HRP20180125T1 - Biciklički supstituirani uracili i njihovo korištenje - Google Patents

Biciklički supstituirani uracili i njihovo korištenje Download PDF

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HRP20180125T1
HRP20180125T1 HRP20180125TT HRP20180125T HRP20180125T1 HR P20180125 T1 HRP20180125 T1 HR P20180125T1 HR P20180125T T HRP20180125T T HR P20180125TT HR P20180125 T HRP20180125 T HR P20180125T HR P20180125 T1 HRP20180125 T1 HR P20180125T1
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hydrogen
alkyl
formula
trifluoromethyl
compound
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HRP20180125TT
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Chantal FÜRSTNER
Jens Ackerstaff
Alexander Straub
Heinrich Meier
Hanna Tinel
Katja Zimmermann
Adrian Tersteegen
Dimitry Zubov
Raimund Kast
Jens Schamberger
Martina SCHÄFER
Kirsten BÖRNGEN
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Bayer Pharma Aktiengesellschaft
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Claims (17)

1. Spoj s formulom (I) [image] naznačen time da R1 je vodik ili (C1-C4)-alkil, R2 je skupina s formulom [image] gdje * je mjesto spajanja na dušikov atom na uracilu, A je -CH2-, -CH2-CH2-, -O-CH2-## ili kisik, gdje ## je mjesto spajanja na fenilni prsten, m je broj 0, 1 ili 2, R4 je halogen, difluorometil, trifluorometil, (C1-C4)-alkil, difluorometoksi, trifluorometoksi ili (C1-C4)-alkoksi, R5A je vodik ili deuterij, R5B je vodik, deuterij ili (C1-C4)-alkil, R6 je vodik ili fluor, R7 je vodik ili fluor, R8 je halogen, difluorometil, trifluorometil, (C1-C4)-alkil ili nitro, R9 je vodik, halogen, difluorometil, trifluorometil, (C1-C4)-alkil, nitro ili (C1-C4)-alkiltio, R3 je skupina s formulom [image] gdje # je mjesto spajanja na dušikov atom na uracilu, prsten Q je 5- do 7-člani heterociklil ili 5- ili 6-člani heteroaril, gdje 5- do 7-člani heterociklil i 5- ili 6-člani heteroaril može biti supstituiran s 1 do 4 supstituenata koji su neovisno odabrani iz skupine koju čine halogen, difluorometil, trifluorometil, trideuterometil, (C1-C6)-alkil, (C3-C7)-cikloalkil, okso, hidroksil, (C1-C4)-alkilkarbonil, (C1-C4)-alkoksikarbonil, aminokarbonil i (C1-C4)-alkilsulfonil, gdje (C1-C6)-alkil i (C3-C7)-cikloalkil mogu zauzvrat biti supstituirani s 1 do 3 supstituenata koji su neovisno odabrani iz skupine koju čine halogen, cijano, trifluorometil, (C3-C7)-cikloalkil, hidroksil, (C1-C4)-alkoksi i 4- do 7-člani heterociklil, i gdje dva (C1-C6)-alkil radikala vezana na atom ugljika u 5- do 7-članom heterociklilu i 5- ili 6-članom heteroarilu, zajedno sa atomom ugljika na koji su vezani, mogu tvoriti 3- do 6-člani karbocikal, R24 je halogen, (C1-C4)-alkil ili (C1-C4)-alkoksi, n je broj 0, 1, 2 ili 3, i soli, solvati i solvati njihovih soli.
2. Spoj s formulom (I) prema zahtjevu 1 naznačen time da R1 je vodik, metil ili etil, R2 je skupina s formulom [image] gdje * je mjesto spajanja na dušikov atom na uracilu, A je -CH2-, -CH2-CH2-, -O-CH2-## ili kisik, gdje ## je mjesto spajanja na fenilni prsten, R4A je vodik, fluor, klor, trifluorometil ili metil, R4B je vodik, fluor, klor, trifluorometil ili metil, uz uvjet da barem jedan od R4A i R4B radikali nisu vodik, R5A je vodik, R5B je vodik, R6 je vodik, R7 je vodik, R8 je fluor, klor, difluorometil, trifluorometil ili metil, R9 je fluor, klor, difluorometil, trifluorometil ili metil, R3 je skupina s formulom [image] [image] gdje # je mjesto spajanja na dušikov atom na uracilu, E1 je CR11 ili N, gdje R11 je vodik, (C1-C4)-alkil, (C3-C7)-cikloalkil ili aminokarbonil, E2 je CR12 ili N, gdje R12 je vodik, (C1-C4)-alkil ili (C3-C7)-cikloalkil, E3 je NR14 ili S, gdje R14 je vodik, (C1-C4)-alkil ili (C3-C7)-cikloalkil, G1 je C=O ili SO2, G2 je CR16AR16B, NR17, O ili S, gdje R16A je vodik, fluor, (C1-C4)-alkil ili hidroksil, R16B je vodik, fluor, klor, (C1-C4)-alkil ili trifluorometil, ili R16A i R16B zajedno sa atomom ugljika na koji su vezani tvore 3- do 6-člani karbocikal, R17 je vodik, (C1-C6)-alkil, (C3-C7)-cikloalkil ili (C1-C4)-alkoksikarbonil, gdje (C1-C6)-alkil može biti supstituiran s 1 do 3 supstituenata koji su neovisno odabrani iz skupine koju čine fluor, trifluorometil, cijano, (C3-C7)-cikloalkil, hidroksil, trifluorometoksi, (C1-C4)-alkoksi, azetidinil, oksetanil, tetrahidrofuranil i pirolidinil, G3 je CR18AR18B, NR19, O ili S, gdje R18A je vodik, fluor, (C1-C4)-alkil ili hidroksil, R18B je vodik, fluor, klor, (C1-C4)-alkil ili trifluorometil, ili R18A i R18B zajedno sa atomom ugljika na koji su vezani tvore 3- do 6-člani karbocikal, R19 je vodik, (C1-C6)-alkil, (C3-C7)-cikloalkil ili (C1-C4)-alkoksikarbonil, gdje (C1-C6)-alkil može biti supstituiran s 1 do 3 supstituenata koji su neovisno odabrani iz skupine koju čine fluor, trifluorometil, cijano, (C3-C7)-cikloalkil, hidroksil, trifluorometoksi, (C1-C4)-alkoksi, azetidinil, oksetanil, tetrahidrofuranil i pirolidinil, G4 je CH2, C=O ili SO2, Ki je CH2 ili O, K2 je CH2 ili O, uz uvjet da samo jedna od K1 i K2 skupina je O, D1, D2, D3 i D4 su svaki neovisno CR23 ili N, gdje R23 je vodik, halogen, (C1-C6)-alkil ili (C3-C7)-cikloalkil, uz uvjet da ne više od 2 od D1, D2, D3 i D4 skupina su N, R24 je fluor ili metil, n je broj 0 ili 1, R10 je (C1-C4)-alkil ili (C3-C7)-cikloalkil, gdje (C1-C4)-alkil može biti supstituiran s 1 ili 2 supstituenata koji su neovisno odabrani iz skupine koju čine fluor, trifluorometil, ciklopropil, ciklobutil, hidroksil, metoksi, etoksi, azetidinil, oksetanil, tetrahidrofuranil i pirolidinil, R13 je vodik, (C1-C4)-alkil ili (C3-C7)-cikloalkil, R15 je vodik, (C1-C6)-alkil ili (C3-C7)-cikloalkil, gdje (C1-C6)-alkil može biti supstituiran s 1 ili 2 supstituenata koji su neovisno odabrani iz skupine koju čine fluor, trifluorometil, ciklopropil, ciklobutil, hidroksil, metoksi, etoksi, azetidinil, oksetanil, tetrahidrofuranil i pirolidinil, R20 je vodik, (C1-C6)-alkil, (C3-C7)-cikloalkil ili (C1-C4)-alkilkarbonil, gdje (C1-C6)-alkil može biti supstituiran s 1 ili 2 supstituenata koji su neovisno odabrani iz skupine koju čine fluor, trifluorometil, ciklopropil, ciklobutil, hidroksil, metoksi, etoksi, azetidinil, oksetanil, tetrahidrofuranil i pirolidinil, R21 je vodik, (C1-C6)-alkil, (C3-C7)-cikloalkil ili (C1-C4)-alkilsulfonil, R22A je vodik ili (C1-C4)-alkil, R22B je vodik ili (C1-C4)-alkil, ili R22A i R22B zajedno sa atomom ugljika na koji su vezani tvore karbonilnu skupinu, i soli, solvati i solvati njihovih soli.
3. Spoj s formulom (I) prema zahtjevu 1 ili 2 naznačen time da R1 je vodik, R2 je skupina s formulom [image] gdje * je mjesto spajanja na dušikov atom na uracilu, A je -CH2-, R4A je klor ili trifluorometil, R4B je vodik, R3 je skupina s formulom [image] gdje # je mjesto spajanja na dušikov atom na uracilu, E1 je CR11 gdje R11 je vodik, E2 je N, G1 je C=O, G2 je CR16AR16B, NR17, O ili S, gdje R16A je vodik, fluor, metil ili hidroksil, R16B je vodik, fluor, metil ili trifluorometil, ili R16A i R16B zajedno sa atomom ugljika na koji su vezani tvore ciklopropilni prsten, R17 je vodik, (C1-C4)-alkil ili (C3-C5) cikloalkil, gdje (C1-C4)-alkil može biti supstituiran s 1 do 3 supstituenata koji su neovisno odabrani iz skupine koju čine fluor, trifluorometil, cijano, ciklopropil, ciklobutil, hidroksil, trifluorometoksi, metoksi, etoksi, azetidinil, oksetanil, tetrahidrofuranil i pirolidinil, R24 je vodik ili fluor, R10 je (C1-C4)-alkil, R15 je vodik, metil ili etil, gdje metil i etil može biti supstituiran s 1 supstituentom odabranim iz skupine koju čine fluor, trifluorometil i ciklopropil, i soli, solvati i solvati njihovih soli.
4. Spoj s formulom (I) prema zahtjevu 1 ili 2 naznačen time da R1 je vodik, R2 je skupina s formulom [image] gdje * je mjesto spajanja na dušikov atom na uracilu, R5A je vodik, R5B je vodik, R6 je vodik, R7 je vodik, R8 je fluor, klor ili trifluorometil, R9 je fluor, klor, trifluorometil ili metil, R3 je skupina s formulom [image] gdje # je mjesto spajanja na dušikov atom na uracilu, E1 je CR11 gdje R11 je vodik, E2 je N, G1 je C=O, G2 je CR16AR16B, NR17, O ili S, gdje R16A je vodik, fluor, metil ili hidroksil, R16B je vodik, fluor, metil ili trifluorometil, ili R16A i R16B zajedno sa atomom ugljika na koji su vezani tvore ciklopropilni prsten, R17 je vodik, (C1-C4)-alkil ili (C3-C5)-cikloalkil, gdje (C1-C4)-alkil može biti supstituiran s 1 do 3 supstituenata koji su neovisno odabrani iz skupine koju čine fluor, trifluorometil, cijano, ciklopropil, ciklobutil, hidroksil, trifluorometoksi, metoksi, etoksi, azetidinil, oksetanil, tetrahidrofuranil i pirolidinil, R24 je vodik ili fluor, R10 je (C1-C4)-alkil, R15 je vodik, metil ili etil, gdje metil i etil mogu biti supstituirani s 1 supstituentom odabranim iz skupine koju čine fluor, trifluorometil i ciklopropil, i soli, solvati i solvati njihovih soli.
5. Spoj s formulom (I) prema zahtjevu 1 naznačen time da ima sustavno ime 1-(1,3-dimetil-2-okso-2,3-dihidro-1H-benzimidazol-5-il)-2,4-diokso-3-[(1R)-4-(trifluorometil)-2,3-dihidro-1H-inden-1-il]-1,2,3,4-tetrahidropirimidin-5-karboksilna kiselina (R enantiomer) i strukturnu formulu [image]
6. Spoj s formulom (I) prema zahtjevu 1 naznačen time da ima sustavno ime 1-(6-fluoro-1,3-dimetil-2-okso-2,3-dihidro-1H-benzimidazol-5-il)-2,4-diokso-3-[(1R)-4-(trifluorometil)-2,3-dihidro-1H-inden-1-il]-1,2,3,4-tetrahidropirimidin-5-karboksilna kiselina (R enantiomer) i strukturnu formulu [image]
7. Spoj s formulom (I) prema zahtjevu 1 naznačen time da ima sustavno ime 1-(3-metil-2-okso-2,3-dihidro-1,3-benzoksazol-6-il)-2,4-diokso-3-[(1R)-4-(trifluorometil)-2,3-dihidro-1H-inden-1-il]-1,2,3,4-tetrahidropirimidin-5-karboksilna kiselina (R enantiomer) i strukturnu formulu [image]
8. Spoj s formulom (I) prema zahtjevu 1 naznačen time da ima sustavno ime 2,4-diokso-3-[(1R)-4-(trifluorometil)-2,3-dihidro-1H-inden-1-il]-1-(1,3,3-trimetil-2-okso-2,3-dihidro-1H-indol-5-il)-1,2,3,4-tetrahidropirimidin-5-karboksilna kiselina (R enantiomer) i strukturnu formulu [image]
9. Spoj s formulom (I) prema zahtjevu 1 naznačen time da ima sustavno ime 1-(1'-metil-2'-okso-1',2'-dihidrospiro[ciklopropan-1,3'-indol]-5'-il)-2,4-diokso-3-[(1R)-4-(trifluorometil)-2,3-dihidro-1H-inden-1-il]-1,2,3,4-tetrahidropirimidin-5-karboksilna kiselina (R enantiomer) i strukturnu formulu [image]
10. Spoj s formulom (I) prema zahtjevu 1 naznačen time da ima sustavno ime 1-(3-metil-2-okso-2,3-dihidro-1,3-benzotiazol-6-il)-2,4-diokso-3-[(1R)-4-(trifluorometil)-2,3-dihidro-1H-inden-1-il]-1,2,3,4-tetrahidropirimidin-5-karboksilna kiselina (R enantiomer) i strukturnu formulu [image]
11. Spoj s formulom (I) prema zahtjevu 1 naznačen time da ima sustavno ime etil 1-(3-metil-2-okso-2,3-dihidro-1,3-benzoksazol-6-il)-2,4-diokso-3-[(1R)-4-(trifluorometil)-2,3-dihidro-1H-inden-1-il]-1,2,3,4-tetrahidropirimidin-5-karboksilat (R enantiomer) i strukturnu formulu [image]
12. Postupak za proizvodnju spojeva formule (I), naznačen time da [A] spoj s formulom (II) [image] gdje R1A je (C1-C4)-alkil, T1 je (C1-C4)-alkil, T2 je (C1-C4)-alkil, reagira u inertnom otapalu, proizvoljno u prisutnosti odgovarajuće baze, sa spojem s formulom (III) H2N-R3 (III) gdje R3 je kako je definirano u zahtjevima 1 do 4 da se dobije spoj s formulom (IV) [image] gdje R1A i R3 su svaki kako je gore definirano, ovo nakon toga reagira u inertnom otapalu, u prisutnosti odgovarajuće baze, sa spojem s formulom (V) X1-R2 (V) gdje R2 je kako je definirano u zahtjevima 1 do 4 i X1 je hidroksil ili prikladna izlazna skupina, naročito klor, brom ili jod da se dobije spoj s formulom (I-1) [image] gdje R1A, R2 i R3 su svaki kako je gore definirano, ili [B] spoj s formulom (VI) [image] gdje R1A i T1 su svaki kako je gore definirano, i T3 je (C1-C4)-alkil se pretvara u inertnom otapalu ili drugačije bez otapala sa spojem s formulom (III) u spoj s formulom (VII) [image] gdje R1A, R3 i T3 su svaki kako je gore definirano, ovo nakon toga reagira u inertnom otapalu s klorosulfonil izocijanatom da se dobije spoj s formulom (IV) i ovo se potom prevodi analogno postupku [A] u spoj s formulom (I-1), ili [C] spoj s formulom (VIII) [image] gdje R2 je kako je definirano u zahtjevima 1 do 4 reagira u inertnom otapalu sa spojem s formulom (IX) [image] gdje R1A i T1 su svaki kako je gore definirano i T5 je (C1-C4)-alkil i ciklizira u prisutnosti odgovarajuće baze da se dobije spoj s formulom (X) [image] gdje R1A i R2 su svaki kako je gore definirano, te ovo nakon toga reagira u inertnom otapalu, u prisutnosti prikladnog katalizatora i odgovarajuće baze, sa spojem s formulom (XI) [image] gdje R3 je kako je gore definirano i T6 je vodik, (C1-C4)-alkil, ili dva T6 radikala zajedno tvore -C(CH3)2-C(CH3)2-most da se dobije spoj s formulom (I-1), ili [D] spoj s formulom (I-1) hidrolizira u inertnom otapalu u prisutnosti odgovarajuće kiseline ili baze da se dobije spoj s formulom (I-2) [image] gdje R2 i R3 su svaki kako je definirano u zahtjevima 1 do 4 i R1B je vodik, bilo koje zaštitne skupine se odvajaju i/ili se spojevi s formulama (I-1) i (I-2), gdje je prikladno, prevode s odgovarajućim (i) otapalima i/ili (ii) bazama ili kiselinama u njihove solvate, soli i/ili solvate soli.
13. Spoj kako je definirano u bilo kojem od zahtjeva 1 do 11 naznačen time da je za uporabu za liječenje i/ili profilaksu bolesti.
14. Spoj kako je definirano u bilo kojem od zahtjeva 1 do 11 naznačen time da je za uporabu u postupku za liječenje i/ili profilaksu zatajenja srca, plućne hipertenzije, kronične opstruktivne plućne bolesti, astme, zatajenja bubrega, nefropatije, fibroznih poremećaja unutarnjih organa i dermatoloških fibroza.
15. Lijek naznačen time da sadrži spoj kako je definirano u bilo kojem od zahtjeva 1 do 11 u kombinaciji s jednim ili više inertnih netoksičnih farmaceutski prikladnih pomoćnih sredstava.
16. Lijek naznačen time da sadrži spoj kako je definirano u bilo kojem od zahtjeva 1 do 11 u kombinaciji s jednim ili više dodatnih aktivnih sastojaka odabranih iz skupine koja se sastoji od kalcijevih antagonista, antagonista angiotenzina AII, inhibitora ACE, inhibitora vazopeptidaze, antagonista endotelina, inhibitora renina, blokatora alfa-receptora, blokatora beta-receptora, antagonista mineralokortikoidnih receptora, inhibitora rho-kinaze, diuretika, inhibitora kinaze, inhibitora matriks metaloproteinaze, stimulatora i aktivatora topive gvanilat ciklaze i inhibitora fosfodiesteraze.
17. Lijek prema zahtjevu 15 ili 16 naznačen time da je za uporabu za liječenje i/ili profilaksu zatajenja srca, plućne hipertenzije, kronične opstruktivne plućne bolesti, astme, zatajenja bubrega, nefropatije, fibroznih poremećaja unutarnjih organa, dermatoloških fibroza.
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Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA112897C2 (uk) * 2012-05-09 2016-11-10 Байєр Фарма Акцієнгезелльшафт Біциклічно заміщені урацили та їх застосування для лікування і/або профілактики захворювань
EP3066097B1 (de) * 2013-11-08 2017-08-16 Bayer Pharma Aktiengesellschaft Salze von 1-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-2,4-dioxo-3-[(1r)-4-(trifluormethyl)-2,3-dihydro-1h-inden-1-yl]-1,2,3,4-tetrahydropyrimidin-5-carbonsäure
WO2015067650A1 (de) * 2013-11-08 2015-05-14 Bayer Pharma Aktiengesellschaft Substituierte 1,2,4-triazin-3,5-dione und ihre verwendung als chymase hemmern
EP3066098A1 (de) * 2013-11-08 2016-09-14 Bayer Pharma Aktiengesellschaft Substituierte uracile und ihre verwendung
CN105873919A (zh) * 2013-11-08 2016-08-17 拜耳医药股份有限公司 作为类糜蛋白酶抑制剂的取代的尿嘧啶
WO2017162661A1 (en) 2016-03-22 2017-09-28 Bayer Pharma Aktiengesellschaft 1h-benzo[de]isoquinoline-1,3(2h)-diones
EP3338780A1 (de) 2016-12-20 2018-06-27 Bayer Pharma Aktiengesellschaft Verwendung von chymaseinhibitoren zur behandlung von endometriose, post-operativer fibrose und erkrankungen die durch fibrosebildung gekennzeichnet sind
CA3061444A1 (en) 2017-04-27 2018-11-01 Bayer Aktiengesellschaft Selective adrenoreceptor .alpha.2c receptor antagonists alone, or in combination with chymase inhibitors for use in the treatment and/or prophylaxis of peripheral artery diseases (pad)
BR112020022340A2 (pt) 2018-05-15 2021-02-02 Bayer Aktiengesellschaft benzamidas substituídas por 1,3-tiazol-2-il para o tratamento de doenças associadas com sensibilização de fibras nervosas
CN110229067A (zh) * 2019-06-05 2019-09-13 南京焕然生物科技有限公司 一种2-氨基茚制备方法
CN113811530B (zh) * 2019-07-03 2022-07-19 南京明德新药研发有限公司 作为糜酶抑制剂的嘧啶酮类化合物及其应用
CN111440141A (zh) * 2020-05-20 2020-07-24 安徽泽升科技有限公司 一种羟甲基取代芳杂环类化合物的制备方法
WO2022135534A1 (zh) * 2020-12-25 2022-06-30 广东东阳光药业有限公司 取代的含氮双环化合物及其用途
CN114671856B (zh) * 2020-12-25 2023-10-20 广东东阳光药业股份有限公司 多取代的尿嘧啶衍生物及其用途
WO2022135514A1 (zh) * 2020-12-25 2022-06-30 广东东阳光药业有限公司 多取代的尿嘧啶衍生物及其用途
TW202339706A (zh) * 2021-12-06 2023-10-16 美商普萊萃歐治療公司 含醯胺的ｌｏｎｐ１抑制劑化合物、用途及方法
US11618751B1 (en) 2022-03-25 2023-04-04 Ventus Therapeutics U.S., Inc. Pyrido-[3,4-d]pyridazine amine derivatives useful as NLRP3 derivatives
TW202404601A (zh) 2022-04-05 2024-02-01 加拿大商索科普拉健康與人類科學兩合公司 用於選擇性消退血栓性或血栓栓塞性疾病中血栓的凝乳酶抑制劑

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6403599B1 (en) * 1995-11-08 2002-06-11 Pfizer Inc Corticotropin releasing factor antagonists
US6114532A (en) 1998-02-03 2000-09-05 Boehringer Ingelheim Pharma Kg Bicyclic heterocycles, the preparation thereof, and their use as pharmaceuticals
DE19834044A1 (de) 1998-07-29 2000-02-03 Bayer Ag Neue substituierte Pyrazolderivate
DE19834047A1 (de) 1998-07-29 2000-02-03 Bayer Ag Substituierte Pyrazolderivate
US6458952B1 (en) 1999-05-19 2002-10-01 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade
EP1219611A4 (en) 1999-09-03 2003-03-19 Ajinomoto Kk NEW PROCESSES FOR THE PRODUCTION OF OXAZEPINE DERIVATIVES
DE19943636A1 (de) 1999-09-13 2001-03-15 Bayer Ag Neuartige Dicarbonsäurederivate mit pharmazeutischen Eigenschaften
DE19943639A1 (de) 1999-09-13 2001-03-15 Bayer Ag Dicarbonsäurederivate mit neuartigen pharmazeutischen Eigenschaften
DE19943634A1 (de) 1999-09-13 2001-04-12 Bayer Ag Neuartige Dicarbonsäurederivate mit pharmazeutischen Eigenschaften
DE19943635A1 (de) 1999-09-13 2001-03-15 Bayer Ag Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften
GB0021315D0 (en) * 2000-08-30 2000-10-18 Dainippon Pharmaceutical Co Heterocyclic compounds and intermediates thereof
AR031176A1 (es) 2000-11-22 2003-09-10 Bayer Ag Nuevos derivados de pirazolpiridina sustituidos con piridina
DE10110749A1 (de) 2001-03-07 2002-09-12 Bayer Ag Substituierte Aminodicarbonsäurederivate
DE10110750A1 (de) 2001-03-07 2002-09-12 Bayer Ag Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften
JP2003017508A (ja) 2001-07-05 2003-01-17 Nec Corp 電界効果トランジスタ
AR038536A1 (es) 2002-02-25 2005-01-19 Upjohn Co N-aril-2-oxazolidinona-5- carboxamidas y sus derivados
DE10220570A1 (de) 2002-05-08 2003-11-20 Bayer Ag Carbamat-substituierte Pyrazolopyridine
JP2003342265A (ja) * 2002-05-22 2003-12-03 Senju Pharmaceut Co Ltd トリアゾリジン誘導体およびその医薬用途
AU2003290735A1 (en) 2002-12-06 2004-06-30 Eli Lilly And Company Inhibitors of monoamine uptake
EP1666067A4 (en) * 2003-08-22 2009-07-22 Teijin Pharma Ltd MEDICAMENT WITH CHYMASE INHIBITOR AS AN ACTIVE SUBSTANCE
DE102004004928A1 (de) 2004-01-31 2005-08-18 Bayer Healthcare Ag Dibenzoxazepine II
JP5319113B2 (ja) 2004-03-26 2013-10-16 メチルジーン インコーポレイテッド ヒストンデアセチラーゼの阻害剤
US7507748B2 (en) 2004-07-22 2009-03-24 Amgen Inc. Substituted aryl-amine derivatives and methods of use
EP2942349A1 (en) 2004-12-23 2015-11-11 Deciphera Pharmaceuticals, LLC Enzyme modulators and treatments
MX2007013595A (es) 2005-05-04 2008-01-24 Renovis Inc Compuestos heterociclicos fusionados y composiciones y usos de estos.
WO2007007161A2 (en) * 2005-07-08 2007-01-18 Orchid Research Laboratories Limited Novel bio-active derivatives
WO2007120339A1 (en) 2005-12-19 2007-10-25 Genentech, Inc. Pyrimidine kinase inhibitors
CA2642406A1 (en) 2006-02-14 2007-08-23 Pfizer Products Inc. Benzoxazinone and benzoxazepinone oxazolidinones as antibacterial agents
AR061570A1 (es) 2006-06-23 2008-09-03 Smithkline Beecham Corp Compuesto de glicina sustituido en el n heteroaromatico composicion farmaceutica que lo comprende, su uso para preparar un medicamento, procedimientos para preparar dicha composicion farmaceutica y para preparar el compuesto
US7790756B2 (en) 2006-10-11 2010-09-07 Deciphera Pharmaceuticals, Llc Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases
GB0622472D0 (en) 2006-11-10 2006-12-20 Addex Pharmaceuticals Sa Novel heterocyclic derivatives
US8314087B2 (en) 2007-02-16 2012-11-20 Amgen Inc. Nitrogen-containing heterocyclyl ketones and methods of use
CA2683785A1 (en) 2007-04-13 2008-10-23 Vertex Pharmaceuticals Incorporated Aminopyrimidines useful as kinase inhibitors
WO2009049112A1 (en) 2007-10-10 2009-04-16 Smithkline Beecham Corporation Prolyl hydroxylase inhibitors
NZ585348A (en) 2007-10-19 2012-02-24 Boehringer Ingelheim Int Heterocycle-substituted piperazino-dihydrothienopyrimidines
JP4790871B2 (ja) * 2008-05-05 2011-10-12 メルク フロスト カナダ リミテツド レニン阻害剤としての３，４−置換ピペリジン誘導体
AU2009263384A1 (en) 2008-06-25 2009-12-30 Daiichi Sankyo Company, Limited Carboxylic acid compound
DE102008030091B4 (de) * 2008-06-25 2011-03-03 Resprotect Gmbh Uracilderivate und deren Verwendung
UA112897C2 (uk) * 2012-05-09 2016-11-10 Байєр Фарма Акцієнгезелльшафт Біциклічно заміщені урацили та їх застосування для лікування і/або профілактики захворювань

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RS56784B1 (sr) 2018-04-30
ECSP14026138A (es) 2015-12-31
PL2847190T3 (pl) 2016-12-30
JP6141414B2 (ja) 2017-06-07
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US20150148340A1 (en) 2015-05-28
US20180256576A1 (en) 2018-09-13
MX357712B (es) 2018-07-20
AU2013258223B2 (en) 2017-11-09
PH12014502496B1 (en) 2015-01-12
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ES2657315T3 (es) 2018-03-02
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IL253950B (en) 2019-07-31
EP2847190B1 (de) 2016-04-06
EA030383B9 (ru) 2018-12-28
CR20140513A (es) 2014-12-02
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JP2015516000A (ja) 2015-06-04
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BR112014028086B1 (pt) 2021-09-21
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EA030383B1 (ru) 2018-07-31
ZA201408146B (en) 2017-01-25
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JP6367421B2 (ja) 2018-08-01
EP2847190A1 (de) 2015-03-18
UA112897C2 (uk) 2016-11-10
CA2872906C (en) 2020-08-04
KR102083281B1 (ko) 2020-05-29
NO3045456T3 (hr) 2018-03-24
EP3045456B1 (de) 2017-10-25
CA2872906A1 (en) 2013-11-14
JP2017160242A (ja) 2017-09-14
AU2017265047A1 (en) 2017-12-14
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TW201734007A (zh) 2017-10-01
EA201492040A1 (ru) 2015-12-30
EA201790032A1 (ru) 2017-05-31
ES2581537T3 (es) 2016-09-06
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US20170020875A1 (en) 2017-01-26

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