HRP20110018T1 - Derivati pirido(2,1-a)-izokinolina kao inhibitori dpp-iv - Google Patents

Derivati pirido(2,1-a)-izokinolina kao inhibitori dpp-iv Download PDF

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HRP20110018T1
HRP20110018T1 HR20110018T HRP20110018T HRP20110018T1 HR P20110018 T1 HRP20110018 T1 HR P20110018T1 HR 20110018 T HR20110018 T HR 20110018T HR P20110018 T HRP20110018 T HR P20110018T HR P20110018 T1 HRP20110018 T1 HR P20110018T1
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pyrido
dimethoxy
hexahydro
amino
isoquinolin
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Boehringer Markus
Kuhn Bernd
Mattei Patrizio
Narquizian Robert
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F. Hoffmann - La Roche Ag
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Abstract

Spojevi formule (I) naznačeni time, da R1 je -C(O)-N(R5)R6 ili -N(R5)R6;R2, R3 i R4 su svaki neovisno vodik, halogen, hidroksi, niži alkil, niži alkoksi ili niži alkenil, pri čemu niži alkil, niži alkoksi i niži alkenil mogu opcijski biti supstituirani nižim alkoksikarbonilom, arilom ili heterociklilom; R5 je vodik, niži alkil, halogenirani niži alkil ili cikloalkil; R6 je niži alkilsulfonil, halogenirani niži alkilsulfonil, cikloalkilsulfonil, niži alkilkarbonil, halogenirani niži alkilkarbonil, cikloalkilkarbonil; ili R5 i R6 zajedno s atomom dušika na koji su priključeni tvore 4-, 5-, 6-ili 7-člani zasićeni ili nezasićeni heterociklički prsten koji opcijski sadrži daljnji heteroatom odabran od dušika, kisika i sumpora, a spomenuti heterociklički prsten je opcijski mono-, di-, ili tri-supstituiran, neovisno, nižim alkilom, halogeniranim nižim alkilom, s okso, diokso i/ili cijano; "niži" znači skupina koja se sastoji od jednog do šest atoma ugljika; i njihove farmaceutski prihvatljive soli. Patent sadrži još 19 patentnih zahtjeva.

Claims (20)

1. Spojevi formule (I) [image] naznačeni time, da R1 je -C(O)-N(R5)R6ili -N(R5)R6; R2, R3 i R4 su svaki neovisno vodik, halogen, hidroksi, niži alkil, niži alkoksi ili niži alkenil, pri čemu niži alkil, niži alkoksi i niži alkenil mogu opcijski biti supstituirani nižim alkoksikarbonilom, arilom ili heterociklilom; R5 je vodik, niži alkil, halogenirani niži alkil ili cikloalkil; R6 je niži alkilsulfonil, halogenirani niži alkilsulfonil, cikloalkilsulfonil, niži alkilkarbonil, halogenirani niži alkilkarbonil, cikloalkilkarbonil; ili R5 i R6 zajedno s atomom dušika na koji su priključeni tvore 4-, 5-, 6-ili 7-člani zasićeni ili nezasićeni heterociklički prsten koji opcijski sadrži daljnji heteroatom odabran od dušika, kisika i sumpora, a spomenuti heterociklički prsten je opcijski mono-, di-, ili tri-supstituiran, neovisno, nižim alkilom, halogeniranim nižim alkilom, s okso, diokso i/ili cijano; "niži" znači skupina koja se sastoji od jednog do šest atoma ugljika; i njihove farmaceutski prihvatljive soli.
2. Spojevi prema zahtjevu 1, naznačeni time, da R1 je -C(O)-N(R5)R6.
3. Spojevi prema zahtjevu 1, naznačeni time, da R1 je -N(R5)R6.
4. Spojevi prema bilo kojem od zahtjeva 1 do 3, naznačeni time, da R2, R3 i R4 su svaki neovisno vodik, hidroksi ili niži alkoksi.
5. Spojevi prema bilo kojem od zahtjeva 1 do 4, naznačeni time, da R2 je niži alkoksi.
6. Spojevi prema bilo kojem od zahtjeva 1 do 5, naznačeni time, da R3je niži alkoksi.
7. Spojevi prema bilo kojem od zahtjeva 1 do 6, naznačeni time, da R4 je vodik.
8. Spojevi prema bilo kojem od zahtjeva 1 do 7, naznačeni time, da R5 je vodik, niži alkil ili halogenirani niži alkil.
9. Spojevi prema bilo kojem od zahtjeva 1 do 8, naznačeni time, da R6 je niži alkilsulfonil, niži alkilkarbonil ili cikloalkil-karbonil.
10. Spojevi prema bilo kojem od zahtjeva 1 do 9, naznačeni time, da R5 i R6 zajedno s atomom dušika na koji su priključeni tvore 4-, 5-, 6-ili 7-člani zasićeni ili nezasićeni heterociklički prsten koji opcijski sadrži atom sumpora ili atom kisika kao daljnji heteroatom u prstenu, dok je spomenuti heterociklički prsten opcijski mono-ili di-supstituiran, neovisno, nižim alkilom, halogeniranim nižim alkilom, s okso, diokso i/ili cijano.
11. Spojevi prema zahtjevu 10, naznačeni time, da su R5 i R6 zajedno s atomom dušika na koji su priključeni, pirolidin, pirolidin-2-on, 4-metilpirolidin-2-on, 4-etil-pirolidin-2-on, 3-metil-pirolidin-2-on, 5-metilpirolidin-2-on, 4-fluoro-metil-pirolidin-2-on, pirolidin-2-karbonitril, piperidin, piperidin-2-on, 4-metil-piperidin-2-on, 5-metil-piperidin-2-on, 5,6-dihidro-1H-piridin-2-on, tiazolidin-3-il, 1,1-diokso-1,2-tiazolidin-2-il, 1,1-diokso[1,2]tiazinan-2-il, azetidin, azepan-2-on, oksazolidin-2-on, 5-metil-oksazolidin-2-on, 5-fluorometil-oksazolidin-2-on, ili [1,3]oksazinan-2-on.
12. Spojevi prema bilo kojem od zahtjeva 1 do 11, naznačeni time, da su odabrani iz skupine koja sadrži: (RS,RS,RS)-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-pirolidin-1-il-metanon, (RS,RS,RS)-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-tiazolidin-3-il-metanon, (RS,RS,RS)-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-azetidin-1-il-metanon, (SS)-1-(RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-karbonil)-pirolidin-2-karbonitril, 1-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-piperidin-2-on, (-)-(S,S,S)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido(2,1-a]izokinolin-3-il)-piperidin-2-on, (+)-(R,R,R)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-piperidin-2-on, 1-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-piperidin-2-on, (RS,RS,RS)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-pirolidin-2-on, 1-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksadro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-pirolidin-2-on, 1-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-etil-pirolidin-2-on, (RS,RS,RS)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-5,6-dihidro-1H-piridin-2-on, 1-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-azepan-2-on, (RS,RS,RS)-3-(1,1-diokso-1,2-tiazolidin-2-il)-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-2-ilamin, (RS,RS,RS)-3-(1,1-diokso[1,2]tiazinan-2-il)-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-2-ilamin, (S,S,S)-3-(1,1-diokso-[1,2]tiazinan-2-il)-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-2-ilamin, (SR)-1-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-pirolidin-2-on, (RS,RS,RS,RS)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-pirolidin-2-on, (R)-1-((S,S,S)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-pirolidin-2-on, (S)-1-((R,R,R)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-pirolidin-2-on, (S,S,S,S)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-pirolidin-2-on, (R,R,R,R)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-pirolidin-2-on, 1-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-fluorometil-pirolidin-2-on, 1-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-5-metil-piperidin-2-on, (RS,RS,RS)-N-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-propionamid, (RS,RS,RS)-N-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-butiramid, ciklopropankarboksilna kiselina ((2RS,3RS,11bRS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-amid, (SR)-1-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-fluorometil-pirolidin-2-on, (RS,RS,RS,RS)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-fluorometil-pirolidin-2-on, (S)-1-((2S,3S,11bS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-fluorometil-pirolidin-2-on, (R)-1-((2S,3S,11bS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-fluorometil-pirolidin-2-on, 3-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-oksazolidin-2-on, 3-((2RS, 3RS, 11bRS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido [2,1-a] izokinolin-3-il)-[1,3]oksazinan-2-on, 1-((2RS,3RS,11bRS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-5-metil-pirolidin-2-on, 3-((2RS,3RS,11bRS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-5-fluorometil-oksazolidin-2-on, 1-((2RS,3RS,11bRS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-3-metil-pirolidin-2-on, 3-((2RS,3RS,11bRS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-5-metil-oksazolidin-2-on, i njihove farmaceutski prihvatljive soli.
13. Spojevi prema bilo kojem od zahtjeva 1 do 11, naznačeni time, da su odabrani iz skupine koja sadrži: (RS,RS,RS)-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-tiazolidin-3-il-metanon, (-)-(S,S,S)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-piperidin-2-on, 1-((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-pirolidin-2-on, (RS,RS,RS)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-5,6-dihidro-1H-piridin-2-on, (S,S,S)-3-(1,1-diokso-[1,2]tiazinan-2-il)-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-2-ilamin, (R)-1-((S,S,S)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-pirolidin-2-on, (S,S,S,S)-1-(2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-metil-pirolidin-2-on, 1-(((RS,RS,RS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-5-metil-piperidin-2-on, (S)-1-((2S,3S,11bS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-fluorometil-pirolidin-2-on, (R)-1-((2S,3S,11bS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-fluorometil-pirolidin-2-on, 3-((2RS,3RS,11bRS)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-5-metil-oksazolidin-2-on, i njihove farmaceutski prihvatljive soli.
14. Postupak proizvodnje spojeva formule (I) kao što su određeni prema bilo kojem zahtjevu 1 do 13, naznačen time, da postupak obuhvaća pretvaranje spoja formule A [image] gdje su R1, R2, R3 i R4kao što su određeni u zahtjevu 1, a P je pogodna amino zaštitna skupina; u spoj formule (I) [image] gdje su R1, R2, R3 i R4kao što su određeni u zahtjevu 1.
15. Farmaceutski sastavi, naznačeni time, da sadrže spoj prema bilo kojem od zahtjeva 1 do 13 i farmaceutski prihvatljivi nosač i/ili adjuvans.
16. Farmaceutski sastavi prema zahtjevu 15, naznačeni time, da se primjenjuju za liječenje i/ili profilaksu bolesti koje su povezane s DPP-IV.
17. Spojevi prema bilo kojem od zahtjeva 1 do 13, naznačeni time, da se koriste kao terapeutski aktivne tvari.
18. Uporaba spojeva prema bilo kojem od zahtjeva 1 do 13, naznačena time, da se primjenjuje u proizvodnji lijekova za liječenje i/ili profilaksu bolesti koje su povezane sa DPP-IV.
19. Uporaba spojeva prema bilo kojem od zahtjeva 1 do 13, naznačena time, da se primjenjuje za proizvodnju lijekova za liječenje i/ili profilaksu dijabetesa, diabetes mellitus neovisnog o inzulinu, oslabljene tolerancije glukoze, upalne bolesti crijeva, Colitis Ulcerosa, Morbus Crohn-ove bolesti, hipertenzije, bolesti kod koje diuretičko sredstvo ima blagotvoran učinak, gojaznosti, i/ili metaboličkog sindroma, ili za zaštitu β-stanica.
20. Spoj prema zahtjevu 1, naznačen time, da je to (S)-1-((S,S,S)-2-amino-9,10-dimetoksi-1,3,4,6,7,11b-heksahidro-2H-pirido[2,1-a]izokinolin-3-il)-4-fluorometil-pirolidin-2-on dihidroklorid.
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Families Citing this family (88)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE374181T1 (de) 2001-06-27 2007-10-15 Smithkline Beecham Corp Fluorpyrrolidine als dipeptidylpeptidaseinhibitoren
US7407955B2 (en) 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US7687625B2 (en) 2003-03-25 2010-03-30 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
AU2004251829B2 (en) * 2003-06-20 2009-12-17 F. Hoffmann-La Roche Ag Hexahydropyridoisoqinolines as DPP-IV inhibitors
US7169926B1 (en) 2003-08-13 2007-01-30 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
CN1867560A (zh) 2003-08-13 2006-11-22 武田药品工株式会社 4－嘧啶酮衍生物及其作为肽基肽酶抑制剂的用途
US7678909B1 (en) 2003-08-13 2010-03-16 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
JP2007505121A (ja) 2003-09-08 2007-03-08 武田薬品工業株式会社 ジペプチジルぺプチダーゼ阻害剤
US7501426B2 (en) 2004-02-18 2009-03-10 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
US7732446B1 (en) 2004-03-11 2010-06-08 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
CN102079743B (zh) 2004-03-15 2020-08-25 武田药品工业株式会社 二肽基肽酶抑制剂
JP2008501714A (ja) 2004-06-04 2008-01-24 武田薬品工業株式会社 ジペプチジルペプチダーゼインヒビター
WO2006019965A2 (en) 2004-07-16 2006-02-23 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
DE102004054054A1 (de) 2004-11-05 2006-05-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine
AU2005311511A1 (en) * 2004-11-30 2006-06-08 F. Hoffmann-La Roche Ag Substituted benzoquinolizines as DPP-IV inhibitors for the treatment of diabetes
WO2006068978A2 (en) 2004-12-21 2006-06-29 Takeda Pharmaceutial Company Limited Dipeptidyl peptidase inhibitors
DOP2006000008A (es) 2005-01-10 2006-08-31 Arena Pharm Inc Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1
ZA200708179B (en) 2005-04-22 2009-12-30 Alantos Pharmaceuticals Holding Inc Dipeptidyl peptidase-IV inhibitors
ES2313672T3 (es) * 2005-05-24 2009-03-01 F. Hoffmann-La Roche Ag Praparacion de (s)-4-fluorometil-dihidro-furan-2-ona.
DE102005035891A1 (de) 2005-07-30 2007-02-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
JP2009504599A (ja) * 2005-08-11 2009-02-05 エフ．ホフマン−ラ ロシュ アーゲー Ｄｐｐ−ｉｖ阻害剤を含有する医薬組成物
DK1942898T4 (da) 2005-09-14 2014-06-02 Takeda Pharmaceutical Dipeptidylpeptidase-inhibitorer til behandling af diabetes
KR101368988B1 (ko) 2005-09-16 2014-02-28 다케다 야쿠힌 고교 가부시키가이샤 디펩티딜 펩티다제 억제제
WO2007112347A1 (en) 2006-03-28 2007-10-04 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
PE20071221A1 (es) 2006-04-11 2007-12-14 Arena Pharm Inc Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas
KR101281962B1 (ko) 2006-04-11 2013-07-08 아레나 파마슈티칼스, 인크. 특정 개체에게서 골 질량을 증가시키는 데에 유용한 화합물을 확인하기 위해 ｇｐｒ119 수용체를 사용하는 방법
JP2009533393A (ja) 2006-04-12 2009-09-17 プロビオドルグ エージー 酵素阻害薬
CA2810839A1 (en) 2006-05-04 2007-11-15 Boehringer Ingelheim International Gmbh A polymorphic form of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(r)-amino-piperidin-1-yl)-xanthine
EP1852108A1 (en) 2006-05-04 2007-11-07 Boehringer Ingelheim Pharma GmbH & Co.KG DPP IV inhibitor formulations
PE20110235A1 (es) 2006-05-04 2011-04-14 Boehringer Ingelheim Int Combinaciones farmaceuticas que comprenden linagliptina y metmorfina
WO2007148185A2 (en) * 2006-06-21 2007-12-27 Pfizer Products Inc. Substituted 3 -amino- pyrrolidino-4 -lactams as dpp inhibitors
US8324383B2 (en) 2006-09-13 2012-12-04 Takeda Pharmaceutical Company Limited Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
CN101516880B (zh) * 2006-09-15 2012-06-20 霍夫曼-拉罗奇有限公司 包括烯胺的旋光拆分的用于制备吡啶并[2,1-a]异喹啉衍生物的方法
WO2008031750A2 (en) * 2006-09-15 2008-03-20 F. Hoffmann-La Roche Ag Process for the preparation of pyrido[2,1-a]isoquinoline derivatives by catalytic asymmetric hydrogenation of an enamine
US7956201B2 (en) * 2006-11-06 2011-06-07 Hoffman-La Roche Inc. Process for the preparation of (S)-4-fluoromethyl-dihydro-furan-2-one
WO2008055945A1 (en) 2006-11-09 2008-05-15 Probiodrug Ag 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases
TW200838536A (en) 2006-11-29 2008-10-01 Takeda Pharmaceutical Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
EP2091948B1 (en) 2006-11-30 2012-04-18 Probiodrug AG Novel inhibitors of glutaminyl cyclase
US8093236B2 (en) 2007-03-13 2012-01-10 Takeda Pharmaceuticals Company Limited Weekly administration of dipeptidyl peptidase inhibitors
EP2865670B1 (en) 2007-04-18 2017-01-11 Probiodrug AG Thiourea derivatives as glutaminyl cyclase inhibitors
CL2008002424A1 (es) * 2007-08-16 2009-09-11 Boehringer Ingelheim Int Composicion farmaceutica que comprende un compuesto derivado de pirazol-o-glucosido; y uso de la composicion farmaceutica para el tratamiento de la diabetes mellitus, tolerancia anormal a la glucosa e hiperglucemia, trastornos metabolicos, entre otras.
CL2008002427A1 (es) 2007-08-16 2009-09-11 Boehringer Ingelheim Int Composicion farmaceutica que comprende 1-cloro-4-(b-d-glucopiranos-1-il)-2-[4-((s)-tetrahidrofurano-3-iloxi)bencil]-benceno combinado con 1-[(4-metilquinazolin-2-il)metil]-3-metil-7-(2-butin-1-il)-8-(3-(r)-aminopiperidin-1-il)xantina; y su uso para tratar diabetes mellitus tipo 2.
AU2008290582B2 (en) * 2007-08-17 2014-08-14 Boehringer Ingelheim International Gmbh Purin derivatives for use in the treatment of fab-related diseases
US20090105480A1 (en) * 2007-08-30 2009-04-23 Ulrike Bromberger Process for the preparation of a dpp-iv inhibitor
US20090163718A1 (en) * 2007-12-19 2009-06-25 Stefan Abrecht PROCESS FOR THE PREPARATION OF PYRIDO[2,1-a] ISOQUINOLINE DERIVATIVES
PE20091730A1 (es) 2008-04-03 2009-12-10 Boehringer Ingelheim Int Formulaciones que comprenden un inhibidor de dpp4
EP2108960A1 (en) 2008-04-07 2009-10-14 Arena Pharmaceuticals, Inc. Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditons modulated by PYY
PE20100156A1 (es) * 2008-06-03 2010-02-23 Boehringer Ingelheim Int Tratamiento de nafld
UY32030A (es) 2008-08-06 2010-03-26 Boehringer Ingelheim Int "tratamiento para diabetes en pacientes inapropiados para terapia con metformina"
BRPI0916997A2 (pt) 2008-08-06 2020-12-15 Boehringer Ingelheim International Gmbh Inibidor de dpp-4 e seu uso
MX2011001525A (es) * 2008-08-15 2011-03-29 Boehringer Ingelheim Int Derivados de purina para su uso en el tratamiento de enfermedades relacionadas con fab.
CN102149407A (zh) 2008-09-10 2011-08-10 贝林格尔.英格海姆国际有限公司 治疗糖尿病和相关病症的组合疗法
US20200155558A1 (en) 2018-11-20 2020-05-21 Boehringer Ingelheim International Gmbh Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug
BRPI0923121A2 (pt) 2008-12-23 2015-08-11 Boehringer Ingelheim Int Formas salinas de compostos orgânico
AR074990A1 (es) 2009-01-07 2011-03-02 Boehringer Ingelheim Int Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina
TWI466672B (zh) 2009-01-29 2015-01-01 Boehringer Ingelheim Int 小兒科病人糖尿病之治療
EP2395988A2 (en) 2009-02-13 2011-12-21 Boehringer Ingelheim International GmbH Antidiabetic medications comprising a dpp-4 inhibitor (linagliptin) optionally in combination with other antidiabetics
EP2395983B1 (en) 2009-02-13 2020-04-08 Boehringer Ingelheim International GmbH Pharmaceutical composition comprisng a sglt2 inhibitor, a dpp-iv inhibitor and optionally a further antidiabetic agent and uses thereof
AR077642A1 (es) 2009-07-09 2011-09-14 Arena Pharm Inc Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo
ES2548913T3 (es) 2009-09-11 2015-10-21 Probiodrug Ag Derivados heterocíclicos como inhibidores de glutaminil ciclasa
CN107115530A (zh) 2009-11-27 2017-09-01 勃林格殷格翰国际有限公司 基因型糖尿病患者利用dpp‑iv抑制剂例如利拉利汀的治疗
ES2586231T3 (es) 2010-03-03 2016-10-13 Probiodrug Ag Inhibidores de glutaminil ciclasa
AU2011226074B2 (en) 2010-03-10 2015-01-22 Vivoryon Therapeutics N.V. Heterocyclic inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5)
EP2547339A1 (en) 2010-03-18 2013-01-23 Boehringer Ingelheim International GmbH Combination of a gpr119 agonist and the dpp-iv inhibitor linagliptin for use in the treatment of diabetes and related conditions
AU2011237775A1 (en) 2010-04-06 2012-11-22 Arena Pharmaceuticals, Inc. Modulators of the GPR119 receptor and the treatment of disorders related thereto
EP2560953B1 (en) 2010-04-21 2016-01-06 Probiodrug AG Inhibitors of glutaminyl cyclase
KR101927068B1 (ko) 2010-05-05 2018-12-10 베링거 인겔하임 인터내셔날 게엠베하 체중 감소 치료에 후속하는 dpp-4 억제제에 의한 순차적 병용 요법
CN102971005A (zh) 2010-06-24 2013-03-13 贝林格尔.英格海姆国际有限公司 糖尿病治疗
CN103539791B (zh) 2010-09-22 2017-01-11 艾尼纳制药公司 Gpr119 受体调节剂和对与其相关的障碍的治疗
US9034883B2 (en) 2010-11-15 2015-05-19 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
AR085689A1 (es) 2011-03-07 2013-10-23 Boehringer Ingelheim Int Composiciones farmaceuticas de metformina, linagliptina y un inhibidor de sglt-2
US8530670B2 (en) 2011-03-16 2013-09-10 Probiodrug Ag Inhibitors
US20140018371A1 (en) 2011-04-01 2014-01-16 Arena Pharmaceuticals, Inc. Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
WO2012145361A1 (en) 2011-04-19 2012-10-26 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
US20140038889A1 (en) 2011-04-22 2014-02-06 Arena Pharmaceuticals, Inc. Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
WO2012145604A1 (en) 2011-04-22 2012-10-26 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012170702A1 (en) 2011-06-08 2012-12-13 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
EP3517539B1 (en) 2011-07-15 2022-12-14 Boehringer Ingelheim International GmbH Substituted dimeric quinazoline derivative, its preparation and its use in pharmaceutical compositions for the treatment of type i and ii diabetes
WO2013055910A1 (en) 2011-10-12 2013-04-18 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
US20130303462A1 (en) 2012-05-14 2013-11-14 Boehringer Ingelheim International Gmbh Use of a dpp-4 inhibitor in podocytes related disorders and/or nephrotic syndrome
WO2013174767A1 (en) 2012-05-24 2013-11-28 Boehringer Ingelheim International Gmbh A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
WO2014074668A1 (en) 2012-11-08 2014-05-15 Arena Pharmaceuticals, Inc. Modulators of gpr119 and the treatment of disorders related thereto
JP6615109B2 (ja) 2014-02-28 2019-12-04 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｄｐｐ−４阻害薬の医学的使用
AU2016229982B2 (en) 2015-03-09 2020-06-18 Intekrin Therapeutics, Inc. Methods for the treatment of nonalcoholic fatty liver disease and/or lipodystrophy
CA3022202A1 (en) 2016-06-10 2017-12-14 Boehringer Ingelheim International Gmbh Combinations of linagliptin and metformin
BR112019020485A2 (pt) 2017-04-03 2020-05-12 Coherus Biosciences, Inc. Agonista ppary para tratamento de paralisia supranuclear progressiva
DK3461819T3 (da) 2017-09-29 2020-08-10 Probiodrug Ag Inhibitorer af glutaminylcyklase

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5681956A (en) 1990-12-28 1997-10-28 Neurogen Corporation 4-aryl substituted piperazinylmethyl phenylimidazole derivatives; a new class of dopamine receptor subtype specific ligands
GB9313913D0 (en) 1993-07-06 1993-08-18 Smithkline Beecham Plc Novel compounds
US5455351A (en) 1993-12-13 1995-10-03 Abbott Laboratories Retroviral protease inhibiting piperazine compounds
DE122010000020I1 (de) 1996-04-25 2010-07-08 Prosidion Ltd Verfahren zur Senkung des Blutglukosespiegels in Säugern
US6011155A (en) 1996-11-07 2000-01-04 Novartis Ag N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
TW492957B (en) 1996-11-07 2002-07-01 Novartis Ag N-substituted 2-cyanopyrrolidnes
CA2819705C (en) 1998-02-02 2014-07-08 Trustees Of Tufts College Method of regulating glucose metabolism, and reagents related thereto
DE19834591A1 (de) 1998-07-31 2000-02-03 Probiodrug Ges Fuer Arzneim Verfahren zur Steigerung des Blutglukosespiegels in Säugern
GB9817118D0 (en) 1998-08-07 1998-10-07 Glaxo Group Ltd Pharmaceutical compounds
CO5150173A1 (es) 1998-12-10 2002-04-29 Novartis Ag Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv
US6110949A (en) 1999-06-24 2000-08-29 Novartis Ag N-(substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
WO2001019805A1 (fr) 1999-09-10 2001-03-22 Takeda Chemical Industries, Ltd. Composes heterocycliques et procede de preparation de ces derniers
AU1916401A (en) 1999-11-12 2001-06-06 Guilford Pharmaceuticals Inc. Dipeptidyl peptidase iv inhibitors and methods of making and using dipeptidyl peptidase iv inhibitors
GB9928330D0 (en) 1999-11-30 2000-01-26 Ferring Bv Novel antidiabetic agents
AU2001228309A1 (en) 2000-01-24 2001-08-07 Novo-Nordisk A/S N-substituted 2-cyanopyroles and -pyrrolines which are inhibitors of the enzyme dpp-iv
JP2003523396A (ja) 2000-02-25 2003-08-05 ノボ ノルディスク アクティーゼルスカブ ベータ細胞変性の抑制
HU227882B1 (hu) * 2000-08-10 2012-05-29 Mitsubishi Tanabe Pharma Corp Prolinszármazékok és gyógyszerként való alkalmazásuk
AU9419701A (en) 2000-10-06 2002-04-22 Tanabe Seiyaku Co Aliphatic nitrogenous five-membered ring compounds
US6861440B2 (en) * 2001-10-26 2005-03-01 Hoffmann-La Roche Inc. DPP IV inhibitors
US6727261B2 (en) * 2001-12-27 2004-04-27 Hoffman-La Roche Inc. Pyrido[2,1-A]Isoquinoline derivatives

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