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    Bridged tricyclic analogs of 2-(carboxycyclopropyl)glycine
    1.
    发明授权
    Bridged tricyclic analogs of 2-(carboxycyclopropyl)glycine 失效
    2-（羧基环丙基）甘氨酸的桥连三环类似物

    公开(公告)号：US06689904B2

    公开(公告)日：2004-02-10

    申请号：US10185445

    申请日：2002-06-27

    申请人： Alexander Alexei Greenfield ,  John Anthony Butera

    发明人： Alexander Alexei Greenfield ,  John Anthony Butera

    IPC分类号： C07C6112

    CPC分类号： C07D493/08 ,  C07C229/50 ,  C07C2603/64

    摘要： This invention provides processes for preparing a group of novel bridged tricyclic compounds having the formula: wherein X is (CH2)n, O, S, SO, SO2 or CR1R2; n is 1 or 2; and R1 and R2 are, independently, hydrogen, halogen, hydroxy, alkyl of one to six carbon atoms, alkoxy of one to six carbon atoms, or R1 and R2, taken together with the carbon to which they are attached, form cycloalkyl of three to six carbon atoms, an alkylidene of up to six carbon atoms or a carbonyl.

    摘要翻译： 本发明提供了制备一组具有下式的新型桥连三环化合物的方法：其中X是（CH 2）n，O，S，SO，SO 2或CR 1 R 2; n为1或2; R 1和R 2独立地是氢，卤素，羟基，1至6个碳原子的烷基，1至6个碳原子的烷氧基或R 1和R 2与 它们所连接的碳形成3至6个碳原子的环烷基，最多6个碳原子的亚烷基或羰基。

    Anthranilic acid analogs
    2.
    发明授权
    Anthranilic acid analogs 失效
    邻氨基苯甲酸类似物

    公开(公告)号：US6127392A

    公开(公告)日：2000-10-03

    申请号：US127753

    申请日：1998-08-03

    申请人： Joseph Richard Lennox ,  Schuyler Adam Antane ,  John Anthony Butera

    发明人： Joseph Richard Lennox ,  Schuyler Adam Antane ,  John Anthony Butera

    IPC分类号： A61K31/27 ,  A61K31/455 ,  C07C233/55 ,  A01N43/40 ,  A01N37/10 ,  C07C205/07 ,  C07C233/54

    CPC分类号： A61K31/455 ,  A61K31/27 ,  C07C233/55

    摘要： Compounds of the formula: wherein:R.sub.1, R.sub.2, R.sub.3, R.sub.4,R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are, independently, hydrogen, COOR.sub.15, halogen, nitro, cyano, C.sub.1-10 alkoxy, C.sub.1-10 haloalkoxy, sulfonic acid, C.sub.1-10 alkylsulfonyl, C.sub.6-12 arylsulfonyl, C.sub.6-12 aralkylsulfonyl, C.sub.1-10 alkylsulfinyl, C.sub.6-12 arylsufinyl, C.sub.6-12 aralkylsulfinyl, sulfamoyl, C.sub.1-10 alkylsulfamido, C.sub.6-12 arylsulfamido, C.sub.1-10 alkanoyl, C.sub.6-12 aryloyl, C.sub.6-12 aralkanoyl, amino, C.sub.1-10 alkylamino, C.sub.2-10 dialkylamino, C.sub.6-12 aralkylamino, C.sub.6-12 arylamino, carboxamido, C.sub.1-10 alkylcarboxamido, C.sub.6-12 arylcarboxamido, C.sub.1-10 haloalkyl, C.sub.1-10 alkyl, C.sub.2-12 alkenyl, C.sub.6-12 aryl, C.sub.6-12 aralkyl; with the proviso that at least one of R.sub.4 and R.sub.5 is COOR.sub.15 ;R.sub.9 is hydrogen, C.sub.1-10 alkyl and C.sub.1-10 haloalkyl;R.sub.10 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 haloalkyl, or C.sub.2-12 alkylidene;R.sub.15 is hydrogen, metal cation, acetylamido, alkoxyacetoyl or a related moiety which delivers the carboxylate in vivo;the dotted line is an optional double bond; with the proviso that when R.sub.10 is an alkylidene moiety, the double bond is absent; andW is nitrogen or carbon bearing a hydrogen, or R.sub.4, R.sub.5 or R.sub.6 as hereinbefore defined; or pharmaceutcal salts thereof, are useful in the treatment of disorders associated with smooth muscle contraction via potassium channel and chloride channel modulation.

    摘要翻译： 下式的化合物：其中：R 1，R 2，R 3，R 4，R 5，R 6，R 7和R 8独立地是氢，COOR 15，卤素，硝基，氰基，C 1-10烷氧基，C 1-10卤代烷氧基，磺酸，C 1 -10烷基磺酰基，C6-12芳基磺酰基，C6-12芳烷基磺酰基，C1-10烷基亚磺酰基，C6-12芳基亚磺酰基，C6-12芳烷基亚磺酰基，氨磺酰基，C1-10烷基磺酰氨基，C6-12芳基磺酰氨基，C1-10烷酰基，C6-12芳基 ，C 6-12芳烷酰基，氨基，C 1-10烷基氨基，C 2-10二烷基氨基，C 6-12芳烷基氨基，C 6-12芳基氨基，甲酰氨基，C 1-10烷基羧酰氨基，C 6-12芳基羧酰胺基，C 1-10卤代烷基，C 1-10烷基， C2-12烯基，C6-12芳基，C6-12芳烷基; 条件是R4和R5中的至少一个是COOR15; R9是氢，C1-10烷基和C1-10卤代烷基; R10是氢，C1-10烷基，C1-10卤代烷基或C2-12亚烷基; R15是氢，金属阳离子，乙酰氨基，烷氧基乙酰基或在体内递送羧酸盐的相关部分; 虚线是可选的双键; 条件是当R 10是亚烷基部分时，双键不存在; 并且W是带有氢的氮或碳，或如上文所定义的R4，R5或R6; 或其药物盐可用于治疗通过钾通道和氯化物通道调节与平滑肌收缩相关的疾病。

    Anthranilic acid analogs
    4.
    发明授权
    Anthranilic acid analogs 失效
    邻氨基苯甲酸类似物

    公开(公告)号：US6046239A

    公开(公告)日：2000-04-04

    申请号：US128493

    申请日：1998-08-03

    申请人： Joseph Richard Lennox ,  Schuyler Adam Antane ,  John Anthony Butera

    发明人： Joseph Richard Lennox ,  Schuyler Adam Antane ,  John Anthony Butera

    IPC分类号： A61K31/192 ,  A61K31/27 ,  A61K31/455 ,  A61K31/195

    CPC分类号： A61K31/27 ,  A61K31/192 ,  A61K31/455

    摘要： Compounds of the formula: ##STR1## wherein: R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are, independently, hydrogen, COOR.sub.15, halogen, nitro, cyano, C.sub.1-10 alkoxy, C.sub.1-10 haloalkoxy, sulfonic acid, C.sub.1-10 alkylsulfonyl, C.sub.6-12 arylsulfonyl, C.sub.6-12 aralkylsulfonyl, C.sub.1-10 alkylsulfinyl, C.sub.6-12 alkylsulfinyl, C.sub.6-12 aralkylsulfinyl, sulfamoyl, C.sub.1-10 alkylsulfamido, C.sub.6-12 alkylsulfamido, C.sub.1-10 alkanoyl, C.sub.6-12 aryloyl, C.sub.6-12 aralkanoyl, amino, C.sub.1-10 alkylamino, C.sub.2-10 dialkylamino, C.sub.6-12 aralkylamino, C.sub.6-12 arylamino, carboxamido, C.sub.1-10 alkylcarboxamido, C.sub.6-12 arylcarboxamido, C.sub.1-10 haloalkyl, C.sub.1-10 alkyl, C.sub.2-12 alkenyl, C.sub.6-12 aryl, C.sub.6-12 aralkyl; with the proviso that at least one of R.sub.4 and R.sub.5 is COOR.sub.15 ;R.sub.9 is hydrogen, C.sub.1-10 alkyl and C.sub.1-10 haloalkyl;R.sub.10 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 haloalkyl, or C.sub.2-12 alkylidene;R.sub.15 is hydrogen, metal cation, acetylamido, alkoxyacetoyl or a related moiety which delivers the carboxylate in vivo;the dotted line is an optional double bond; with the proviso that when R.sub.10 is an alkylidene moiety, the double bond is absent; andW is nitrogen or carbon bearing a hydrogen, or R.sub.4, R.sub.5 or R.sub.6 as hereinbefore defined; or pharmaceutical salts thereof, are useful in the treatment of disorders associated with smooth muscle contraction via potassium channel and chloride channel modulation.

    摘要翻译： 下式的化合物：其中：R 1，R 2，R 3，R 4，R 5，R 6，R 7和R 8独立地是氢，COOR 15，卤素，硝基，氰基，C 1-10烷氧基，C 1-10卤代烷氧基，磺酸，C 1 -10烷基磺酰基，C6-12芳基磺酰基，C6-12芳烷基磺酰基，C1-10烷基亚磺酰基，C6-12烷基亚磺酰基，C6-12芳烷基亚磺酰基，氨磺酰基，C1-10烷基磺酰氨基，C6-12烷基磺酰氨基，C1-10烷酰基，C6-12芳基 ，C 6-12芳烷酰基，氨基，C 1-10烷基氨基，C 2-10二烷基氨基，C 6-12芳烷基氨基，C 6-12芳基氨基，甲酰氨基，C 1-10烷基羧酰氨基，C 6-12芳基羧酰胺基，C 1-10卤代烷基，C 1-10烷基， C2-12烯基，C6-12芳基，C6-12芳烷基; 条件是R4和R5中的至少一个是COOR15; R9是氢，C1-10烷基和C1-10卤代烷基; R10是氢，C1-10烷基，C1-10卤代烷基或C2-12亚烷基; R15是氢，金属阳离子，乙酰氨基，烷氧基乙酰基或在体内递送羧酸盐的相关部分; 虚线是可选的双键; 条件是当R 10是亚烷基部分时，双键不存在; 并且W是带有氢的氮或碳，或如上文所定义的R4，R5或R6; 或其药用盐可用于治疗通过钾通道和氯化物通道调节与平滑肌收缩相关的病症。

    Anthranilic acid analogs
    6.
    发明授权
    Anthranilic acid analogs 失效
    邻氨基苯甲酸类似物

    公开(公告)号：US6096770A

    公开(公告)日：2000-08-01

    申请号：US128492

    申请日：1998-08-03

    申请人： Joseph Richard Lennox ,  Schuyler Adam Antane ,  John Anthony Butera

    发明人： Joseph Richard Lennox ,  Schuyler Adam Antane ,  John Anthony Butera

    IPC分类号： C07C233/63 ,  C07D263/34 ,  A01N43/76 ,  A01N43/80 ,  A61K31/195 ,  A61K31/42

    CPC分类号： C07D263/34 ,  C07C233/63 ,  C07C2101/10

    摘要： Compounds of the formula: ##STR1## wherein: R.sub.1, R.sub.2 and R.sub.3 are, independently, hydrogen, nitro, cyano, C.sub.1-10 haloalkoxy, amino, C.sub.1-10 alkylamino, sulfo, sulfamoyl, C.sub.1-10 alkylsulfonamido, C.sub.2-10 alkylcarboxamido C.sub.2-10 alkanoyl, C.sub.1-10 alkylsulfonyl, C.sub.1-10 haloalkylsulfonyl, C.sub.1-10 carboxyl, C.sub.1-10 haloalkyl and C.sub.6-12 aryl; with the provisos: (1) that R.sub.1, R.sub.2 and R.sub.3 may not all simultaneously be hydrogen, and (2) when R.sub.1 and R.sub.2 are hydrogen, R.sub.3 may not be meta-CF.sub.3 ;R.sub.4, R.sub.5 and R.sub.6 are, independently, hydrogen, halogen, nitro, cyano, C.sub.1-10 carboalkoxy, C.sub.1-10 haloalkoxy, amino C.sub.1-10 alkylamino, sulfo, sulfamoyl, C.sub.1-10 alkylsulfonamido, C.sub.2-10 alkylcarboxamido C.sub.2-10 alkanoyl, C.sub.1-10 alkylsulfonyl, C.sub.1-10 haloalkylsulfonyl, C.sub.1-10 carboxyl, C.sub.1-10 haloalkyl, C.sub.1-10 alkyl and C.sub.6-12 aryl;R.sub.7 is hydrogen, metal cation, acetylamido, alkoxyacetoyl or a related moiety which delivers the carboxylate in vivo; andX, Y and Z may form a C.sub.3-13 carbocyclic ring, oxazole, isoxazole, thiazole, isothiazole, furan, thiophene, 2H-pyrrole, pyrrole, 2-pyrroline, 3-pyrroline, imidazole, pyrazole, 1,2,3-oxadiazole or 1,2,3-triazole bound to the carbon skeleton; or pharmaceutically acceptable salts thereof useful in the treatment of disorders associated with smooth muscle contraction via potassium channel and chloride channel modulation.

    摘要翻译： 下式的化合物：其中：R 1，R 2和R 3独立地是氢，硝基，氰基，C 1-10卤代烷氧基，氨基，C 1-10烷基氨基，磺基，氨磺酰基，C 1-10烷基磺酰氨基，C 2-10烷基甲酰氨基C2-10 烷酰基，C 1-10烷基磺酰基，C 1-10卤代烷基磺酰基，C 1-10羧基，C 1-10卤代烷基和C 6-12芳基; 条件是：（1）R1，R2和R3可能不全部同时为氢，（2）当R 1和R 2为氢时，R 3可以不是间位CF 3; R4，R5和R6独立地是氢，卤素，硝基，氰基，C1-10烷氧基，C1-10卤代烷氧基，氨基C1-10烷基氨基，磺基，氨磺酰基，C1-10烷基磺酰氨基，C2-10烷基羧酰胺基C2-10烷酰基 ，C 1-10烷基磺酰基，C 1-10卤代烷基磺酰基，C 1-10羧基，C 1-10卤代烷基，C 1-10烷基和C 6-12芳基; R7是氢，金属阳离子，乙酰氨基，烷氧基乙酰基或在体内递送羧酸盐的相关部分; X，Y和Z可以形成C3-13碳环，恶唑，异恶唑，噻唑，异噻唑，呋喃，噻吩，2H-吡咯，吡咯，2-吡咯啉，3-吡咯啉，咪唑，吡唑，1,2,3 - 二唑或1,2,3-三唑与碳骨架结合; 或其药学上可接受的盐，其可用于治疗通过钾通道和氯化物通道调节与平滑肌收缩相关的病症。