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    • 2. 发明申请
    • INHIBITORS OF IKK-β SERINE-THREONINE PROTEIN KINASE
    • IKK-ß丝氨酸蛋白激酶激酶的抑制剂
    • WO2008053185A1
    • 2008-05-08
    • PCT/GB2007/004117
    • 2007-10-29
    • CHROMA THERAPEUTICS LTD.MOFFAT, David, Festus, CharlesDAVIES, Stephen, JohnCHARLTON, Michael, HughHIRST, Simon, ChristopherONIONS, Stuart, ThomasWILLIAMS, Jonathon, Gareth
    • MOFFAT, David, Festus, CharlesDAVIES, Stephen, JohnCHARLTON, Michael, HughHIRST, Simon, ChristopherONIONS, Stuart, ThomasWILLIAMS, Jonathon, Gareth
    • C07D333/38A61K31/381
    • C07D333/38
    • Compounds of formula (IA) or (IB) are inhibitors of IkB kinase (IKK) activity, and are useful in the treatment of autoimmune and inflammatory diseases wherein R 7 is hydrogen or optionally substituted (C 1 C 6 )alkyl; ring A is an optionally substituted aryl or heteroaryl ring of 5-13 ring atoms; Z is a radical of formula R-L 1 -Y 1 -(CH 2 ) z -, wherein: z is 0 or 1; R is a radical of formula (X) or (Y) R1 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; R 6 is hydrogen, or optionally substituted C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl or heteroaryl or -(C=O)R 3 , -(C=O)OR 3 , Or -(C=O)NR 3 wherein R 3 is hydrogen.or optionally substituted (C 1 -C 6 )alkyl; Y 1 is a bond, -(C=O)-, -S(O 2 )-, -C(=O)O-, -OC(=O)-, -(C=O)NR 3 -, -NR 3 (C=O)-, -S(O 2 )NR 3 -, -NR 3 S(O 2 )-, or -NR 3 (C=O)NR 4 -, wherein R 3 and R 4 are independently hydrogen or optionally substituted (CrC6)alkyl, L 1 is a divalent linker radical of formula -(Alk 1 ) m (Q) n (Alk 2 ) p - wherein m, n, p, Q, Alk 1 and AIk 2 are as defined in the claims.
    • 式(IA)或(IB)的化合物是IkB激酶(IKK)活性的抑制剂,可用于治疗其中R 7为氢或任选取代的自身免疫性和炎性疾病(C 1 C 6 )烷基; 环A是任选取代的5-13个环原子的芳基或杂芳基环; Z是式RL的基团,其中:z(Z 2)z 是0或1; R是式(X)或(Y)的基团,R 1是羧酸基团(-COOH)或可被一个或多个细胞内酯酶水解成羧酸基团的酯基; R 6是氢或任选取代的C 1 -C 6烷基,C 3 -C 3 - 芳基或杂芳基或 - (C = O)R 3, - (C = O)OR 3或 - (C = O) 其中R 3为氢或任选取代的(C 1 -C 6 -C 6)烷基; - (C = O) - , - S(O)2 - , - C(= O)O-,-OC(= O ) - , - (C = O)NR 3 - , - NR 3(C = O) - , - S(O NR 3 - , - NR 3 S(O 2 - ) - 或-NR 3(C = O )NR 4 - ,其中R 3和R 4独立地是氢或任选取代的(C 1 -C 6)烷基,L 1, SUP>是二价连接基团,式 - (Alk 1)2(Q)n(Alk 2) )其中m,n,p,Q,Alk 1和Alk 2如权利要求中所定义。
    • 5. 发明申请
    • AMINOHETEROARYL COMPOUNDS AS FOR THE TREATMENT OF DISEASES MEDIATED BY C-MET KINASE ACTIVITY
    • 用于治疗由C-MET激酶活性介导的疾病的氨基酸化合物
    • WO2008053157A1
    • 2008-05-08
    • PCT/GB2007/004013
    • 2007-10-19
    • CHROMA THERAPEUTICS LTD.DRUMMOND, Alan, HastingsKING-UNDERWOOD, JohnONIONS, Stuart, ThomasWILLIAMS, Johathan, GarethHIRST, Simon, Christopher
    • DRUMMOND, Alan, HastingsKING-UNDERWOOD, JohnONIONS, Stuart, ThomasWILLIAMS, Johathan, GarethHIRST, Simon, Christopher
    • C07D401/04C07D401/14A61K31/4439A61P35/00
    • C07D401/14C07D401/04
    • Compounds of formula (I), are inhibitors of c-Met kinase activity, useful inter alia in the treatment of hyperproliferative diseases: wherein X is -N= or -CH=; ring A is optionally substituted mono- or bi-cyclic aryl or heteroaryl having from 5 to 12 ring atoms; ring B is (i) optionally substituted phenyl, (ii) optionally substituted monocyclic heterocyclic having 5 or 6 ring atoms and having one or two nitrogens as the sole ring heteroatoms, (iii) optionally substituted bicyclic ring system of 9 or 10 ring atoms having one two or three ring nitrogens and optionally a ring oxygen as the sole ring heteroatoms; R 2 is selected from hydrogen, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 3 -C 6 )cycloalkyl, and mono- or bi-cyclic heterocyclic having from 5 to 12 ring atoms, R 3 and R 4 are (a) independently selected from hydrogen, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 3 -C 6 )cycloalkyl, and mono- or bi-cyclic heterocyclic having from 5 to 12 ring atoms; or (b) R 3 and R 4 taken together with the carbon to which they are attached form a (C 3 -C 6 )cycloalkyl ring; or (c) one of R 3 and R 4 is as defined in case (a) while the other is a divalent radical selected from -(CH 2 ) 3 - or -(CH 2 ) 4 - in which one or two non-adjacent carbons are replaced by oxygen, sulfur or -NR 3 - wherein Ra is hydrogen or (C 1 -C 3 ) alkyl; R 5 is hydrogen and R 6 is a radical of formula (IA), or R 6 is hydrogen and R 5 is a radical of formula -(Z 1 ) w -(CH 2 ) Z -L 1 -Y 1 -CH(R 7 )-NHR 8 wherein R 7 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; and R 8 is hydrogen; or optionally substituted (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, aryl or heteroaryl Or -(C=O)R 9 , -(C=O)OR 9 , Or -(C=O)NR 9 wherein R 9 is hydrogen or optionally substituted (C 1 -C 6 )alkyl; and -(Z 1 ) w -(CH 2 ) Z -L 1 -Y 1 - is a linker radical as defined in the claims.
    • 式(I)化合物是c-Met激酶活性的抑制剂,尤其用于治疗过度增殖性疾病:其中X是-N =或-CH =; 环A是具有5至12个环原子的任选取代的单环或双环芳基或杂芳基; 环B是(i)任选取代的苯基,(ii)具有5或6个环原子并具有一个或两个氮原子作为唯一环杂原子的任选取代的单环杂环,(iii)具有9或10个环原子的任选取代的双环体系,其具有 一个二或三环氮和任选的环氧作为唯一的环杂原子; R 2选自氢,卤素,(C 1 -C 6 -C 6)烷基,(C 2 -C 6 - C 6 -C 6烯基,(C 3 -C 6)环烷基和具有5至12个环原子的单环或双环杂环 R 3和R 4是(a)独立地选自氢,卤素,(C 1 -C 6 - (C 1 -C 6)烷基,(C 2 -C 6 -C 6)链烯基,(C 3 -C 6 -C 6)环烷基, 和具有5至12个环原子的单环或双环杂环; 或(b)R 3和R 4与它们所连接的碳一起形成(C 3 -C 3)烷基, 6个)环烷基环; 或(c)R 3和R 4中的一个如情况(a)中所定义,而另一个是选自以下的二价基团: - (CH 2) 其中一个或两个不相邻的碳被氧,硫取代,或者 - (CH 2)3 - 或-NR 3 - ,其中R a是氢或(C 1 -C 3 -C 3)烷基; R 5是氢,R 6是式(IA)的基团,或者R 6是氢,R 5是氢, SUB>是式的基团 - (Z 1)Z - (CH 2)2 Z - 其中R 7是(CH 3)NHR 8,其中R 7是氢, 是羧酸基团(-COOH)或可被一个或多个细胞内羧酸酯酶水解成羧酸基团的酯基; 并且R 8是氢; 或任选取代的(C 1 -C 6 -C 6)烷基,(C 3 -C 7 -C 7)环烷基,芳基 或杂芳基或 - (C = O)R 9, - (C = O)或9或 - (C = O)NR 9 其中R 9是氢或任选取代的(C 1 -C 6 -C 6)烷基; 和 - (Z 1) - - - - (CH 2) - Z - L - 1 - 如权利要求中所定义的连接基团。