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    • 5. 发明公开
    • Quinolin-4-yl derivatives
    • Chinolin -4-基 - 衍生物
    • EP1088818A1
    • 2001-04-04
    • EP00120890.9
    • 2000-09-26
    • F. HOFFMANN-LA ROCHE AG
    • Alanine, AlexanderBurner, SergeBuettelmann, BerndHeitz Neidhart, Marie-PauleJaeschke, GeorgPinard, EmmanuelWyler, René
    • C07D215/46A61K31/47C07D405/04C07D401/04A61P25/28
    • C07D215/233C07D215/46C07D401/04C07D405/04C07D409/04
    • The invention relates to compounds of formula
      wherein

      R 1 is hydrogen, lower alkyl, lower alkoxy, hydroxy, amino, nitro, cyano, lower alkyl-amino, di-lower alkyl-amino or halogen;
      R 2 is phenyl, optionally substituted by lower alkyl, lower alkoxy, halogen, trifluoromethyl, amino, lower alkyl-amino or di-lower alkyl-amino 2,3 -dihydro-benzofuran-5-yl, chroman-6-yl, naphthalen-2-yl, indan-5-yl, lower alkenyl-phenyl, 5,6,7,8-tetrahydro-naphthalenyl, 2,3-dihydro-isoindol-2-yl, 1,2,3,4-tetrahydro-naphthalenyl, benzofuran-2-yl, benzo[b]thiophen-2-yl, lower alkyl-phenyl, 3,4-dihydro-1H-isoquinolin-2-yl or thiophen-3-yl;
      R 3 and R 4 are independently from each other hydrogen or lower alkyl;
      R 5 is hydrogen, lower alkyl, -CH 2 OH or -CH 2 NR 6 R 7 ;
      R 6 and R 7 are independently from each other hydrogen, lower alkyl, - (CH 2 ) n -phenyl, cycloalkyl, -(CH 2 ) m -morpholinyl or form together with the N-atom a saturated ring with 4-6 C-atoms;
      n is 0-3;
      m is 2 or 3;
      X is -NR 8 - or -O-; or
      X and R 5 are together >N(CH 2 ) 2 -; or
      X and R 3 are together >N(CH 2 ) 3 -; and
      R 8 is hydrogen or lower alkyl;
      and to pharmaceutically acceptable acid addition salts thereof, with the exception of the following compounds

      (6-chloro-2-phenyl-4-quinolinyl)-(+)-2-aminobutanol;
      (6-methyl-2-phenyl-4-quinolinyl)-(+)-2-aminobutanol;
      (6-methoxy-2-phenyl-4-quinolinyl)-(+)-2-aminobutanol; and
      (8-methoxy-2-phenyl-4-quinolinyl)-(+)-2-aminobutanol, which may be used for the treatment of diseases, which relate to the NMDA receptor specific blockers.
    • 本发明涉及式CHEM的化合物,其中R 1是氢,低级烷基,低级烷氧基,羟基,氨基,硝基,氰基,低级烷基 - 氨基,二 - 低级烷基 - 氨基或卤素; R 2是任选被低级烷基,低级烷氧基,卤素,三氟甲基,氨基,低级烷基 - 氨基或二 - 低级烷基 - 氨基2,3-二氢 - 苯并呋喃-5-基,苯并二氢吡喃-6-基 萘-2-基,茚满-5-基,低级烯基 - 苯基,5,6,7,8-四氢 - 萘基,2,3-二氢 - 异吲哚-2-基, 四氢萘基,苯并呋喃-2-基,苯并噻吩-2-基,低级烷基 - 苯基,3,4-二氢-1H-异喹啉-2-基或噻吩-3-基; R 3和R 4彼此独立地为氢或低级烷基; R 5是氢,低级烷基,-CH 2 OH或-CH 2 NR 6 R 7; R 6和R 7彼此独立地为氢,低级烷基, - (CH 2)n - 苯基,环烷基, - (CH 2)m - 吗啉基或与N-原子一起形成饱和环与4- 6个C原子; n为0-3; m为2或3; X是-NR 8 - 或-O-; 或X和R 5一起为N(CH 2)2 - ; 或X和R 3一起为N(CH 2)3 - ; 和R 8是氢或低级烷基; 和其药学上可接受的酸加成盐,但以下化合物(6-氯-2-苯基-4-喹啉基) - (+) - 2-氨基丁醇; (6-甲基-2-苯基-4-喹啉基) - (+) - 2-氨基丁醇; (6-甲氧基-2-苯基-4-喹啉基) - (+) - 2-氨基丁醇; 和(8-甲氧基-2-苯基-4-喹啉基) - (+) - 2-氨基丁醇,其可用于治疗涉及NMDA受体特异性阻断剂的疾病。
    • 6. 发明公开
    • Triazole and imidazole derivatives
    • Triazolderivate
    • EP1070708A1
    • 2001-01-24
    • EP00114183.7
    • 2000-07-13
    • F. HOFFMANN-LA ROCHE AG
    • Alanine, AlexanderBuettelmann, BerndHeitz Neidhart, Marie-PauleJaeschke, GeorgPinard, EmmanuelWyler, René
    • C07D249/08A61K31/4196C07D403/10C07D233/64A61P25/28
    • C07D233/64C07D249/08C07D401/06C07D403/10C07D405/10
    • The present invention relates to compounds of the general formula
      wherein

      R 1 ― R 4 signify independently hydrogen, -CF 3 , -OCF 3 , OCHF 2 , -OCH 2 F, lower alkyl, lower alkoxy, halogen, hydroxy, phenyl, benzyl, amino, nitro, pyrrol-1-yl, lower alkyl-sulfonyl, lower alkyl-sulfanyl, cyano or benzyloxy; or
      R 2 and R 3 may be together ―O-(CH 2 ) 2 -O-, -O-CH 2 -O-, -O-(CH 2 ) 2 -, -(CH 2 ) 3 - or ―CH=CH-CH=CH-;
      X signifies ―N=, -N(R 8 )- or ―CH=;
      Y signifies ―N=, =N-, -N(R 8 )- or ―CH=; wherein one of X or Y has to be nitrogen;
      R 5 signifies the group
      wherein
      R 6 and R 7 signify independently from each other hydrogen, lower alkyl, -C(O)-lower alkyl, hydroxy-lower alkyl, lower alkenyl, -C(O)CH 2 OH or
      R 6 and R 7 may be together with the N-atom ―(CH 2 ) n -, -(CH 2 ) 2 -O-(CH 2 ) 2 -, -CH 2 -CH=CH-CH 2 , -CH 2 -CH[OC(O)CH 3 ]-(CH 2 ) 2 , -CH 2 -CH[NHC(O)CH 3 ]-(CH 2 ) 2 , -O-(CH 2 ) 3 -, -CH 2 -CH(OCH 3 )-(CH 2 ) 2 -, -CH 2 -CH(halogen)-(CH 2 ) 2 -, -(CH 2 ) 2 -CH(O-phenyl)-(CH 2 ) 2 -, -(CH 2 ) 2 -N(CHO)-(CH 2 ) 2 -, -(CH 2 ) 2 -N(COCH 3 )-(CH 2 ) 2 -, -CH 2 -CH(OH)-(CH 2 ) 3 -, -(CH 2 ) 2 -CH(OH)-(CH 2 ) 2 - or -(CH 2 ) 2 -N(benzyl)-CH 2 ) 2 -;
      n signifies 3 to 5; and
      R 8 signifies hydrogen, lower alkyl, lower alkenyl, lower alkinyl, -(CH 2 ) m -O-lower alkyl, -(CH 2 ) m -OH, -(CH 2 ) m -CHF 2 , -(CH 2 ) m -CH 2 F, -(CH 2 ) m -C(O)-lower alkyl, - (CH 2 ) m -C(O)O-lower alkyl, -(CH 2 ) m -CH(OH)-lower alkyl, -(CH 2 ) m -CH(OH)-(CH 2 ) m OH, -(CH 2 ) m -C 6 H 5 , which phenyl ring is optionally substituted by lower alkyl, lower alkoxy or hydroxy, -(CH 2 ) m -C(=CH 2 )-lower alkyl, - (CH 2 ) m -cycloalkyl, -(CH 2 ) m -CN, -(CH 2 ) m -pyridin-4-yl, -(CH 2 ) m -pyridin-3-yl or - (CH 2 ) m -pyridin-2-yl;
      m signifies 0 to 4;
      and to their pharmaceutically acceptable acid addition salts. These compounds may be used for the treatment of diseases related to the NMDA receptor subtype selective blockers.
    • 本发明涉及通式的化合物,其中R 1 -R 4独立地表示氢,-CF 3,-OCF 3,OCHF 2,-OCH 2 F,低级烷基,低级烷氧基,卤素,羟基,苯基, 苄基,氨基,硝基,吡咯-1-基,低级烷基 - 磺酰基,低级烷基 - 硫烷基,氰基或苄氧基; 或R 2和R 3可以一起-O-(CH 2)2 -O - , - O-CH 2 -O-,-O-(CH 2)2 - , - (CH 2)3 - 或-CH = CH-CH = CH-; X表示-N =,-N(R 8) - 或-CH =; Y表示-N =,= N-,-N(R 8) - 或-CH =; 其中X或Y中的一个必须是氮; R 5表示基团,其中R 6和R 7彼此独立地表示氢,低级烷基,-C(O) - 低级烷基,羟基 - 低级烷基,低级烯基,-C( O)CH 2 OH或R 6和R 7可以与N-原子 - (CH 2)n - , - (CH 2)2 -O-(CH 2)2 - , - CH 2 -CH = CH-CH 2 ,-CH 2 -CH(O)CH 3 - (CH 2)2,-CH 2 -CHNC(O)CH 3 - (CH 2)2,-O-(CH 2)3 - , - CH 2 -CH(OCH 3) - )2-,-CH 2 -CH(卤素) - (CH 2)2 - , - (CH 2)2 -CH(O-苯基) - (CH 2)2 - , - (CH 2)2 -N(CHO) - )2-, - (CH 2)2 -N(COCH 3) - (CH 2)2 - , - CH 2 -CH(OH) - (CH 2)3 - , - (CH 2)2 -CH(OH) - (CH 2)2 - 或 - (CH 2)2 -N(苄基)-CH 2)2 - ; n表示3到5; (CH2)m-OH, - (CH2)m-CHF2, - (CH2)m-CH2F, - (CH2)m-CHF2, - (CH 2)m C(O) - 低级烷基, - (CH 2)m C(O)O-低级烷基, - (CH 2)m -CH(OH) - 低级烷基, - (CH 2)m -CH(OH) (CH2)mOH, - (CH2)m-C6H5,该苯基环任选被低级烷基,低级烷氧基或羟基取代, - (CH 2)m C(= CH 2) - 低级烷基, - (CH 2)m - (CH 2)m - 吡啶-3-基或 - (CH 2)m - 吡啶-2-基; - (CH 2)m - m表示0到4; 及其药学上可接受的酸加成盐。 这些化合物可用于治疗与NMDA受体亚型选择性阻断剂有关的疾病。
    • 8. 发明公开
    • 4-Hydroxy-piperidine derivatives
    • 4-羟基 - 哌啶衍生物
    • EP0846683A1
    • 1998-06-10
    • EP97121040.6
    • 1997-12-01
    • F. HOFFMANN-LA ROCHE AG
    • Alanine, AlexanderBüttelmann, BerndHeitz Neidhart, Marie-PaulePinard, EmmanuelWyler, René
    • C07D211/48C07D405/06A61K31/445A61K31/34A61K31/35C07D401/06
    • C07D401/06C07D211/48C07D405/06
    • The present invention relates to 4-hydroxy-piperidine derivatives of the general formula
      wherein

      X denotes -O-, -NH-, -CH 2 -, -CH=, -CHOH-, -CO-, -S-, -SO- or -SO 2 -;
      R 1 -R 4 are, independently from each other, hydrogen, hydroxy, lower-alkyl-sulfonylamino, 1- or 2-imidazolyl or acetamido;
      R 5 -R 8 are, independently from each other, hydrogen, hydroxy, lower-alkyl, halogen, lower-alkoxy, trifluoromethyl or trifluoromethyloxy;
      a and b may be a double bond, provided that when "a" is a double bond, "b" cannot be a double bond;
      n is 0-2;
      m is 1-3;
      p is 0 or 1
      and to pharmaceutically acceptable addition salts thereof.
      Compounds of the present invention are NMDA(N-methyl-D-aspartate)-receptor subtype selective blockers, which can be used in mediating processes underlying development of CNS including learning and memory formation and function.
    • 本发明涉及以下通式的4-羟基 - 哌啶衍生物,其中X表示-O - , - NH - , - CH 2 - , - CH =, - CHOH - , - CO - , - -SO2-; R1-R4彼此独立地为氢,羟基,低级烷基 - 磺酰基氨基,1-或2-咪唑基或乙酰氨基; R5-R8彼此独立地为氢,羟基,低级烷基,卤素,低级烷氧基,三氟甲基或三氟甲氧基; a和b可以是双键,条件是当“a”是双键时,“b”不能是双键; n是0-2; m是1-3; p是0或1,并且涉及其药学上可接受的加成盐。 本发明的化合物是NMDA(N-甲基-D-天冬氨酸) - 受体亚型选择性阻断剂,其可以用于介导CNS发展的过程,包括学习和记忆形成和功能。