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NUEVAS HETEROARILDIHIDROPIRIMIDINAS 6-FUSIONADAS PARA EL TRATAMIENTO Y LA PROFILAXIS DE LA INFECCION POR VIRUS DE LA HEPATITIS B
专利权人:
F. HOFFMANN-LA ROCHE AG
发明人:
GUO, Lei,HU, Taishan,KOU, Buyu,LIN, Xianfeng,SHEN, Hong,ZHU, Wei,YAN, Shixiang,ZHANG, Zhisen,ZHANG, Weixing,ZHOU, Mingwei,SHI, Houguang
申请号:
PE0012602016
公开号:
PE13382016A1
申请日:
2015.03.04
申请国别(地区):
PE
年份:
2016
代理人:
摘要:
The present Invention relates to heteroarildihidropirimidinas 6 - FUSED (HAP) of formula (i), and pharmaceutically acceptable salts, enantiomers or Diastereomers of the same where R1 is H, alkyl or Halogen C1 - 6 R2 and R3 are H or Halogen alkyl R4 is C1 - 6 R5 is H, hidroxialquilo C1 6, ENT Re R6 is H, or C1 - 6 alcoxicarbonilo Carboxy - X is cmh2m carbonyl or sulfonyl and - CH2 -,- or, or - N (R7) R7 is H, alkyl C1 - 6 W is - CH2 - C - (alkyl C1 - 6) 2 -, - or - or carbonyl n is 0 OR 1 and M is 0 to 7.Preferred compounds are: (4R) - 4 - (2 - Chloro - 5 - fluoro - phenyl) - 6 - [(3 - oxo - 1, 3, 4, 8, 9, 9a - hexahidropirazino [1,2-c] [1,3] oxazin - 2 - yl) methyl] - 2 - thiazole IL - 2 - 1.4 - dihydropyrimidine - 5 - carboxylate (4R) - 4 - (2 - Chloro - 5 - fluoro - phenyl) - 6 - [(4 - oxo - 6, 7, 9, 9a - tetrahydro - 1H - 2.1 - pirazino [c] [1,4] oxazin - 8 - il) meti L - 2 -] thiazol-2-yl - 1.4 - dihydropyrimidine - 5 - carboxylate, among others.It also relates to a method, a Composition and a method of treatment. These PAHs induce the formation of Aberrant capsids, being useful in the treatment of hepatitis B virus (HBV)La presente invencion se refiere a heteroarildihidropirimidinas 6-fusionadas (HAP) de formula (I), sales farmaceuticamente aceptables, enantiomeros o diastereomeros de las mismas donde: R1 es H, halogeno o alquilo C1-6 R2 y R3 son H o halogeno R4 es alquilo C1-6 R5 es H, hidroxialquilo C1-6, entre otros R6 es H, alcoxicarbonilo C1-6 o carboxi-CmH2m- X es carbonilo o sulfonilo Y es -CH2-, -O-, o -N(R7)- R7 es H, alquilo C1-6, entre otros W es -CH2-, -C(alquilo C1-6)2-, -O- o carbonilo n es 0 o 1 y m es 0 a 7. Son compuestos preferidos: (4R)-4-(2-cloro-4-fluoro-fenil)-6-[(6-oxo-1, 3, 4, 8, 9, 9a-hexahidropirazino[1,2-c][1,3]oxazin-2-il)metil]-2-tiazol-2-il-1,4-dihidropirimidin-5-carboxilato de metilo (4R)-4-(2-cloro-4-fluoro-fenil)-6-[(4-oxo-6, 7, 9, 9a-tetrahidro-1H-pirazino[2,1-c][1,4]oxazin-8-il)metil]-2-tiazol-2-il-1,4-dihidropirimidin-5-carbo
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