinoline, 5-[4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]quinoline, 5-[4-(2,3-dihydro-5-fluoro-7-benzofuranyl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]quinolin-2[1H]-one, 6-fluoro-5-[4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]-2-methylquinoline, 8-fluoro-5-[4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]-2-methylquinoline or 5-[4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]-2-methylisoquinol-1(2H)-one. 4. (+)-Enantiomeri spojeva prema zahtjevu 3.4. (+)-Enantiomers of compounds according to claim 3. 5. (-)-Enantiomeri spojeva prema zahtjevu 3.5. (-)-Enantiomers of compounds according to claim 3. 6. Postupak za pripravu spojeva općih formula IIa i IIb, naznačen time da izobuten reagira uz primjenu Lewisove kiseline kao katalizatora s trifluoralkilpiruvatom u spoj opće formule XII [image] pri čemu R3 znači C1-C5 alkil, koji se po želji može podvrgnuti odjeljivanju enantiomera i potom kao kiralni spoj ili kao racemat reagirati s 5-fluor-2,3-dihidrobezofuranom [image] u Friedel-Craftsovoj reakciji alkiliranja u spojeve opće formule X, [image] koji se mogu, po želji, podvrgnuti odjeljivanju enantiomera i zatim spoj opće formule X – kao kiralni spoj ili kao racemat – reducirati u alkohol XI [image] i nakon toga oksidirati u alkohol (III) [image] ili se spoj X može izravno reducirati u aldehid III, pri čemu dobiveni aldehid (III) nakon toga reagira u spojeve opće formule IIa ili IIb, gdje u uvjetima reduktivnog aminiranja, po potrebi u dva stupnja, reagira s 5-aminokinolinskim derivatom ili 5-aminoizokinolinskim derivatom [image] gdje R1 i R2 imaju značenja navedena u zahtjevu 1.6. Process for the preparation of compounds of the general formulas IIa and IIb, characterized by the fact that isobutene reacts with the use of Lewis acid as a catalyst with trifluoroalkylpyruvate in the compound of the general formula XII [image] where R3 means C1-C5 alkyl, which can optionally be subjected to enantiomer separation and then reacted as a chiral compound or as a racemate with 5-fluoro-2,3-dihydrobezofuran [image] in the Friedel-Crafts alkylation reaction to compounds of the general formula X, [image] which can, if desired, be subjected to enantiomer separation and then compound of the general formula X – as a chiral compound or as a racemate – reduce to alcohol XI [image] and then oxidize to alcohol (III) [image] or compound X can be directly reduced to aldehyde III, whereby the resulting aldehyde (III) then reacts to compounds of the general formula IIa or IIb, where under conditions of reductive amination, if necessary in two stages, it reacts with a 5-aminoquinoline derivative or 5-aminoisoquinoline derivative [image] where R1 and R2 have the meanings specified in claim 1. 7. Postupak prema zahtjevu 6, naznačen time, da se odjeljivanje enantiomera zbiva u bilo kojem prikladnom stupnju uz pomoć kolonske kromatografije s kiralnom fazom.7. The method according to claim 6, characterized in that the separation of enantiomers takes place in any suitable degree with the help of column chromatography with a chiral phase. 8. Postupak prema zahtjevu 6, naznačen time da se prikladan racemični međuprodukt u sintezi uz pomoć kiralne pomoćne tvari prevodi ili u dijastereomerne soli ili u dijastereomere, nakon čega se provodi odjeljivanje dijastereomera te odcjepljenje pomoćnoga reagensa.8. The method according to claim 6, characterized in that a suitable racemic intermediate in the synthesis is converted either into diastereomeric salts or into diastereomers with the help of a chiral auxiliary substance, after which separation of diastereomers and separation of the auxiliary reagent is carried out. 9. Postupak prema zahtjevu 7, pri čemu se odjeljivanje enantiomera događa na stupnju spoja opće formule III, X ili XI.9. The process according to claim 7, wherein the separation of enantiomers occurs at the level of the compound of the general formula III, X or XI. 10. Postupak prema zahtjevu 8, pri čemu je kiralna pomoćna tvar kiralna baza, kiralni diol, kiralni alkohol ili kiralna kiselina.10. The method according to claim 8, wherein the chiral excipient is a chiral base, chiral diol, chiral alcohol or chiral acid. 11. Postupak za pripravu spojeva opće formule IIa i IIb, naznačen time, da aldehid (III) [image] u kiralnom ili racemičnom obliku u uvjetima reduktivnog aminiranja, po potrebi u dva stupnja, reagira s 5-aminokinolinskim derivatom ili 5-aminoizokinolinskim derivatom [image] gdje R1 i R2 imaju značenja navedena u zahtjevu 1.11. Process for the preparation of compounds of the general formula IIa and IIb, characterized in that the aldehyde (III) [image] in chiral or racemic form under conditions of reductive amination, if necessary in two stages, reacts with 5-aminoquinoline derivative or 5-aminoisoquinoline derivative [image] where R1 and R2 have the meanings specified in claim 1. 12. Postupak za pripravu spojeva opće formule IIa i IIb prema zahtjevu 11, naznačen time da se spoj opće formule III dobije ili redukcijom spoja opće formule X – uzetoga u obliku kiralnoga spoja ili racemata – [image] gdje R3 znači C1-C5 alkil, metodama koje su poznate stručnjaku, prevede u alkohol XI [image] i zatim oksidira isto tako stručnjaku poznatim metodama u aldehid (III) ili redukcijom spoja X – uzetoga u obliku kiralnog spoja ili racemata - metodama koje su poznate stručnjaku, prevede izravno u aldehid III. [image] 12. Process for the preparation of compounds of the general formula IIa and IIb according to claim 11, characterized in that the compound of the general formula III is obtained or by reducing the compound of the general formula X - taken in the form of a chiral compound or racemate - [image] where R3 means C1-C5 alkyl, by methods known to the expert, convert it into alcohol XI [image] and then oxidizes to aldehyde (III) by methods known to the expert as well or by reduction of compound X - taken in the form of a chiral compound or racemate - by methods known to the expert, it is converted directly into aldehyde III. [image] 13. Postupak za pripravu spojeva opće formule IIa i IIb prema zahtjevu 12, naznačen time da se spoj opće formule X dobije tako da se spoj opće formule XII [image] gdje R3 znači C1-C5 alkil, po želji podvrgne odjeljivanju enantiomera, zatim kao kiralni spoj ili kao racemat s 5-fluor-2,3-dihidrobenzofuranom [image] reagira u Friedel-Craftsovoj reakciji alkiliranja u spojeve opće formule X [image] koji se, po želji, mogu podvrgnuti odjeljivanju enantiomera.13. Process for the preparation of compounds of the general formula IIa and IIb according to claim 12, characterized in that the compound of the general formula X is obtained so that the compound of the general formula XII [image] where R3 means C1-C5 alkyl, optionally subjected to enantiomer separation, then as a chiral compound or as a racemate with 5-fluoro-2,3-dihydrobenzofuran [image] reacts in the Friedel-Crafts alkylation reaction to compounds of the general formula X [image] which, if desired, can be subjected to enantiomer separation. 14. Postupak za pripravu spojeva općih formula IIa i IIb prema zahtjevu 13, naznačen time da se dobije spoj opće formule XII, tako da izobuten reagira uz primjenu Lewisove kiseline kao katalizatora s trifluoralkilpiruvatom u spoj opće formule XII [image] pri čemu R3 znači C1-C5 alkil, koji se po želji može podvrgnuti odjeljivanju enantiomera.14. Process for the preparation of compounds of the general formulas IIa and IIb according to claim 13, characterized in that a compound of the general formula XII is obtained, so that isobutene reacts with the use of a Lewis acid as a catalyst with trifluoroalkylpyruvate to form a compound of the general formula XII [image] wherein R 3 means C 1 -C 5 alkyl, which can optionally be subjected to enantiomer separation. 15. Postupak prema zahtjevu 6 ili 14, naznačen time da je katalizator Lewisova kiselina kiralna.15. The method according to claim 6 or 14, characterized in that the Lewis acid catalyst is chiral. 16. Postupak prema zahtjevu 6 ili 11, naznačen time da se spoj opće formule XII iz zahtjeva 6 ili spoj opće formule III iz zahtjeva 11 uzimaju kiralni.16. Process according to claim 6 or 11, characterized in that the compound of general formula XII from claim 6 or the compound of general formula III from claim 11 are taken as chiral. 17. Postupak prema najmanje jednom od zahtjeva 12-14, naznačen time, da se dobiveni međuprodukti uvijek mogu podvrgnuti odjeljivanju enantiomera ili, nakon reakcije s kiralnim pomoćnim tvarima, odjeljivanju dijastereomera.17. The process according to at least one of claims 12-14, characterized in that the obtained intermediates can always be subjected to separation of enantiomers or, after reaction with chiral auxiliaries, separation of diastereomers. 18. Spoj formule III [image] u kiralnom ili racemičnom obliku.18. Compound of formula III [image] in chiral or racemic form. 19. Primjena spojeva iz najmanje jednog od zahtjeva 1-5 za pripravu lijekova.19. Application of compounds from at least one of claims 1-5 for the preparation of medicines. 20. Primjena spojeva prema najmanje jednom od zahtjeva 1-5 za pripravu lijeka za liječenje upalnih oboljenja.20. Use of compounds according to at least one of claims 1-5 for the preparation of a drug for the treatment of inflammatory diseases. 21. Primjena spojeva prema najmanje jednom od zahtjeva 1-5 za pripravu lijekova koji se mogu lokalno aplicirati.21. Use of compounds according to at least one of claims 1-5 for the preparation of drugs that can be applied locally. 22. Farmaceutski preparati koji sadrže najmanje jedan spoj prema zahtjevu 1-5 ili njihove smjese kao i farmaceutski pogodne nosače.22. Pharmaceutical preparations containing at least one compound according to claim 1-5 or their mixtures as well as pharmaceutically suitable carriers.
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Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7402596B2 (en) 2005-03-24 2008-07-22 Renovis, Inc. Bicycloheteroaryl compounds as P2X7 modulators and uses thereof
TWI464148B (en) 2006-03-16 2014-12-11 Evotec Us Inc Bicycloheteroaryl compounds as p2x7 modulators and uses thereof
KR20090033865A (en) * 2006-07-07 2009-04-06 보오슈 앤드 롬 인코포레이팃드 A composition comprising a dissociated glucocorticoid receptor agonist and an immunosuppressive agent for treating dry eye
ES2403512T3 (en) * 2006-08-07 2013-05-20 Bausch & Lomb Incorporated Compositions and methods to treat, control, reduce, or improve infections and their sequelae
PT2051710E (en) * 2006-08-07 2012-02-08 Bausch & Lomb Compositions and methods for treating, reducing, ameliorating, or alleviating posterior-segment ophthalmic diseases
PL2056799T3 (en) * 2006-08-31 2014-01-31 Bausch & Lomb Compositions and methods for treating or preventing glaucoma or progression thereof
CN101553214B (en) 2006-09-11 2012-12-26 博士伦公司 Compositions and methods for treating, controlling, reducing, ameliorating, or preventing allergy
US20110104159A1 (en) * 2006-09-11 2011-05-05 Rohrs Brian R Compositions and methods for treating, controlling, reducing, ameliorating, or preventing allergy
US20110105559A1 (en) * 2006-09-11 2011-05-05 Rohrs Brian R Compositions and Methods for Treating, Controlling, Reducing, Ameliorating, or Preventing Allergy
EP2086921A2 (en) * 2006-11-09 2009-08-12 Bausch & Lomb Incorporated Synthesis of selected stereoisomers of certain substituted alcohols
CA2683512C (en) * 2007-04-18 2014-12-02 Intendis Gmbh Process for the manufacture of non-steroidal anti-inflammatory agents and intermediates thereof
EP1982976A1 (en) * 2007-04-18 2008-10-22 Intendis GmbH Process for the manufacture of non-steroidal anti-inflammatory agents and intermediates thereof
EP2016935A1 (en) * 2007-07-09 2009-01-21 Intendis GmbH Pharmaceutical composition for topical application of poorly soluble compounds
US20090042936A1 (en) * 2007-08-10 2009-02-12 Ward Keith W Compositions and Methods for Treating or Controlling Anterior-Segment Inflammation
US20090087443A1 (en) * 2007-09-27 2009-04-02 Bartels Stephen P Pharmacological Adjunctive Treatment Associated with Glaucoma Filtration Surgery
JP2011502989A (en) * 2007-11-01 2011-01-27 ボーシュ アンド ローム インコーポレイティド Non-aqueous water-miscible materials as vehicles for drug delivery
US20110077270A1 (en) * 2009-04-21 2011-03-31 Pfeffer Bruce A Compositions and Methods for Treating Ocular Inflammation with Lower Risk of Increased Intraocular Pressure
CN101983961B (en) * 2010-11-24 2012-05-09 浙江启明生化科技有限公司 Preparation method of 5-amino-2-methylquinoline
US20120316199A1 (en) 2011-06-07 2012-12-13 Ward Keith W Compositions and methods for treating, controlling, reducing, or ameliorating inflammatory pain
WO2017137375A1 (en) 2016-02-12 2017-08-17 Bayer Animal Health Gmbh Mapracorat for use in the treatment of canine dermatitis
CN111732493B (en) * 2017-01-16 2023-01-24 宜昌尚诺德生物医药科技有限公司 Synthesis process of arylamine compound
AU2020211303A1 (en) 2019-01-22 2021-07-15 Akribes Biomedical Gmbh Selective Glucocorticoid Receptor Modifiers for treating impaired skin wound healing

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE9017900U1 (en) * 1990-12-22 1993-01-28 Boehringer Ingelheim Kg, 55218 Ingelheim 3,4-Dihydro-1-benzyl-6,7-dimethoxy-α-[di-2-(2,3,4-trimethoxyphenyl)ethyl] aminocarbonyl-isoquinoline
NO306992B1 (en) * 1993-01-28 2000-01-24 Takeda Chemical Industries Ltd Quinoline derivatives, pharmaceutical preparations containing the compounds and the use of the compounds
RU2127271C1 (en) * 1997-03-13 1999-03-10 Пермская государственная фармацевтическая академия 2-chloro-5,6,7,8-tetrahydroquinoline-4-carboxylic acid 5-nitrofurfurylidene hydrazide eliciting an antibacterial activity
UA73492C2 (en) * 1999-01-19 2005-08-15 Aromatic heterocyclic compounds as antiinflammatory agents
DE10215316C1 (en) * 2002-04-02 2003-12-18 Schering Ag Quinoline and isoquinoline derivatives, a pharmaceutical agent and their use as anti-inflammatory agents
BR0317928A (en) * 2003-01-03 2005-11-29 Boehringer Ingelheim Pharma 1-Propanol and 1-Propylamine derivatives and their use as glycorticoid binders
US20040224992A1 (en) * 2003-02-27 2004-11-11 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
US7179919B2 (en) * 2004-03-18 2007-02-20 Boehringer Ingelheim Pharmaceuticals, Inc. Stereoselective synthesis of certain trifluoromethyl-substituted alcohols

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