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    • 2. 发明申请
    • BENZO [E] [1, 3 ] OXAZIN-4-ONE DERIVATIVES AS PHOSPHOINOSITIDE 3-KINASE INHIBITORS
    • 苯并[E] [1,3]氧嗪-4-酮衍生物作为磷酸三磷酸酶抑制剂
    • WO2011012883A1
    • 2011-02-03
    • PCT/GB2010/051221
    • 2010-07-23
    • KARUS THERAPEUTICS LIMITEDSHUTTLEWORTH, Stephen JosephSILVA, Franck AlexandreCECIL, Alexander Richard LiamHILL, Thomas James
    • SHUTTLEWORTH, Stephen JosephSILVA, Franck AlexandreCECIL, Alexander Richard LiamHILL, Thomas James
    • C07D265/24A61K31/536A61P35/00A61P9/00A61P37/00A61P29/00A61P5/00
    • C07D265/24
    • Compounds of formula (I): wherein: W is O, N-H, N-alky!, N-alkenyl, N-alkynyl, N-aryl, N-heteroaryl or S; each X is independently CH or N; R 1 is formula (b) or R 3 is H, alkyl, NH 2 , OH, =0 or halogen; each A and B are independently CH or N; D is NHR 4 ; R 4 is H, alkyl, -C(O)- alkyl. -C(O)-NH 2 , -C(O)-NH- alkyl, -SO 2 - alky!, -SO 2 -NH 2 or -SO 2 -NH- alkyl; R 2 is aryl substituted with at least one nitrogen-containing group or R 2 is a nitrogen-containing heteroaryl, cycloalkyl substituted with a nitrogen-containing group, nitrogen-containing cycloalkyl, C 1 -C 6 mono alkylamino, C 1 C 6 bis alkylamino, C 1 C 6 acylamino, C 1 -C 6 aminoalkyl, mono (C 1 C 6 alkyl) amino C 1 -C 6 alkyl, bis (C 1 C 6 alkyl) amino C 1 C 6 alkyl, C 1 -C 6 -acylamino or C 1 C 6 alkynyl-NR 11 ; R 11 is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, halogen, O-alkyl, NH-alkyl, N-dialkyl, -C(O)-R 7 , -C(O)-NH 2 , -C(O)-NH-R 7 , -SO 2 -R 7 , -SO 2 -NH 2 , -SO 2 -NH- R 7 , NH-acyl, NH-sulfonyl, NR 7 -acyl, NR 7 -suIfonyl, N-C(O)-NH-R 7 , N-SO 2 -NH-R 7 , N-C(O)-NR 7 R 7 or N-SO 2 -NR 7 R 7 ; and R 7 is alkyl, aryl or heteroaryl, are useful as PI3K inhibitors and are useful in therapy.
    • 式(I)化合物:其中:W为O,N-H,N-烷基,N-烯基,N-炔基,N-芳基,N-杂芳基或S; 每个X独立地是CH或N; R1是式(b)或R3是H,烷基,NH2,OH,= 0或卤素; 每个A和B独立地是CH或N; D是NHR4; R4是H,烷基,-C(O) - 烷基。 -C(O)-NH 2,-C(O)-NH-烷基,-SO 2 - 烷基,-SO 2 -NH 2或-SO 2 -NH-烷基; R2是被至少一个含氮基取代的芳基,或R2是含氮杂芳基,被含氮基取代的环烷基,含氮环烷基,C1-C6单烷基氨基,C1C6双烷基氨基,C1C6酰基氨基,C1- (C 1 -C 6烷基)氨基C 1 -C 6烷基,双(C 1 -C 6烷基)氨基C 1 -C 6烷基,C 1 -C 6酰基氨基或C 1 -C 6炔基-NR 11; R 11是H,烷基,烯基,炔基,芳基,杂芳基,卤素,O-烷基,NH-烷基,N-二烷基,-C(O)-R 7,-C(O)-NH 2,-C(O) NH-R7,-SO2-R7,-SO2-NH2,-SO2-NH-R7,NH-酰基,NH-磺酰基,NR7-酰基,NR7-磺酰基,NC(O) NH-R7,NC(O)-NR7R7或N-SO2-NR7R7; 和R7是烷基,芳基或杂芳基,可用作PI3K抑制剂,并且可用于治疗。
    • 10. 发明申请
    • INDOLE DERIVATIVES AS LIGANDS OF CRTH2 RECEPTORS
    • 作为CRTH2受体配体的衍生物
    • WO2010142934A1
    • 2010-12-16
    • PCT/GB2009/050671
    • 2009-06-12
    • PULMAGEN THERAPEUTICS (ASTHMA) LIMITEDHYND, GeorgeMONTANA, John GaryFINCH, HarryARIENZO, RosaAHMED, Shahadat
    • HYND, GeorgeMONTANA, John GaryFINCH, HarryARIENZO, RosaAHMED, Shahadat
    • C07D209/10C07D401/06C07D401/12C07D401/14C07D403/06A61P37/00A61K31/4439C07D409/06C07D409/14C07D413/06C07D417/06C07D417/14A61K31/4178A61K31/422A61K31/404
    • C07D417/14C07D209/10C07D401/06C07D401/12C07D401/14C07D403/06C07D409/06C07D413/06C07D417/06
    • The following compounds are CRTH2 antagonists, useful in treatment of respiratory disease: {3-[3-chloro-4-(pyridine-2-sulfonyl)isothiazol-5-ylmethyl]-5-fluoro-2- methylindol-1-yl}acetic acid, [3-(5-benzenesulfonyl-3-methyl-3H-imidazol-4-ylmethyl)-5-fluoro-2- methylindol-1-yl]acetic acid, [3-(5-benzenesulfonyloxazol-4-ylmethyl)-5-fluoro-2-methylindol-1-yl]acetic acid, [3-(3-benzenesulfonyl-4-met ylthiophen-2-ylmethyl)-5-fluoro-2-methylindol-1- yl]acetic acid, {5-fluoro-2-methyl-3-[2-(pyridin-2-ylsulfamoyl)benzyl]indol-1-yl}acetic acid, {5-fluoro-2-methyl-3-[4-methyl-3-(pyridine-2-sulfonyl)thiophen-2- ylmethyl]indol-1-yl}acetic acid, {5-fluoro-2-methyl-3-[3-methyl-5-(pyridine-2-sulfonyl)-3H-imidazol-4- ylmethyl]indol-1-yl}acetic acid, {5-fluoro-3-[2-(3-fluorophenylsulfamoyl)pyridin-3-ylmethyl]-2-methylindol-1- yl}acetic acid, [3-(4-benzenesulfonyloxazol-5-ylmethyl)-5-fluoro-2-methylindol-1- yl]acetic acid, {3-[2-(3-cyanophenylsulfamoyl)benzyl]-5-fluoro-2-methylindol-1-yl}acetic acid, [3-(4-benzenesulfonylthiazol-5-ylmethyl)-5-chloro-2-methyl-indol-1-yl]acetic acid, [3-(4-benzenesulfonyl-2-methylthiazol-5-ylmethyl)-5-fluoro-2-methylindol-1- yl]acetic acid, and [3-(4-benzenesulfonyl-3-methylisothiazol-5-ylmethyl)-5-fluoro-2- methylindol-1-yl]acetic acid.
    • 以下化合物是可用于治疗呼吸系统疾病的CRTH2拮抗剂:{3- [3-氯-4-(吡啶-2-磺酰基)异噻唑-5-基甲基] -5-氟-2-甲基吲哚-1-基} 乙酸,[3-(5-苯磺酰基-3-甲基-3H-咪唑-4-基甲基)-5-氟-2-甲基吲哚-1-基]乙酸[3-(5-苯磺酰基恶唑-4-基甲基 )-5-氟-2-甲基吲哚-1-基]乙酸,[3-(3-苯磺酰基-4-甲基噻吩-2-基甲基)-5-氟-2-甲基吲哚-1-基]乙酸, {5-氟-2-甲基-3- [2-(吡啶-2-基氨磺酰基)苄基]吲哚-1-基}乙酸{5-氟-2-甲基-3- [4-甲基-3- (吡啶-2-磺酰基)噻吩-2-基甲基]吲哚-1-基}乙酸{5-氟-2-甲基-3- [3-甲基-5-(吡啶-2-磺酰基) 咪唑-4-基甲基]吲哚-1-基}乙酸,{5-氟-3- [2-(3-氟苯基氨磺酰基)吡啶-3-基甲基] -2-甲基吲哚-1-基}乙酸[3 - (4-苯磺酰氧基-5-基甲基)-5-氟-2-甲基吲哚-1-基]乙酸{3- [2-(3-氰基苯基氨磺酰基)苄基] -5-氟-2-甲基吲哚-1-基] 乙酸,[3- (4-苯磺酰基噻唑-5-基甲基)-5-氯-2-甲基 - 吲哚-1-基]乙酸[3-(4-苯磺酰基-2-甲基噻唑-5-基甲基)-5-氟-2- 甲基吲哚-1-基]乙酸和[3-(4-苯磺酰基-3-甲基异噻唑-5-基甲基)-5-氟-2-甲基吲哚-1-基]乙酸。