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HRP20160952T1 - Fuzionirani benzoksazepinoni kao modulatori jonskih kanala - Google Patents

Fuzionirani benzoksazepinoni kao modulatori jonskih kanala Download PDF

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HRP20160952T1
HRP20160952T1 HRP20160952TT HRP20160952T HRP20160952T1 HR P20160952 T1 HRP20160952 T1 HR P20160952T1 HR P20160952T T HRP20160952T T HR P20160952TT HR P20160952 T HRP20160952 T HR P20160952T HR P20160952 T1 HRP20160952 T1 HR P20160952T1
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Croatia
Prior art keywords
dihydrobenzo
oxazepin
phenyl
trifluoromethoxy
methyl
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HRP20160952TT
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Britton Kenneth CORKEY
Elfatih Elzein
Robert H. JIANG
Rao V. KALLA
Dmitry Koltun
Xiaofen Li
Ruben Martinez
Eric Q. PARKHILL
Thao Perry
Jeff Zablocki
Chandrasekar Venkataramani
Michael Graupe
Juan Guerrero
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Gilead Sciences, Inc.
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Application filed by Gilead Sciences, Inc. filed Critical Gilead Sciences, Inc.
Publication of HRP20160952T1 publication Critical patent/HRP20160952T1/hr

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Claims (18)

1. Spoj formule II: [image] gdje: m je 0, 1 ili 2; n je 0, 1, 2 ili 3; R2 je -C1-6 alkilen-R5, -C1-6 alkilen-L-R5 ili -C1-6 alkilen-L-C1-6 alkilen-R5; L je -O-, -C(O)-, -NHS(O)2-, -S(O)2NH-, -C(O)NH- ili -NHC(O)-; svaki R3 je nezavisno vodik, deuterij ili C1-6 alkil; svaki R4 je nezavisno vodik, deuterij ili C1-6 alkil; R5 je cikloalkil, aril, heteroaril ili heterociklil; gdje navedeni cikloalkil, aril, heteroaril ili heterociklil su po izboru supstituirani sa jednim, dva ili tri supstituta nezavisno odabranih iz grupe koja se sastoji od C1-6 alkila, halo, cikloalkila, heterociklila, heteroarila, -N(R20)(R22), -C(O)-OR20, -CN, i -O-R20; gdje navedeni C1-6 alkil ili heteroaril su po izboru dalje supstituirani sa jednim, dva ili tri supstituta nezavisno odabranih iz grupe koja se sastoji od halo, C1-6 alkil i aril; i gdje je navedeni C1-6 alkil po izboru dalje supstituiran sa jednim, dva ili tri halo.; svaki R10 je nezavisno odabran iz grupe koja se sastoji od halo, -NO)2,-CN, -SF5, -Si(CH3)3, -O-R20, -S-R20, -C(O)-R20, -C(O)-OR20, -N(R20)(R22), -C(O)-N(R20)(R22), -N(R20)-C(O)-R22, -N(R20)-C(O)-OR22, -N(R20)-S(O)2-R26, -S(O)2-R20, -O-S(O)2-R20, -S(O)2-N(R20)(R22), C1-6 alkil, C2-4 alkenil, C2-4 alkinil, cikloalkil, aril, heteroaril i heterociklil; gdje navedeni C1-6 alkil, C2-4 alkenil, C2-4 alkinil, cikloalkil, aril, heteroaril ili heterociklil su po izboru supstituirani sa jednim, dva ili tri supstituta nezavisno odabranih iz grupe koja se sastoji od halo, -NO2, arila, heterociklila, heteroarila, C1-6 alkila, C1-3 haloalkila, cikloalkila, -N(R20)(R22), -C(O)-R20, -C(O)-OR20, -C(O)-N(R20)(R22), -CN i -O-R20; R17 je halo, ili C1-6 alkil; R20 i R22 su u svakom primjeru nezavisno odabrani iz grupe koja se sastoji od vodika, C1-6 alkila, C2-6 alkenila, C2-6 alkinila, cikloalkila, heterociklila, arila i heteroarila; gdje C1-6 alkil, C2-6 alkenil, C1-6 alkinil, cikloalkil, heterociklil, aril i heteroaril su po izboru supstituirani sa jednim, dva ili tri supstituta nezavisno odabranih iz grupe koja se sastoji od hidroksila, halo, C1-4 alkil, acilamino, okso, -NO2, -S(O)2R26, -CN, C1-3 alkoksi, -CF3, -OCF3, -OCH2CF3, -C(O)-NH2, aril, cikloalkil i heteroaril; i gdje je navedeni heteroaril po izboru dalje supstituiran sa C1-4 alkilom ili cikloalkilom; ili kada su R20 i R22 vezani za zajednički atom azota R20 i R22 mogu se spojiti da formiraju heterociklični ili heteroarilni prsten koji je zatim po izboru supstituiran sa jednim, dva ili tri supstituta nezavisno odabranih iz grupe koja se sastoji od hidroksila, halo, C1-4 alkil, aralkil, ariloksi, aralkiloksi, acilamino, -NO2, -S(O)2R26, -CN, C1-3 alkoksi,-CF3, -OCF3, aril, heteroaril i cicloalkil; i svaki R26 je nezavisno odabran iz grupe koja se sastoji od vodika, C1-4 alkila, arila i cikloalkila; gdje C1-4 alkil, aril i cikloalkil mogu biti dalje supstituirani sa 1 do 3 supstituta nezavisno odabranih iz grupe koja se sastoji od hidroksila, halo, C1-4 alkoksi, -CF3 i -OCF3; gdje u svakom primjeru nezavisno cikloalkil grupa sadrži od 3 do 20 atoma ugljika; arilna grupa sadrži od 6 do 20 atoma ugljika; heteroarilna grupa sadrži jedan ili više prstenova koji sadrže 1 do 15 atoma ugljika i 1 do 4 heteroatoma odabranih od kisika, azota i sumpora u najmanje jednom prstenu; i heterociklična grupa koja je monoradikalna zasićena grupa ima jedan prsten ili više kondenziranih prstenova, koji imaju od 1 do 40 atoma ugljika i od 1 do 4 heteroatoma, odabranih od azota, sumpora, fosfora, i/ili kisika u okviru prstena; ili farmaceutski prihvatljiva sol, ester, stereoizomer, smjesa stereoizomera ili tautomer tog spoja.
2. Spoj iz patentnog zahtjeva 1, gdje R2 je -C1-6 alkilen-R5 ili -C1-6 alkilen-L-R5.
3. Spoj iz patentnog zahtjeva 1, gdje R2 je [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image]
4. Spoj iz patentnog zahtjeva 1, gdje n je 1, 2 ili 3; i svaki R10 je nezavisno odabran iz grupe koja se sastoji od halo, -O-R20, -O-S(O)2-R20, C1-4 alkila i cikloalkila; i gdje su navedeni alkil i cikloalkil po izboru supstituirani sa jednim, dva ili tri halo ili -CN; i R20 je nezavisno odabran iz grupe koja se sastoji od C1-6 alkila, cikloalkila i arila; i gdje su alkil i aril po izboru supstituirani sa jednim, dva ili tri halo ili cikloalkila.
5. Spoj iz patentnog zahtjeva 1, gdje n je 1, 2 ili 3; i svaki R10 je nezavisno 2-fluor, 3-fluor, 4-fluor, 2-hlor, 4-hlor, 2-metil, 4-metil, 4-etil, 4-izopropil, 4-terc-butil, 4-difluormetil, 4-trifluormetil, 4-ciklopropil, 4-izobutoksi, 4-difluormetoksi, 4-trifluormetoksi, 4-(2,2,2-trifluoretoksi), 4-trifluormetilsulfoksil, 4-(2,2,2-trifluoretil), 4-ciklopropoksi, 4-ciklobutilmetoksi, 4-fluorfenoksi, 4-fenoksi ili 3-fenoksi.
6. Spoj iz patentnog zahtjeva 1, gdje su R20 i R22 u svakom primjeru nezavisno odabrani iz grupe koja se sastoji od vodika, C1-6 alkila i heteroarila.
7. Spoj iz patentnog zahtjeva 1, gdje je svaki R3 nezavisno vodik, deuterij, metil, ili izopropil; m je 0 ili 1; i R17 je halo.
8. Spoj iz patentnog zahtjeva 1, gdje je spoj predstavljen Formulom IIB: [image] gdje: n je 0, 1, 2 ili 3; R2 je -C1-6 alkilen-R5; R5 je cikloalkil, aril, heteroaril ili heterociklil; gdje su navedeni cikloalkil, aril, heteroaril ili heterociklil po izboru supstituirani sa jednim, dva ili tri supstituta nezavisno odabranih iz grupe koja se sastoji od C1-6 alkila, halo, -N(R20)(R22), -C(O)-OR20, -CN i -O-R20; i gdje je navedeni C1-6 alkil po izboru dalje supstituiran sa jednim, dva ili tri halo; svaki R10 je nezavisno odabran iz grupe koja se sastoji od halo, -NO2, - CN, -SF5, -Si(CH3)3, -O-R20, -S-R20, -C(O)-R20, -C(O)-OR20, -N(R20)(R22), -C(O)-N(R20)(R22), -N(R20)-C(O)-R22, -N(R20)-C(O)-OR22, -N(R20)-S(O)2-R26, -S(O)2-R20, -O-S(O)2-R20, -S(O)2-N(R20)(R22), C1-6 alkil, C2-4 alkenil, C2-4 alkinil, cikloalkil, aril, heteroaril i heterociklil; gdje su navedeni C1-6 alkil, C2-4 alkenil, C2-4 alkinil, cikloalkil, aril, heteroaril ili heterociklil po izboru supstituirani sa jednim, dva ili tri supstituta nezavisno odabranih iz grupe koja se sastoji od halo, -NO2, aril, heterociklil, heteroaril, C1-6 alkil, C1-3 haloalkil, cikloalkil, -N(R20)(R22), -C(O)-R20, -C(O)-OR20, -C(O)-N(R20)(R22), -CN i -O-R20; R20 i R22 su u svakom primjeru nezavisno odabrani iz grupe koja se sastoji od vodika, C1-6 alkila, C2-6 alkenila, C2-6 alkinila, cikloalkila, heterociklila, arila i heteroarila; i gdje su C1-6 alkil, C2-6 alkenil, C2-6 alkinil, cikloalkil, heterociklil, aril i heteroaril po izboru supstituirani sa jednim, dva ili tri supstituta koja su nezavisno odabrana iz grupe koja se sastoji od hidroksila, halo, C1-4 alkil, acilamino, okso, -NO2, -S(O)2R26, -CN, C1-3 alkoksi, -CF3, -OCF3, -OCH2CF3 i -C(O)-NH2; ili kada su R20 i R22 vezani za zajednički atom azota R20 i R22 mogu se spojiti da formiraju heterociklični ili heteroarilni prsten koji je zatim po izboru supstituiran sa jednim, dva ili tri supstituta nezavisno odabranih iz grupe koja se sastoji od hidroksil, halo, C1-4 alkil, aralkil, ariloksi, aralkiloksi, acilamino, -NO2, --S(O)2R26, -CN, C1-3 alkoksi, -CF3 i -OCF3; i svaki R26 je nezavisno odabran iz grupe koja se sastoji od vodika, C1-4 alkila, arila i cikloalkila; gdje C1-4 alkil, aril i cikloalkil mogu dalje biti supstituirani sa od 1 do 3 supstituta nezavisno odabranih iz grupe koja se sastoji od hidroksil, halo, C1-4 alkoksi, -CF3 i-OCF3; ili farmaceutski prihvatljiva sol, ester, stereoizomer, smjesa stereoizomera ili tautomer tog spoja.
9. Spoj iz patentnog zahtjeva 1, gdje se spoj odabran iz grupe sastoji od: 4-((3-metiloksetan-3-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-1); 4-(2-(pirolidin-1-il)etil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-3); 4-((5-ciklobutil-1,3,4-oksadiazol-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-4); 4-((2,3-dihidrobenzo[b][1,4]dioksin-6-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-5); 4-(hinolin-2-ilmetil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-7); 4-(ciklopropilmetil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-10); (S)-3-metil-4-(pirimidin-2-ilmetil)-7-(4-(trifluormetil)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-12); (R)-3-metil-4-(pirimidin-2-ilmetil)-7-(4-(trifluormetil)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-13); 6-((5-okso-7-(4-(trifluormetoksi)fenil)-2,3-dihidrobenzo[f][1,4]oksazepin-4(5H)-il)metil)pikolinonitril (II-14); 7-(4-(trifluormetoksi)fenil)-4-((6-(trifluormetil)piridin-2-il)metil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-15); 7-(4-(trifluormetoksi)fenil)-4-((6-(trifluormetil)piridin-3-il)metil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-16); 4-((6-metilpiridin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-17); (2R,11aS)-2-amino-7-(4-(trifluormetil)fenil)-2,3,11,11a- tetrahidrobenzo[f]pirolo[2,1-c][1,4]oksazepin-5(1H)-on (II-21); 4-(pirazin-2-ilmetil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-31); 4-((5-metiloksazol-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-33); 7-(4-(trifluormetoksi)fenil)-4-(2-(2,5,5-trimetil-1,3-dioksan-2-il)etil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-35); 4-((5-(piridin-2-il)izoksazol-3-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-41); 4-((4,6-dimetoksipirimidin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-42); etil 3-((5-okso-7-(4-(trifluormetoksi)fenil)-2,3-dihidrobenzo[f][1,4]oksazepin-4(5H)-il)metil)benzoat (II-43); 4-(2-(pirimidin-2-il)etil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-44); 4-(3,4-difluorbenzil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-45); 4-(2-hlorbenzil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-47); 4-(2,6-dihlorbenzil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-48); 4-(2,6-difluorbenzil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-49); 4-(2-(1H-pirazol-1-il)etil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-50); (2S,11aS)-2-amino-7-(4-(trifluormetil)fenil)-2,3,11,11a-tetrahidrobenzo[f]pirolo[2,1-c][1,4]oksazepin-5(1H)-on (II-51); 4-(2-(piridin-2-il)etil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-54); 4-(2-fluorbenzil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-57); 4-(pirimidin-2-ilmetil)-7-(4-(trifluormetil)fenil)-3,4-dihidrobenzo[f] [1,4]oksazepin-5(2H)-on (II-61); 4-(4-fluorbenzil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-62); 4-((1-metil-1H-pirazol-3-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-64); 4-((5-hlorpirimidin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-65); 4-(piridin-4-ilmetil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-67); 4-((5-ciklopropil-1,3,4-oksadiazol-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-68); 4-(2-(pirimidin-2-iloksi)etil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-69); 4-(piridin-3-ilmetil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-70); 4-(piridin-2-ilmetil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-72); 4-(pirimidin-2-ilmetil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-73); 4-((3-metilpiridin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-75); 4-(pirimidin-2-ilmetil)-7-p-tolil-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-87); 7-(4-hlorfenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-88); 7-(4-izopropilfenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-89); 7-(4-etilfenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-91); 7-(4-ciklopropilfenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-92); (R)-4-(1-(pirimidin-2-il)etil)-7-(4-(trifluormetil)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-95); 7-(4-izobutoksifenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-97); 7-(4-tert-butilfenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-98); 7-(4-ciklopropoksifenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-102); 7-(4-fluorfenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-104); 7-(2-fluor-4-(trifluormetil)fenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo [f] [1,4]oksazepin-5(2H)-on (II,-105); 7-(3-fluor-4-(2,2,2-trifluoretoksi)fenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-106); 4-(pirimidin-2-ilmetil)-7-(4-(2,2,2-trifluoretoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-107); 7-(2-hlor-4-(trifluormetil)fenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-110); 7-(4-(trifluormetoksi)fenil)-4-((4-(trifluormetil)pirimidin-2-il)metil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-113); 7-(4-(trifluormetoksi)fenil)-4-((5-(6-(trifluormetil)piridin-3-il)pirimidin-2-il)metil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-115); 7-(4-hlor-2-fluorfenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-117); 1-(4-(5-okso-4-(pirimidin-2-ilmetil)-2,3,4,5-tetrahidrobenzo[f][1,4]oksazepin-7-il)fenil)ciklopentankarbonitril (II-122); 7-(4-etoksifenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-123); 7-(4-(difluormetil)fenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-124); 4-((4-morfolinopirimidin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f] [1,4]oksazepin-5(2H)-on (II-133); 4-benzil-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-134); 4-(imidazo[1,2-a]piridin-2-ilmetil)-7-(4-(trifluormetil)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-135); 7-(3-fluor-4-(trifluormetil)fenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-136); 4-((4-metoksipirimidin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f] [1,4]oksazepin-5(2H)-on (II-137); 4-((4-metilpirimidin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-138); 4-((4-(piperidin-1-il)pirimidin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-139); 4-((4-(dimetilamino)pirimidin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-140); 4-benzil-7-(4-(trifluormetil)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-141); 4-((3-metoksipiridin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-143); 7-(4-(ciklobutilmetoksi)fenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-144); 7-(2-metil-4-(trifluormetil)fenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-145); 7-(2-metil-4-(trifluormetoksi)fenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-146); 4-((1-(difluormetil)-1H-pirazol-3-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-147); 7-(4-(trifluormetoksi)fenil)-4-((3-(trifluormetil)-1H-pirazol-1-il)metil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-148); 4-(pirimidin-2-ilmetil)-7-(4-(2,2,2-trifluoretil)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-150); 4-(piridin-2-ilmetil)-7-(4-(2,2,2-trifluoretil)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-151); 4-((1-ciklopentil-1H-pirazol-3-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-152); 4-((1-etil-1H-pirazol-3-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-153); 4-((1-metil-1H-imidazol-4-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-154); 4-((4-metil-1H-pirazol-1-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-155); 4-((4-hlor-1H-pirazol-1-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-156); 7-(4-(difluormetil)fenil)-4-(piridin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-157); 7-(4-hlor-3-fluorfenil)-4-(piridin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-158); 7-(4-(difluormetoksi)fenil)-4-(piridin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-159); 4-((1-metil-1H-pirazol-4-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-160); 4-(pirimidin-2-ilmetil)-7-(2,3,4-trifluorfenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-162); 7-(3,4-difluorfenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-163); 4-((3-fluorpiridin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-164); 4-benzil-9-fluor-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-165); 4-benzil-9-fluor-7-(4-(trifluormetil)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-166); 4-benzil-8-fluor-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-167); 4-benzil-8-fluor-7-(4-(trifluormetil)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-168); 7-(4-hlor-3-fluorfenil)-4-((3-fluorpiridin-2-il)metil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-169); 7-(2-fluor-4-(trifluormetil)fenil)-4-((3-fluorpiridin-2-il)metil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-170); 4-(5-okso-4-(pirimidin-2-ilmetil)-2,3,4,5-tetrahidrobenzo[f][1,4]oksazepin-7-il)fenil trifluormetansulfonat (II-171); 4-((5-metilpirazin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-172); 2,2,3,3-tetradeutero-4-(pirimidin-2-ilmetil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-174); 4-((6-metilpirazin-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-175); 4-((3-fluorpiridin-2-il)metil)-7-(4-(trifluormetil)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-176); N-(2-(5-okso-7-(4-(trifluormetoksi)fenil)-2,3-dihidrobenzo[f][1,4]oksazepin-4(5H)-il)etil)benzensulfonamid (II-177); N-(2-(5-okso-7-(4-(trifluormetoksi)fenil)-2,3-dihidrobenzo[f][1,4]oksazepin-4(5H)-il)etil)ciklopropansulfonamid (II-179); 4-((1-metil-1H-imidazol-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-186); 4-((1-benzil-1H-imidazol-2-il)metil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-187); 4-(imidazo[1,2-a]piridin-2-ilmetil)-7-(4-(trifluormetoksi)fenil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-189); N-ciklopropil-3-(5-okso-7-(4-(trifluormetoksi)fenil)-2,3-dihidrobenzo[f][1,4]oksazepin-4(5H)-il)propan-1-sulfonamid (II-190); N-(2-(5-okso-7-(4-(trifluormetoksi)fenil)-2,3-dihidrobenzo[f][1,4]oksazepin-4(5H)-il)etil)pirimidin-2-karboksamid (II-192); 7-(4-(4-fluorfenoksi)fenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-193); 7-(4-fenoksifenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-194); i 7-(3-fenoksifenil)-4-(pirimidin-2-ilmetil)-3,4-dihidrobenzo[f][1,4]oksazepin-5(2H)-on (II-195); ili farmaceutski prihvatljiva sol, ester, stereoizomer, smjesa stereoizomera ili tautomer tog spoja.
10. Spoj iz patentnog zahtjeva 1 koji ima strukturu: [image] ili njegova farmaceutski prihvatljiva sol;. spoj koji ima strukturu: [image] ili njegova farmaceutski prihvatljiva sol; spoj koji ima strukturu: [image] ili njegova farmaceutski prihvatljiva sol; spoj koji ima strukturu: [image] ili njegova farmaceutski prihvatljiva sol; spoj koji ima strukturu: [image] ili njegova farmaceutski prihvatljiva sol; spoj koji ima strukturu: [image] ili spoj koji ima strukturu: [image]
11. Spoj iz patentnog zahtjeva 1 koji ima strukturu: [image]
12. Spoj iz patentnog zahtjeva 1 koji ima strukturu: [image]
13. Farmaceutska kompozicija koja sadrži farmaceutski prihvatljiv ekscipijens i terapijski efikasnu količinu spoja u skladu sa bilo kojim od patentnih zahtjeva od 1 do 12 ili njegovu farmaceutski prihvatljivu sol.
14. Spoj u skladu sa bilo kojim od patentnih zahtjeva od 1 do 12 ili njegova farmaceutski prihvatljiva sol za upotrebu u terapiji; poželjno za upotrebu u liječenju stanja bolesti kod čovjeka koje je olakšano liječenjem agensom koji je sposoban da reducira kasnu struju natrijuma.
15. Spoj za upotrebu prema patentnom zahtjevu 14, gdje je stanje bolesti odabrano iz grupe koja se sastoji od atrijalne aritmije, ventrikularne aritmije, srčane insuficijencije, dijastolne srčane insuficijencije, sistolne srčane insuficijencije, akutne srčane insuficijencije, stabilne angine, nestabilne angine, naporom inducirane angine, kongestivnog srčanog oboljenja, ishemije, rekurentne ishemije, reperfuzione povrede, miokardijalnog infarkta, akutnog koronarnog sindroma, periferne arterijalne bolesti, plućne hipertenzije i intermitentne klaudikacije; ili gdje je stanje bolesti dijabetes ili dijabetesna periferna neuropatija; ili gdje stanje bolesti rezultira jednim ili više neuropatskih bolova, epilepsijom, migrenom, napadima grčenja ili paralizom.
16. Kompozicija koja sadrži spoj u skladu sa bilo kojim patentnim zahtevom od 1 do 12 u kombinaciji sa najmanje jednim terapijskim agensom.
17. Kompozicija prema patentnom zahtjevu 16 za upotrebu u terapiji, poželjno za upotrebu u liječenju bolesti ili stanja povezanih sa kardiovaskularnim poremećajima, poželjno angine uključujući stabilnu anginu, nestabilnu anginu, naporom induciranu anginu, varijantnu anginu, aritmija, intermitentne klaudikacije, infarkta miokarda uključujući infarkt miokarda bez elevacije ST segmenta, plućne hipertenzije uključujući plućnu arterijsku hipertenziju, srčane insuficijencije uključujući kongestivnu srčanu insuficijenciju i dijastolnu srčanu insuficijenciju i srčanu insuficijenciju sa očuvanom ejekcionom frakcijom, akutnu srčanu insuficijenciju ili rekurentnu ishemiju.
18. Kompozicija prema patentnom zahtjevu 16 ili kompozicija za upotrebu prema patentnom zahtjevu 17, gdje je drugi terapijski agens odabran iz grupe koja se sastoji od anti-anginalnih lijekova, agenasa protiv srčane insuficijencije, trombolitičkih agenasa, antiaritmijskih agenasa, antihipertenzivnih agenasa i agenasa za snižavanje lipida.
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Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI625121B (zh) 2009-07-13 2018-06-01 基利科學股份有限公司 調節細胞凋亡信號之激酶的抑制劑
EP2464645B1 (en) * 2009-07-27 2017-07-05 Gilead Sciences, Inc. Fused heterocyclic compounds as ion channel modulators
EA026385B9 (ru) 2010-07-02 2017-08-31 Джилид Сайэнс, Инк. Конденсированные гетероциклические соединения в качестве модуляторов ионных каналов
ES2785475T3 (es) 2011-05-10 2020-10-07 Gilead Sciences Inc Compuestos heterocíclicos fusionados como moduladores de canales iónicos
NO3175985T3 (hr) 2011-07-01 2018-04-28
UY34171A (es) * 2011-07-01 2013-01-31 Gilead Sciences Inc Compuestos heterocíclicos fusionados como moduladores del canal iónico
US9040678B2 (en) 2011-08-05 2015-05-26 Illumina, Inc. Functionalization and purification of molecules by reversible group exchange
UY34573A (es) 2012-01-27 2013-06-28 Gilead Sciences Inc Inhibidor de la quinasa que regula la señal de la apoptosis
CA2862670A1 (en) * 2012-01-27 2013-08-01 Gilead Sciences, Inc. Combination therapies using late sodium ion channel blockers and potassium ion channel blockers
MY191087A (en) 2013-03-15 2022-05-30 Global Blood Therapeutics Inc Compounds and uses thereof for the modulation of hemoglobin
WO2014179492A1 (en) * 2013-05-01 2014-11-06 Gilead Sciences, Inc. Combination therapy for the treatment of arrhythmias or heart failure
KR20160035060A (ko) * 2013-08-01 2016-03-30 길리애드 사이언시즈, 인코포레이티드 비대성 심근병증을 치료하는 방법
EP3027190A1 (en) * 2013-08-01 2016-06-08 Gilead Sciences, Inc. Compound and methods for treating long qt syndrome
UA120353C2 (uk) * 2013-09-10 2019-11-25 Хромоселл Корпорейшн Модулятори натрієвого каналу для лікування болю і діабету
EA202092627A1 (ru) 2013-11-18 2021-09-30 Глобал Блад Терапьютикс, Инк. Соединения и их применения для модуляции гемоглобина
MX2016008077A (es) * 2013-12-19 2016-10-12 Gilead Sciences Inc Compuestos heterociclicos fusionados como moduladores del canal ionico.
CA2881544A1 (en) 2014-02-13 2015-08-13 Anna Chiu Solid forms of a late sodium current inhibitor
CN104844535A (zh) 2014-02-13 2015-08-19 吉利德科学公司 用于制备稠合杂环离子通道调节剂的方法
WO2015153153A1 (en) 2014-04-02 2015-10-08 Gilead Sciences, Inc. Methods of treating patients having implantable cardiac devices
KR20190035960A (ko) 2014-09-24 2019-04-03 길리애드 사이언시즈, 인코포레이티드 간 질환의 치료 방법
MA41252A (fr) 2014-12-23 2017-10-31 Gilead Sciences Inc Formes solides d'un inhibiteur d'ask 1
MX2017008417A (es) 2014-12-23 2017-09-28 Gilead Sciences Inc Procedimientos para preparar inhibidores de cinasa 1 reguladora de señal de apoptosis (ask1).
US20170007617A1 (en) * 2015-07-09 2017-01-12 Gilead Sciences Drive Intravenous formulations of a late sodium current inhibitor
CN109071504B (zh) 2016-02-05 2022-03-08 戴纳立制药公司 受体相互作用蛋白激酶1的抑制剂
EP3464270B1 (en) 2016-05-24 2022-02-23 Genentech, Inc. Heterocyclic inhibitors of cbp/ep300 and their use in the treatment of cancer
JP2019527738A (ja) 2016-08-12 2019-10-03 ナンジン ゲイター メディテック カンパニー, リミテッドNanjing Gator Meditech Company, Ltd. プロテインキナーゼ調節剤
WO2018048977A1 (en) 2016-09-08 2018-03-15 Auspex Pharmaceuticals, Inc. Deuterium-substituted oxazepin compounds
JP7349359B2 (ja) 2016-10-17 2023-09-22 エフ． ホフマン－ラ ロシュ アーゲー 二環式ピリドンラクタム及びその使用方法。
AR110252A1 (es) 2016-11-30 2019-03-13 Gilead Sciences Inc Compuestos heterocíclicos fusionados como inhibidores de la quinasa cam
PL3552017T3 (pl) 2016-12-09 2022-08-08 Denali Therapeutics Inc. Związki użyteczne jako inhibitory RIPK1
WO2018213491A1 (en) * 2017-05-16 2018-11-22 Praxis Precision Medicines, Inc. Methods of treating epilepsy and neurodevelopmental disorders
CN110913858B (zh) 2017-05-17 2024-09-24 戴纳立制药公司 激酶抑制剂及其用途
TWI795440B (zh) 2017-09-15 2023-03-11 美商佛瑪治療公司 作為ＣＢＰ／ｐ３００抑制劑之四氫─咪唑並喹啉化合物
US11760701B2 (en) 2018-02-27 2023-09-19 The Research Foundation For The State University Of New Yrok Difluoromethoxylation and trifluoromethoxylation compositions and methods for synthesizing same
WO2019173761A1 (en) 2018-03-09 2019-09-12 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services C-abl tyrosine kinase inhibitory compound embodiments and methods of making and using the same
CA3105099A1 (en) 2018-06-29 2020-01-02 Forma Therapeutics, Inc. Inhibiting creb binding protein (cbp)
WO2020086857A1 (en) 2018-10-24 2020-04-30 Vanderbilt University Wdr5 inhibitors and modulators
KR102172595B1 (ko) * 2018-12-19 2020-11-02 인하대학교 산학협력단 벤조옥사제핀 유도체 화합물을 포함하는 비만 예방 또는 치료용 약학 조성물
CN109879830A (zh) * 2019-03-27 2019-06-14 安徽师范大学 一种含环外双键的氧氮杂环庚烷衍生物及其制备方法
US20220242849A1 (en) * 2019-06-04 2022-08-04 Vanderbilt University Wdr5 inhibitors and modulators
US11801243B2 (en) 2020-09-23 2023-10-31 Forma Therapeutics, Inc. Bromodomain inhibitors for androgen receptor-driven cancers
US11795168B2 (en) 2020-09-23 2023-10-24 Forma Therapeutics, Inc. Inhibiting cyclic amp-responsive element-binding protein (CREB) binding protein (CBP)
AU2022222470A1 (en) 2021-02-19 2023-09-21 Sudo Biosciences Limited Tyk2 inhibitors and uses thereof
AU2022222472A1 (en) 2021-02-19 2023-09-28 Sudo Biosciences Limited Tyk2 inhibitors and uses thereof
MX2024008648A (es) 2022-01-12 2024-09-23 Denali Therapeutics Inc Formas cristalinas de (s)-5-bencil-n-(5-metil-4-oxo-2,3,4,5-tetrah idropirido [3,2- b][1,4]oxacepin-3-il)-4h-1,2,4-triazol-3-carboxam ida.
CN118556044A (zh) * 2022-01-29 2024-08-27 江苏恒瑞医药股份有限公司 稠杂环类化合物、其制备方法及其在医药上的应用
EP4495119A1 (en) 2022-03-16 2025-01-22 Jiangsu Hengrui Pharmaceuticals Co., Ltd. Fused heterocyclic compound, and preparation method therefor and medical use thereof
WO2023204308A1 (ja) * 2022-04-22 2023-10-26 帝人ファーマ株式会社 オキサゼピン誘導体

Family Cites Families (225)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2867618A (en) 1957-02-14 1959-01-06 Dow Chemical Co 3, 4-dihydro-2h-1, 3-benzoxazine
US2826575A (en) 1957-05-06 1958-03-11 Dow Chemical Co 3, 3'-alkylenebis
NL128591C (hr) 1965-07-02
US3441649A (en) 1966-08-18 1969-04-29 Univ Minnesota Suppression of cardiac ventricular fibrillation and cardiac arrhythmias with bretylium tosylate
US3594372A (en) 1968-08-13 1971-07-20 American Home Prod Pyrimido(4,5-e)(1,4)oxazepin-5-ones and derivatives thereof
US3845770A (en) 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
US4062881A (en) 1974-07-26 1977-12-13 Cincinnati Milacron Chemicals, Inc. Sulfide containing tin stabilizers
US4230705A (en) 1976-09-22 1980-10-28 American Cyanamid Company 6-Phenyl-1,2,4-triazolo[4,3-b]pyridazines and their uses in treating anxiety
US4242515A (en) 1979-03-28 1980-12-30 American Cyanamid Company Substituted 3-alkyl-6-phenyl-1,2,4-triazolo-[4,3-a]pyridines
US4244953A (en) 1979-10-24 1981-01-13 American Cyanamid Company Substituted 6-phenyl-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyridines
JPS5675428A (en) 1979-11-21 1981-06-22 Ayanori Takabe Hypoglycemic agent containing procainamide hydrochloride
US4326525A (en) 1980-10-14 1982-04-27 Alza Corporation Osmotic device that improves delivery properties of agent in situ
DE3382028D1 (de) * 1982-09-30 1991-01-10 Robins Co Inc A H Kondensierte aromatische oxazepinone und sulphuranaloge, ihrer herstellung und verwendung als histamin-antagonist.
US4812565A (en) 1982-09-30 1989-03-14 A. H. Robins Company, Incorporated Fused aromatic oxazepinones, thiazepinones, diazepinones and sulfur analogs thereof
US5364620A (en) 1983-12-22 1994-11-15 Elan Corporation, Plc Controlled absorption diltiazem formulation for once daily administration
US4654343A (en) 1985-10-31 1987-03-31 American Cyanamid Company N-substituted-N[3-(1,2,4-triazolo[4,3-b]pyridazin-6-yl)phenyl]alkanamides, carbamates and ureas
US5023252A (en) 1985-12-04 1991-06-11 Conrex Pharmaceutical Corporation Transdermal and trans-membrane delivery of drugs
JPH061779B2 (ja) 1987-07-31 1994-01-05 田中電子工業株式会社 半導体装置の製造方法
RO96410B1 (ro) * 1987-02-16 1989-03-02 Institutul Politehnic Derivati de 1,4-benzoxazepinona si procedeu pentru prepararea lor
US4746655A (en) 1987-06-10 1988-05-24 A. H. Robins Company, Incorporated Fused aromatic-spiropiperidine oxazepinones(and thiones)
US5001139A (en) 1987-06-12 1991-03-19 American Cyanamid Company Enchancers for the transdermal flux of nivadipine
US4992445A (en) 1987-06-12 1991-02-12 American Cyanamid Co. Transdermal delivery of pharmaceuticals
US4902514A (en) 1988-07-21 1990-02-20 Alza Corporation Dosage form for administering nilvadipine for treating cardiovascular symptoms
DE4010488A1 (de) 1990-03-31 1991-10-02 Hoechst Ag Benzoxazinderivate, verfahren zu ihrer herstellung und ihre verwendung zum behandeln oder zur prophylaxe von krankheiten
CA2044564A1 (en) 1990-06-28 1991-12-29 Quirico Branca Amino acid derivatives
CN1060467A (zh) 1990-09-25 1992-04-22 武田药品工业株式会社 1，3-苯并嗪衍生物、其生产方法和用途
JPH04209692A (ja) 1990-12-03 1992-07-31 Asahi Glass Co Ltd フォトクロミック材料
ATE136296T1 (de) 1991-05-10 1996-04-15 Takeda Chemical Industries Ltd Pyridinderivate, deren herstellung und anwendung
EP0593603B1 (en) * 1991-06-28 2002-11-20 Smithkline Beecham Corporation Bicyclic fibrinogen antagonists
US5939412A (en) 1992-06-26 1999-08-17 Smithkline Beecham Corporation Bicyclic fibrinogen antagonists
US5250679A (en) * 1991-10-18 1993-10-05 Genentech, Inc. Nonpeptidyl platelet aggregation inhibitors having specificity for the GPIIb III.sub. receptor
US5674863A (en) * 1991-10-18 1997-10-07 Genentech, Inc. Nonpeptidyl integrin inhibitors having specificity for the GPIIb IIIa receptor
US5272158A (en) 1991-10-29 1993-12-21 Merck & Co., Inc. Fibrinogen receptor antagonists
JPH061779A (ja) 1992-02-06 1994-01-11 Wakamoto Pharmaceut Co Ltd ベンズオキサジノン誘導体
JPH06107647A (ja) 1992-08-12 1994-04-19 Takeda Chem Ind Ltd １，３−ベンゾオキサジン誘導体の製造法
US5442055A (en) 1992-11-13 1995-08-15 Tanabe Seiyaku Co., Ltd. Azetidinone compound and process for preparation thereof
US6011150A (en) 1992-11-13 2000-01-04 Tanabe Seiyaku Co., Ltd. Azetidinone compound and process for preparation thereof
GB9225860D0 (en) 1992-12-11 1993-02-03 Smithkline Beecham Plc Novel treatment
GB9226302D0 (en) 1992-12-17 1993-02-10 Smithkline Beecham Plc Pharmaceuticals
US5550229A (en) 1993-06-23 1996-08-27 Tanabe Seiyaku Co., Ltd. Alkylation process for preparing azetidinone compound and starting compound therefor
DE19526173A1 (de) 1995-07-18 1997-01-30 Hoechst Ag Polyfullerenaddukte, Verfahren zu ihrer regioselektiven Herstellung und deren Verwendung
JPH09157262A (ja) 1995-12-08 1997-06-17 Tanabe Seiyaku Co Ltd アゼチジノン誘導体及びその合成中間体の製法
US5773186A (en) 1996-02-19 1998-06-30 Fuji Photo Film Co., Ltd. Heat-sensitive recording material
GB9619492D0 (en) 1996-09-18 1996-10-30 Smithkline Beecham Plc Novel treatment
CA2288172A1 (en) 1997-04-18 1998-10-29 Smithkline Beecham P.L.C. A bicyclic aryl or a bicyclic heterocyclic ring containing compounds having a combined 5ht1a, 5ht1b and 5ht1d receptor antagonistic activity
WO1998054135A1 (fr) 1997-05-30 1998-12-03 Meiji Seika Kaisha, Ltd. Composes heterocycliques azotes et medicament contre l'hyperlipemie en contenant
JP3964053B2 (ja) 1997-07-10 2007-08-22 三井化学株式会社 遷移金属化合物からなるオレフィン重合用触媒ならびに重合方法
CA2300906A1 (en) 1997-09-08 1999-03-18 Unilever Plc Method for enhancing the activity of an enzyme
CZ290883B6 (cs) 1998-01-21 2002-11-13 Merck Sharp And Dohme Limited Triazolopyridazinové deriváty, způsob jejich výroby a farmaceutický prostředek je obsahující
CA2319173A1 (en) * 1998-02-11 1999-08-19 Jingwu Duan Novel cyclic sulfonamide derivatives as metalloproteinase inhibitors
ZA991301B (en) 1998-02-18 1999-09-13 Neurosearch As Glutamate receptor modulators.
CA2334836A1 (en) 1998-06-16 1999-12-23 Merck Sharp & Dohme Limited Triazolo-pyridine derivatives as ligands for gaba receptors
JP2002527520A (ja) 1998-10-21 2002-08-27 ノボ ノルディスク アクティーゼルスカブ 新規化合物、その製造及び使用
KR20020005662A (ko) 1999-04-09 2002-01-17 기따자또 이찌로 질소함유 복소환화합물 및 벤즈아미드화합물 및 그 것을함유해서 되는 의약
US6627651B1 (en) 1999-05-07 2003-09-30 Takeda Chemical Industries, Ltd. Cyclic compounds and uses thereof
US6121916A (en) 1999-07-16 2000-09-19 Eaton-Vorad Technologies, L.L.C. Method and apparatus for recognizing stationary objects with a moving side-looking radar
JP2003510251A (ja) 1999-08-27 2003-03-18 ザ、プロクター、エンド、ギャンブル、カンパニー ブリーチ増強成分、組成物および洗濯方法
BR0013616B1 (pt) 1999-08-27 2011-12-27 composiÇço de alvejamento e composto catalisador orgÂnico de lavanderia.
DE60024463T2 (de) 1999-08-27 2006-08-17 The Procter & Gamble Company, Cincinnati Stabile substanzen, zusammensetzungen und waschverfahren zu deren verwendung
AU6935600A (en) 1999-08-27 2001-03-26 Procter & Gamble Company, The Color safe laundry methods employing cationic formulation components
AU7072200A (en) 1999-08-27 2001-03-26 Procter & Gamble Company, The Fast-acting formulation components, compositions and laundry methods employing same
MXPA02002126A (es) 1999-08-27 2002-09-18 Procter & Gamble Metodos de lavanderia que conservan el color, que emplean componentes de formulacion zwitterionicos.
EP1206513A2 (en) 1999-08-27 2002-05-22 The Procter & Gamble Company Controlled availability of formulation components, compositions and laundry methods employing same
IL135092A0 (en) 2000-03-15 2001-05-20 Kidron Agrochem Ltd A composition for the control of pests
EP1286994A1 (en) 2000-05-15 2003-03-05 Darwin Discovery Limited Hydroxamic and carboxylic acid derivatives having mmp and tnf inhibitory activity
US6956033B2 (en) 2000-08-01 2005-10-18 Ono Pharmaceutical Co., Ltd. 3,4-dihydroisoquinoline derivative compound and a pharmaceutical agent comprising it as active ingredient
US20040058915A1 (en) 2000-08-29 2004-03-25 Khanna Ish Kumar Compounds containing a bicyclic ring system useful as alpha v beta 3 antagonists
JP2002205992A (ja) 2000-11-08 2002-07-23 Takeda Chem Ind Ltd 二環式トリアゾロン誘導体およびそれを含有する除草剤
ATE341343T1 (de) 2000-12-26 2006-10-15 Sankyo Co Medizinische zusammensetzungen mit diuretischem und die insulinresistenz verbesserndem mittel
NZ526528A (en) 2001-03-09 2005-02-25 Pfizer Prod Inc Triazolopyridines as anti-inflammatory agents
US6998408B2 (en) 2001-03-23 2006-02-14 Bristol-Myers Squibb Pharma Company 6-5, 6-6, or 6-7 Heterobicycles as factor Xa inhibitors
US20030114448A1 (en) 2001-05-31 2003-06-19 Millennium Pharmaceuticals, Inc. Inhibitors of factor Xa
JP2005089298A (ja) 2001-09-18 2005-04-07 Japan Tobacco Inc ナフタレン化合物及びその医薬用途
GB0124627D0 (en) 2001-10-15 2001-12-05 Smithkline Beecham Plc Novel compounds
MXPA04004477A (es) 2001-11-13 2004-08-11 Schering Corp Antagonistas del neuropeptido neuroquinina-1(nk1).
US7196108B2 (en) 2002-03-08 2007-03-27 Incyte San Diego Inc. Bicyclic heterocycles for the treatment of diabetes and other diseases
JP2003277384A (ja) 2002-03-26 2003-10-02 Kyorin Pharmaceut Co Ltd 縮合ニ環式ピリジン誘導体
JP2003321461A (ja) 2002-04-25 2003-11-11 Kyorin Pharmaceut Co Ltd 縮合ビフェニル誘導体
US20040152696A1 (en) * 2002-08-01 2004-08-05 Euro-Celtique S.A. 2-substituted bicyclic benzoheterocyclic compounds and their use as sodium channel blockers
JP2005539020A (ja) 2002-08-13 2005-12-22 ワーナー−ランバート カンパニー リミティド ライアビリティー カンパニー マトリクスメタロプロテイナーゼ阻害物質としてのクロモン誘導体
AU2003249531A1 (en) 2002-08-13 2004-02-25 Warner-Lambert Company Llc Azaisoquinoline derivatives as matrix metalloproteinase inhibitors
US20040242572A1 (en) 2002-08-24 2004-12-02 Boehringer Ingelheim International Gmbh New carboxamide compounds having melanin concentrating hormone antagonistic activity, pharmaceutical preparations comprising these compounds and process for their manufacture
DE10238865A1 (de) 2002-08-24 2004-03-11 Boehringer Ingelheim International Gmbh Neue Carbonsäureamid-Verbindungen mit MCH-antagonistischer Wirkung, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
PA8579601A1 (es) 2002-08-30 2004-05-07 Pfizer Prod Inc Compuestos antiinflamatorios de di y trifloruro-triazolo-piridinas
US7005523B2 (en) 2002-08-30 2006-02-28 Pfizer Inc. Cycloalkyl-[4-(trifluorophenyl)-oxazol-5yl]-triazolo-pyridines
AU2003262073A1 (en) 2002-09-20 2004-04-08 Tsumura And Co. Antitussives
US20040204404A1 (en) 2002-09-30 2004-10-14 Robert Zelle Human N-type calcium channel blockers
GB0223730D0 (en) 2002-10-11 2002-11-20 Novartis Ag Organic compounds
WO2004037997A2 (en) 2002-10-22 2004-05-06 The Trustees Of The University Of Pennsylvania Fragments and activity of rel protein in m. tuberculosis adn other uses thereof
BR0315796A (pt) 2002-11-07 2005-09-13 Merck & Co Inc Composto, composição farmacêutica, e, métodos para tratar diabetes, para tratar hiperglicemia, e para tratar obesidade em um mamìfero
CN100430386C (zh) 2002-11-07 2008-11-05 默克公司 苯丙氨酸衍生物作为二肽基肽酶抑制剂用于治疗或预防糖尿病
UA80317C2 (en) 2003-01-13 2007-09-10 Cortex Pharma Inc Method of treating cognitive decline due to sleep deprivation and stress
AR044503A1 (es) 2003-03-18 2005-09-14 Merck & Co Inc Triazoles sustituidos con biarilo como bloqueantes del canal de sodio
DE10317526A1 (de) 2003-04-16 2004-11-04 Degussa Ag Verfahren zum Delignifizieren von ligninhaltigen Faserstoffen
CA2521625A1 (en) 2003-04-17 2004-11-04 Merck & Co., Inc. Heterocyclic cyclopentyl tetrahydroisoquinoline and tetrahydropyridopyridine modulators of chemokine receptor activity
EP1631546A1 (en) 2003-04-25 2006-03-08 H. Lundbeck A/S Sustituted indoline and indole derivatives
WO2004101509A2 (en) 2003-05-06 2004-11-25 Case Western Reserve University Functionalized benzoxazines, polymers and copolymers thereof
WO2005002520A2 (en) 2003-07-01 2005-01-13 Merck & Co., Inc. Ophthalmic compositions for treating ocular hypertension
WO2005011690A1 (en) 2003-07-21 2005-02-10 Solvay Pharmaceuticals Gmbh Use of 3,7-diazabicyclo`3, 3,1 !nonane compounds for the treatment and/or prophylaxis of anti-arrhythmic events in male human patients
NZ545717A (en) 2003-08-05 2009-12-24 Vertex Pharma Hydrogenated quinazoline derivatives as inhibitors of voltage-gated ion channels
US20050239767A1 (en) 2003-10-28 2005-10-27 Chan Michael K Intermolecular SNAr of the heterocycle-activated nitro and fluoro groups-application in the synthesis of polyazamacrocyclic ligands
RU2006121487A (ru) 2003-12-18 2007-12-27 Пфайзер Продактс Инк. (Us) СПОСОБЫ ЛЕЧЕНИЯ ОСТРОГО ВОСПАЛЕНИЯ У ЖИВОТНЫХ С ПОМОЩЬЮ ИНГИБИТОРОВ р38 МАР-киназы
EA011764B1 (ru) 2004-03-05 2009-06-30 Ниссан Кемикал Индастриз, Лтд. Изоксазолинзамещённое производное бензамида и пестицид
US7306631B2 (en) 2004-03-30 2007-12-11 The Procter & Gamble Company Keratin dyeing compounds, keratin dyeing compositions containing them, and use thereof
GB0412986D0 (en) 2004-06-10 2004-07-14 Xention Discovery Ltd Compounds
WO2006002470A1 (en) 2004-06-30 2006-01-12 Monash University Chiral ligands for asymmetric catalysis
JP2006063064A (ja) 2004-07-27 2006-03-09 Takeda Chem Ind Ltd 受容体作動剤
JP2007297283A (ja) 2004-07-28 2007-11-15 Santen Pharmaceut Co Ltd 新規桂皮酸関連化合物
AU2005272627A1 (en) * 2004-08-13 2006-02-23 Amgen Inc. Substituted benzofused heterocycles
US7521457B2 (en) 2004-08-20 2009-04-21 Boehringer Ingelheim International Gmbh Pyrimidines as PLK inhibitors
EP1784188B1 (en) 2004-08-23 2010-07-14 Merck Sharp & Dohme Corp. Fused triazole derivatives as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes
US7750010B2 (en) 2004-09-13 2010-07-06 Merck Sharp & Dohme Corp. Tricyclic anilide spirohydantion CGRP receptor antagonists
AR050948A1 (es) 2004-09-24 2006-12-06 Hoffmann La Roche Derivados de ftalazinona; su obtencion y su utilizacion en la fabricacion de medicamentos para el tratamiento del cancer.
WO2006048727A1 (en) 2004-11-02 2006-05-11 Pfizer Products Inc. Piperazinylphenalkyl lactam/amine ligands for the 5ht1b receptor
JP2006203875A (ja) 2004-12-24 2006-08-03 Matsushita Electric Ind Co Ltd 受信装置
WO2006091897A2 (en) 2005-02-25 2006-08-31 Adenosine Therapeutics, Llc Derivatives of 8-substituted xanthines
TW200643015A (en) 2005-03-11 2006-12-16 Akzo Nobel Nv 2-(4-oxo-4H-quinazolin-3-yl)acetamide derivatives
US20080176830A1 (en) * 2005-04-14 2008-07-24 Adams Nicholas D Compounds, Compositions, and Methods
AR056317A1 (es) 2005-04-20 2007-10-03 Xenon Pharmaceuticals Inc Compuestos de oxindol y composicion farmaceutica
WO2006125119A1 (en) 2005-05-17 2006-11-23 Sarcode Corporation Compositions and methods for treatment of eye disorders
TW200714597A (en) 2005-05-27 2007-04-16 Astrazeneca Ab Chemical compounds
US7572807B2 (en) 2005-06-09 2009-08-11 Bristol-Myers Squibb Company Heteroaryl 11-beta-hydroxysteroid dehydrogenase type I inhibitors
US7632837B2 (en) 2005-06-17 2009-12-15 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid-1 receptor modulators
US7572808B2 (en) 2005-06-17 2009-08-11 Bristol-Myers Squibb Company Triazolopyridine cannabinoid receptor 1 antagonists
AU2006259294A1 (en) 2005-06-17 2006-12-28 Wyeth Tricyclic compounds useful as serotonin inhibitors and 5-HT1A agonists and antagonists
WO2007004028A2 (en) 2005-06-30 2007-01-11 Ranbaxy Laboratories Limited Processes for the preparation of penems and its intermediate
WO2007023750A1 (ja) 2005-08-26 2007-03-01 National University Corporation University Of Toyama 乾燥羊膜及び羊膜の乾燥処理方法
JP2009508963A (ja) 2005-09-21 2009-03-05 インサイト・コーポレイション アミド化合物および医薬組成物としてのその使用
WO2007038209A2 (en) 2005-09-23 2007-04-05 Schering Corporation Fused tetracyclic mglur1 antagonists as therapeutic agents
US20090022694A1 (en) 2005-10-18 2009-01-22 Distefano Peter Sirt1 inhibition
TW200804290A (en) 2005-11-15 2008-01-16 Astrazeneca Ab Compounds and uses thereof
US7851464B2 (en) 2005-11-18 2010-12-14 Merck Sharp & Dohme Corp. Spirolactam aryl CGRP receptor antagonists
AU2006316646A1 (en) 2005-11-18 2007-05-31 Merck Sharp & Dohme Corp. Spirolactam bicyclic CGRP receptor antagonists
TW200734342A (en) 2005-12-15 2007-09-16 Astrazeneca Ab New compounds for the treatment of cardiac arrhythmias
US20070142376A1 (en) 2005-12-16 2007-06-21 Alcon, Inc. Control of intraocular pressure using alk5 modulation agents
US8013073B2 (en) 2005-12-30 2011-09-06 Chevron Oronite Company Llc Method for preparing polyolefins containing vinylidine end groups using nonaromatic heterocyclic compounds
CN101410397A (zh) 2006-03-31 2009-04-15 诺瓦提斯公司 有机化合物
EP2018863B9 (en) * 2006-05-16 2015-02-18 Takeda Pharmaceutical Company Limited Fused heterocyclic compound and use thereof
MX2008015908A (es) 2006-06-12 2009-01-28 Vertex Pharma Tienopirimidinas utiles como moduladores de canales de iones.
US20080011523A1 (en) 2006-06-29 2008-01-17 Packard Thomas G Rotor energy augmented vehicle
WO2008005338A1 (en) 2006-06-29 2008-01-10 Arena Pharmaceuticals, Inc. Modulators of the histamine h3-receptor useful for the treatment of disorders related thereto
US8778977B2 (en) 2006-06-30 2014-07-15 Sunesis Pharmaceuticals, Inc. Pyridinonyl PDK1 inhibitors
WO2008007661A1 (fr) * 2006-07-11 2008-01-17 Takeda Pharmaceutical Company Limited Composé hétérocyclique tricycique et son utilisation
US20100035756A1 (en) 2006-07-12 2010-02-11 Syngenta Limited Triazolophyridine derivatives as herbicides
PE20080403A1 (es) 2006-07-14 2008-04-25 Amgen Inc Derivados heterociclicos fusionados y metodos de uso
US8217177B2 (en) 2006-07-14 2012-07-10 Amgen Inc. Fused heterocyclic derivatives and methods of use
CA2661299A1 (en) 2006-08-22 2008-02-28 Ranbaxy Laboratories Limited Beta -hydroxy-and amino-substituted carboxylic acids as matrix metalloproteinase inhibitors
CA2665214A1 (en) 2006-10-06 2008-05-29 Abbott Laboratories Novel imidazothiazoles and imidazoxazoles
WO2008118141A2 (en) 2006-10-17 2008-10-02 Acadia Pharmaceuticals Inc. Use of cannabinoid modulating compounds in combination with other therapeutic compounds for adjunctive therapy
CN101535276B (zh) 2006-10-23 2013-08-28 赛福伦公司 作为ALK和c-MET抑制剂的2,4-二氨基嘧啶稠合双环衍生物
CA2822776A1 (en) 2006-10-28 2008-05-08 Methylgene Inc. Inhibitors of histone deacetylase
WO2008053913A1 (fr) * 2006-11-02 2008-05-08 Shionogi & Co., Ltd. Dérivé de sulfonylurée capable d'inhiber sélectivement mmp-13
JP2010514696A (ja) 2006-12-21 2010-05-06 ギリアード・パロ・アルト・インコーポレイテッド 心血管症状の低減
US8076350B2 (en) 2006-12-22 2011-12-13 Abbott Laboratories Spirocyclic azaadamantane derivatives and methods of use
CL2008000252A1 (es) 2007-01-29 2008-03-14 Xenon Pharmaceuticals Inc Compuestos derivados de quinazolinona o pirimidinona; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar enfermedades mediadas por los canales de calcio, tales como dolor, depresion, enfermedades cardiovasculares, respir
JP2010520237A (ja) 2007-02-28 2010-06-10 メルク・シャープ・エンド・ドーム・コーポレイション ナトリウムチャネル遮断薬としての置換ベンゾジアゼピノン、ベンゾオキサアゼピノン及びベンゾチアゼピノン
US8247403B2 (en) 2007-03-07 2012-08-21 Takeda Pharmaceutical Company Limited Benzoxazepine derivatives and use thereof
GB0706072D0 (en) 2007-03-28 2007-05-09 Sterix Ltd Compound
WO2008128086A1 (en) 2007-04-12 2008-10-23 Cv Therapeutics, Inc. Ranolazine for enhancing insulin secretion
CN101657198A (zh) * 2007-04-12 2010-02-24 Cv医药有限公司 增强胰岛素分泌的雷诺嗪
WO2008134553A1 (en) 2007-04-26 2008-11-06 Xenon Pharmaceuticals Inc. Methods of using bicyclic compounds in treating sodium channel-mediated diseases
WO2008144483A2 (en) * 2007-05-18 2008-11-27 Armgo Pharma, Inc. Agents for treating disorders involving modulation of ryanodine receptors
US8188083B2 (en) 2007-06-28 2012-05-29 Abbott Laboratories Triazolopyridazines
US20090012103A1 (en) * 2007-07-05 2009-01-08 Matthew Abelman Substituted heterocyclic compounds
US20090036425A1 (en) 2007-08-02 2009-02-05 Pfizer Inc Substituted bicyclolactam compounds
WO2009026444A1 (en) 2007-08-22 2009-02-26 President And Fellows Of Harvard College Ryanodine channel binders and uses thereof
CA2699384A1 (en) 2007-09-12 2009-03-19 Wyeth Llc Isoquinolinyl and isoindolinyl derivatives as histamine-3 antagonists
US8119658B2 (en) 2007-10-01 2012-02-21 Bristol-Myers Squibb Company Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors
NZ585306A (en) 2007-12-19 2012-05-25 Genentech Inc 8-Anilinoimidazopyridines and their use as anti-cancer and/or anti-inflammatory agents
PE20091339A1 (es) 2007-12-21 2009-09-26 Glaxo Group Ltd Derivados de oxadiazol con actividad sobre receptores s1p1
US20110112079A1 (en) 2008-01-09 2011-05-12 Thomas Craig J Phosphodiesterase inhibitors
US20090203707A1 (en) 2008-02-06 2009-08-13 Sridharan Rajamani Methods for treating pain
WO2009101917A1 (ja) 2008-02-13 2009-08-20 Eisai R & D Management Co., Ltd. ビシクロアミン誘導体
JP2009286773A (ja) 2008-03-14 2009-12-10 Bayer Cropscience Ag 殺虫性縮環式アリール類
WO2009137499A1 (en) 2008-05-05 2009-11-12 Envivo Pharmaceuticals, Inc. Inhibitors of histone deacetylase
US20110288070A1 (en) 2008-05-05 2011-11-24 ROGERS Kathryn Methods for treating cognitive disorders using inhibitors of histone deacetylase
DE102008024182A1 (de) 2008-05-19 2009-11-26 Merck Patent Gmbh Verbindungen für organische elektronische Vorrichtung
CA2725573A1 (en) 2008-06-06 2009-12-10 Abbott Laboratories Novel 1,2,4 oxadiazole compounds and methods of use thereof
CN102124000B (zh) 2008-06-17 2014-09-17 阿斯利康(瑞典)有限公司 吡啶化合物
EP2307027A4 (en) 2008-07-11 2012-08-15 Neumedics TETRACYCLINE DERIVATIVES WITH REDUCED ANTIBIOTIC ACTIVITY AND NEUROPROTECTIVE PROPERTIES
EP2314583B1 (en) 2008-08-12 2015-02-25 Nippon Soda Co., Ltd. Nitrogenated heterocyclic derivative, and agricultural or horticultural bactericidal agent
CN102186812A (zh) 2008-08-18 2011-09-14 宇部兴产株式会社 制备氟烷基芳基亚磺酰基化合物及其氟化的化合物的方法
WO2010028173A2 (en) 2008-09-04 2010-03-11 Gilead Palo Alto, Inc. Method of treating atrial fibrillation
WO2010053757A1 (en) * 2008-10-29 2010-05-14 Gilead Palo Alto, Inc. 2 -oxoquinoxalin blockers of the late sodium channel
US8389500B2 (en) * 2008-10-30 2013-03-05 Gilead Sciences, Inc. Fused heterocyclic compounds as ion channel modulators
US20100113514A1 (en) * 2008-10-30 2010-05-06 Gilead Palo Alto, Inc. Fused heterocyclic compounds as ion channel modulators
WO2010056865A1 (en) * 2008-11-14 2010-05-20 Gilead Palo Alto, Inc. Quinoline derivatives as ion channel modulators
WO2010068461A1 (en) * 2008-11-25 2010-06-17 Gilead Palo Alto, Inc. Co-administration of ranolazine and cardiac glycosides
CN106336400A (zh) 2008-12-08 2017-01-18 萌蒂制药国际有限公司 酪氨酸激酶蛋白受体拮抗剂
CN102307871A (zh) 2008-12-08 2012-01-04 西特里斯药业公司 作为沉默调节蛋白调节剂的异吲哚啉酮和相关的类似物
JP5271069B2 (ja) 2008-12-24 2013-08-21 三和シヤッター工業株式会社 開閉装置
CA2747419C (en) * 2009-01-12 2014-07-08 Icagen, Inc. Sulfonamide derivatives
FR2943342B1 (fr) * 2009-03-20 2011-03-04 Servier Lab Nouveaux derives de benzothiadiazepines,leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
PE20120773A1 (es) 2009-03-27 2012-07-19 Presidio Pharmaceuticals Inc Anillos triciclicos fusionados sustituidos como inhibidores del virus de hepatitis c
US20100305093A1 (en) * 2009-04-09 2010-12-02 Exelixis, Inc. Inhibitors of mTOR and Methods of Making and Using
EP2464645B1 (en) * 2009-07-27 2017-07-05 Gilead Sciences, Inc. Fused heterocyclic compounds as ion channel modulators
WO2011036280A1 (en) 2009-09-28 2011-03-31 F. Hoffmann-La Roche Ag Benzoxazepin pi3k inhibitor compounds and methods of use
WO2011042920A1 (en) 2009-10-07 2011-04-14 Decode Genetics Ehf Genetic variants indicative of vascular conditions
WO2011056985A2 (en) 2009-11-04 2011-05-12 Gilead Sciences, Inc. Substituted heterocyclic compounds
CN102791687B (zh) 2009-12-18 2015-02-11 北京凯因科技股份有限公司 C型肝炎病毒复制的新型抑制剂
TWI508726B (zh) 2009-12-21 2015-11-21 Gilead Sciences Inc 治療心房纖維性顫動之方法
EA026385B9 (ru) 2010-07-02 2017-08-31 Джилид Сайэнс, Инк. Конденсированные гетероциклические соединения в качестве модуляторов ионных каналов
WO2012019071A1 (en) * 2010-08-06 2012-02-09 The Trustees Of Columbia University In The City Of New York Methods of preventing and treating sarcopenia
WO2012019076A1 (en) * 2010-08-06 2012-02-09 The Trustees Of Columbia University In The City Of New York Compositions and methods for preventing and treating cardiac ischemia/reperfusion injury
WO2012037105A1 (en) * 2010-09-14 2012-03-22 The Trustees Of Columbia University In The City Of New York Methods of treating, ameliorating or preventing stress-induced neuronal disorders and diseases
WO2012036233A1 (ja) 2010-09-17 2012-03-22 塩野義製薬株式会社 メラニン凝集ホルモン受容体アンタゴニスト活性を有する縮合へテロ環誘導体
ES2566828T3 (es) 2010-09-21 2016-04-15 Purdue Pharma L.P. Análogos de buprenorfina como agonistas y/o antagonistas del receptor opioide
US8999967B2 (en) 2010-09-29 2015-04-07 Presidio Pharmaceuticals, Inc. Tricyclic fused ring inhibitors of hepatitis C
EP2643316A2 (en) * 2010-11-24 2013-10-02 Exelixis, Inc. Benzoxazepines as inhibitors of p13k/mtor and methods of their use and manufacture
JP5675428B2 (ja) 2011-02-25 2015-02-25 サンドビック株式会社 ベルトプレス装置
CA2825966A1 (en) 2011-03-21 2012-09-27 F. Hoffmann-La Roche Ag Benzoxazepin compounds selective for pi3k p110 delta and methods of use
ES2785475T3 (es) 2011-05-10 2020-10-07 Gilead Sciences Inc Compuestos heterocíclicos fusionados como moduladores de canales iónicos
CA2836904C (en) 2011-06-03 2019-09-24 Signpath Pharma Inc. Liposomal mitigation of drug-induced long qt syndrome and potassium delayed-rectifier current
TWI567061B (zh) 2011-07-01 2017-01-21 吉李德科學股份有限公司 用於治療成癮之化合物
UY34171A (es) 2011-07-01 2013-01-31 Gilead Sciences Inc Compuestos heterocíclicos fusionados como moduladores del canal iónico
NO3175985T3 (hr) 2011-07-01 2018-04-28
EP2758053A1 (en) 2011-09-21 2014-07-30 Gilead Sciences, Inc. Sodium channel blockers reduce glucagon secretion
US8623860B2 (en) 2011-12-30 2014-01-07 Boehringer Ingelheim International Gmbh Azetidine derivatives, pharmaceutical compositions and uses thereof
WO2013097052A1 (en) 2011-12-30 2013-07-04 Abbott Laboratories Bromodomain inhibitors
CA2862670A1 (en) 2012-01-27 2013-08-01 Gilead Sciences, Inc. Combination therapies using late sodium ion channel blockers and potassium ion channel blockers
BR112014000049A2 (pt) 2012-03-27 2017-02-07 Bayer Ip Gmbh pirrolotriazinas substituídas com hidroximelilarilo e sua utilização
WO2013185764A2 (en) 2012-06-13 2013-12-19 Acesion Pharma Pharmaceutical compositions for combination therapy
WO2014134419A1 (en) 2013-03-01 2014-09-04 Gilead Sciences, Inc. Use of ikach blockers for the treatment of cardiac diseases
CN104844535A (zh) 2014-02-13 2015-08-19 吉利德科学公司 用于制备稠合杂环离子通道调节剂的方法
CA2881544A1 (en) 2014-02-13 2015-08-13 Anna Chiu Solid forms of a late sodium current inhibitor

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