公开(公告)号：US06610715B1

公开(公告)日：2003-08-26

申请号：US09959947

申请日：2001-11-13

申请人： Yong Sik Youn ,  Myung Xik Xiang ,  Byoung Chol Suh ,  Jong Hoon Kim ,  Kwang Hyuk Lee ,  Eui Kyung Kim ,  Jae Kyu Shin ,  Chung Keun Rhee

发明人： Yong Sik Youn ,  Myung Xik Xiang ,  Byoung Chol Suh ,  Jong Hoon Kim ,  Kwang Hyuk Lee ,  Eui Kyung Kim ,  Jae Kyu Shin ,  Chung Keun Rhee

IPC分类号： A61K31175

CPC分类号： C07D213/77 ,  C07C251/86 ,  C07C281/04 ,  C07C281/14 ,  C07C281/18 ,  C07C337/08 ,  C07C2601/08 ,  C07D213/81 ,  C07D215/42 ,  C07D233/88 ,  C07D239/42 ,  C07D295/30

摘要： The present invention provides novel cathecol hydrazone derivatives of formula (I) or pharmaceutically acceptable salts thereof, wherein R1 is C1-7 alkyl or C3-7 cycloalkyl; R2 is hydrogen, hydroxy, C1-5 alkyl or —CH2CH2C(═O)NH2; R3 and R4 are independently hydrogen, C1-7 alkyl, —C(═X)—R5, or 2-, 3- or 4-pyridyl, prymidyl or phenyl substituted with one or two selected from a group consisting of halogen, C1-6 alkoxy, nitro, trifluoromethyl, C1-6 alkyl and carboxyl, or R3 and R4 are directly bonded by C3-4 containing oxygen, sulfur or nitrogen to form a heterocyclic ring, X is oxygen, sulfur or NH and R5 is C1-7 alkyl, —NHR6, CONH2 or 2-, 3- or 4-pyridyl, prymidyl or phenyl substituted with one selected from a group consisting of halogen, C1-6 alkoxy, nitrile, trifluoromethyl, C1-6 alkyl and carboxyl, and R6 is hydrogen, hydroxy, NH2, C1-5 alkoxy, C1-5 alkyl, pyridyl or phenyl.

摘要翻译： 本发明提供式（I）的新型导管腙衍生物或其药学上可接受的盐，其中R 1为C 1-7烷基或C 3-7环烷基; R2是氢，羟基，C1-5烷基或-CH2CH2C（= O）NH2; R 3和R 4独立地是氢，C 1-7烷基，-C（= X）-R 5或2-，3-或4-吡啶基，莽谷酰基或被一个或两个选自卤素，C1- 6烷氧基，硝基，三氟甲基，C 1-6烷基和羧基，或者R 3和R 4直接通过含有氧，硫或氮的C 3-4键合，形成杂环，X是氧，硫或NH，R 5是C 1-7 烷基，-NHR 6，CONH 2或2-，3-或4-吡啶基，脯氨酰基或被选自卤素，C 1-6烷氧基，腈，三氟甲基，C 1-6烷基和羧基的一个取代的苯基，R 6是 氢，羟基，NH 2，C 1-5烷氧基，C 1-5烷基，吡啶基或苯基。

公开(公告)号：US06103729A

公开(公告)日：2000-08-15

申请号：US931303

申请日：1997-09-16

申请人： Chung Keun Rhee ,  Myung Xik Xiang ,  Byoung Chool Suh ,  Kwang Hyuk Lee ,  Youn Ha Lee ,  Young Gi Kim

发明人： Chung Keun Rhee ,  Myung Xik Xiang ,  Byoung Chool Suh ,  Kwang Hyuk Lee ,  Youn Ha Lee ,  Young Gi Kim

IPC分类号： C07D231/40 ,  C07D233/10 ,  C07D239/90 ,  C07D239/91 ,  C07D333/38 ,  C07D487/04 ,  C07D495/04 ,  A61K31/519 ,  C07D487/22

CPC分类号： C07D487/04 ,  C07D231/40 ,  C07D233/10 ,  C07D239/90 ,  C07D239/91 ,  C07D333/38 ,  C07D495/04

摘要： A phosphodiesterase IV inhibiting cathecol derivatives of the general formula I: ##STR1## or a pharmaceutically acceptable salt thereof in which R1 is C.sub.1-7 alkyl; C.sub.3-7 cycloalkane; phenyl optionally substituted with lower alkyl lower alkoxy, nitro or halogen; pyrimidine optionally substituted with lower alkyl, lower alkoxy, nitro or halogen; or pyridine optionally substituted with lower alkyl, lower alkoxy, nitro or halogen; X, Y and Z are each independently oxygen, nitrogen or sulfur optionally substituted with C.sub.1-7 alkyl, C.sub.3-7 cycloalkane or phenyl; W is oxygen or sulfur is disclosed. In addition, a process for producing the compound of the general formula I and a pharmaceutical composition containing pharmaceutically effective amount of the compound of the general formula I are disclosed.

摘要翻译： 通式I的磷酸二酯酶IV抑制性维管醇衍生物或其药学上可接受的盐，其中R 1为C 1-7烷基; C3-7环烷烃; 任选被低级烷基低级烷氧基，硝基或卤素取代的苯基; 任选被低级烷基，低级烷氧基，硝基或卤素取代的嘧啶; 或任选被低级烷基，低级烷氧基，硝基或卤素取代的吡啶; X，Y和Z各自独立地为氧，氮或硫，任选被C 1-7烷基，C 3-7环烷烃或苯基取代; W是氧或硫。 此外，公开了制备通式I化合物的方法和含有药学有效量的通式I化合物的药物组合物。

公开(公告)号：US06172227B2

公开(公告)日：2001-01-09

申请号：US08931306

申请日：1997-09-16

申请人： Myung Xik Xiang ,  Byoung Chool Suh ,  Chung Keun Rhee ,  Kwang Hyuk Lee ,  Youn Ha Lee ,  Young Gi Kim

发明人： Myung Xik Xiang ,  Byoung Chool Suh ,  Chung Keun Rhee ,  Kwang Hyuk Lee ,  Youn Ha Lee ,  Young Gi Kim

IPC分类号： C07D40112

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D239/50 ,  C07D249/08 ,  C07D401/04 ,  C07D403/04 ,  C07D405/06 ,  C07D405/14

摘要： Novel 4,5-diamino pyrimidine derivatives are described by the following general formula I: in which X is a direct bond, C1-4 alkylene, C1-4 alkyleneoxy, C1-4 alkoxyphenyl or phenyl C1-4 alkylene; Y is a direct bond or C1-2 alkyl, R1 is (i) 5-15 membered cyclic or fused heterocompound which includes one or two atoms selected from a group consisting of nitrogen, oxygen and sulfur and which is substituted with one or two substituents selected from a group consisting of hydrogen, halogen, nitro, hydroxy, C1-6 alkyl, C3-6 alkenyl and halogen C1-4 alkoxy, (ii) C4-10 carbocyclic compound or (iii) hydroxy C1-4 alkoxy, R2 is 5-15 membered cyclic or fused heterocompound which includes one or two nitrogen atoms and, optionally, one oxygen or sulfur atom, and which is substituted with one or two substituents selected from a group consisting of hydrogen, hydroxy, halogen, nitro, hydroxy C1-5 alkyl, C1-6 alkyl, C3-6 alkenyl and halogen C1-4 alkoxy; R3 is hydrogen, in which R4 and R5 are each independently selected from a group consisting of hydroxy, C1-6 alkyl, C3-7 cycloalkyl, C3-6 alkenyl, halogen C1-6 alkyl, halogen C2-6 alkenyl and C1-4alkoxy or R4 and R5 represent each independently in which R6 is selected from a group consisting of hydrogen, hydroxy, C1-6 alkyl, C3-6 alkenyl, halogen C1-6 alkyl, halogen, nitro and C1-4 alkoxy.

摘要翻译： 新的4,5-二氨基嘧啶衍生物由以下通式I描述：其中X是直接键，C 1-4亚烷基，C 1-4亚烷基氧基，C 1-4烷氧基苯基或苯基C 1-4亚烷基; Y是直接键或C1-2烷基，R1是（i）5-15元环或稠合杂化合物，其包含一个或两个选自氮，氧和硫的原子，并被一个或两个取代基取代 选自氢，卤素，硝基，羟基，C 1-6烷基，C 3-6烯基和卤素C 1-4烷氧基，（ii）C 4-10碳环化合物或（iii）羟基C 1-4烷氧基，R 2为 5-15元环或稠合杂化合物，其包含一个或两个氮原子和任选的一个氧或硫原子，并被一个或两个选自氢，羟基，卤素，硝基，羟基C1 烷基，C 1-6烷基，C 3-6烯基和卤素C 1-4烷氧基; R 3是氢，其中R 4和R 5各自独立地选自羟基，C 1-6烷基，C 3-7环烷基，C 3-6烯基，卤素C 1-6烷基，卤素C 2-6烯基和C 1-4烷氧基 或R 4和R 5各自独立地表示，其中R 6选自氢，羟基，C 1-6烷基，C 3-6烯基，卤素C 1-6烷基，卤素，硝基和C 1-4烷氧基。