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    • 3. 发明申请
    • 5-AMINO-4-HYDROXY-7- (IMIDAZO [1,2-A] PYRIDIN-6- YLMETHYL)-8-METHYL-NONAMIDE DERIVATIVES AND RELATED COMPOUNDS AS RENIN INHIBITORS FOR THE TREATMENT OF HYPERTENSION
    • 5-氨基-4-羟基-7-(咪唑并[1,2-A]吡啶-6-基]甲基)-8-甲基壬酰胺衍生物及相关化合物作为治疗高血压的RININ抑制剂
    • WO2007031558A1
    • 2007-03-22
    • PCT/EP2006/066369
    • 2006-09-14
    • SPEEDEL EXPERIMENTA AGHEROLD, PeterMAH, RobertTSCHINKE, VincenzoSTUTZ, StefanSTOJANOVIC, AleksandarMARTI, ChristianeBEHNKE, DirkJELAKOVIC, Stjepan
    • HEROLD, PeterMAH, RobertTSCHINKE, VincenzoSTUTZ, StefanSTOJANOVIC, AleksandarMARTI, ChristianeBEHNKE, DirkJELAKOVIC, Stjepan
    • C07D471/04C07D405/12A61K31/443A61K31/4433A61K31/437A61P9/12A61P9/10
    • C07D405/12C07D471/04
    • Compounds of the general formula (I) or its salt or a compound in which one or more atoms are replaced by their stable, nonradio-active isotopes, in particular its pharmaceutically acceptable salt; in which X is -CH 2 -; R 1 is a mono- to tetrasubstituted, mono- or bicyclic, unsaturated heterocyclic radical having 1 to 4 nitrogen atoms, R 2 is C 1-6 alkyl or C 3-6 cycloalkyl; R 3 is independently of one another H, C 1-6 alkyl, C 1-6 alkoxycarbonyl or C 1-6 alkanoyl; R 4 is C 2-6 alkenyl, C 1-6 alkyl, unsubstituted or substituted aryl- C 1-6 alkyl or C 3-8 cycloalkyl; R 5 is -L m -R 6 ; L is C 1-6 alkylene which is optionally substituted by 1-4 halogen, or a linker: formula (II) n = 0, 1 or 2; m = 0 or 1; R 6 is a radical composed of 2 cyclic systems selected from bicyclo[x.y.z]alkyl, spiro[o.p]alkyl, mono- or bioxabicyclo[x.y.z]alkyl or mono- or bioxaspiro[o.p]alkyl, all of which may be substituted by 1-3 substituents selected from C 1-6 alkyl, C 1-6 alkoxy, cyano, halogen, C 1-6 alkoxy- C 1-6 alkyl, hydroxy-C 1-6 alkyl or dialkylamino, or if m = 0: is also saturated C 3-8 heterocyclyl which comprises 1-2 oxygen atoms, substituted by 1-3 substituents selected from C 1-6 alkyl, C 1-6 alkoxy, cyano, halogen, C 1-6 alkoxy- C 1-6 alkyl, hydroxy- C 1-6 alkyl or dialkylamino, or if m = 1: is also saturated C 3-8 heterocyclyl which comprises 1-2 oxygen atoms, optionally substituted by 1-3 substituents selected from C 1-6 alkyl, C 1-6 alkoxy, cyano, halogen, C 1-6- alkoxy-C 1-6 alkyl, hydroxy-C 1-6 alkyl or dialkylamino; have renin- inhibiting properties and can be used as medicines for the treatment of hypertension.
    • 通式(I)的化合物或其盐或其中一个或多个原子被其稳定的非放射性活性同位素替代的化合物,特别是其药学上可接受的盐; 其中X是-CH 2 - ; R 1是具有1至4个氮原子的单 - 四取代,单或双环不饱和杂环基,R 2是C 1-6 - 烷基或C 3-6环烷基; R 3彼此独立地为H,C 1-6烷基,C 1-6烷氧基羰基或C 1-6烷基, / SUB>烷酰基; R 4是C 2-6链烯基,C 1-6烷基,未取代或取代的芳基-C 1-6烷基, 烷基或C 3-8环烷基; R 5是-L m -R 6; L是任选被1-4个卤素取代的C 1-6亚烷基或连接基:式(II)n = 0,1或2; m = 0或1; R 6是由选自双环[xyz]烷基,螺[op]烷基,单或生双环[xyz]烷基或单或者生物密封[op]烷基的2个环状体组成的基团,全部 其可以被1-3个选自C 1-6烷基,C 1-6 - 烷氧基,氰基,卤素,C 1-6 - 烷基的取代基取代, 烷基,C 1-6烷基或二烷基氨基,或者如果m = 0,也是饱和的C 3 -C 6烷基, 8个杂环基,其包含1-2个氧原子,被1-3个选自C 1-6 - 烷基,C 1-6 - 烷氧基,氰基, 卤素,C 1-6烷氧基-C 1-6烷基,羟基-C 1-6烷基或二烷基氨基,或者如果m = 1 :也包括1-2个氧原子的饱和C 3-8杂环基,任选地被1-3个选自C 1-6烷基的取代基取代,C 1 -C 6烷基, 1-6烷氧基,氰基,卤素,C 1-6 - 烷氧基-C 1-6烷基,羟基-C 1-6烷基, 烷基或二烷基氨基; 具有肾素抑制性质,可用作治疗高血压的药物。
    • 7. 发明申请
    • 5-AMINO-4-HYDROXY-7-(1H-INDOLMETHYL)-8-METHYLNONAMIDE DERIVATIVES AS RENIN INHIBITORS FOR THE TREATMENT OF HYPERTENSION
    • 作为治疗高血压的RININ抑制剂的5-氨基-4-羟基-7-(1H-吲哚基甲基)-8-甲基壬酰胺衍生物
    • WO2005090305A1
    • 2005-09-29
    • PCT/EP2005/051244
    • 2005-03-17
    • SPEEDEL EXPERIMENTA AGHEROLD, PeterSTUTZ, StefanMAH, RobertTSCHINKE, VincenzoSTOJANOVIC, AleksandarJOTTERAND, NathalieQUIRMBACH, MichaelBEHNKE, DirkMARTI, Christiane
    • HEROLD, PeterSTUTZ, StefanMAH, RobertTSCHINKE, VincenzoSTOJANOVIC, AleksandarJOTTERAND, NathalieQUIRMBACH, MichaelBEHNKE, DirkMARTI, Christiane
    • C07D209/20
    • C07C237/06C07C237/22C07D209/12C07D231/56C07D401/12C07D403/12C07D405/12C07D409/12C07D417/12
    • The application relatés to novel alkanamides of the general formula (I) where X is -CH 2 - or >CH-OH; (A) R 1 is e.g. an optionally substituted heterocyclyl radical or an optionally substituted polycyclic, unsaturated hydrocarbon radical where X is hydroxymethylene; R 2 is C 1 -C 6 -alkyl or C 3 -C 6 -cydoalkyl; R 3 are each independently H, C 1 -C 6 -alkyl, C 1-6 -alkoxycarbonyl or C 1 -C 6 -alkanoyl; R 4 is C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 2 -C 6 -alkenyl or unsubstituted or substituted aryl­C 1 -C 6 -alkyl; R 5 is C l -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyloxy­ C 1 -C 6 -alkyl, C 1 -C 6 -aminoalkyl, C 1 -C 6 -alkylamino-C 1 -C 6 -alkyl, C 1 -C 6 -dialkylamino-C l -C 6 -alkyl, C 1 -C 6 -alkanoylamido-C 1 -C 6 -alkyl, HO(O)C-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-O-(O)C-C 1 -C 6 -alkyl, H 2 N-C(O)-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-HN-C(O)-C 1 -C 6 -alkyl, (C 1 ,-C 6 -alkyl) 2 N-C(O)-C 1 -C 6 -alkyl, C 2 -C 8 -alkenyl, C 2 -C 8 -alkynyl, cyano-C 1 -C 6 -alkyl, halo-C l -C 6 -alkyl, optionally substituted aryl-­C o -C 6 -alkyl, optionally substituted C 3 -C 8 -cycloalkyl-C o -C 6 -alkyl or optionally substituted heterocydyl-C o -C 6 -alkyl; to a process for their preparation and to the use of these compounds as medicines, especially as renin inhibitors for the treatment of hypertension.
    • 本发明涉及通式(I)的新型烷酰胺,其中X为-CH 2 - 或> CH-OH; (A)R 1是例如。 任选取代的杂环基或任选取代的多环不饱和烃基,其中X是羟基亚甲基; R 2是C 1 -C 6 - 烷基或C 3 -C 6 - 环烷基; R 3各自独立地为H,C 1 -C 6 - 烷基,C 1-6 - 烷氧基羰基或C 1 -C 6 - 烷酰基; R 4是C 1 -C 6 - 烷基,C 3 -C 6 - 环烷基,C 2 -C 6 - 烯基或未取代或取代的芳基C 1 -C 6烷基; R 5是C 1 -C 6烷基,C 1 -C 6羟基烷基,C 1 -C 6烷氧基-C 1 -C 6烷基,C 1 -C 6烷酰氧基C 1 -C 6烷基,C 1 -C 6氨基烷基,C 1 -C 6 - 烷基氨基-C 1 -C 6 - 烷基,C 1 -C 6 - 二烷基氨基-C 1 -C 6 - 烷基,C 1 -C 6 - 烷酰基氨基-C 1 -C 6烷基,HO(O)C 1 -C 6 - (O)C 1 -C 6烷基,H 2 N-C(O)-C 1 -C 6 - 烷基,C 1 -C 6烷基-NH-C(O)-C 1 -C 6 - 烷基,(C 1 -C 6) - 烷基)N 2 -C(O)-C 1 -C 6 - 烷基,C 2 -C 8 - 烯基,C 2 -C 8 - 炔基,氰基-C 1 -C 6烷基,卤代-C 1 -C 6烷基,任选取代的芳基-Co- C 6 - 烷基,任选取代的C 3 -C 8 - 环烷基-C 0 -C 6 - 烷基或任选取代的杂环-Co-C 6 - 烷基; 其制备方法和这些化合物作为药物的使用,特别是用作治疗高血压的肾素抑制剂。