Viral polymerase inhibitors

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 405/04 (2006.01) A61K 31/4184 (2006.01) A61K 31/437 (2006.01) A61K 31/4439 (2006.01) A61P 31/12 (2006.01) A61P 31/22 (2006.01) C07D 235/18 (2006.01) C07D 401/04 (2006.01) C07D 403/04 (2006.01) C07D 405/14 (2006.01) C07D 407/04 (2006.01) C07D 409/04 (2006.01) C07D 409/14 (2006.01) C07D 417/14 (2006.01) C07D 471/04 (2006.01)

Patent

CA 2448737

An isomer, enantiomer, diastereoisomer, or tautomer of a compound, represented by formula (I): wherein R1 is selected from: H, haloalkyl, (C1-6)alkyl, (C2- 6)alkenyl, (C3-7)cycloalkyl, (C2-6)alkynyl, (C5-7)cycloalkenyl, 6 or 10- membered aryl, Het all optionally substituted; R2 is selected from (C1- 6)alkyl, (C3-7)cycloalkyl, (C6-10)bicycloalkyl, 6- or 10-membered aryl, or Het all optionally substituted; B is N or CR5, wherein R5 is H, halogen, haloalkyl, (C1-6)alkyl, (C3-7)cycloalkyl or (C1-6)alkyl-(C3-7)cycloalkyl; X is N or CR5; D is N or CR5; each of Y1 and Y2 is independently O or S; Z is O, N, or NRz wherein Rz is H, (C1-6)alkyl, (C3-7)cycloalkyl or (C1-6)alkyl-(C3- 7)cycloalkyl; R3 and R4 are each independently H, (C1-6)alkyl, first (C3- 7)cycloalkyl, 6- or 10-membered aryl, Het (C1-6)alkyl-6- or 10-membered aryl, (C1-6)alkyl-Het; or each R3 and R4 are independently covalently bonded together to form second (C3-7)cycloalkyl, or heterocycle, all optionally substituted; or when Z is N, either R3 or R4 are independently covalently bonded thereto to form a nitrogen-containing heterocycle; R7 is H, (C1-6 alkyl), (C3-7)cycloalkyl or (C1-6)alkyl-(C3-7)cycloalkyl; or R7 is covalently bonded to either of R3 or R4 to form a heterocycle; A is (C1-6) alkyl-CONHR8 wherein R8 is-6- or 10-membered aryl, or Het; or A is a 6- or 10-membered aryl, or Het said aryl or Het being optionally substituted; or a salt or a derivative thereof; such compounds being potent inhibitors of HCV NS5B polymerase.

L'invention concerne un isomère, un énantiomère, un distéréoisomère ou un tautomère d'un composé représenté par la formule (I), dans laquelle R?1¿ est choisi parmi H, haloalkyle, (C¿1-6?)alkyle, (C¿2-6?)alcényle, (C¿3-7?)cycloalkyle, (C¿2-6?)alkynyle, (C¿5-7?)cycloalcényle, aryle à 6 ou 10 éléments ou Het, tous éventuellement substitués, R?2¿ est choisi parmi (C¿1-6?)alkyle, (C¿3-7?)cycloalkyle, (C¿6-10?)bicycloalkyle, aryle à 6 ou 10 éléments ou Het, tous éventuellement substitués, B est N ou CR?5¿, où R?5¿ est H, halogène, haloalkyle, (C¿1-6?)alkyle, (C¿3-7?)cycloalkyle ou (C¿1-6?)alkyle-(C¿3-7?)cycloalkyle, X est N ou CR?5¿, D est N ou CR?5¿, chacun de Y¿1? et Y¿2? est indépendamment O ou S, Z est O, N ou NR?z¿, où R?z¿ est H, (C¿1-6?)alkyle, (C¿3-7?)cycloalkyle ou (C¿1-6?)alkyle-(C¿3-7?)cycloalkyle, R?3¿ et R?4¿ sont chacun indépendamment H, (C¿1-6?)alkyle, un premier (C¿3-7?)cycloalkyle, aryle à 6 ou 10 éléments, Het, (C¿1-6?)alkyle-aryle à 6 ou 10 éléments, (C¿1-6?)alkyle-Het, ou R?3¿ et R?4¿ sont indépendamment liés ensemble par covalence de manière à former un second (C¿3-7?)cycloalkyle, ou un hétérocycle, tous éventuellement substitués, ou lorsque Z est N, R?3¿ ou R?4¿ est indépendamment lié par covalence à celui-ci de manière à former un hétérocycle contenant de l'azote, R?7¿ est H, (C¿1-6?)alkyle, (C¿3-7?)cycloalkyle ou (C¿1-6?)alkyle-(C¿3-7?)cycloalkyle, ou R?7¿ est lié par covalence à R?3¿ ou R?4¿ de manière à former un hétérocycle, A est (C¿1-6?)alkyl-CONHR?8¿, où R?8¿ est aryle à 6 ou 10 éléments ou Het, ou A est aryle à 6 ou 10 éléments ou Het, ledit aryle ou Het étant éventuellement substitué. L'invention concerne également un sel ou un dérivé correspondant, lesdits composés étant de puissants inhibiteurs de la polymérase du VHC NS5B.

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